Effects of Breathing Exercises in Patients With Chronic Obstructive Pulmonary Disease: A Network Meta-analysis.

OBJECTIVE: A network meta-analysis of randomized controlled trials (RCTs) was conducted to compare and rank the effectiveness of various breathing exercises for patients with chronic obstructive pulmonary disease (COPD). DATA SOURCES: We searched PubMed, Web of Science, Embase, and the Cochrane Library databases to determine the articles. STUDY SELECTION: Publications investigating the effect of breathing exercises on exercise capacity (six-minute walk test [6MWT]), pulmonary function (the ratio of the first second forced expiratory volume of forced vital capacity [FEV1/FVC]), quality of life (St George's Respiratory Questionnaire [SGRQ]), inspiratory muscle pressure (maximum inspiratory pressure [PImax]), and dyspnea (Borg scale) were searched. DATA EXTRACTION: Data extracted by 2 researchers were entered into predesigned tables for data extraction. The quality of the literature was assessed using the Cochrane Collaboration's tool. DATA SYNTHESIS: A total of 43 RCTs involving 1977 participants were analyzed. To boost exercise capacity, the top 2 exercises were inspiratory muscle training (75%), Chinese traditional fitness exercises (13%); To improve pulmonary function, the top 2 exercises were Chinese traditional fitness exercises (32%), diaphragm breathing (30%); To raise patients' quality of life, the top 2 exercises were yoga (52%), diaphragm breathing (28%); To increase inspiratory muscle pressure, the top 2 exercises were pursed-lip breathing (47%), Chinese traditional fitness exercises (25%); To improve dyspnea, the top 2 exercises were yoga (44%), inspiratory muscle training (22%). CONCLUSIONS: Various breathing exercises for COPD patients confer benefits that manifest in diverse ways. Pulmonary rehabilitation specialists could administer personalized breathing exercises tailored to each patient's condition to attain optimal therapeutic outcomes.

A systematic review of parental burnout and related factors among parents.

BACKGROUND: Parenting is both a complex and stressful endeavor, so parents sometimes experience parenting burnout. The main objective of this study was to provide an overview of factors related to general parental burnout (PB) among parents with at least one child based on the Ecological Systems Theory (EST). METHODS: PubMed, Web of Science, EBSCO, CNKI and WanFang were systematically searched for studies published from 2010 to July 2023 for peer-reviewed articles using keywords extracted from Medical Subject Headings such as "parenting", "parental", "burnout", "psychological burnout", "burn-out syndrome". Studies were included if they described associations between factors and PB among parents of children aged 0-18 years old in the general population, and published in an English or Chinese language peer-reviewed journal. The Quality Assessment Tool for Studies with Diverse Designs (QATSDD) was employed to assess the risk of bias of included studies. RESULTS: Of 2037 articles, 26 articles met the inclusion criteria. Based on the Ecological Systems Theory (EST), we found that microsystem-individual factors such as gender, educational level, income, parental personality, internalization of maternal parental motivation, unmitigated communion, self-compassion and concern for others, alexithymia, anxiety and depressive symptoms, parental perfectionism, resilience, low self-esteem and high need for control, mother's attachment style were identified as being associated with parenting burnout. Mesosystem-interpersonal factors involve parent-child relationship and marital satisfaction. The exosystem-organizational or community factors include the number of children in the household, neighborhood and the number of hours spent with children, child's illness, child's behavior problems and social support. The macrosystem-society/policy or culture factors are mainly personal values and cultural values. CONCLUSIONS: This systematic review found several factors that have been investigated in relation to PB. However, the majority of the factors were reported by one or two studies often implementing a cross-sectional design. Nevertheless, we still recommend that health policymakers and administrators relieve parenting burnout among parents with children by adjusting these modifiable factors.

A Multiple Targeting Nanoprobe for Identifying Cancer Metastatic Sites Based on Detection of Various mRNAs in Circulating Tumor Cells.

Identification of cancer metastatic sites is of importance for adjusting therapeutic interventions and treatment choice. However, identifying the location of metastatic lesions with easy accessibility and high safety is challenging. Here we demonstrate that cancer metastatic sites can be accurately detected by a triple targeting nanoprobe. Through coencapsulating molecular beacons probing a cancer biomarker (CXCR4 mRNA), a lung metastatic biomarker (CTSC mRNA), and a bone metastatic biomarker (JAG1 mRNA), the nanoprobe decorated by SYL3C conjugated hyaluronic acid and ICAM-1 specific aptamer conjugated hyaluronic acid can target diverse phenotyped circulating tumor cells (CTCs) during epithelial-mesenchymal and mesenchymal-epithelial transitions in whole blood for sensitive probing. The detection of CTCs from cancer patients shows that the nanoprobe can provide accurate information to distinguish different cancer metastasis statuses including nonmetastasis, lung metastasis, and bone metastasis. This study proposes an efficient screening tool for identifying the location of distant metastatic lesions via facile blood biopsy.

Impact of caregiving on frailty in older spousal caregivers: A retrospective cohort study.

Older spousal caregivers bear the dual burden of managing health changes and caring for their partners. This study aimed to investigate the association between spousal caregiving and frailty in older adults. A retrospective cohort study with a 4-year follow-up was conducted using seven waves of data from the Health and Retirement Study (2006-2018). The mean age of participants was 65.1 years. A significant correlation was found between spousal caregiving and frailty increase. Multilevel analysis demonstrated a significant difference in the changes in frailty index over 12 years between caregivers and non-caregivers. This study uncovered a significant association between spousal caregiving and frailty in older adults, suggesting that becoming a spousal caregiver is not only linked to higher levels of frailty but also accelerates its progression. Healthcare providers can tailor support services to assist caregivers in managing challenges and promoting healthy aging.

The effect of body mass index on self-rated health in middle-aged and older adults: evidence from the China health and retirement longitudinal study.

BACKGROUND AND AIMS: Health promotion for middle-aged and older people has received a lot of attention recently in the context of healthy aging. Furthermore, it is unclear how body mass index (BMI) presently affects self-rated health (SRH), a reliable and representative indicator of health. METHODS: This study used longitudinal follow-up data from the China Health and Retirement Longitudinal Study (CHARLS). Systematic collection of information on the socio-demographic, lifestyle, and health status of the subjects. Binary logistic regression was used to investigate the relationship between BMI and SRH, and gender-specific variations were examined. Subgroup analysis was used to examine interactions, and the results of the research stability were demonstrated. RESULTS: After adjusting for age, gender, education level, marital status, place of residence, number of chronic diseases, alcohol consumption, smoking, depressive symptoms, and SRH at baseline, it was found that obesity grade 1 and obesity grade 2 were good contributors to SRH compared to normal weight individuals, and this association was different in males and females. According to the results of the subgroup analyses, those under 65 years old, with junior high school or less education, with a spouse, residing in a city, having one chronic disease, and not smoking or drinking, respectively, all had stable positive associations between obesity and SRH. CONCLUSIONS: Our findings suggest that obesity may be associated with good SRH. Teams of healthcare professionals should revisit the potential impact of obesity among middle-aged and older adults and focus on developing prevention strategies for morbid obesity.

Detection of mRNAs of Ribosomal Protein L15 and E-Cadherin in Living Circulating Tumor Cells at Single Cell Resolution To Study Tumor Heterogeneity.

To study the heterogeneity of circulating tumor cells (CTCs) is of crucial importance to analyze cancer progression and metastasis. However, in situ detection of highly heterogeneous CTCs in peripheral blood still faces an elusive challenge. Here, we show direct detection of two metastasis-related mRNAs of diverse CTCs in whole blood by a triple-targeting nanoprobe. In the nanoprobe, two kinds of molecular beacons, MB1 to detect RPL15 mRNA and MB2 to detect E-cadherin (E-cad) mRNA, are loaded in a highly efficient delivery vector decorated with EpCAM-targeted SYL3C, EGFR-targeted CL4, and CD44-targeted hyaluronic acid chains to specifically deliver MB1/MB2 into epithelial, mesenchymal, and stem CTCs in unprocessed peripheral blood. The numbers of RPL15+ and E-cad+ CTCs are positively correlated with the metastasis stages of cancer patients. This study provides an effective strategy to realize direct observation on diverse metastasis-related genes in living CTCs with different phenotypes to provide accurate information on cancer heterogeneity and metastasis.

In Situ Detection of Nanotoxicity in Living Cells Based on Multiple miRNAs Probed by a Peptide Functionalized Nanoprobe.

The potential toxicity of nanoparticles, especially for clinically applicable ones, has become a critical concern. Technologies that can in situ-evaluate the toxicity of nanoparticles with high sensitivity are urgently needed. In this study, a facile strategy was developed for sensitive detection on the nanotoxicity of nanoparticles with low toxicity or a low dose. A functional nanoprobe loaded with molecular beacons was constructed to realize in situ evaluation of the nanotoxicity through probing multiple miRNAs in nanoparticle-exposed living cells. Being composed of protamine complexed with molecular beacons for miRNA detection and decorated by TAT and KALA peptides, the dual-peptide functionalized nanoprobe can efficiently deliver molecular beacons into living cells to realize the real-time monitoring of early biomarkers (miR-21 and miR-221) to evaluate nanotoxicity. Using mesoporous silica nanoparticles (MSNs) with different surface modifications as typical representatives of low toxic nanoparticles, we demonstrate that our nanoprobe can sensitively detect miRNA changes in cells under diverse exposure conditions, that is, MSN-NH2 exhibits the strongest capability to upregulate miR-21 and miR-221, and the upregulation is exposure dose- and time-dependent. Our approach is much more sensitive as compared with conventional methods to study cytotoxicity such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell morphology observation, and reactive oxygen species (ROS) assay. This study paves a path for effective and facile nanotoxicity evaluation and provides insights into the biological impacts of MSNs.

Precise Detection on Cell-Cell Fusion by a Facile Molecular Beacon-Based Method.

Cell-cell fusion studies provide an experimental platform for evaluating disease progression and investigating cell infection. However, to realize sensitive and quantitative detection on cell-cell fusion is still a challenge. Herein, we report a facile molecular beacon (MB)-based method for precise detection on cell-cell fusion. By transfection of the spike protein (S protein) and enhanced green fluorescent protein (EGFP) in HEK 293 cells, the virus-mimicking fusogenic effector cells 293-S-EGFP cells were constructed to interact with target cells. Before mixing the effector cells with the target cells, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression in 293-S-EGFP cells was silenced, and the MB for GAPDH mRNA detection was delivered into the GAPDH silenced 293-S-EGFP cells. Once cell-cell fusion occurred, MB migrated from the GAPDH silenced effector cells to the target cells and hybridized with GAPDH mRNA in the target cells to induce fluorescence emission. The cell-cell fusion can be easily visualized and quantitated by fluorescence microscopy and flow cytometry. The fluorescence intensity is strongly dependent on the number of fused target cells. This MB-based method can easily identify the differences in the cell fusions for various target cells with different angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) expression levels, resulting in dramatically different fluorescence intensities in fused target cells. Our study provides a convenient and efficient quantitative detection approach to study cell-cell fusion.

Bioinspired supramolecular fibers drawn from a multiphase self-assembled hydrogel.

Inspired by biological systems, we report a supramolecular polymer-colloidal hydrogel (SPCH) composed of 98 wt % water that can be readily drawn into uniform ([Formula: see text]6-[Formula: see text]m thick) "supramolecular fibers" at room temperature. Functionalized polymer-grafted silica nanoparticles, a semicrystalline hydroxyethyl cellulose derivative, and cucurbit[8]uril undergo aqueous self-assembly at multiple length scales to form the SPCH facilitated by host-guest interactions at the molecular level and nanofibril formation at colloidal-length scale. The fibers exhibit a unique combination of stiffness and high damping capacity (60-70%), the latter exceeding that of even biological silks and cellulose-based viscose rayon. The remarkable damping performance of the hierarchically structured fibers is proposed to arise from the complex combination and interactions of "hard" and "soft" phases within the SPCH and its constituents. SPCH represents a class of hybrid supramolecular composites, opening a window into fiber technology through low-energy manufacturing.

Association of a body shape index with femur bone mineral density among older adults: NHANES 2007-2018.

This study investigated the relationship between A body shape index (ABSI) and bone mineral density (BMD) in older Americans and found a negative linear association, which was particularly pronounced in diabetic population. An early focus on ABSI in the elderly population will help in the prevention of osteoporosis. OBJECTIVE: A body shape index (ABSI) is an abdominal obesity index developed based on epidemiological statistics and high ABSI indicates that waist circumference (WC) is higher than expected for a given height and weight and corresponds to a more central concentration of body volume. The objective of this study was to determine whether there is a linear or nonlinear relationship between ABSI and total femur bone mineral density (BMD) in older Americans and whether the relationship between the ABSI and total femur BMD varies across populations. METHODS: This cross-sectional study was based on data from the 2007-2018 National Health and Nutrition Examination Survey (NHANES). Weighted multiple linear regression, restricted cubic spline (RCS) curves, subgroup analysis, and interaction tests were used to examine the association between ABSI and total femur BMD. RESULTS: This study included 2505 older adults. This study found a negative linear correlation between ABSI and total femur BMD (ß = -3.2, 95%CI: -5.0, -1.4, p < 0.001). When participants were grouped according to quartiles of ABSI, those in the upper quartile had lower total femur BMD compared to those in the bottom quartile of ABSI. This negative association remained consistent across gender, age, education level, smoking, physical activity and BMI subgroups. However, in the diabetes subgroup, ABSI showed a stronger negative association with total femur BMD. CONCLUSIONS: The study shows a negative linear association between ABSI and total femur BMD in older Americans, with this negative association being stronger in the diabetic population.

Association of weight-adjusted waist index with hyperuricemia and gout among middle-aged and older adults in America: a cross-sectional analysis of NHANES 2007-2014.

OBJECTIVES: The weight-adjusted waist circumference index (WWI), a novel obesity indicator, gives better accuracy in assessing both muscle and fat mass. Our goal was to evaluate the relationship between WWI and the occurrence of hyperuricemia/gout among middle-aged and older adults in America. METHODS: We analyzed the National Health and Nutrition Examination Survey (NHANES) data from the 2007-2014 cycles. Logistic regression analyses, subgroup analyses, and restricted cubic splines (RCS) were performed to evaluate the association between WWI and hyperuricemia/gout prevalence. RESULTS: A total of 5332 adults aged 50 years and above were included in this study. The prevalence of hyperuricemia and gout was 23.20% and 6.70% respectively. The fourth quartile of WWI was associated with a 56% higher risk for hyperuricemia, compared with the first quartile (OR = 1.56, 95% CI 1.07-2.27, P trend < 0.001). A similar association was found between continuous WWI increase and OR of hyperuricemia in the fully adjusted model (OR = 1.35, 95% CI = 1.13-1.61, P < 0.05). However, WWI was not significantly associated with the prevalence of gout. The RCS model suggested a significant linear relationship between WWI and the risk of hyperuricemia/gout. Stratification analysis showed that the positive associations of WWI with the risk of hyperuricemia were more pronounced in participants who were women, aged 50-59, smokers, no physical activity, non-diabetes, hypertension, and hyperlipidemia. CONCLUSIONS: Our findings suggest a positive correlation between WWI and hyperuricemia among middle-aged and older adults in America. Employing WWI as a tool for hyperuricemia prevention may be meaningful. Key Points • Weight-adjusted waist circumference index is a new obesity evaluation index. • Weight-adjusted waist circumference index is associated with hyperuricemia not gout. • The association is more pronounced in participants who were women, aged 50-59, smokers, no physical activity, non-diabetes, hypertension, and hyperlipidemia.

Associations between self-perceptions of aging and social functioning in older adults: An analysis based on health and retirement study data.

OBJECTIVES: Self-perception of aging (SPA) and social functioning are two important variables in the process of healthy aging, but the relationship between them is still unclear. This study aimed to explore the association between SPA and social functioning in older adults. METHODS: We conducted a longitudinal study utilizing data from the Health and Retirement Study. The sample comprised individuals aged 50 and above. Socio-demographic, psychosocial, and lifestyle information of study participants was systematically collected at baseline (2012 and 2014) and during follow-up four years later (2016 and 2018). SPA was measured using a scale assessing individuals' attitudes toward their aging process. Social functioning was evaluated through 22 questions, reflecting individuals' abilities to engage in and perform various roles and tasks in their daily lives. Multilevel modeling was employed to analyze the relationship between SPA and social functioning. Differences in social functioning changes among various SPA groups were assessed through the Generalized Estimating Equations methodology. RESULTS: The study included 8,454 participants with an average age of 68.3 years (SD = 9.92). The multilevel model revealed a significant correlation between SPA and social functioning (ß = 0.131; P < 0.001). This relationship persisted after adjusting the model (ß = 0.088; P < 0.001). Generalized Estimating Equations indicated noteworthy differences in social functioning changes among distinct SPA groups (P = 0.034). DISCUSSION: Positive SPA is associated with the healthy social functioning of older adults. Healthcare providers could target modifiable aspects of SPA to enhance the social function of older adults and promote successful aging.

3D hierarchically fractal structure stabilized anode for achieving long-term cycle life of aqueous Zn-ion batteries.

The cycling stability of aqueous Zn-ion battery (AZIB) is a serious issue for their successful application, mainly due to the considerable growth of Zn dendrites and the existence of side effects during operation. Herein, the hierarchically three-dimensional (3D) fractal structure of the ZnO/Zn/CuxO@Cu (ZZCC) anode is prepared by a two-step process, where CuxO nanowires are prepared on Cu foam by thermal oxidation method and Zn layer and ZnO surface are formed by plating. This fractal structure increases the electrodynamic surfaces and reduces the local current density, which can regulate Zn plating and inhibit dendritic growth and side effects. Apparently, the symmetric ZZCC-based cell shows a long-term operation time of 3000 h at 1 mA cm-2 with 1 mAh cm-2, and an operation time of more than 1000 h with a discharge depth of 15.94%. Compared with the bare Zn foil anode, the AZIB assembled with the composite of Mn-doped vanadium oxide and reduced graphene oxide cathode and ZZCC anode (MnVO@rGO//ZZCC) exhibits significantly improved cyclability (i.e. with 88.5% capacity retention) and achieves a Coulomb efficiency of 99.4% at 2 A g-1. This hierarchically 3D structure strategy to design anodes with superior cyclic stability contributes to the next generation of secure energy.

Dendrite-free Zn anode enabled by combining carbon nanoparticles hydrophobic layer with crystal face reconstruction toward high-performance Zn-ion battery.

Aqueous zinc ion batteries (ZIBs) have been considered promising energy storage systems due to their excellent electrochemical performance, environmental toxicity, high safety and low cost. However, uncontrolled dendrite growth and side reactions at the zinc anode have seriously hindered the development of ZIBs. Herein, we prepared the carbon nanoparticles layer coated zinc anode with (103) crystal plane preferential oriented crystal structure (denoted as C@RZn) by a facile one-step vapor deposition method. The preferential crystallographic orientation of (103) crystal plane promotes zinc deposition at a slight angle, effectively preventing the formation of Zn dendrites on the surface. In addition, the hydrophobic layer of carbon layer used as an inert physical barrier to prevent corrosion reaction and a buffer during volume changes, thus improving the reversibility of the zinc anode. As a result. the C@RZn anode achieves a stable cycle performance of more than 3000 h at 1 mA cm-2 with CE of 99.77 % at 5 mA cm-2. The full battery with C@RZn anode and Mn-doped V6O13 (MVO) cathode show stability for 5000 cycles at the current density of 5 A g-1. This work provides a new approach for the design of multifunctional interfaces for Zn anode.

Aptamer/Peptide-Functionalized Nanoprobe for Detecting Multiple miRNAs in Circulating Malignant Cells to Study Tumor Heterogeneity.

Identification of diverse biomarkers in heterogenic circulating malignant cells (CMCs) such as circulating tumor cells (CTCs) and circulating tumor endothelial cells (CTECs) has crucial significance in tumor diagnosis. However, it remains a substantial challenge to achieve in situ detection of multiple miRNA markers in living cells in blood. Herein, we demonstrate that an aptamer/peptide-functionalized vector can deliver molecular beacons into targeted living CMCs in peripheral blood of patients for in situ detection of multiple cancer biomarkers, including miRNA-21 (miR-21) and miRNA-221 (miR-221). Based on miR-21 and miR-221 levels, heterogenic CMCs are identified for both nondistant metastatic and distant metastatic cancer patients. CMCs from nondistant metastatic and distant metastatic cancer patients exhibit similar miR-21 levels, while the miR-221 level in CMCs of the distant metastatic cancer patient is higher than that of the nondistant metastatic cancer patient. With the capability to realize precise probing of multiple intracellular biomarkers in living CMCs at the single-cell resolution, the nanoprobe can reveal the tumor heterogeneity and provide useful information for diagnosis and prognosis. The nanoprobe we developed would accelerate the progress toward noninvasive precise cancer diagnosis.

ATRX loss suppresses the type I interferon response in sarcoma cells through chromatin remodeling.

Sarcomas constitute a heterogeneous group of mesenchymal cancers and are particularly common in children and adolescents, leading to significant lethality. Therefore, it is necessary to understand the underlying mechanisms by which genetic alterations promote sarcoma progression. Here, we demonstrate that loss-of-function of ATRX, a member of the SWI/SNF DNA-remodeling family, represses the interferon (IFN)-ß response by inducing chromatin remodeling in sarcoma cells. We show that ATRX mutations are associated with worse prognosis and attenuate IFN-α/ß response in patients with specific types of sarcomas. Using poly(I:C) as a stimulation model, we show that natural ATRX mutation or ATRX depletion via CRISPR/Cas9 or siRNA significantly suppresses the expression of IFNB1 and other cytokines in sarcoma cells. Moreover, RNA-seq data reveal that ATRX ablation globally influences the expression pattern of poly(I:C)-stimulated genes (PSGs). Through ATAC-seq, we show that ATRX loss enhance chromatin accessibility generally, which consistent with the heterochromatin modulating function of ATRX. However, a set of PSGs display a decrease of chromatin accessibility after ATRX depletion, indicating that ATRX promote the transcription of these genes through chromatin remodeling. Thus, we highlight that ATRX mutation plays critical roles in blocking Type I IFN signaling in sarcoma cells and point out the clinical importance of this effect on sarcoma treatment.

Biomimetic Nanophotosensitizer Amplifies Immunogenic Pyroptosis and Triggers Synergistic Cancer Therapy.

Immunotherapy is considered to be an effective treatment for cancer and has drawn extensive interest. Nevertheless, the insufficient antigenicity and immunosuppressive tumor microenvironment often cause unsatisfactory therapeutic efficacy. Herein, a photo-activated reactive oxygen species (ROS) amplifying system (defined as "M-Cu-T") is developed to induce antitumor immune response by triggering a tumor-specific immunogenic pyroptosis. In M-Cu-T, M1 macrophage membrane-based vesicles are used for drug loading and tumor targeting, photosensitizers (meso-tetra(4-aminophenyl) porphyrin, TAPP) are used as a pyroptosis inducer, copper ions (Cu2+ ) can enhance ROS-induced pyroptosis by consuming antioxidant systems in cells. As expected, the prepared M-Cu-T targets enrichment into tumor cells and cascades the generation of ROS, which further induces pyroptosis through caspase 3-mediated gasdermin E (GSDME) cleavage under laser activation. The pyroptotic cancer cells accompanying secrete related pattern molecules, induce immunogenic cell death, and activate antitumor immunity for immunotherapy. An effective tumor ablation is observed in LLC and CT26 cancer mouse models. This study provides inspiration for boosting the immunogenicity and achieving satisfactory therapeutic effects in cancer therapy.

Multi-Targeting Nano-Systems Targeting Heterogeneous Cancer Cells for Therapeutics and Biomarker Detection.

Cancer heterogeneity plays a vital part in cancer resistance and metastasis. To provide a reliable approach to exert a therapy action and evaluate its efficiency in heterogeneous cancer cells, a multiple targeting delivery vector composed of histone encapsulating the therapeutic or diagnostic agent, hyaluronic acid targeting CD44 overexpressed in stem tumor cells, SYL3C aptamer targeting epithelial cell adhesion molecule (EpCAM) overexpressed in epithelial cancer cells, and CL4 aptamer targeting epidermal growth factor receptor (EGFR) overexpressed in mesenchymal cancer cells, is developed. The vector can efficiently target different cancer cells and circulating tumor cells (CTCs) in the peripheral blood of patients for mucin 1 (MUC1) knockout. Furthermore, the multiple targeting vector can be used to co-encapsulate three types of molecular beacons for probing various mRNA biomarkers at single-cell resolution after genome editing. This study provides an efficient approach for exerting therapeutic actions in heterogeneous cancer cells and assessing the therapeutic efficacy by detection of cancer biomarkers via liquid biopsy.

A Multifunctional Delivery System for Remodulating Cell Behaviors of Circulating Malignant Cells to Prevent Cell Fusion.

Cell fusion plays a critical role in cancer progression and metastasis. However, effective modulation of the cell fusion behavior and timely evaluation on the cell fusion to provide accurate information for personalized therapy are facing challenges. Here, it demonstrates that the cancer cell fusion behavior can be efficiently modulated and precisely detected through employing a multifunctional delivery vector to realize cancer targeting delivery of a genome editing plasmid and a molecular beacon-based AND logic gate. The multifunctional delivery vector decorated by AS1411 conjugated hyaluronic acid and NLS-GE11 peptide conjugated hyaluronic acid can specifically target circulating malignant cells (CMCs) of cancer patients to deliver the genome editing plasmid for epidermal growth factor receptor (EGFR) knockout. The cell fusion between CMCs and endothelial cells can be detected by the AND logic gate delivered by the multifunctional vector. After EGFR knockout, the edited CMCs exhibit dramatically inhibited cell fusion capability, while unedited CMCs can easily fuse with human umbilical vein endothelial cells (HUVEC) to form hybrid cells. This study provides a new therapeutic strategy for preventing cancer progression and a reliable tool for evaluating cancer cell fusion for precise personalized therapy.

Lymph-Node-Targeted Drug Delivery for Effective Immunomodulation to Prolong the Long-Term Survival After Heart Transplantation.

The chronic rejection responses and side effects of the systematic administration of immunosuppressants are the main obstacles to heart allograft and patient survival. The development of xenotransplantation also urgently requires more efficient immune regulation strategies. Herein, it is demonstrated that lymph-node (LN)-targeted drug delivery can realize LN-specific immunomodulation with attenuated immune suppression on distant peripheral immune organs to effectively prolong long-term survival after heart transplantation in a chronic murine heart transplantation model. A chemokine C-C motif ligand 21 (CCL21) specific aptamer for LN targeting is decorated onto the surface of the hybrid nanoparticular delivery vector mainly composed of CaCO3 /CaP/heparin. The targeting delivery system can dramatically enhance accumulation of the loaded immunosuppressant, fingolimod hydrochloride (FTY720), in draining lymph nodes (dLNs) for inducing powerful immune suppression. By promoting the generation of endogenous regulatory T cells (Tregs ) and decreasing the proportion of effector T cells (Teffs ) in dLNs after heart transplantation, the LN-targeting strategy can effectively regulate local immune responses instead of systemic immunity, which reduces the incidence of long-term complications. This study provides an efficient strategy to improve the survival rate after organ transplantation by precise and localized immunoregulation with minimized side effects of immunosuppression.