Spindle and kinetochore-related complex subunit 3 has a protumour function in osteosarcoma by activating the Notch pathway.

Increasing expression of spindle and kinetochore-related complex subunit 3 (SKA3) is related to the progression of multiple malignancies. However, the role of SKA3 in osteosarcoma remains unexplored. The present study aimed to investigate the relevance of SKA3 in osteosarcoma. Preliminarily, SKA3 expression in osteosarcoma was assessed through The Cancer Genome Atlas (TCGA) analysis, which revealed high levels of SKA3 transcripts in osteosarcoma tissues. Subsequent examination of clinical tissues confirmed the abundant expression of SKA3 in osteosarcoma. Downregulation of SKA3 expression in osteosarcoma cell lines resulted in repressive effects on cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT), while upregulation of SKA3 expression had the opposite effect. Gene set enrichment analysis (GSEA) revealed that the Notch pathway is enriched in SKA3 high groups based on different expressed genes from the TCGA data. Further investigation showed that the levels of Notch1, Notch1 intracellular domain (NICD1), hairy and enhancer of split 1 (HES1), and hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) were downregulated in SKA3-silenced osteosarcoma cells, and upregulated in SKA3-overexpressed osteosarcoma cells. Activation of the Notch pathway by increasing NICD1 expression reversed the antitumour effects induced by SKA3 silencing, while deactivation of the Notch pathway diminished the protumour effects induced by SKA3 overexpression. Moreover, SKA3-silenced osteosarcoma cells exhibited a reduced capacity for xenograft formation in nude mice. In conclusion, SKA3 plays a cancer-enhancing role in osteosarcoma through its effect on the Notch pathway. Reducing the expression of SKA3 could be a potential therapeutic approach for treating osteosarcoma.

Acid-Responsive Polymer Micelles for Targeted Delivery and Bioorthogonal Activation of Prodrug through Ru Catalyst in Tumor Cells.

Bioorthogonal reactions present a promising strategy for minimizing off-target toxicity in cancer chemotherapy, yet a dependable nanoplatform is urgently required. Here, we have fabricated an acid-responsive polymer micelle for the specific delivery and activation of the prodrug within tumor cells through Ru catalyst-mediated bioorthogonal reactions. The decomposition of micelles, triggered by the cleavage of the hydrazone bond in the acidic lysosomal environment, facilitated the concurrent release of Alloc-DOX and the Ru catalyst within the cells. Subsequently, the uncaging process of Alloc-DOX was demonstrated to be induced by the high levels of glutathione within tumor cells. Notably, the limited glutathione inside normal cells prevented the conversion of Alloc-DOX into active DOX, thereby minimizing the toxicity toward normal cells. In tumor-bearing mice, this nanoplatform exhibited enhanced efficacy in tumor suppression while minimizing off-target toxicity. Our study provides an innovative approach for in situ drug activation that combines safety and effectiveness in cancer chemotherapy.

Consensus statement on extracellular vesicles in liquid biopsy for advancing laboratory medicine.

Extracellular vesicles (EVs) represent a diverse class of nanoscale membrane vesicles actively released by cells. These EVs can be further subdivided into categories like exosomes and microvesicles, based on their origins, sizes, and physical attributes. Significantly, disease-derived EVs have been detected in virtually all types of body fluids, providing a comprehensive molecular profile of their cellular origins. As a result, EVs are emerging as a valuable addition to liquid biopsy techniques. In this collective statement, the authors share their current perspectives on EV-related research and product development, with a shared commitment to translating this newfound knowledge into clinical applications for cancer and other diseases, particularly as disease biomarkers. The consensus within this document revolves around the overarching recognition of the merits, unresolved questions, and existing challenges surrounding EVs. This consensus manuscript is a collaborative effort led by the Committee of Exosomes, Society of Tumor Markers, Chinese anti-Cancer Association, aimed at expediting the cultivation of robust scientific and clinically applicable breakthroughs and propelling the field forward with greater swiftness and efficacy.

circ_0000592 facilitates the progression of esophageal squamous cell carcinoma via miR-155-5p/FZD5 axis.

Esophageal squamous cell carcinoma (ESCC) is one of the gastrointestinal malignancies with high prevalence and poor prognosis. Previous reports suggested that circular ribose nucleic acids might exert regulatory functions in ESCC. This study aims to explore the role of circ_0000592 in ESCC progression, providing novel insights into the diagnosis and therapeutic avenues for ESCC. The GSE131969 data set was utilized to assess circ_0000592 expression in ESCC. The validation was performed in the tumorous tissues of ESCC patients (n = 80) and human-immortalized ESCC cell lines. The correlation between circ_0000592 expression and prognosis was analyzed. The impact of circ_0000592 on ESCC cell activity was evaluated through downregulating circ_0000592, as well as encompassing cell viability, migration, and invasion abilities. The downstream pathway of circ_0000592 was explored by binding site prediction from the TargetScan database, followed by in vitro and in vivo experiments. An in vivo xenograft tumor model was established to highlight the role of circ_0000592 in ESCC. Patients with ESCC exhibited higher circ_0000592 expression levels compared to noncancerous patients, which were associated with reduced survival time, higher TNM stage, and increased lymph node metastasis. The circ_0000592 downregulation suppressed cell viability, migration, and invasion abilities in vitro. Mechanistically, circ_0000592 countered the inhibitory effects on the target gene Frizzled 5 (FZD5) through interactions with miR-155-5p. The overexpression of miR-155-5p curtailed the luciferase activity of circ_0000592 in ESCC cells, inhibiting downstream molecule FZD5 protein expression and subsequently mitigating the detrimental consequences of escalated circ_0000592 expression in ESCC cells. Consistently, circ_0000592 downregulation curbed proliferation and metastasis of ESCC tumors in vivo. In summary, circ_0000592 promoted the progress of ESCC by counteracting the inhibitory impact on FZD5 through its interaction with miR-155-5p. Together, our findings highlighted circ_0000592 as a prospective therapeutic target for ESCC.

Nanoplatelets modified with RVG for targeted delivery of miR-375 and temozolomide to enhance gliomas therapy.

Gliomas are one of the most frequent primary brain tumors and pose a serious threat to people's lives and health. Platelets, a crucial component of blood, have been applied as drug delivery carriers for disease diagnosis and treatment. In this study, we designed engineered nanoplatelets for targeted delivery of therapeutic miR-375 and temozolomide (TMZ, a first-line glioma treatment agent) to enhance glioma therapy. Nanoplatelets were prepared through mild ultrasound, TMZ and miR-375 were co-loaded through ultrasound and electrostatic interactions, respectively, to combine chemotherapy with gene therapy against glioma. To improve the blood brain barrier (BBB) crossing efficiency and glioma targeting ability, the nanoplatelets were modified with central nervous system-specific rabies viral glycoprotein peptide (RVG) through thiol-maleimide click reaction. The RVG modified nanoplatelets co-loaded TMZ and miR-375 (NR/TMZ/miR-375) not only inherited the good stability and remarkable biocompatibility of platelets, but also promoted the cellular uptake and penetration of glioma tissues, and effectively induced cell apoptosis to enhance the therapeutic effect of drugs. In vivo studies showed that NR/TMZ/miR-375 significantly increased the circulation time of TMZ, and exhibited superior combined antitumor effects. In summary, this multifunctional 'natural' nanodrug delivery system provides a potent, scalable, and safety approach for platelet-based combined cancer chemotherapy and gene therapy.

Circ_0023990 Promotes the Proliferation, Invasion, and Glycolysis of Esophageal Squamous Cell Carcinoma Cells Via Targeting miR-6884-5p/PAK1 Axis.

Circular RNAs are emerging players in human cancers, including esophageal squamous cell carcinoma (ESCC). Herein, we assessed the expression level of circ_0023990 and explored the molecular mechanisms of circ_0023990 in ESCC. circ_0023990, miR-6884-5p, and PAK1 expressions in ESCC tissues and cells were detected by quantitative real-time polymerase chain reaction and western blot. ESCC cells were transfected with different constructs to alter the expression of circ_0023990, miR-6884-5p, and PAK1. The effect of circ_0023990 on the proliferation, invasion, and glycolysis of ESCC cells was observed. The interaction between circ_0023990 and miR-6884-5p and between miR-6884-5p and PAK1 were explored. A mouse model of ESCC was established to study the in vivo effect of circ_0023990 knockdown on tumor formation.The expression levels of circ_0023990 was upregulated in ESCC tissues and cells. Inhibiting circ_0023990 suppressed the proliferation, invasion, and glycolysis of ESCC cells. circ_0023990 might target miR-6884-5p and consequently modulate the expression and activity of PAK1. Knockdown of circ_0023990 led to significantly reduced tumor volume and weight in mice with ESCC.These findings overall suggest an oncogenic role of circ_0023990 in ESCC. Future research is warranted to confirm the expression pattern and clinical significance of circ_0023990 in ESCC.

Manganese dioxide nanoparticles provoke inflammatory damage in BV2 microglial cells via increasing reactive oxygen species to activate the p38 MAPK pathway.

With the widespread use of manganese dioxide nanoparticles (nano MnO2), health hazards have also emerged. The inflammatory damage of brain tissues could result from nano MnO2, in which the underlying mechanism is still unclear. During this study, we aimed to investigate the role of ROS-mediated p38 MAPK pathway in nano MnO2-induced inflammatory response in BV2 microglial cells. The inflammatory injury model was established by treating BV2 cells with 2.5, 5.0, and 10.0 µg/mL nano MnO2 suspensions for 12 h. Then, the reactive oxygen species (ROS) scavenger (20 nM N-acetylcysteine, NAC) and the p38 MAPK pathway inhibitor (10 µM SB203580) were used to clarify the role of ROS and the p38 MAPK pathway in nano MnO2-induced inflammatory lesions in BV2 cells. The results indicated that nano MnO2 enhanced the expression of pro-inflammatory cytokines IL-1ß and TNF-α, elevated intracellular ROS levels and activated the p38 MAPK pathway in BV2 cells. Controlling intracellular ROS levels with NAC inhibited p38 MAPK pathway activation and attenuated the inflammatory response induced by nano MnO2. Furthermore, inhibition of the p38 MAPK pathway with SB203580 led to a decrease in the production of inflammatory factors (IL-1ß and TNF-α) in BV2 cells. In summary, nano MnO2 can induce inflammatory damage by increasing intracellular ROS levels and further activating the p38 MAPK pathway in BV2 microglial cells.

Exosomal PD-L1 confers chemoresistance and promotes tumorigenic properties in esophageal cancer cells via upregulating STAT3/miR-21.

Chemotherapy resistance remains a major obstacle in the treatment of esophageal cancer. Previous researches have shown that an increase in exosomal PD-L1 expression was positively associated with a more advanced clinical stage, a poorer prognosis as well as drug resistance in patients with esophageal squamous cell carcinoma (ESCC). To explore the role of exosomal PD-L1 in ESCC, we performed bioinformatics analysis as well as several in vitro/in vivo functional experiments in a parental sensitive cell line EC-9706 and its derivative, a paclitaxel-resistant subline EC-9706R, and found that the exosomal PD-L1 from EC-9706R was higher than that from EC-9706. Moreover, exosomes from EC-9706R significantly increased invasion, migration and chemoresistance of EC-9706. Anti-PD-L1 treatment in combination with chemotherapy also led to reduced tumor burden in vivo. Inhibition of the release of exosomes by GW4869 or inhibition of STAT3 phosphorylation by stattic could effectively reverse the resistance to paclitaxel mediated by exosomal PD-L1. Furthermore, we found that PD-L1, miR-21, and multidrug resistance (MDR1) gene are involved in the process of exosomal transfer. Moreover, PD-L1 could enhance miR-21 expression by increasing the enrichment of STAT3 on miR-21 promoter. Our results suggested that exosomal PD-L1 may contribute to drug resistance to paclitaxel by regulating the STAT3/miR-21/PTEN/Akt axis and promote tumorigenic phenotype. This study provides a novel potential therapeutic approach to reverse chemoresistance and tumor progression through exosomal PD-L1 in ESCC patients.

High focusing efficiency metalens with large numerical aperture at terahertz frequency.

Metalenses have been widely investigated for their features of high design freedom. For practical applications, it is necessary to maximize the efficiency of the metalens. However, it is a great challenge to realize both a high numerical aperture (NA) and high-efficiency metalens in the community. Here, we introduce a method to design a hybrid metalens with a large numerical aperture and high focusing efficiency at terahertz frequency. The hybrid metalens consists of gradient metasurfaces in the central area and metagrating in the peripheral area to achieve high-efficiency beam focusing. To verify this concept, a hybrid metalens with a numerical aperture of 0.95 was designed at λ = 118.8 µm. The simulation results demonstrate that the focusing efficiency of the hybrid metalens is 65.8%. The experimental results show that the designed metalens is able to increase the focusing efficiency from 22.8% to 41.7%. The full widths at half maxima (FWHMs) of the focused spots of the hybrid metalens in the x direction and y direction are 0.72λ and 0.45λ, respectively. The proposed high-efficiency hybrid metalens has promising application prospects in various applications of a complex optical system.

Mesenchymal stromal cell-derived magnetic nanovesicles for enhanced skin retention and hair follicle growth.

BACKGROUND AIMS: Extracellular vesicles and exosome-mimetic nanovesicles (NVs) derived from mesenchymal stromal cells (MSCs) have emerged as promising to promote hair growth. However, short local skin retention after subcutaneous administration hinders their clinical applications. METHODS: In this study, we prepared magnetic nanovesicles (MNVs) from iron oxide nanoparticle-incorporated MSCs. MNVs contained more therapeutic growth factors than NVs derived from naive MSCs, and their localization and internalization were manipulated by external magnetic field. RESULTS: Following the subcutaneous injection of MNVs into a mouse model of depilation-induced hair regeneration, the magnetic attraction increased their skin retention. Then, the cellular proliferation and ß-catenin signaling in hair follicles (HF) were markedly enhanced by MNV injection and magnetic field application. Furthermore, an acceleration of HF growth was revealed by histological analysis. CONCLUSIONS: The proposed strategy can enhance the therapeutic potential of MSC-derived NVs for hair regeneration and other dermatological diseases.

Porphyromonas gingivalis promotes progression of esophageal squamous cell cancer via TGFß-dependent Smad/YAP/TAZ signaling.

Microbial dysbiosis in the upper digestive tract is linked to an increased risk of esophageal squamous cell carcinoma (ESCC). Overabundance of Porphyromonas gingivalis is associated with shorter survival of ESCC patients. We investigated the molecular mechanisms driving aggressive progression of ESCC by P. gingivalis. Intracellular invasion of P. gingivalis potentiated proliferation, migration, invasion, and metastasis abilities of ESCC cells via transforming growth factor-ß (TGFß)-dependent Drosophila mothers against decapentaplegic homologs (Smads)/Yes-associated protein (YAP)/Transcriptional coactivator with PDZ-binding motif (TAZ) activation. Smads/YAP/TAZ/TEA domain transcription factor1 (TEAD1) complex formation was essential to initiate downstream target gene expression, inducing an epithelial-mesenchymal transition (EMT) and stemness features. Furthermore, P. gingivalis augmented secretion and bioactivity of TGFß through glycoprotein A repetitions predominant (GARP) up-regulation. Accordingly, disruption of either the GARP/TGFß axis or its activated Smads/YAP/TAZ complex abrogated the tumor-promoting role of P. gingivalis. P. gingivalis signature genes based on its activated effector molecules can efficiently distinguish ESCC patients into low- and high-risk groups. Targeting P. gingivalis or its activated effectors may provide novel insights into clinical management of ESCC.

Methods for extending working distance using modified photonic crystal for near-field lithography.

Near-field lithography has evident advantages in fabricating super-resolution nano-patterns. However, the working distance (WD) is limited due to the exponential decay characteristic of the evanescent waves. Here, we proposed a novel photolithography method based on a modified photonic crystal (PC), where a defect layer is embedded into the all-dielectric multilayer structure. It is shown that this design can amend the photonic band gap and enhance the desired high-kwaves dramatically, then the WD in air conditions could be extended greatly, which would drastically relax the engineering challenges for introducing the near-field lithography into real-world manufacturing applications. Typically, deep subwavelength patterns with a half-pitch of 32 nm (i.e.,λ/6) could be formed in photoresist layer at an air WD of 100 nm. Moreover, it is revealed that diversified two-dimensional patterns could be produced with a single exposure using linear polarized light. The analyses indicate that this improved dielectric PC is applicable for near-field lithography to produce super-resolution periodic patterns with large WD, strong field intensity, and great uniformity.

Prognostic value of prognostic nutritional index and its variations in advanced non-small-cell lung cancer patients treated with anlotinib monotherapy.

BACKGROUND: Anlotinib is a third-line or further therapy for advanced non-small-cell lung cancer (NSCLC). However, the lack of simple biomarkers to predict the curative effect of anlotinib creates significant unmet needs in exploring the markers. This study aimed to explore the relationship between the prognostic nutritional index (PNI) and its variations and efficacy of anlotinib. METHODS: Data for patients with advanced NSCLC who received anlotinib were collected at Ningbo Medical Center Lihuili Hospital. The data included the values of pretreatment PNI (pre-PNI), posttreatment PNI (post-PNI), and ΔPNI (post-PNI minus the pre-PNI). The Kaplan-Meier method was used to generate survival curves, whereas univariate and multivariate Cox regression analyses were used to analyze survival predictors. RESULTS: A high disease control rate was associated with a high pre-PNI (p = 0.007), high post-PNI (p = 0.000), and high ΔPNI (p = 0.006). Univariable analysis revealed that pre-PNI ≤41.80, post-PNI ≤42.48, and ΔPNI ≤0.20 were significant risk factors for poor survival. According to the multivariate analysis, progression-free survival (PFS) in patients with post-PNI ≤42.48 was significantly shorter than in patients with higher values (median PFS: 1.5 months vs. 4.0 months, p = 0.010). CONCLUSIONS: Pre-PNI, ΔPNI, and post-PNI were found to be predictive factors for response in advanced NSCLC patients treated with anlotinib as a third-line or further treatment. Only post-PNI was a reliable predictor of PFS. Therefore, PNI and its variations, particularly post-PNI, are affordable and accessible predictors of NSCLC patients treated with anlotinib in clinical work.

Inflammation-based prognostic scoring system for predicting the prognosis of advanced small cell lung cancer patients receiving anlotinib monotherapy.

BACKGROUND: According to the randomized multicenter phase II trial (ALTER1202), anlotinib has been approved as a third-line therapy for advanced small-cell lung cancer (SCLC). Some studies showed the predictive function of inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in the different cancers treated with anti-vascular targeting drugs. However, none of the studies showed the roles of NLR, PLR, and LMR in SCLC patients receiving anlotinib. Thus, our objective was to establish a scoring system based on inflammation to individuate patient stratification and selection based on NLR, PLR, and LMR. METHODS: NLR, PLR, and LMR and their variations were calculated in 53 advanced SCLC patients receiving anlotinib as a third- or further-line treatment at Ningbo Medical Center Lihuili Hospital between January 2019 and December 2021. Kaplan-Meier curves were plotted. Both univariate and multivariate Cox regressions were used to identify predictors of survival. RESULTS: Disease control rate was related to pre-NLR, pre-PLR, pre-LMR, post-NLR elevation, post-PLR elevation, and post-LMR elevation. The multivariate analysis determined post-NLR elevation, pre-PLR > 240.56, and pre-LMR ≤1.61 to be independently associated with progression-free survival, not overall survival. The inflammation-based prognostic scoring system demonstrated favorable predictive ability from the receiver operating characteristic curve (AUC: 0.791, 95% CI: 0.645-0.938). CONCLUSIONS: Post-NLR variation, pre-PLR, and pre-LMR were independent prognostic factors for PFS in advanced SCLC receiving anlotinib monotherapy. The inflammation-based prognostic scoring system can accurately predict effectiveness and survival.

Enlarging focal depth using epsilon-near-zero metamaterial for plasmonic lithography.

Plasmonic lithography can utilize evanescent waves to produce subdiffraction patterns. However, the high loss and shallow depth of patterns severely obstruct its application in practice. In this work, a large focal depth is achieved for deep subwavelength lithography. It is accomplished by employing radially polarized light to excite surface plasmons on a concentric annular grating and combining designed epsilon-near-zero metamaterial to select a high spatial frequency mode, which can shape an evanescent Bessel beam in a photoresist (PR). Moreover, the intensity distribution of the subdiffraction beam can be further enhanced and uniformized by adding reflective layers. It is shown that a needle-like beam with a focal depth of over 500 nm (1.23λ) is formed in the PR layer, and the full width at half maximum of the beam is widened from only 80 nm (0.2λ) to 94 nm (0.23λ). The analyses indicate that this design is applicable for direct writing lithography to produce super-resolution patterns with small feature size, high aspect ratio, and strong field intensity.

CRISPR/Cas technology promotes the various application of Dunaliella salina system.

Dunaliella salina (D. salina) has been widely applied in various fields because of its inherent advantages, such as the study of halotolerant mechanism, wastewater treatment, recombinant proteins expression, biofuel production, preparation of natural materials, and others. However, owing to the existence of low yield or in the laboratory exploration stage, D. salina system has been greatly restricted for practical production of various components. In past decade, significant progresses have been achieved for research of D. salina in these fields. Among them, D. salina as a novel expression system demonstrated a bright prospect, especially for large-scale production of foreign proteins, like the vaccines, antibodies, and other therapeutic proteins. Due to the low efficiency, application of traditional regulation tools is also greatly limited for exploration of D. salina system. The emergence of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system offers a precise editing tool to overcome the obstacles of D. salina system. This review not only comprehensively summarizes the recent progresses of D. salina in domain of gene engineering but also gives a deep analysis of problems and deficiencies in different fields of D. salina. Moreover, further prospects of CRISPR/Cas system and its significant challenges have been discussed in various aspects of D. salina. It provides a great referencing value for speeding up the maturity of D. salina system, and also supplies practical guiding significance to expand the new application fields for D. salina. KEY POINTS: • The review provides recent research progresses of various applications of D. salina. • The problems and deficiencies in different fields of D. salina were deeply analyzed. • The further prospects of CRISPR/Cas technology in D. salina system were predicted. • CRISPR/Cas system will promote the new application fields and maturity for D. salina.

Recent progress in the development of upconversion nanomaterials in bioimaging and disease treatment.

Multifunctional lanthanide-based upconversion nanoparticles (UCNPs), which feature efficiently convert low-energy photons into high-energy photons, have attracted considerable attention in the domain of materials science and biomedical applications. Due to their unique photophysical properties, including light-emitting stability, excellent upconversion luminescence efficiency, low autofluorescence, and high detection sensitivity, and high penetration depth in samples, UCNPs have been widely applied in biomedical applications, such as biosensing, imaging and theranostics. In this review, we briefly introduced the major components of UCNPs and the luminescence mechanism. Then, we compared several common design synthesis strategies and presented their advantages and disadvantages. Several examples of the functionalization of UCNPs were given. Next, we detailed their biological applications in bioimaging and disease treatment, particularly drug delivery and photodynamic therapy, including antibacterial photodynamic therapy. Finally, the future practical applications in materials science and biomedical fields, as well as the remaining challenges to UCNPs application, were described. This review provides useful practical information and insights for the research on and application of UCNPs in the field of cancer.

Engineered exosomes for targeted co-delivery of miR-21 inhibitor and chemotherapeutics to reverse drug resistance in colon cancer.

BACKGROUND: 5-Fluorouracil (5-FU) has been commonly prescribed for patients with colorectal cancer (CRC), but resistance to 5-FU is one of the main reasons for failure in CRC. Recently, microRNAs (miRNAs) have been established as a means of reversing the dilemma by regulating signaling pathways involved in initiation and progression of CRC. However, how to safely and effectively deliver miRNA to target cells becomes a main challenge. RESULTS: In this study, Engineered exosomes were exploited to simultaneously deliver an anticancer drug 5-FU and miR-21 inhibitor oligonucleotide (miR-21i) to Her2 expressing cancer cells. Purified engineered exosomes from the donor cells loaded with 5-FU and miR-21i via electroporation to introduce into 5-FU-resistant colorectal cancer cell line HCT-1165FR. Furthermore, systematic administration of 5-FU and miR-21i loaded exosomes in tumor bearing mice indicated a significantly anti-tumor effect. The results showed that the engineered exosome-based 5-FU and miR-21i co-delivery system could efficiently facilitate cellular uptake and significantly down-regulate miR-21 expression in 5-FU resistant HCT-1165FR cell lines. Consequently, the down-regulation of miR-21 induced cell cycle arrest, reduced tumor proliferation, increased apoptosis and rescued PTEN and hMSH2 expressions, regulatory targets of miR-21. Of particular importance was the significant reduction in tumor growth in a mouse model of colon cancer with systematic administration of the targeting miR-21i. More excitedly, the combinational delivery of miR-21i and 5-FU with the engineered exosomes effectively reverse drug resistance and significantly enhanced the cytotoxicity in 5-FU-resistant colon cancer cells, compared with the single treatment with either miR-21i or 5-FU. CONCLUSION: The strategy for co-delivering the functional small RNA and anticancer drug by exosomes foreshadows a potential approach to reverse the drug resistance in CRC and thus to enhance the efficacy of the cancer treatment.

PTPN14, a target gene of miR-4295, restricts the growth and invasion of osteosarcoma cells through inactivation of YAP1 signalling.

Non-receptor tyrosine phosphatase 14 (PTPN14) has emerged as a novel tumour-suppressor in a wide range of human cancer types. However, the role of PTPN14 in osteosarcoma remains undetermined. In the present study, we aimed to explore the expression pattern, biological function, and regulation of PTPN14 in osteosarcoma. Low PTPN14 expression levels were detected in osteosarcoma cells, and PTPN14 overexpression markedly decreased the proliferation, colony formation, and invasive potential of osteosarcoma cells. Bioinformatics analysis predicted PTPN14 as a potential target gene of microRNA-4295 (miR-4295), and this prediction was validated by a dual-luciferase reporter assay. PTPN14 expression was negatively modulated by miR-4295 in osteosarcoma cells. Moreover, PTPN14 expression was inversely correlated with miR-4295 expression in osteosarcoma tissues. Notably, miR-4295 inhibition significantly restricted the proliferation and invasion of osteosarcoma cells. PTPN14 overexpression or miR-4295 inhibition increased the phosphorylation of Yes-associated protein 1 (YAP1) and impeded YAP1 nuclear translocation, leading to inhibition of YAP1-mediated transcriptional activity. However, the miR-4925-inhibition-mediated antitumour effect was partially reversed by PTPN14 knockdown. Overall, these results demonstrate that PTPN14 is a miR-4295 target gene and it exerts a tumour-suppressive function in osteosarcoma cells via inactivation of YAP1. Our study uncovers a miR-4295-PTPN14-YAP1 signalling pathway that may play a crucial role in the progression of osteosarcoma.

Super-resolution photolithography using dielectric photonic crystal.

Although plasmonic photolithography can break through the diffraction limit and produce super-resolution patterns, the intrinsic high loss from metal severely obstructs its application in practice. Here we proposed a novel photolithography method based on a dielectric photonic crystal (PC) structure, where the nanofilms are analyzed systematically. It is shown that the PC can efficiently transmit the desired high-k waves, which is advantageous in generating deep subwavelength patterns and realizing super-resolution lithography. Typically, a PC composed of stacked nine films of a multilayer is demonstrated. The nanopatterns with a period of 60 nm are formed in the photoresist layer. Furthermore, this PC-based lithography system is tolerant to the surface roughness in a multilayer. The analyses indicate that this dielectric PC-based design is applicable for super-resolution lithography to produce periodic patterns with strong field intensity, high aspect ratios, and great uniformity.