Periosteum-bone inspired hierarchical scaffold with endogenous piezoelectricity for neuro-vascularized bone regeneration.

The development of scaffolds for repairing critical-sized bone defects heavily relies on establishing a neuro-vascularized network for proper penetration of nerves and blood vessels. Despite significant advancements in using artificial bone-like scaffolds infused with various agents, challenges remain. Natural bone tissue consists of a porous bone matrix surrounded by a neuro-vascularized periosteum, with unique piezoelectric properties essential for bone growth.

ITPR1-AS1 promotes small cell lung cancer metastasis by facilitating P21 splicing and stabilizing DDX3X to activate the cRaf-MEK-ERK cascade.

The mechanisms underlying the involvement of long non-coding RNAs (lncRNAs) in the metastasis of small cell lung cancer (SCLC) remain largely unknown. Here, we identified that the lncRNA ITPR1-AS1 was upregulated in SCLC and lymph node metastasis tissues and positively correlated with SCLC malignant features. The overexpression of ITPR1-AS1 in SCLC was an independent risk factor for the overall survival of patients with SCLC.

Development and validation of immunogenic cell death-applied prediction model for esophageal carcinoma.

Evidence suggests that immunogenic cell death (ICD) releases cancer antigens that promote cytotoxic T-cell responses, potentially improving immunotherapy. However, the relationship between ICDs and esophageal cancer (EC) remains unclear. This study aimed to determine the role of ICDs in EC and to construct an ICD-based prognostic panel.

Electrospun cellulose acetate nanofibrous composites for multi-responsive shape memory actuators and self-powered pressure sensors.

Soft actuators and sensors have attracted extensive scientific interest attributed to their great potential applications in various fields, but the integration of actuating and sensing functions in one material is still a big challenge. Here, we developed an electrospun cellulose acetate (CA)/carbon nanotube nanofiborous composite with both functional applications as multi-responsive shape memory actuators and triboelectric nanogenerator (TENG) based sensors. Attributed to excellent thermo- and light-induced shape memory performance, the CA nanofiborous composites showed high heavy-lift capability as light driven actuators, able to lift burdens 1050 times heavier than their own weight.

Comprehensive profiling of EGFR mutation subtypes reveals genomic-clinical associations in non-small-cell lung cancer patients on first-generation EGFR inhibitors.

Common sensitizing mutations in epidermal growth factor receptor (cEGFR), including exon 19 deletions (19-Del) and exon 21 L858R substitution, are associated with high sensitivity to EGFR-TKIs in NSCLC patients. The treatment for NSCLC patients with uncommon EGFR (uEGFR) mutations remains a subject of debate due to heterogeneity in treatment responses. In this manuscript, the targeted next-generation sequencing (NGS) data of a large cohort of EGFR-mutated NSCLC patients was assessed to elucidate genomic profiles of tumors carrying cEGFR or uEGFR mutations.

Intelligent Gold Nanoparticles with Oncogenic MicroRNA-Dependent Activities to Manipulate Tumorigenic Environments for Synergistic Tumor Therapy.

Tumorigenic environments, especially aberrantly overexpressed oncogenic microRNAs, play a critical role in various activities of tumor progression. However, developing strategies to effectively utilize and manipulate these oncogenic microRNAs for tumor therapy is still a challenge. To address this challenge, spherical nucleic acids (SNAs) consisting of gold nanoparticles in the core and antisense oligonucleotides as the shell are fabricated.

Multimodal obstruction of tumorigenic energy supply via bionic nanocarriers for effective tumor therapy.

Sufficient energy generation based on effective transport of nutrient via abundant blood vessels in tumor tissue and subsequent oxidative metabolism in mitochondria is critical for growth, proliferation and migration of tumor. Thus the strategy to cut off this transport pathway (blood vessels) and simultaneously close the power house (mitochondria) is highly desired for tumor treatment. Herein, we fabricated a bionic nanocarrier with core-shell-corona structure to give selective and effective tumor therapy via stepwise destruction of existed tumor vessel, inhibition of tumor angiogenesis and dysfunction of tumor mitochondria.

The facile formation of hierarchical mesoporous silica nanocarriers for tumor-selective multimodal theranostics.

The combination of therapeutic and diagnostic functions in a single platform has aroused great interest due to the more optimal synergistic effects that can be obtained as compared to any single theranostic approach alone. However, current nanotheranostics are normally formed via complicated construction steps involving the pre-synthesis of each component and further conjugation via chemical bonds, which may cause low integration efficiency and limit production and applications. Herein, a tumor-targeting and tumor-responsive all-in-one nanoplatform based on mesoporous silica nanocarriers (MSNs) was fabricated via a facile approach utilizing efficient and nondestructive physical interactions for long-wavelength fluorescence imaging-guided synergistic chemo-catalytic-photothermal tumor therapy.

On-demand manipulation of tumorigenic microenvironments by nano-modulator for synergistic tumor therapy.

Proper manipulation of tumorigenic microenvironments has been considered as one of the most effective approaches for tumor therapy, which is still a challenge to be well performed. Herein, a nano-modulator was fabricated to manipulate the hypoxia, glucose, radicals and local temperature in tumor tissue as needed, which consists of hemoglobin (Hb) and ferric ion (Fe) co-conjugated polydopamine (PDA) as core, glucose oxidase (GOD) as shell, and folic acid (FA) modified polyethylene glycol (PEG) as corona. The PEG-FA corona not only protected Hb and GOD against protease in blood circulation, but serve as tumor targeting agent for tumor specific accumulation of the nano-modulator.

Novel Near-Infrared Light-Induced Triple-Shape Memory Composite Based on Poly(ethylene--vinyl alcohol) and Iron Tannate.

Remote controllability and multiple-shape memory performance are two important functions for shape memory polymers (SMPs) in engineering applications, which are still a challenge to achieve via a facile approach. Herein, we synthesized a shape memory composite with near-infrared (NIR) light-induced triple-shape memory performance by in situ formation of iron tannate (FeTA) nanoparticles in cross-linked poly(ethylene--vinyl alcohol) (EVOH). EVOH possessed two transition temperatures enabling the composites with triple-shape memory behavior, while FeTA nanoparticles served as the photothermal conversion factor for NIR light-induced responsiveness.

Multifunctional hierarchical nanohybrids perform triple antitumor theranostics in a cascaded manner for effective tumor treatment.

Gene therapy based on transfection of RNAs/DNAs offers tremendous promise for tumor treatment. However, the relatively weak therapeutic efficiency of current genetic nanohybrids in vivo has limited the application of this strategy. Herein, we fabricated multifunctional core-shell-corona nanohybrids by combining cascaded theranostics for enhanced gene therapy.

Meiotic nuclear divisions 1 (MND1) fuels cell cycle progression by activating a KLF6/E2F1 positive feedback loop in lung adenocarcinoma.

Background: Considering the increase in the proportion of lung adenocarcinoma (LUAD) cases among all lung cancers and its considerable contribution to cancer-related deaths worldwide, we sought to identify novel oncogenes to provide potential targets and facilitate a better understanding of the malignant progression of LUAD.

Methods: The results from the screening of transcriptome and survival analyses according to the integrated Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) data were combined, and a promising risk biomarker called meiotic nuclear divisions 1 (MND1) was selectively acquired. Cell viability assays and subcutaneous xenograft models were used to validate the oncogenic role of MND1 in LUAD cell proliferation and tumor growth.

Modular immune-homeostatic microparticles promote immune tolerance in mouse autoimmune models.

The therapeutic goal for autoimmune diseases is disease antigen-specific immune tolerance without nonspecific immune suppression. However, it is a challenge to induce antigen-specific immune tolerance in a dysregulated immune system. In this study, we developed immune-homeostatic microparticles (IHMs) that treat multiple mouse models of autoimmunity via induction of apoptosis in activated T cells and reestablishment of regulatory T cells.

Treatment of infarcted heart tissue via the capture and local delivery of circulating exosomes through antibody-conjugated magnetic nanoparticles.

The systemic biodistribution of endogenous extracellular vesicles is central to the maintenance of tissue homeostasis. Here, we show that angiogenesis and heart function in infarcted heart tissue can be ameliorated by the local accumulation of exosomes collected from circulation using magnetic nanoparticles. The nanoparticles consist of a FeO core and a silica shell that is decorated with poly (ethylene glycol) conjugated through hydrazone bonds to two types of antibody, which bind either to CD63 antigens on the surface of extracellular vesicles or to myosin-light-chain surface markers on injured cardiomyocytes.

Lymphatic Metastasis of NSCLC Involves Chemotaxis Effects of Lymphatic Endothelial Cells through the CCR7-CCL21 Axis Modulated by TNF-α.

Metastasis and recurrence are the main causes of lung adenocarcinoma patients' death. Lymphatic metastasis is the main way of non-small cell lung cancer (NSCLC) metastasis. C-C chemokine receptor type 7 (CCR7) overexpression has been demonstrated to mediate occurrence and progression of NSCLC.

Nanocomposite hydrogel with NIR/magnet/enzyme multiple responsiveness to accurately manipulate local drugs for on-demand tumor therapy.

Chemotherapy is one of the most commonly utilized approaches to treat malignant tumor. However, the well-controlled chemotherapy able to accurately manipulate local drugs for on-demand tumor treatment is still a challenge. Herein, a magnet and light dual-responsive hydrogel combining thermosensitive poly(N-acryloyl glycinamide) (PNAGA), doxorubicin (DOX) loaded and polyester (PE) capped mesoporous silica nanocarriers (MSNs) as well as FeO nanoparticles (FeO NPs) grafted graphene oxide (GO) was fabricated to address above issue.

Substrate-independent polymer coating with stimuli-responsive dexamethasone release for on-demand fibrosis inhibition.

Tissue fibrosis caused by implantation of tissue engineering scaffolds is an urgent problem in clinical research. In this work, a substrate-independent coating with on-demand release of an antifibrotic drug has been fabricated to effectively address this issue. This coating was formed through a substrate-independent layer-by-layer (LBL) technique via a cationic polyelectrolyte (poly-diallyldimethylammonium, PDDA) and an anionic polyelectrolyte (poly-styrenesulfonate, PSS), where parts of PSS and PDDA were physically replaced by carboxyl functionalized polyethylene glycol grafted onto antifibrotic drug dexamethasone (DEX-PEG-COOH).

Identification of LBX2 as a novel causal gene of lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is the most predominant histological type of lung cancer with a poor prognosis. In this study, we demonstrate that LBX2 regulates cell proliferation, migration and invasion and the potential molecular mechanism in LUAD.

Methods: The Cancer Genome Atlas dataset was accessed to screen for novel genes and immunohistochemistry (IHC) assays were performed to determine the association between LBX2 expression and clinicopathological features of LUAD.

CircRNA circ_POLA2 promotes lung cancer cell stemness via regulating the miR-326/GNB1 axis.

Circular RNAs (CircRNAs) are a group of noncoding RNAs that have essential function in the development and progression of various cancers. The expression pattern and function of circRNA in lung cancer is not fully understood. In the present study, we aimed to investigate the expression profiles and underlying mechanism of circRNA circ_POLA2 in lung cancer cell stemness.

Tumor-specific nanomedicine via sequential catalytic reactions for accurate tumor therapy.

Catalytic medicine based on various catalysts has attracted increasing interest for the treatment of tumors. However, the direct application of conventional catalysts may cause serious side effects to healthy tissue and low therapeutic efficiency against tumor tissue, due to their weak specificity for the tumor microenvironment (TME). Herein, a tumor-targeting and TME-responsive nanoreactor containing ferroferric oxide nanoparticles (FeO NPs) and glucose oxidase (GOD) was developed to perform hyaluronidase (HAase) and glutathione (GSH)-triggered chain catalytic reactions in tumor tissue.

A tumor-targeted nanoplatform with stimuli-responsive cascaded activities for multiple model tumor therapy.

Herein, a rambutan-like nanocomplex (PDA-SNO-GA-HA-DOX, PSGHD for short) was designed to enable effective and accurate tumor therapy. The PSGHD nanocomplex consists of an S-nitrosothiol-functionalized polydopamine (PDA-SNO) core and a gambogic acid-derivatized hyaluronic acid (HA-GA) shell with doxorubicin (DOX) as the cargo. Due to the HA section, the PSGHD nanocomplex can be rapidly and selectively internalized by tumor cells instead of healthy cells in 12 h of co-incubation.

Decoding tumor mutation burden and driver mutations in early stage lung adenocarcinoma using CT-based radiomics signature.

Background: Tumor mutation burden (TMB) is an important determinant and biomarker for response of targeted therapy and prognosis in patients with lung cancer. The present study aimed to determine whether radiomics signature could non-invasively predict the TMB status and driver mutations in patients with resectable early stage lung adenocarcinoma (LUAD).

Methods: A total of 61pulmonary nodules (PNs) from 51 patients post-operatively diagnosed LUAD were enrolled for analysis.

MiRNA Delivery System Based on Stimuli-Responsive Gold Nanoparticle Aggregates for Multimodal Tumor Therapy.

In this work, a composite of microRNA-124-5p mimics (miR-124-5p) and gold nanoparticle (AuNP) aggregates was fabricated to combine the gene therapy and photothermal therapy for effective tumor medicine. The AuNP aggregates cross-linked by cystamine not only serve as photothermal therapeutic agents but are able to condense miR-124-5p as nanocarrier for gene delivery because of the coulomb interaction. The release of miR-124-5p could be initiated by the cleavage of cystamine when the nanocarrier enter the cytoplasm of tumor cells through endocytosis, where contains high concentration of glutathione (GSH).