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Aims: To compare the effectiveness of different types of eHealth interventions in improving exercise endurance and quality of life in chronic obstructive pulmonary disease (COPD) patients., Background: COPD is a chronic airway disease characterized by persistent respiratory symptoms and airflow limitation. eHealth interventions have been accepted and recognized by healthcare professionals and COPD patients as an effective alternative to pulmonary rehabilitation. However, it is not clear which eHealth interventions are effective and preferred for exercise endurance and quality of life in COPD patients., Design: A systematic review and network meta-analysis based on PRISMA-NMA., Methods: We searched nine electronic databases to identify randomized controlled trials addressing the effect of eHealth interventions on the exercise endurance and quality of life of COPD patients from their inception to 30 October 2022. First, a random-effects model was chosen to conduct a traditional meta-analysis to directly investigate the efficacy of different eHealth interventions. Next, a network meta-analysis was performed to evaluate the relative efficacy of the eHealth interventions for COPD. The quality of the data was assessed using the Cochrane Risk of Bias tool., Results: Fifty-one studies containing six eHealth interventions (telemonitoring, application [APP], web-based interventions, phone calls, virtual reality and combined interventions [≥two types]) were included in the final analysis. Network meta-analysis showed that telemonitoring, APP, web-based interventions and combined interventions improved exercise endurance in COPD patients, with telemonitoring being the most effective. Web-based interventions and apps are effective in improving the quality of life, and web-based interventions are the most effective., Conclusions: This study confirms that eHealth interventions can improve exercise endurance and quality of life in COPD patients. In the future, healthcare professionals can promote the use of telemedicine in COPD patients to enhance their exercise endurance and quality of life according to their individual needs., Relevance to Clinical Practice: This evidence suggests that eHealth interventions can improve exercise endurance and quality of life in COPD patients. Therefore, in the future, eHealth interventions could be used to maximize their effectiveness in improving exercise endurance and quality of life in COPD patients., (© 2024 John Wiley & Sons Ltd.)

Extracellular vesicles (EVs) are lipid bilayer-enclosed vesicles released by cells. EVs encapsulate proteins and nucleic acids of their parental cell and efficiently deliver the cargo to recipient cells. These vesicles act as mediators of intercellular communication and thus play a crucial role in various physiological and pathological processes. Moreover, EVs hold promise for clinical use. They have been explored as drug delivery vehicles, therapeutic agents, and targets for disease diagnosis. In the landscape of cancer research, while strides have been made in EV-focused cancer physiopathology, liquid biopsy, and drug delivery, the exploration of EVs as immunotherapeutic agents may not have seen substantial progress to date. Despite promising findings reported in cell and animal studies, the clinical translation of EV-based cancer immunotherapeutics encounters challenges. Here, we review the existing strategies used in EV-based cancer immunotherapy, aiming to propel the development of this emerging yet crucial field., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Yundi Chen et al.)

Liposomes as drug vehicles have advantages, such as payload protection, tunable carrying capacity and improved biodistribution. However, due to the dysfunction of targeting moieties and payload loss during preparation, immunoliposomes have yet to be favoured in commercial manufacturing. Here we report a chemical modification-free biophysical approach for producing immunoliposomes in one step through the self-assembly of a chimeric nanobody (cNB) into liposome bilayers. cNB consists of a nanobody against human epidermal growth factor receptor 2 (HER2), a flexible peptide linker and a hydrophobic single transmembrane domain. We determined that 64% of therapeutic compounds can be encapsulated into 100-nm liposomes, and up to 2,500 cNBs can be anchored on liposomal membranes without steric hindrance under facile conditions. Subsequently, we demonstrate that drug-loaded immunoliposomes increase cytotoxicity on HER2-overexpressing cancer cell lines by 10- to 20-fold, inhibit the growth of xenograft tumours by 3.4-fold and improve survival by more than twofold., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Aims and Objectives: To compare the effectiveness of non-pharmacological interventions in enhancing sleep quality in older people., Background: Sleep problems in older adults have become increasingly prominent. Sleep problems not only affect the health and quality of life of older people, but also the range of chronic diseases caused by sleep problems also impose a huge burden on social services and health care. Non-pharmacological interventions are an effective alternative to pharmacological therapies, but it is unclear which non-pharmacological therapies are most effective in enhancing sleep quality in older adults., Design: A systematic review and network meta-analysis based on PRISMA-NMA., Methods: A total of seven databases were searched from the establishment of the database to March 2023. After literature screening and data extraction, the Cochrane Bias assessment tool 2.0 version of randomised controlled trials (RCTs) was used to evaluate literature quality. A network meta-analysis was performed to evaluate the relative efficacy of the non-pharmacological interventions on sleep quality., Results: A total of 71 RCTs involving nine non-pharmacological interventions were included. The results of the network meta-analysis showed that the joint intervention may be the most effective non-pharmacological intervention to enhance sleep quality in older adults., Conclusion: This study confirms that non-pharmacological interventions can improve sleep quality in older adults. The use of non-pharmacological interventions can be promoted by healthcare professionals in the future to improve the quality of sleep and thus the physical and mental health of older people., Relevance to Clinical Practice: This evidence suggests that joint interventions may be most effective. Therefore, in the future, a combination of non-pharmacological interventions could be used to maximise their effectiveness in improving sleep quality in older people and promoting healthy aging., No Patient or Public Contribution: No patient or public contribution is not applicable to this study., (© 2024 John Wiley & Sons Ltd.)

Microbes are pivotal in contemporary cancer research, influencing various biological behaviors in cancer. The previous notion that the lung was sterile has been destabilized by the discovery of microbiota in the lower airway and lung, even within tumor tissues. Advances of biotechnology enable the association between intratumor microbiota and lung cancer to be revealed. Nonetheless, the origin and tumorigenicity of intratumor microbiota in lung cancer still remain implicit. Additionally, accumulating evidence indicates that intratumor microbiota might serve as an emerging biomarker for cancer diagnosis, prognosis, and even a therapeutic target across multiple cancer types, including lung cancer. However, research on intratumor microbiota's role in lung cancer is still nascent and warrants more profound exploration. Herein, this paper provides an extensive review of recent advancements in the following fields, including 1) established and emerging biotechnologies utilized to study intratumor microbiota in lung cancer, 2) causation between intratumor microbiota and lung cancer from the perspectives of translocation, cancerogenesis and metastasis, 3) potential application of intratumor microbiota as a novel biomarker for lung cancer diagnosis and prognosis, and 4) promising lung cancer therapies via regulating intratumor microbiota. Moreover, this review addresses the limitations, challenges, and future prospects of studies focused on intratumor microbiota in lung cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Rapid automatized naming (RAN) has been proven to be important for students' academic performance, but it remains unclear whether and how dealing with stressors (e.g., active coping) is associated with children's development of RAN. To examine this question, this research views the growth of RAN as a cross-stressor adaptation process and proposes that school-aged children may build up adapted and modified stress response systems through active coping in dealing with stressors and cognitive tasks. Based on the broaden-and-build theory and the mind-body unity theory, we explored the impact of active coping on RAN and hypothesized that subjective vitality and aerobic fitness chain mediated the relationship between active coping and RAN. We used two Likert-like scales to measure active coping and subjective vitality, used a number-reading task to measure RAN, and used the progressive aerobic cardiovascular endurance run (PACER) test to measure aerobic fitness. We recruited 303 elementary students in grades 3-5 in China. Results showed that both subjective vitality and aerobic fitness mediated the impact of active coping on time for RAN. Further, the chain indirect effect of active coping→subjective vitality→aerobic fitness→time for RAN was significant, but the reversed chain mediation was not significant. General resources (e.g., subjective vitality) have been shown to be relatively more important than simple physical resources (e.g., aerobic fitness) for RAN. These preliminary findings may contribute to both the cross-stressor-adaptation and active coping literature and have potential implications for improving RAN in school-aged children., (© 2023 Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Cell-derived small extracellular vesicles have been exploited as potent drug vehicles. However, significant challenges hamper their clinical translation, including inefficient cytosolic delivery, poor target-specificity, low yield, and inconsistency in production. Here, we report a bioinspired material, engineered fusogen and targeting moiety co-functionalized cell-derived nanovesicle (CNV) called eFT-CNV, as a drug vehicle. We show that universal eFT-CNVs can be produced by extrusion of genetically modified donor cells with high yield and consistency. We demonstrate that bioinspired eFT-CNVs can efficiently and selectively bind to targets and trigger membrane fusion, fulfilling endo-lysosomal escape and cytosolic drug delivery. We find that, compared to counterparts, eFT-CNVs significantly improve the treatment efficacy of drugs acting on cytosolic targets. We believe that our bioinspired eFT-CNVs will be promising and powerful tools for nanomedicine and precision medicine., (© 2023. The Author(s).)

This study aimed to identify potential trajectory groups of successful aging in older adults and to explore the influencing factors of each trajectory group. We used four waves of longitudinal data from the China Health and Retirement Longitudinal Study from 2011 to 2018, which involved 1,949 older adults. The developmental trajectories were determined using growth mixture modeling (GMM), and the influencing factors of each trajectory group were identified using multinomial logistic analysis. We identified three different groups of successful aging trajectories: high level-declining group (45%), medium level-declining group (39%), and low level-steady group (16%). Gender, education, marital status, place of residence, self-rated health, life satisfaction, and retirement pension were the influencing factors for the high level-declining group. Influencing factors for the medium level-declining group included gender, education, self-rated health, life satisfaction, and retirement pension. Healthcare professionals should formulate targeted measures according to different trajectory categories to promote successful aging in older adults., Competing Interests: Declaration of Competing Interest No conflict of interest exists in the submission of this manuscript, and the manuscript is approved by all authors for publication. I declare, on behalf of myself and my co-author, that the work described is original research that has not been published previously and is not under consideration for publication (and will not be submitted) elsewhere before a decision is made by your journal., (Copyright © 2023. Published by Elsevier Inc.)

Background: The pathological differentiation of invasive adenocarcinoma (IAC) has been linked closely with epidemiological characteristics and clinical prognosis. However, the current models cannot accurately predict IAC outcomes and the role of pathological differentiation is confused. This study aimed to establish differentiation-specific nomograms to explore the effect of IAC pathological differentiation on overall survival (OS) and cancer-specific survival (CSS)., Methods: The data of eligible IAC patients between 1975 and 2019 were collected from the Surveillance, Epidemiology, and End Results (SEER) database, and randomly divided in a ratio of 7:3 into a training cohort and a validation cohort. The associations between pathological differentiation and other clinical characteristics were evaluated using chi-squared test. The OS and CSS analyses were performed using the Kaplan-Meier estimator, and the log-rank test was used for nonparametric group comparisons. Multivariate survival analysis was performed using a Cox proportional hazards regression model. The discrimination, calibration, and clinical performance of nomograms were assessed by area under receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis (DCA)., Results: A total of 4,418 IAC patients (1,001 high-differentiation, 1,866 moderate-differentiation, and 1,551 low-differentiation) were identified. Seven risk factors [age, sex, race, tumor-node-metastasis (TNM) stage, tumor size, marital status, and surgery] were screened to construct differentiation-specific nomograms. Subgroup analyses showed that disparate pathological differentiation played distinct roles in prognosis, especially in patients with older age, white race, and higher TNM stage. The AUC of nomograms for OS and CSS in the training cohort were 0.817 and 0.835, while in the validation cohort were 0.784 and 0.813. The calibration curves showed good conformity between the prediction of the nomograms and the actual observations. DCA results indicated that these nomogram models could be used as a supplement to the prediction of the TNM stage., Conclusions: Pathological differentiation should be considered as an independent risk factor for OS and CSS of IAC. Differentiation-specific nomogram models with good discrimination and calibration capacity were developed in the study to predict the OS and CSS in 1-, 3- and 5-year, which could be used predict prognosis and select appropriate treatment options., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-2308/coif). All authors report that this study was supported by the Natural Science Foundation of Jiangsu Province (No. BK20210068), the Top Talent Support Program for Young and Middle-aged People of Wuxi Municipal Health Commission (No. HB2020003), Mega-project of Wuxi Commission of Health (No. Z202216), and the High-end Medical Expert Team of the 2019 Taihu Talent Plan (No. 2019-THRCTD1). The authors have no other conflicts of interest to declare., (2023 Translational Cancer Research. All rights reserved.)

Background: Immune checkpoint blockade (ICB) only works well for a certain subset of patients with non-small cell lung cancer (NSCLC). Therefore, biomarkers for patient stratification are desired, which can suggest the most beneficial treatment., Methods: In this study, three datasets (GSE126044, GSE135222, and GSE136961) of immunotherapy from the Gene Expression Omnibus (GEO) database were analyzed, and seven intersected candidates were extracted as potential biomarkers for ICB followed by validation with The Cancer Genome Atlas (TCGA) dataset and the in-house cohort data., Results: Among these candidates, we found that human leukocyte antigen-DR alpha (HLA-DRA) was downregulated in NSCLC tissues and both tumor and immune cells expressed HLA-DRA. In addition, HLA-DRA was associated with an inflamed tumor microenvironment (TME) and could predict the response to ICB in NSCLC. Moreover, we validated the predictive value of HLA-DRA in immunotherapy using an in-house cohort. Furthermore, HLA-DRA was related to the features of inflamed TME in not only NSCLC but also in most cancer types., Conclusion: Overall, HLA-DRA could be a promising biomarker for guiding ICB in NSCLC., (© 2022. The Author(s).)

Lipid droplets are lipid-rich cytosolic organelles that play roles in cell signaling, membrane trafficking, and many other cellular activities. Recent studies revealed that lipid droplets in cancer cells have various biological functions, such as energy production, membrane synthesis, and chemoresistance, thereby fostering cancer progression. Accordingly, the administration of antilipemic agents could improve anti-cancer treatment efficacy given hydrophobic chemotherapeutic drugs could be encapsulated into lipid droplets and then expelled to extracellular space. In this study, we investigated whether statins could promote treatment efficacy of lipid droplet-rich ovarian SKOV-3 cells and the potential influences on generation and composition of cell-derived extracellular vesicles and particles (EVP). Our studies indicate that statins can significantly lower lipid biosynthesis. Moreover, statins can inhibit proliferation, migration, and invasion of SKOV-3 cells and enhance chemosensitivity in vitro and in vivo . Furthermore, statins can lower EVP secretion but enforce the release of cholesterol-enriched EVPs, which can further lower lipid contents in parental cells. It is the first time that the influence of statins on EVP generation and EVP-lipid composition is observed. Overall, we demonstrated that statins could inhibit lipid production, expel cholesterol to extracellular space via EVPs, and improve chemosensitivity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Xu, Wang, Prisinzano, Yuan, Lu, Zheng, Mao and Wan.)

Immune checkpoint inhibitors (ICI) targeting PD-1/PD-L1 have been approved for the treatment of a variety of cancers. However, the efficacy of antibody-based ICIs could be further improved by mitigating anti-drug antibodies, proteolytic cleavage, and on-target off-tumor toxicity. One strategy for accomplishing this is through the use of extracellular vesicles (EVs), cell derived submicron vesicles with many unique properties. We constructed an engineered MDA-MB-231 cell line for harvesting EVs. This was accomplished by overexpressing a high-affinity variant human PD-1 protein (havPD-1), while simultaneously knocking out intrinsic PD-L1 and beta-2 microglobulin. The engineered havPD-1 EVs reduced PD-L1 overexpressing cancer cell proliferation and induced cellular apoptosis. Moreover, the EVs were shown to efficiently block PD-L1 mediated T cell suppression. Meanwhile antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity were not observed. The havPD-1 EVs treatment resulted in robust anti-tumor activity in both preventative co-implantation and therapeutic xenograft tumor models reconstituted with human T cells. The efficacy of the havPD-1 EVs was shown to be comparable to clinical anti-PD1 monoclonal antibodies. Additionally, loading the havPD-1 EVs with a potent PARP inhibitor was shown to further augment treatment efficacy. In brief, the engineered universal EVs harboring havPD-1 proteins can be used for cancer concurrent immunotherapy and chemotherapy., Competing Interests: All authors declare that they have no conflicts of interest and no competing interest., (© 2021 The Authors.)

Patients with triple-negative breast cancer (TNBC) have a relatively poor prognosis and cannot benefit from endocrine and/or targeted therapy. Considerable effort has been devoted toward the elucidation of the molecular mechanisms and potential diagnostic/therapeutic targets. However, it is inefficient and often ineffective to study the biological nuances of TNBC in large-scale clinical trials. In contrast, the investigation of the association between molecular alterations induced through controlled variables and relevant physiochemical characteristics of TNBC cells in laboratory settings is simple, definite, and efficient in exploring the molecular mechanisms. In this study, microgravity was selected as the sole variable of study as it can inhibit cancer cell viability, proliferation, metastasis, and chemoresistance. Identifying the key molecules that shift cancer cells toward a less aggressive phenotype may facilitate future TNBC studies. We focused on extracellular vesicles (EV) derived from TNBC MDA-MB-231 cells in microgravity, which mediate intercellular communication by transporting signaling molecules between cells. Our results show that in comparison with cells in full gravity, EV release rate decreased in microgravity while average EV size increased. In addition, we found EVs may be superior to cells in analyzing differentially expressed proteins, especially those that are down-regulated ones and usually unidentified or neglected in analysis of intact cellular contents. Proteomic analysis of both EVs and cells further revealed a significant correlation with GTPases and proliferation of MDA-MB-231 cells in microgravity. Altogether, our findings would further inspire in-depth correlative cancer biological studies and subsequent clinical research.

Extracellular vesicles (EVs) are lipid-enclosed submicron-sized vesicles that are secreted by all eukaryotic cells. EVs can selectively encapsulate tissue-specific small molecules from parent cells and efficiently deliver them to recipient cells. As signal mediators of intercellular communication, the molecules packaged in EVs play critical roles in the pathophysiology of diseases. In relevant clinical translation, EV contents have been used for cancer diagnosis and treatment monitoring. To further promote EV-based cancer liquid biopsy toward large-scale clinical implementation, the efficient and specific isolation of pure tumor-derived EVs from body fluids is a prerequisite. However, the existing EV isolation methods are unable to address certain technical challenges, such as lengthy procedures, low throughput, low specificity, heavy protein contamination, etc., and thus, new approaches for EV isolation are required. Here, we report a multivalent, long single-stranded aptamer with repeated units for EV enrichment and retrieval. After short incubation of biotin-labeled multivalent aptamers (MAs) with the samples, EVs can be quickly secured by MAs, anchored onto streptavidin-coated microspheres, and further retrieved via digestion of the DNA aptamer. Approximately 45% of EVs can be isolated from the spiked samples in 40 min with a depletion of 84.7% of albumin contamination. In addition, 93.1% of the isolated EVs can be retrieved via DNase-mediated aptamer degradation in 10 min for downstream molecular analyses. Our findings suggest that MAs can efficiently and specifically isolate EVs derived from malignant lymphocytes, and this simple method could facilitate the EV-centered study of acute lymphoblastic leukemia.

In recent years, personalized cancer immunotherapy, especially stratification-driven precision treatments have gained significant traction. However, due to the heterogeneity in clinical cohorts, the uncombined analysis of stratification/therapeutics may lead to confusion in determining ideal therapeutic options. We report that the coupled immune stratification and drug repurposing could facilitate identification of therapeutic candidates in patients with lung adenocarcinoma (LUAD). First, we categorized the patients into four groups based on immune gene profiling, associated with distinct molecular characteristics and clinical outcomes. Then, the weighted gene co-expression network analysis (WGCNA) algorithm was used to identify co-expression modules of each groups. We focused on C3 group which is characterized by low immune infiltration (cold tumor) and wild-type EGFR, posing a significant challenge for treatment of LUAD. Five drug candidates against the C3 status were identified which have potential dual functions to correct aberrant immune microenvironment and also halt tumorigenesis. Furthermore, their steady binding affinity against the targets was verified through molecular docking analysis. In sum, our findings suggest that such coupled analysis could be a promising methodology for identification and exploration of therapeutic candidates in the practice of personalized immunotherapy.

Extracellular vesicles (EVs) are cell-derived vesicles which encapsulate a variety of molecules. Numerous studies have demonstrated EVs as signaling mediators of intercellular communication and are heavily involved under physiological and pathological conditions. In translational medicine, EVs have been used for disease diagnosis and treatment monitoring. EVs as natural nanocarriers for drug delivery and therapeutic EVs are also under intense investigation. While still in its infancy, relevant EV studies have been growing. For EV-centered research to thrive, a few fundamental unanswered questions, such as EV biogenesis, EV secretion rate (SR), EV content sorting mechanisms, etc. require further investigation. In this study, we measured the SR of EVs derived from 6 cancerous cell lines. Several factors that may interfere with EV secretion, isolation, and storage were also investigated. Our results show that the SR of EVs derived from various cancer cells was significantly different, indicating a heterogeneous EV secretion behavior among cell types. Moreover, 5 different drugs that interfere with cellular metabolism significantly influenced EV release. In addition, we found that (1) more EVs can be harvested at 24 h compared to 48 h of serum-free cell culture with a similar degree of FBS contamination; (2) filtration of the cell culture supernatant with a 0.22 μm filter causes ∼70% loss of EVs; (3) the isolation efficiency of EVs with the prevalent ultracentrifugation is only ∼14%; (4) storage at 4 °C for 3 days causes ∼21% loss of EVs. Overall, our findings provide a guideline for proper EV collection and storage in laboratory settings.

The high moisture content of wet sewage sludge generated from wastewater treatment process not only brings high cost of sewage disposal, but also limits its utilization as resource. In this study, an efficient strategy of directly utilizing wet sludge to develop advanced carbocatalyst via a hydrothermal coupled pyrolysis process was proposed. The possible application of as-synthesized carbocatalyst was evaluated by activating peroxymonosulfate (PMS) to degrade a model pollutant of sulfamethoxazole (SMX). Experimental results showed that about 100% of SMX and 59% of total organic carbon (TOC) could be removed within 15 min. Moisture content in wet sludge also affected the performances of as-obtained carbocatalysts. Further studies verified that singlet oxygen ( 1 O 2 ) dominated SMX degradation, which was generated in the process of PMS activation by CO groups on the surface of carbocatalyst. In the preliminary ecological test, a lower ecotoxicity of SMX degradation solution compared with the original solution was observed. This study demonstrated the feasibility of directly utilizing wet sludge for advanced carbocatalyst fabrication, which provided another solution for wet sludge treatment and utilization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A considerable amount of sewage sludge (SS) is generated from wastewater treatment process, which is hazardous to the environment and in urge to be disposed. In this study, for the first time, we prepared carbocatalyst with abundant surface oxygen functional groups using the hazardous waste of SS as precursor via a facile hydrothermal coupled pyrolysis process. The hydrothermal treatment was found to be crucial for enhancing the oxygen content of sludge carbon (SC), most of which existed as ketonic groups. Catalytic performances of the developed SCs were examined by activating peroxymonosulfate (PMS) to degrade bisphenol A (BPA). Sample with more ketonic group performed better for BPA degradation. Under optimal reaction conditions, 100 % of BPA and 69.53 % of TOC could be removed in 20 min. Singlet oxygen ( 1 O 2 ) was suggested to be the main reactive oxygen species for degrading BPA and a BPA degradation pathway was proposed. The BPA solution showed decreased bio-toxicity after the oxidation process according to the acute ecotoxicity test. This study demonstrated the importance of surface functional groups on carbocatalyst for advanced oxidation process, which could be induced by a facile hydrothermal treatment. The feasibility of utilizing hazardous SS for advanced carbocatalyst fabrication was also revealed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Extracellular vesicles (EVs) are lipid-bilayer-enclosed vesicles of submicron size that are secreted by various cells. As mediators of intercellular communication, EVs can alter the physiological state of recipient cells by delivering encapsulated proteins and nucleic acids. Incontestably, growing evidence has shown important biological roles and the clinical relevance of EVs. The use of stem cell-derived EVs as a cell-free therapeutic modality for skin treatment has emerged as a promising application in dermatology. However, the moderate isolation efficiency of prevalent ultracentrifugation and low secretion rate make the massive low-cost production of EVs difficult. Here, we report development of engineered EVs (eEV) derived from human umbilical cord mesenchymal stem cells (hucMSCs) for skin treatment. Ultrasonication was used to shear intact hucMSCs for only 1 min, followed by regular centrifugation and filtration for producing nanoscale eEVs. This approach has ∼20-fold higher yield and ∼100-fold faster production than that of naturally secreted EVs (nsEV), while the production cost decreased to less than 10%. The eEVs have similar morphology, size distribution, and typical protein markers compared to nsEVs. Moreover, in vitro, both nsEVs and eEVs promote the proliferation and migration of dermal fibroblasts and increase in the expression of collagen, elastin, and fibronectin, whereas the matrix metalloproteinases-1 (MMP-1) and MMP-3 production can be significantly reduced. The wound-healing study in mice showed that both nsEVs and eEVs promote wound recovery in comparison with the controls. In sum, our results indicate that hucMSC-derived eEVs prepared by ultrasonication potentially can be used to increase skin extracellular matrix and enhance skin rejuvenation., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

Extracellular vesicles (EVs) are cell-released vesicles of submicrometer size. EVs contain a tissue-specific signature wherein a variety of proteins and nucleic acids are selectively packaged. Recent studies validate that EVs can be used for cancer diagnostics, staging, and treatment monitoring. EV-related clinical translation requires effective EV isolation as a prerequisite. However, lengthy procedures, low yield, low throughput, and high levels of contaminants disqualify the existing isolation approaches for large-scale clinical use. Hence, new approaches for rapid, efficient, and low-cost isolation of EVs in high purity for flexible analyses of the diverse contents in real-world clinical settings are highly desired yet are currently unavailable. Here, we report the effective use of heparin/polymer-coated microspheres (HPM) for EV isolation and retrieval. Approximately 81% of EVs can be isolated from plasma in 1 h with depletion of ∼99.5% plasma protein and nucleic acid contaminants, and 72% of isolated EVs can be retrieved with saline in 5 min for various cargo analyses. This approach was further validated with clinical samples derived from patients with malignant ground-glass opacity (GGO). In eight patients, the mutation concordance between EV DNA and tissue DNA is 39.8%. The prevalence and mutation count of EGFR , TP53 , and NF1 are higher than those of other oncogenes and antioncogenes that are intensely associated with lung adenocarcinoma. Moreover, different mutation prevalence and patterns between smokers and nonsmokers can be observed. Our findings suggest that the combination of HPM assay and targeted sequencing of EV DNA could be translated in the differential diagnosis of malignant GGO with short turnaround time.

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.