Power and electronic components that are self‐healable, deformable, transparent, and self‐powered are highly desirable for next‐generation energy/electronic/robotic applications. Here, an ...energy‐harvesting triboelectric nanogenerator (TENG) that combines the above features is demonstrated, which can serve not only as a power source but also as self‐powered electronic skin. This is the first time that both of the triboelectric‐charged layer and electrode of the TENG are intrinsically and autonomously self‐healable at ambient conditions. Additionally, comparing with previous partially healable TENGs, its fast healing time (30 min, 100% efficiency at 900% strain), high transparency (88.6%), and inherent superstretchability (>900%) are much more favorable. It consists of a metal‐coordinated polymer as the triboelectrically charged layer and hydrogen‐bonded ionic gel as the electrode. Even after 500 cutting‐and‐healing cycles or under extreme 900%‐strain, the TENG retains its functionality. The generated electricity can be used directly or stored to power commercial electronics. The TENG is further used as self‐powered tactile‐sensing skin in diverse human–machine interfaces including smart glass, an epidermal controller, and phone panel. This TENG with merits including fast ambient‐condition self‐healing, high transparency, intrinsic stretchability, and energy‐extraction and actively‐sensing abilities, can meet wide application needs ranging from deformable/portable/transparent electronics, smart interfaces, to artificial skins.
The first entirely, intrinsically, and autonomously self‐healable, highly transparent, and superstretchable triboelectric nanogenerator is developed for not only energy sources but also self‐powered electronic skins. This unprecedented triboelectric nanogenerator with energy‐extracting and activity‐sensing abilities is timely and able to usher vast emerging fields including flexible/self‐powered electronics, smart interfaces, and prosthetic and robotic skins.
Here we demonstrate that the photoactivity of Au-decorated TiO2 electrodes for photoelectrochemical water oxidation can be effectively enhanced in the entire UV–visible region from 300 to 800 nm by ...manipulating the shape of the decorated Au nanostructures. The samples were prepared by carefully depositing Au nanoparticles (NPs), Au nanorods (NRs), and a mixture of Au NPs and NRs on the surface of TiO2 nanowire arrays. As compared with bare TiO2, Au NP-decorated TiO2 nanowire electrodes exhibited significantly enhanced photoactivity in both the UV and visible regions. For Au NR-decorated TiO2 electrodes, the photoactivity enhancement was, however, observed in the visible region only, with the largest photocurrent generation achieved at 710 nm. Significantly, TiO2 nanowires deposited with a mixture of Au NPs and NRs showed enhanced photoactivity in the entire UV–visible region. Monochromatic incident photon-to-electron conversion efficiency measurements indicated that excitation of surface plasmon resonance of Au is responsible for the enhanced photoactivity of Au nanostructure-decorated TiO2 nanowires. Photovoltage experiment showed that the enhanced photoactivity of Au NP-decorated TiO2 in the UV region was attributable to the effective surface passivation of Au NPs. Furthermore, 3D finite-difference time domain simulation was performed to investigate the electrical field amplification at the interface between Au nanostructures and TiO2 upon SPR excitation. The results suggested that the enhanced photoactivity of Au NP-decorated TiO2 in the UV region was partially due to the increased optical absorption of TiO2 associated with SPR electrical field amplification. The current study could provide a new paradigm for designing plasmonic metal/semiconductor composite systems to effectively harvest the entire UV–visible light for solar fuel production.
Malignant pleural effusion is a common complication in metastatic breast cancer (MBC); however, changes in the pleural microenvironment are poorly characterized, especially with respect to estrogen ...receptor status. Histologically, MBC presents with increased microvessels beneath the parietal and visceral pleura, indicating generalized angiogenic activity. Breast cancer‐associated pleural fluid (BAPF) was collected and cultured with HUVECs to recapitulate the molecular changes in subpleural endothelial cells. The clinical progression of triple‐negative breast cancer (TNBC) is much more aggressive than that of hormone receptor‐positive breast cancer (HPBC). However, BAPF from HPBC (BAPF‐HP) and TNBC (BAPF‐TN) homogeneously induced endothelial proliferation, migration, and angiogenesis. In addition, BAPF elicited negligible changes in the protein marker of endothelial‐mesenchymal transition. Both BAPF‐HP and BAPF‐TN exclusively upregulated JNK signaling among all MAPKs in HUVECs. By contrast, the response to the JNK inhibitor was insignificant in Transwell and tube formation assays of the HUVECs cultured with BAPF‐TN. The distinct contribution of p‐JNK to endothelial angiogenesis was consequently thought to be induced by BAPF‐HP and BAPF‐TN. Due to increased angiogenic factors in HUVECs cultured with BAPF, vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor was applied accordingly. Responses to VEGFR2 blockade were observed in both BAPF‐HP and BAPF‐TN concerning endothelial migration and angiogenesis. In conclusion, the above results revealed microvessel formation in the pleura of MBC and the underlying activation of p‐JNK/VEGFR2 signaling. Distinct responses to blocking p‐JNK and VEGFR2 in HUVECs cultured with BAPF‐HP or BAPF‐TN could lay the groundwork for future investigations in treating MBC based on hormone receptor status.
Current study evaluated the angiogenic response of HUVECs cultured with breast cancer‐associated pleural fluid (BAPF) obtained from hormone positive (HP) and triple negative (TN) breast cancer, respectively. Both BAPF‐HP and BAPF‐TN stimulated endothelial angiogenesis with upregulation of vascular endothelial growth factor receptor 2 (VEGFR2) and p‐JNK expressions. In contrast, application of p‐JNK inhibitor only showed efficacy in HUVECs cultured with BAPF‐HP, but not BAPF‐TN. Blockade of VEGFR2 signaling revealed potent inhibition on endothelial motility and angiogenesis induced by BAPF‐HP and BAPF‐TN.
Malignant pleural effusion (MPE) and paramalignant pleural effusion (PPE) remain debilitating complications in lung cancer patients with poor prognosis and limited treatment options. The role of ...vascular endothelial cells has not been explored in the pleural environment of lung cancer. By integrating MPE and PPE as malignant‐associated pleural fluid (MAPF), the current study aimed to evaluate the effect of MAPF on cell proliferation, migration and angiogenesis of HUVEC. First, increased capillaries were identified in the subpleural layer of lung adenocarcinoma. Compatible with pathological observations, the ubiquitous elevation of HUVEC survival was identified in MAPF culture regardless of the underlying cancer type, the driver gene mutation, prior treatments and evidence of malignant cells in pleural fluid. Moreover, MAPF enhanced HUVEC motility with the formation of lamellipodia and filopodia and focal adhesion complex. Tube formation assay revealed angiogenic behavior with the observation of sheet‐like structures. HUVEC cultured with MAPF resulted in a significant increase in MAPK phosphorylation. Accompanied with VEGFR2 upregulation in MAPF culture, there was increased expressions of p‐STAT3, HIF‐1α and Nf‐kB. VEGF/VEGFR2 blockade regressed endothelial migration and angiogenesis but not cell proliferation. Our data indicate the angiogenic activities of MAPF on vascular endothelial cells that revealed increased pleural capillaries in lung cancer. Targeting the VEGF/VEGFR2 pathway might modulate the angiogenic propensity of MAPF in future clinical investigations.
Increased microvessel formation manifested in the subpleural layer of lung carcinoma specimens. In addition, the potency of MAPF to promote endothelial viability and motility was universal regardless of the histological type of cancer, the presence of malignant cells in pleural fluid, and whether or not patients harbored gene mutations. Blockade of VEGFR2 signaling did not compromise MAPF‐induced endothelial viability, and more bioactive factors were, thus, needed to investigate the drug development of MAPF.
Aims
Papillary renal neoplasm with reverse polarity (PRNRP) is a newly defined entity with distinct histomorphology and recurrent KRAS mutation. It has been estimated to constitute 4% of previously ...diagnosed papillary renal cell carcinoma (PRCC). Renal papillary adenoma (PA) is suggested to be the precursor of PRCC. This study aimed to investigate the association between PRNRP and PA, particularly the morphologically similar type D PA.
Methods and results
Nephrectomy specimens of PRCC and PA from our 10‐year pathology archives were retrieved and reviewed. GATA3 immunohistochemistry and RAS/BRAF testing were performed in all cases reclassified as PRNRP and all PAs with sufficient materials. Overall, PRNRP accounted for 9.1% (10 of 110) of PRCC and there was no recurrence/metastasis with a mean follow‐up period of 39 months. Three novel morphological features were described, including clear cell change, mast cell infiltration and metaplastic ossification. Nine of the 10 PRNRPs showed diffuse and strong GATA3 expression and KRAS missense mutations at codon 12. One case exhibited moderate GATA3 staining on 80% of the tumour cells and RAS/BRAF wild‐type. In a total of 73 PAs, 11 were classified as type D. GATA3 expression was significantly more frequent in type D versus non‐type D PAs (100 versus 35%, P < 0.01). KRAS missense mutations were identified in six of eight (75%) of the type D PAs but none of the 18 non‐type D PAs.
Conclusions
Type D PA was different from other types of PA and represented an analogue or a small‐sized PRNRP for their identical morphology, immunophenotype and molecular signature.
Polyamines, often elevated in cancer cells, have been shown to promote cell growth and proliferation. Whether polyamines regulate other cell functions remains unclear. Here, we explore whether and ...how polyamines affect genome integrity. When DNA double-strand break (DSB) is induced in hair follicles by ionizing radiation, reduction of cellular polyamines augments dystrophic changes with delayed regeneration. Mechanistically, polyamines facilitate homologous recombination-mediated DSB repair without affecting repair via non-homologous DNA end-joining and single-strand DNA annealing. Biochemical reconstitution and functional analyses demonstrate that polyamines enhance the DNA strand exchange activity of RAD51 recombinase. The effect of polyamines on RAD51 stems from their ability to enhance the capture of homologous duplex DNA and synaptic complex formation by the RAD51-ssDNA nucleoprotein filament. Our work demonstrates a novel function of polyamines in the maintenance of genome integrity via homology-directed DNA repair.
Epithelial-mesenchymal transition (EMT) is a pivotal mechanism for cancer dissemination. However, EMT-regulated individual cancer cell invasion is difficult to detect in clinical samples. Emerging ...evidence implies that EMT is correlated to collective cell migration and invasion with unknown mechanisms. We show that the EMT transcription factor Snail elicits collective migration in squamous cell carcinoma by inducing the expression of a tight junctional protein, claudin-11. Mechanistically, tyrosine-phosphorylated claudin-11 activates Src, which suppresses RhoA activity at intercellular junctions through p190RhoGAP, maintaining stable cell-cell contacts. In head and neck cancer patients, the Snail-claudin-11 axis prompts the formation of circulating tumour cell clusters, which correlate with tumour progression. Overexpression of snail correlates with increased claudin-11, and both are associated with a worse outcome. This finding extends the current understanding of EMT-mediated cellular migration via a non-individual type of movement to prompt cancer progression.
Abstract
Background
Sarcopenia is an age-related, multifactorial syndrome. Previous studies have shown that air pollutants are associated with inflammation and oxidative stress. However, the ...association between long-term exposure to air pollution and sarcopenia is not completely understood.
Methods
The Taiwan National Health Research Database (NHIRD) contains medical records of almost all Taiwanese residents. Daily air pollution data collected by the Taiwan Environmental Protection Agency was used to analyze concentrations of sulfur oxide (SO
2
), carbon monoxide (CO), nitrogen monoxide (NO), nitrogen dioxide (NO
2
), and particulate matter (PM
2.5
, PM
10
). The databases were merged according to the insurants’ living area and the location of the air quality monitoring station. We categorized the pollutants into quartiles (Q1, Q2, Q3, and Q4).
Results
Our study population consisted of 286,044 patients, among whom 54.9% were female and 45.1% were male. Compared to Q1 levels of pollutants, Q4 levels of SO
2
(adjusted hazard ratio aHR = 8.43; 95% confidence interval CI = 7.84, 9.07); CO (aHR = 3.03; 95%CI = 2.83, 3.25); NO (aHR = 3.47; 95%CI = 3.23, 3.73); NO
2
(aHR = 3.72; 95%CI = 3.48, 3.98); PM
2.5
(aHR = 21.9; 95% CI = 19.7, 24.5) and PM
10
(aHR = 15.6; 95%CI = 14.1, 17.4) increased risk of sarcopenia.
Conclusions
Our findings indicated a significantly increased risk of sarcopenia in both male and female residents exposed to high levels of air pollutants.
Parkinson’s disease (PD) is a common neurodegenerative disease with progressive loss of dopaminergic neurons in substantia nigra and the presence of α-synuclein-immunoreactive inclusions. Gaucher’s ...disease is caused by homozygous mutations in β-glucocerebrosidase gene (GBA). GBA mutation carriers have an increased risk of PD. Coptis chinensis (C. chinensis) rhizome extract is a major herb widely used to treat human diseases. This study examined the association of GBA L444P mutation with Taiwanese PD in 1016 cases and 539 controls. In addition, the protective effects of C. chinensis rhizome extract and its active constituents (berberine, coptisine, and palmatine) against PD were assayed using GBA reporter cells, LC3 reporter cells, and cells expressing mutated (A53T) α-synuclein. Case-control study revealed that GBA L444P carriers had a 3.93-fold increased risk of PD (95% confidence interval (CI): 1.37–11.24, p = 0.006) compared to normal controls. Both C. chinensis rhizome extract and its constituents exhibited chemical chaperone activity to reduce α-synuclein aggregation. Promoter reporter and endogenous GBA protein analyses revealed that C. chinensis rhizome extract and its constituents upregulated GBA expression in 293 cells. In addition, C. chinensis rhizome extract and its constituents induced autophagy in DsRed-LC3-expressing 293 cells. In SH-SY5Y cells expressing A53T α-synuclein, C. chinensis rhizome extract and its constituents reduced α-synuclein aggregation and associated neurotoxicity by upregulating GBA expression and activating autophagy. The results of reducing α-synuclein aggregation, enhancing GBA expression and autophagy, and protecting against α-synuclein neurotoxicity open up the therapeutic potentials of C. chinensis rhizome extract and constituents for PD.
CUB domain‐containing protein 1 (CDCP1) contributes to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance by regulating EGFR signaling pathways and is a potential ...target in lung cancer treatment. This study aims to identify a CDCP1 reducer that synergistically improves TKI treatment. Utilizing a high‐throughput drug screening system, a phytoestrogen 8‐isopentenylnaringenin (8PN) was identified. Upon 8PN treatment, CDCP1 protein levels and malignant features were reduced. 8PN exposure caused the accumulation of lung cancer cells in G0/G1 phase and increased the proportion of senescent cells. In EGFR TKI‐resistant lung cancer cells, the combination of 8PN and TKI synergistically reduced cell malignance, inhibited downstream EGFR pathway signaling, and exerted additive effects on cell death. Moreover, combination therapy effectively reduced tumor growth and enhanced tumor necrosis in tumor xenograft mice models. Mechanistically, 8PN increased interleukin (IL)6 and IL8 expression, induced neutrophil infiltration, and enhanced neutrophil‐mediated cytotoxicity to attenuate lung cancer cell growth. In conclusion, 8PN enhances the anticancer efficacy of EGFR TKI on lung cancer and triggers neutrophil‐dependent necrosis, highlighting the potential to overcome TKI resistance in lung cancer patients who have EGFR mutation.
CUB domain‐containing protein 1 (CDCP1) contributes to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in lung cancer treatment. 8‐isopentenylnaringenin (8PN) was identified as a CDCP1 reducer to suppress CDCP1 proteins via lysosomal degradation and reduced lung cancer progression. The combination of 8PN and EGFR TKIs showed a synergistic anticancer effect. Mechanically, 8PN increases interleukin (IL)6 and IL8 expressions to recruit neutrophils, leading to reactive oxygen species production for tumor necrosis.
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