Giant gateable thermoelectric conversion by tuning the ion linkage interactions in covalent organic framework membranes.

Efficient energy conversion using ions as carriers necessitates membranes that sustain high permselectivity in high salinity conditions, which presents a significant challenge. This study addresses the issue by manipulating the linkages in covalent-organic-framework membranes, altering the distribution of electrostatic potentials and thereby influencing the short-range interactions between ions and membranes. We show that a charge-neutral covalent-organic-framework membrane with ß-ketoenamine linkages achieves record permselectivity in high salinity environments. Additionally, the membrane retains its permselectivity under temperature gradients, providing a method for converting low-grade waste heat into electrical energy. Experiments reveal that with a 3 M KCl solution and a 50 K temperature difference, the membrane generates an output power density of 5.70 W m-2. Furthermore, guided by a short-range ionic screening mechanism, the membrane exhibits adaptable permselectivity, allowing reversible and controllable operations by finely adjusting charge polarity and magnitude on the membrane's channel surfaces via ion adsorption. Notably, treatment with K3PO4 solutions significantly enhances permselectivity, resulting in a giant output power density of 20.22 W m-2, a 3.6-fold increase over the untreated membrane, setting a benchmark for converting low-grade heat into electrical energy.

Optimizing selectivity via membrane molecular packing manipulation for simultaneous cation and anion screening.

Advancing membranes with enhanced solute-solute selectivity is essential for expanding membrane technology applications, yet it presents a notable challenge. Drawing inspiration from the unparalleled selectivity of biological systems, which benefit from the sophisticated spatial organization of functionalities, we posit that manipulating the arrangement of the membrane's building blocks, an aspect previously given limited attention, can address this challenge. We demonstrate that optimizing the face-to-face orientation of building blocks during the assembly of covalent-organic-framework (COF) membranes improves ion-π interactions with multivalent ions. This optimization leads to extraordinary selectivity in differentiating between monovalent cations and anions from their multivalent counterparts, achieving selectivity factors of 214 for K+/Al3+ and 451 for NO3-/PO43-. Leveraging this attribute, the COF membrane facilitates the direct extraction of NaCl from seawater with a purity of 99.57%. These findings offer an alternative approach for designing highly selective membrane materials, offering promising prospects for advancing membrane-based technologies.

Sleep disturbance as a poor prognostic predictor in patients with advanced non-small-cell lung cancer treated with immune checkpoint inhibitors: A prospective study.

BACKGROUND: Sleep disturbances are highly prevalent in oncology and often exacerbate symptoms, leading to reduced quality of life, which in turn may further affect the tolerability and efficacy of oncological treatments. Sleep disturbance and cancer have an intimate and complicated relationship, and may be a negative predictor of cancer treatment. The present study aimed to characterize the relationship between sleep disturbance and immune checkpoint inhibitor (ICI) therapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Data from 171 patients with advanced NSCLC, who underwent ICI treatment between December 2020 and October 2022, were analysed in our prospective study. Sleep disturbances were evaluated according to the Pittsburgh Sleep Quality Index (PSQI), with a cut-off value of 5, to investigate the impact of sleep disturbance on the survival of patients with NSCLC and the efficacy of ICI treatment. RESULTS: The median progression-free survival (PFS) was10.4 months (9 5% confidence interval [CI]:9.84-10.97). Univariate and multivariate analyses revealed that sleep disturbance and depressive symptom predicted worse prognosis with shortened PFS. Patients who experienced sleep disturbance exhibited a significant reduction in PFS (9.2 vs. 11.8 months; HR: 1.83 [9 5% CI 1.27-2.6 5]; p = 0.001), as did those with depressive states (HR 1.5 5 [9 5% CI 1.06-2.28]; p = 0.02 5). Additionally, patients with sleep disturbance and depressive symptoms exhibited significantly lower objective response rates and disease control rates. CONCLUSION: Sleep disturbance could be a factor for prognosis in patients with advanced NSCLC undergoing first- or second-line treatment with ICIs, including shorter PFS and reduced efficacy.

Covalent organic framework membrane reactor for boosting catalytic performance.

Membrane reactors are known for their efficiency and superior operability compared to traditional batch processes, but their limited diversity poses challenges in meeting various reaction requirements. Herein, we leverage the molecular tunability of covalent organic frameworks (COFs) to broaden their applicability in membrane reactors. Our COF membrane demonstrates an exceptional ability to achieve complete conversion in just 0.63 s at room temperature-a benchmark in efficiency for Knoevenagel condensation. This performance significantly surpasses that of the corresponding homogeneous catalyst and COF powder by factors of 176 and 375 in turnover frequency, respectively. The enhanced concentration of reactants and the rapid removal of generated water within the membrane greatly accelerate the reaction, reducing the apparent activation energy. Consequently, this membrane reactor enables reactions that are unattainable using both COF powders and homogeneous catalysts. Considering the versatility, our findings highlight the substantial promise of COF-based membrane reactors in organic transformations.

Clinical efficacy and safety of transvaginal natural orifice transluminal endoscopic surgery for benign adnexal disease: a prospective trial.

BACKGROUND: There is a scarcity of prospective clinical research evidence regarding the utilization of transvaginal natural orifice translumenal endoscopic surgery (vNOTES) as a treatment option for ovarian cysts. The objective of this study was to assess the feasibility and safety of employing vNOTES for the management of ovarian cysts. METHODS: Our study included women between the ages of 18 and 70 who intended to undergo surgical intervention for benign lesions. Stratified blocked randomization was employed to allocate participants into groups. The main objective was to assess whether the assigned group adhered to the recommended surgical technique for ovarian cystectomy or adnexectomy, without any deviation to alternative surgical methods. RESULTS: A total of 196 patients were included in the study, with all surgeries in each group being conducted according to the assigned procedures. Among them, the ovarian cystectomy layer included 58 cases in the vNOTES group and 58 cases in the conventional laparoscopy (CL) groups. The adnexectomy layer included 40 cases in the vNOTES group and 40 cases in the CL group. Utilizing a sensitivity analysis, the two-sided 95% lower confidence limit was determined to be 5.5% for the disparity in proportions between the vNOTES groups and CL groups. These lower limits fell below the predetermined non-inferiority margin of 10%. CONCLUSIONS: The study findings demonstrate that vNOTES was not inferior to CL in terms of adnexectomy or ovarian cystectomy. vNOTES can be considered a more minimally invasive surgical approach, as it results in reduced postoperative pain, faster recovery, and absence of visible incisions. Overall, vNOTES proves to be a safe, feasible, and less invasive treatment option. TRIAL REGISTRATION: This study retrospectively registered with the China Clinical Trial Registry with the registration number ChiCTR2100052223(22-10-2021).

RHBDF1 modulates cisplatin sensitivity of small cell lung cancer through YAP1/Smad2 signaling pathway.

Small cell lung cancer (SCLC) is a fatal tumor type that is prone to drug resistance. In our previous study, we showed that human rhomboid-5 homolog-1 (RHBDF1) was differentially expressed in 5 intrinsic cisplatin-resistant SCLC tissues compared with 5 intrinsic cisplatin-sensitive SCLC tissues by RNA sequencing, which intrigued us. We performed gain- and loss-of-function experiments to investigate RHBDF1 function, bioinformatics analysis, qRT-PCR, western blotting, and immunoprecipitation to elucidate the molecular mechanisms as well as detect RHBDF1 expression in SCLC by immunohistochemistry. We found that RHBDF1 knockdown promoted cell proliferation and cisplatin chemoresistance and inhibited apoptosis in vitro and in vivo. These effects could be reversed by overexpressing RHBDF1 in vitro. Mechanistically, RHBDF1 interacted with YAP1, which increased the phosphorylation of Smad2 and transported Smad2 to the nucleus. Among clinical specimens, the RHBDF1 was a low expression in SCLC and was associated with clinicopathological features and prognosis. We are the first to reveal that RHBDF1 inhibited cell proliferation and promoted cisplatin sensitivity in SCLC and elucidate a novel mechanism through RHBDF1/YAP1/Smad2 signaling pathway which played a crucial role in cisplatin chemosensitivity. Targeting this pathway can be a promising therapeutic strategy for chemotherapy resistance in SCLC.

Influence of malnutrition according to the glim criteria on the chemotherapy toxicities in patients with advanced lung cancer.

BACKGROUND: Cancer-associated malnutrition is highly prevalent in advanced lung cancer, and 50% of global cancer-related deaths are attributed to cancer-associated malnutrition. Platinum-containing chemotherapy is the standard treatment for advanced lung cancer. Unfortunately, it can cause exacerbated toxicities, which can also have a negative impact on patient's prognosis and quality of life. The Global Leadership Initiative on Malnutrition (GLIM) criteria have been proposed as the world's first accepted diagnostic criteria for malnutrition. However, the effectiveness of GLIM criteria in predicting chemotherapy toxicities in patients with advanced lung cancer is unclear. The aim of this study was to apply the GLIM criteria to assess the prevalence of pre-treatment diagnosis of malnutrition in patients with advanced non-small cell lung cancer (NSCLC) and to determine the impact of nutritional status on patient's chemotherapy toxicity. METHODS: We conducted a study of hospitalized patients with pathologically and clinically diagnosed advanced NSCLC who presented to our hospital from May 2021 to January 2022. Initially, the Nutritional Risk Screening-2002 (NRS-2002) was used for nutritional risk screening, and nutritional status was assessed using the Scored Patient-Generated Subjective Global Assessment (PG-SGA) and GLIM criteria. Chemotherapy toxicity was assessed and graded according to CTCAE5.0, and chemotherapy efficacy was assessed according to RECIST1.1. Kappa test was used to analyze the agreement between PG-SGA and GLIM criteria. Univariate and multivariate logistic regression analyses were used to determine the relationship between malnutrition and chemotherapy toxicity. RESULTS: A total of 215 patients with advanced NSCLC were evaluated for nutritional status. Most of the patients had normal BMI (61.86%) before the start of treatment, 40% were well-nourished as assessed by the PG-SGA tool, and 51.17% were well-nourished as assessed by GLIM criteria. Consistency analysis showed moderate agreement (Kappa = 0.463, P < 0.001) and their correlation was also moderate (Spearman, rs = 0.475, P < 0.001). The objective response rate (ORR) (P = 0.040) and disease control rate (DCR) (P < 0.001) were significantly lower in malnourished patients diagnosed according to GLIM criteria than in well-nourished patients. Multivariate analysis showed that malnutrition (OR = 1.531,95%CI 0.757-3.009; OR = 6.623,95%CI 1.390-31.567, P = 0.046) diagnosed by GLIM criteria was an independent predictor of chemotherapy toxicity. Conclusions Malnutrition diagnosed by GLIM criteria better predicts toxicity during chemotherapy, determines the degree of clinical benefit of chemotherapy, and may affect patient prognosis.

Efficacy and safety of combined anlotinib-oral etoposide treatment for patients with platinum-resistant ovarian cancer.

OBJECTIVE: Despite the availability of numerous treatment options, managing patients with platinum-resistant ovarian cancer (PROC) remains challenging, and the prognosis of PROC is notably unfavorable. This retrospective study aimed to assess the efficacy and safety of combined anlotinib-oral etoposide treatment for patients with PROC. METHODS: Data of 23 patients who were diagnosed with PROC from January 2020 to November 2022 and treated with anlotinib combined with oral etoposide for at least 2 cycles were retrospectively analyzed. RESULTS: Among per-protocol patients, 9 (45.0%; 95% confidence interval [CI]=21.1-68.9) of 20 patients achieved partial response and 17 (85.0%, 95% CI=67.9-100.0) of 20 patients achieved disease control. The median progression-free survival was 8.7 months (95% CI=5.3-11.6). The incidence of adverse events (any grade) was 100%, and the incidence of grade 3-4 adverse events was 54.5%. CONCLUSION: Anlotinib combined with etoposide emerged effective for the treatment of PROC.

A retrospective clinical analysis of 11 cases of PEComa from different sites.

PURPOSE: The objective of this paper is to offer a thorough examination of the clinical presentations, etiology, and treatment strategies associated with perivascular epithelioid cell tumors (PEComas). METHODS: This retrospective study examined the comprehensive archival data of PEComa cases diagnosed at Beijing Hospital from 2015 to 2023. The pathology slides of all patients were thoroughly reassessed by two experienced pathologists. A thorough retrospective analysis was undertaken, incorporating clinicopathological data including gender, age at diagnosis, initial clinical manifestations, signs, disease onset site, tumor markers, imaging findings, therapeutic modalities, pathological features, immunohistochemical profiles, treatment responses, and prognostic indicators. Patients were evaluated for disease severity according to established pathological classification criteria and were followed up until the designated analysis cut-off date. In instances where patients were unable to be monitored on-site, they were contacted via telephone for postoperative follow-up inquiries. RESULTS: This study included 11 patients with ages ranging from 17 to 66 years old, presenting with the disease in multiple anatomical sites, including the retroperitoneum (2/11), liver (4/11), kidney (4/11), lung (1/11), and broad ligament of the uterus (1/11). Most patients presented with non-specific clinical symptoms and were subsequently diagnosed with space-occupying lesions upon physical examination. The tumor demonstrated progressive growth and enlargement, which could result in compression of neighboring organs. Preoperative imaging alone is insufficient for a definitive diagnosis of PEComa, but MRI can provide an initial evaluation of the tumor's potential malignancy. Molecular marker testing specific to PEComa, such as HMB-45 (90.0%), SMA (81.8%), Melan-A (90.9%), vimentin (90.9%), and Desmin (36.3%), was conducted on all patients. No adjuvant therapies were administered postoperatively. Upon analysis, no instances of relapse at the primary site or the development of new tumors at other sites were observed. Regular imaging reviews of three patients with malignant PEComa post-surgery showed no evidence of recurrence. CONCLUSIONS: The clinical presentation, tumor biomarkers, and imaging characteristics of PEComa lack specificity, necessitating dependence on pathology and immunohistochemistry for precise diagnosis. The mainstay of treatment consists of surgical resection, with patients typically experiencing a favorable prognosis.

Platinum Nanoparticles-Enhanced Ferritin-Mn2+ Interaction for Magnetic Resonance Contrast Enhancement and Efficient Tumor Photothermal Therapy.

Nanoplatforms with high Mn2+ coordination can display efficient T1 magnetic resonance imaging (MRI) contrast enhancement. Herein, an earth gravity-like method for enhanced interaction between Ferritin (Fn) and Mn2+ by the growth of platinum nanoparticles (PNs) in Fn's cage structure via a biomineralization method is first proposed. Fn has good biocompatibility and can provide a suitable growth site for PNs. PNs with negative charge have certain attraction to Mn2+ with positive charge, improving Fn's loading capacity of Mn2+ by attraction force; and thus, achieving efficient MRI contrast enhancement. In addition, PNs can be applied for efficient photothermal therapy (PTT) under near infrared ray (NIR) irradiation. Systemic delivery of this nanoplatform shows obvious MRI contrast enhancement and tumor progression inhibition after NIR irradiation, as well as no obvious side effects. Therefore, this nanoplatform has the potential to contribute to nanotheranostic for clinical transformation.

The gain effect of microbial consortia induced by adaptive domestication for efficient conversion of Chinese cabbage waste by anaerobic fermentation.

The resource-based treatment of Chinese cabbage waste by anaerobic fermentation can effectively mitigate air, soil, and groundwater pollution. However, the compatibility between fermentative microorganisms and the environment might be a crucial limiting factor for the resource recycling of Chinese cabbage waste. Therefore, the gain effect of microbial consortia (JMRS, JMRST, JMRSZ, JCCW, JCCWT and JCCWZ) induced by adaptive domestication for efficient conversion of Chinese cabbage waste by anaerobic fermentation were explored in this study. A total of 42 single subsamples with same weights were randomly divided into seven treatments: sterile deionized water (Control); anaerobic fermentation inoculated with JMRS (MRS); anaerobic fermentation inoculated with JMRST (MRST); anaerobic fermentation inoculated with JMRSZ (MRSZ); anaerobic fermentation inoculated with JCCW (CCW); anaerobic fermentation inoculated with JCCWT (CCWT); anaerobic fermentation inoculated with JCCWZ (CCWZ) and samples were taken on days 30 and 60 after anaerobic fermentation. The results exhibited that all the treatments contributed to high levels of lactic acid (178.77-201.79 g/kg dry matter) and low levels of ammonia-N (12.99-21.03 g/kg total nitrogen). Meanwhile, MRSZ enhanced (p < 0.05) acetic acid levels (1.53 g/kg dry matter) and resulted in the lowest yeast counts. Microbiologically, the addition of microbial consortia decreased the linear discriminant analysis (LDA) scores of Massilia and Stenotrophomonas maltophilia. Moreover, MRSZ enriched (p < 0.05) Lactobacillus hilgardii, and decreased (p < 0.05) the abundance of bacteria containing mobile elements and potentially pathogenic bacteria. In conclusion, JMRSZ improved the efficient conversion of Chinese cabbage waste for resource utilization.

Visible Light-Mediated Selective Aerobic Oxidation of Alcohols Catalyzed by Disulfide in Batch and Flow.

Selective aerobic oxidation of alcohols in batch and flow can be realized under light irradiation, utilizing disulfide as the photocatalyst, and a variety of primary and secondary alcohols were converted to the corresponding aldehydes or ketones in up to 99% yield and high selectivity. The reaction efficiency could be increased even further by combining a continuous-flow strategy. Detailed mechanistic studies have also been achieved to determine the role of oxygen and disulfides in this oxidation.

Enhancing ion selectivity by tuning solvation abilities of covalent-organic-framework membranes.

Understanding the molecular-level mechanisms involved in transmembrane ion selectivity is essential for optimizing membrane separation performance. In this study, we reveal our observations regarding the transmembrane behavior of Li+ and Mg2+ ions as a response to the changing pore solvation abilities of the covalent-organic-framework (COF) membranes. These abilities were manipulated by adjusting the lengths of the oligoether segments attached to the pore channels. Through comparative experiments, we were able to unravel the relationships between pore solvation ability and various ion transport properties, such as partitioning, conduction, and selectivity. We also emphasize the significance of the competition between Li+ and Mg2+ with the solvating segments in modulating selectivity. We found that increasing the length of the oligoether chain facilitated ion transport; however, it was the COF membrane with oligoether chains containing two ethylene oxide units that exhibited the most pronounced discrepancy in transmembrane energy barrier between Li+ and Mg2+, resulting in the highest separation factor among all the evaluated membranes. Remarkably, under electro-driven binary-salt conditions, this specific COF membrane achieved an exceptional Li+/Mg2+ selectivity of up to 1352, making it one of the most effective membranes available for Li+/Mg2+ separation. The insights gained from this study significantly contribute to advancing our understanding of selective ion transport within confined nanospaces and provide valuable design principles for developing highly selective COF membranes.

Leritrelvir for the treatment of mild or moderate COVID-19 without co-administered ritonavir: a multicentre randomised, double-blind, placebo-controlled phase 3 trial.

Background: Leritrelvir is a novel α-ketoamide based peptidomimetic inhibitor of SARS-CoV-2 main protease. A preclinical study has demonstrated leritrelvir poses similar antiviral activities towards different SARS-CoV-2 variants compared with nirmatrelvir. A phase 2 clinical trial has shown a comparable antiviral efficacy and safety between leritrelvir with and without ritonavir co-administration. This trial aims to test efficacy and safety of leritrelvir monotherapy in adults with mild-to-moderate COVID-19. Methods: This was a randomised, double-blind, placebo-controlled, multicentre phase 3 trial at 29 clinical sites in China. Enrolled patients were from 18 to 75 years old, diagnosed with mild or moderate COVID-19 and not requiring hospitalization. Patients had a positive SARS-CoV-2 nucleic acid test (NAT) and at least one of the COVID-19 symptoms within 48 h before randomization, and the interval between the first positive SARS-CoV-2 NAT and randomization was ≤120 h (5 days). Patients were randomly assigned in a 1:1 ratio to receive a 5-day course of either oral leritrelvir 400 mg TID or placebo. The primary efficacy endpoint was the time from the first dose to sustained clinical recovery of all 11 symptoms (stuffy or runny nose, sore throat, shortness of breath or dyspnea, cough, muscle or body aches, headache, chills, fever ≥37 °C, nausea, vomiting, and diarrhea). The safety endpoint was the incidence of adverse events (AE). Primary and safety analyses were performed in the intention-to-treat (ITT) population. This study is registered with ClinicalTrials.gov, NCT05620160. Findings: Between Nov 12 and Dec 30, 2022 when the zero COVID policy was abolished nationwide, a total of 1359 patients underwent randomization, 680 were assigned to leritrelvir group and 679 to placebo group. The median time to sustained clinical recovery in leritrelvir group was significantly shorter (251.02 h [IQR 188.95-428.68 h]) than that of Placebo (271.33 h [IQR 219.00-529.63 h], P = 0.0022, hazard ratio [HR] 1.20, 95% confidence interval [CI], 1.07-1.35). Further analysis of subgroups for the median time to sustained clinical recovery revealed that (1) subgroup with positive viral nucleic acid tested ≤72 h had a 33.9 h difference in leritrelvir group than that of placebo; (2) the subgroup with baseline viral load >8 log 10 Copies/mL in leritrelvir group had 51.3 h difference than that of placebo. Leritrelvir reduced viral load by 0.82 log10 on day 4 compared to placebo. No participants in either group progressed to severe COVID-19 by day 29. Adverse events were reported in two groups: leritrelvir 315 (46.46%) compared with placebo 292 (43.52%). Treatment-relevant AEs were similar 218 (32.15%) in the leritrelvir group and 186 (27.72%) in placebo. Two cases of COVID-19 pneumonia were reported in placebo group, and one case in leritrelvir group, none of them were considered by the investigators to be leritrelvir related. The most frequently reported AEs (occurring in ≥5% of participants in at least one group) were laboratory finding: hypertriglyceridemia (leritrelvir 79 [11.7%] vs. placebo 70 [10.4%]) and hyperlipidemia (60 [8.8%] vs. 52 [7.7%]); all of them were nonserious. Interpretation: Leritrelvir monotherapy has good efficacy for mild-to-moderate COVID-19 and without serious safety concerns. Funding: This study was funded by the National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine, Guangdong Science and Technology Foundation, Guangzhou Science and Technology Planning Project and R&D Program of Guangzhou Laboratory.

Low-Temperature Synthesis of Cyano-Rich Modified Surface-Alkalinized Heterojunctions with Directional Charge Transfer for Photocatalytic In Situ Generation and Consumption of Peroxides.

The synthesis of low-temperature poly(heptazine imide) (PHI) presents a significant challenge. In this context, we have developed a novel low-temperature synthesis strategy for PHI in this work. This strategy involves the introduction of Na+ ions, which etch and disrupt the conjugated structure of carbon nitride (CN) during assisted thermal condensation. This disruption leads to the partial decomposition of the heptazine ring structure, resulting in the formation of C≡N functionalities on the CN surface, which are enriched with hydroxyl groups and undergo cyano modification. The formation of heterojunctions between CN and ZnO, which facilitate charge transfer along an immobilization pathway, accelerated charge transfer processes and improved reactant adsorption as well as electron utilization efficiency. The resulting catalyst was employed for the room temperature, atmospheric pressure, and solvent-free photocatalytic selective oxidation of cumene (CM), achieving a cumene conversion rate of 28.7% and a remarkable selectivity of 92.0% toward the desired product, cumene hydroperoxide (CHP). Furthermore, this CHP induced oxidative reactions, as demonstrated by the successful oxidation of benzylamine to imine and the oxidation of sulfide to sulfoxide, both yielding high product yields. Additionally, the utilization of a continuous-flow device significantly reduces the reaction time required for these oxidation processes. This work not only introduces an innovative approach to environmentally friendly, sustainable, clean, and efficient PHI synthesis but also underscores the promising potential and advantages of carbon nitride-based photocatalysts in the realm of sustainable and green organic transformations.

Enhancing Sustainable Energy Conversion Efficiency by Incorporating Photoelectric Responsiveness into Multiporous Ionic Membrane.

The evolution of porous membranes has revitalized their potential application in sustainable osmotic-energy conversion. However, the performance of multiporous membranes deviates significantly from the linear extrapolation of single-pore membranes, primarily due to the occurrence of ion-concentration polarization (ICP). This study proposes a robust strategy to overcome this challenge by incorporating photoelectric responsiveness into permselective membranes. By introducing light-induced electric fields within the membrane, the transport of ions is accelerated, leading to a reduction in the diffusion boundary layer and effectively mitigating the detrimental effects of ICP. The developed photoelectric-responsive covalent-organic-framework membranes exhibit an impressive output power density of 69.6 W m-2 under illumination, surpassing the commercial viability threshold by ≈14-fold. This research uncovers a previously unexplored benefit of integrating optical electric conversion with reverse electrodialysis, thereby enhancing energy conversion efficiency.

Anticancer effect of hUC-MSC-derived exosome-mediated delivery of PMO-miR-146b-5p in colorectal cancer.

Antisense oligonucleotide (ASO) is a novel therapeutic platform for targeted cancer therapy. Previously, we have demonstrated that miR-146b-5p plays an important role in colorectal cancer progression. However, a safe and effective strategy for delivery of an ASO to its targeted RNA remains as a major hurdle in translational advances. Human umbilical cord mesenchymal cell (hUC-MSC)-derived exosomes were used as vehicles to deliver an anti-miR-146b-5p ASO (PMO-146b). PMO-146b was assembled onto the surface of exosomes (e) through covalent conjugation to an anchor peptide CP05 (P) that recognized an exosomal surface marker, CD63, forming a complex named ePPMO-146b. After ePPMO-146b treatment, cell proliferation, uptake ability, and migration assays were performed, and epithelial-mesenchymal transition progression was evaluated in vitro. A mouse xenograft model was used to determine the antitumor effect and distribution of ePPMO-146b in vivo. ePPMO-146b was taken up by SW620 cells and effectively inhibited cell proliferation and migration. The conjugate also exerted antitumor efficacy in a xenograft mouse model of colon cancer by systematic administration, where PPMO-146b was enriched in tumor tissue. Our study highlights the potential of hUC-MSC-derived exosomes anchored with PPMO-146b as a novel safe and effective approach for PMO backboned ASO delivery.