Cancer-secreted exosomal miRNAs are emerging mediators of cancer-stromal cross-talk in the tumor environment. Our previous miRNAs array of cervical squamous cell carcinoma (CSCC) clinical specimens ...identified upregulation of miR-221-3p. Here, we show that miR-221-3p is closely correlated with peritumoral lymphangiogenesis and lymph node (LN) metastasis in CSCC. More importantly, miR-221-3p is characteristically enriched in and transferred by CSCC-secreted exosomes into human lymphatic endothelial cells (HLECs) to promote HLECs migration and tube formation in vitro, and facilitate lymphangiogenesis and LN metastasis in vivo according to both gain-of-function and loss-of-function experiments. Furthermore, we identify vasohibin-1 (VASH1) as a novel direct target of miR-221-3p through bioinformatic target prediction and luciferase reporter assay. Re-expression and knockdown of VASH1 could respectively rescue and simulate the effects induced by exosomal miR-221-3p. Importantly, the miR-221-3p-VASH1 axis activates the ERK/AKT pathway in HLECs independent of VEGF-C. Finally, circulating exosomal miR-221-3p levels also have biological function in promoting HLECs sprouting in vitro and are closely associated with tumor miR-221-3p expression, lymphatic VASH1 expression, lymphangiogenesis, and LN metastasis in CSCC patients. In conclusion, CSCC-secreted exosomal miR-221-3p transfers into HLECs to promote lymphangiogenesis and lymphatic metastasis via downregulation of VASH1 and may represent a novel diagnostic biomarker and therapeutic target for metastatic CSCC patients in early stages.
Heterojunction engineering, especially 2D/2D heterojunctions, is regarded as a quite promising strategy to manipulate the photocatalytic performance of semiconductor catalysts. In this manuscript, a ...direct Z‐scheme 2D/2D heterojunction of CsPbBr3/Bi2WO6 is designed and fabricated by a simple electrostatic self‐assembly process. By using ultrathin nanosheets with several atomic layers as the building blocks, a close CsPbBr3/Bi2WO6 heterointerface over large area with quite a short charge transport distance is obtained, which enables a valid Z‐scheme interfacial charge transfer between Bi2WO6 and CsPbBr3 and thus boosts charge separation. The CsPbBr3/Bi2WO6 heterojunction exhibits a superior photocatalytic performance toward CO2 reduction. By incorporating Pt nanoparticles as the cocatalyst, a high photoelectron consumption rate of 324.0 µmol g−1 h−1 under AM 1.5G irradiation (150 mW cm−2) is obtained, which is 12.2 fold higher than that of CsPbBr3 nanosheets. Moreover, a stable product yield of up to 1582.0 µmol g−1 and electron consumption yield of 8603.0 µmol g−1 for photocatalytic CO2 reduction to CO (11.4%) and CH4 (84.3%) can be achieved after 30 h of continuous catalytic reaction. The accelerated photogenerated charge transfer and spatial charge separation are investigated in detail by ultrafast spectra, photoelectrochemical test, and Kelvin probe force microscopy.
A Z‐Scheme 2D/2D heterojunction of CsPbBr3/Bi2WO6 is fabricated using a simple electrostatic assembly process. The as‐formed heterojunction possesses a large interface contact area and quite a short charge transport distance, which enable efficient Z‐scheme charge transfer and separation between Bi2WO6 and CsPbBr3, as well as remarkably enhanced performance toward photocatalytic CO2 reduction.
Porphyrin-based frameworks, as specific kinds of metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), have been widely used in energy-related conversion processes, including the ...oxygen reduction reaction (ORR), oxygen evolution reaction (OER) and CO
2
reduction reaction (CO
2
RR), and also in energy-related storage technologies such as rechargeable Zn-air batteries. This review starts by summarizing typical crystal structures, molecular building blocks, and common synthetic procedures of various porphyrin-based frameworks used in energy-related technologies. Then, a brief introduction is provided and representative applications of porphyrin-based frameworks in ORR, OER, Zn-air batteries, and CO
2
RR are discussed. The performance comparison of these porphyrin-based frameworks in each field is also summarized and discussed, which pinpoints a clear structure-activity relationship. In addition to utilizing highly active porphyrin units for catalytic conversions, regulating the porous structures of porphyrin-based frameworks will enhance mass transfer and growing porphyrin-based frameworks on conductive supports will accelerate electron transfer, which will result in the improvement of the electrocatalytic performance. This review is therefore valuable for the rational design of more efficient porphyrin-based framework catalytic systems in energy-related conversion and storage technologies.
The recent progress made on porphyrin-based frameworks and their applications in energy-related conversion technologies (
e.g.
, ORR, OER and CO
2
RR) and storage technologies (
e.g.
, Zn-air batteries).
Incorporation of N,S‐codoped nanotube‐like carbon (N,S‐NTC) can endow electrode materials with superior electrochemical properties owing to the unique nanoarchitecture and improved kinetics. Herein, ...α‐MnS nanoparticles (NPs) are in situ encapsulated into N,S‐NTC, preparing an advanced anode material (α‐MnS@N,S‐NTC) for lithium‐ion/sodium‐ion batteries (LIBs/SIBs). It is for the first time revealed that electrochemical α → β phase transition of MnS NPs during the 1st cycle effectively promotes Li‐storage properties, which is deduced by the studies of ex situ X‐ray diffraction/high‐resolution transmission electron microscopy and electrode kinetics. As a result, the optimized α‐MnS@N,S‐NTC electrode delivers a high Li‐storage capacity (1415 mA h g−1 at 50 mA g−1), excellent rate capability (430 mA h g−1 at 10 A g−1), and long‐term cycling stability (no obvious capacity decay over 5000 cycles at 1 A g−1) with retained morphology. In addition, the N,S‐NTC‐based encapsulation plays the key roles on enhancing the electrochemical properties due to its high conductivity and unique 1D nanoarchitecture with excellent protective effects to active MnS NPs. Furthermore, α‐MnS@N,S‐NTC also delivers high Na‐storage capacity (536 mA h g−1 at 50 mA g−1) without the occurrence of such α → β phase transition and excellent full‐cell performances as coupling with commercial LiFePO4 and LiNi0.6Co0.2Mn0.2O2 cathodes in LIBs as well as Na3V2(PO4)2O2F cathode in SIBs.
α‐MnS nanoparticles are in situ encapsulated into N,S‐codoped nanotube‐like carbon (α‐MnS@N,S‐NTC) as an advanced anode for Li/Na‐ion batteries. The α → β phase transition during the 1st cycle in LIBs is for the first time revealed by ex situ X‐ray diffraction and high‐resolution transmission electron microscopy studies, which improves the electrode kinetics and Li‐storage properties. α‐MnS@N,S‐NTC also exhibits superior performance in Li/Na‐ion half/full cells.
Parkinson's disease (PD) is a neurodegenerative disorder with no absolute cure. The evidence of the involvement of gut microbiota in PD pathogenesis suggests the need to identify certain molecule(s) ...derived from the gut microbiota, which has the potential to manage PD. Osteocalcin (OCN), an osteoblast-secreted protein, has been shown to modulate brain function. Thus, it is of interest to investigate whether OCN could exert protective effect on PD and, if yes, whether the underlying mechanism lies in the subsequent changes in gut microbiota.
The intraperitoneal injection of OCN can effectively ameliorate the motor deficits and dopaminergic neuronal loss in a 6-hydroxydopamine-induced PD mouse model. The further antibiotics treatment and fecal microbiota transplantation experiments confirmed that the gut microbiota was required for OCN-induced protection in PD mice. OCN elevated Bacteroidetes and depleted Firmicutes phyla in the gut microbiota of PD mice with elevated potential of microbial propionate production and was confirmed by fecal propionate levels. Two months of orally administered propionate successfully rescued motor deficits and dopaminergic neuronal loss in PD mice. Furthermore, AR420626, the agonist of FFAR3, which is the receptor of propionate, mimicked the neuroprotective effects of propionate and the ablation of enteric neurons blocked the prevention of dopaminergic neuronal loss by propionate in PD mice.
Together, our results demonstrate that OCN ameliorates motor deficits and dopaminergic neuronal loss in PD mice, modulating gut microbiome and increasing propionate level might be an underlying mechanism responsible for the neuroprotective effects of OCN on PD, and the FFAR3, expressed in enteric nervous system, might be the main action site of propionate. Video abstract.
Low‐dimensional lead halide perovskite materials recently have drawn much attention owing to the intriguing broadband emissions; however, the toxicity of lead will hinder their future development. ...Now, a lead‐free (C4H14N2)2In2Br10 single crystal with a unique zero‐dimensional (0D) structure constituted by InBr63− octahedral and InBr4− tetrahedral units is described. The single crystal exhibits broadband photoluminescence (PL) that spans almost the whole visible spectrum with a lifetime of 3.2 μs. Computational and experimental studies unveil that an excited‐state structural distortion in InBr63− octahedral units enables the formation of intrinsic self‐trapped excitons (STEs) and thus contributing the broad emission. Furthermore, femtosecond transient absorption (fs‐TA) measurement reveals that the ultrafast STEs formation together with an efficient intersystem crossing has made a significant contribution to the long‐lived and broad STE‐based emission behavior.
A lead‐free indium‐based (C4H14N2)2In2Br10 single crystal was synthesized and characterized; it has a unique 0D crystal structure. An intrinsic self‐trapped exciton‐based ultra‐broad photoluminescence has been observed as a result of an excited‐state structural distortion in InBr63− octahedrons.
To assess the benefits of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as neoadjuvant/adjuvant therapies in locally advanced
mutation-positive non-small-cell lung cancer.
This ...was a multicenter (17 centers in China), open-label, phase II, randomized controlled trial of erlotinib versus gemcitabine plus cisplatin (GC chemotherapy) as neoadjuvant/adjuvant therapy in patients with stage IIIA-N2 non-small-cell lung cancer with
mutations in exon 19 or 21 (EMERGING). Patients received erlotinib 150 mg/d (neoadjuvant therapy, 42 days; adjuvant therapy, up to 12 months) or gemcitabine 1,250 mg/m
plus cisplatin 75 mg/m
(neoadjuvant therapy, two cycles; adjuvant therapy, up to two cycles). Assessments were performed at 6 weeks and every 3 months postsurgery. The primary end point was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; secondary end points were pathologic complete response, progression-free survival (PFS), overall survival, safety, and tolerability.
Of 386 patients screened, 72 were randomly assigned to treatment (intention-to-treat population), and 71 were included in the safety analysis (one patient withdrew before treatment). The ORR for neoadjuvant erlotinib versus GC chemotherapy was 54.1% versus 34.3% (odds ratio, 2.26; 95% CI, 0.87 to 5.84;
= .092). No pathologic complete response was identified in either arm. Three (9.7%) of 31 patients and zero of 23 patients in the erlotinib and GC chemotherapy arms, respectively, had a major pathologic response. Median PFS was significantly longer with erlotinib (21.5 months) versus GC chemotherapy (11.4 months; hazard ratio, 0.39; 95% CI, 0.23 to 0.67;
< .001). Observed adverse events reflected those most commonly seen with the two treatments.
The primary end point of ORR with 42 days of neoadjuvant erlotinib was not met, but the secondary end point PFS was significantly improved.
Low‐dimensional luminescent lead halide perovskites have attracted tremendous attention for their fascinating optoelectronic properties, while the toxicity of lead is still considered a drawback. ...Herein, we report a novel lead‐free zero‐dimensional (0D) indium‐based perovskite (Cs2InBr5⋅H2O) single crystal that is red‐luminescent with a high photoluminescence quantum yield (PLQY) of 33 %. Experimental and computational studies reveal that the strong PL emission might originate from self‐trapping excitons (STEs) that result from an excited‐state structural deformation. More importantly, the in situ transformation between hydrated Cs2InBr5⋅H2O and the dehydrated form is accompanied with a switchable dual emission, which enables it to act as a PL water‐sensor in humidity detection or the detection of traces of water in organic solvents.
Unleaded and unleashed: A highly emissive lead‐free indium‐based perovskite single crystal, Cs2InBr5⋅H2O, was successfully prepared. The versatile material is the first reversible metal halide perovskite photoluminescence water sensor and paves the way for the application of metal halide perovskites in water detection.
A robust, inexpensive, and efficient photocatalytic system consisting of an artificial water‐soluble FeFe‐H2ase mimic 1, CdTe quantum dots, and ascorbic acid (H2A), for H2 production in pure water at ...room temperature has been developed. With this system, 786 μmol (17.6 mL) H2 were obtained after 10 h irradiation (λ>400 nm) with TON up to 505 and TOF up to 50 h−1 under optimized conditions.
Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II–IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with ...EGFR-mutant stage IB–IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II–IIIA (N1–N2) NSCLC.
We did a randomised, open-label, phase 3 trial at 27 centres in China. We enrolled patients aged 18–75 years with completely resected (R0), stage II–IIIA (N1–N2), EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC. Patients were stratified by N stage and EGFR mutation status and randomised (1:1) by Pocock and Simon minimisation with a random element to either gefitinib (250 mg once daily) for 24 months or intravenous vinorelbine (25 mg/m2 on days 1 and 8) plus intravenous cisplatin (75 mg/m2 on day 1) every 3 weeks for four cycles. The primary endpoint was disease-free survival in the intention-to-treat population, which comprised all randomised patients; the safety population included all randomised patients who received at least one dose of study medication. Enrolment to the study is closed but survival follow-up is ongoing. The study is registered with ClinicalTrials.gov, number NCT01405079.
Between Sept 19, 2011, and April 24, 2014, 483 patients were screened and 222 patients were randomised, 111 to gefitinib and 111 to vinorelbine plus cisplatin. Median follow-up was 36·5 months (IQR 23·8–44·8). Median disease-free survival was significantly longer with gefitinib (28·7 months 95% CI 24·9–32·5) than with vinorelbine plus cisplatin (18·0 months 13·6–22·3; hazard ratio HR 0·60, 95% CI 0·42–0·87; p=0·0054). In the safety population, the most commonly reported grade 3 or worse adverse events in the gefitinib group (n=106) were raised alanine aminotransferase and asparate aminotransferase (two 2% patients with each event vs none with vinorelbine plus cisplatin). In the vinorelbine plus cisplatin group (n=87), the most frequently reported grade 3 or worse adverse events were neutropenia (30 34% patients vs none with gefitinib), leucopenia (14 16% vs none), and vomiting (eight 9% vs none). Serious adverse events were reported for seven (7%) patients who received gefitinib and 20 (23%) patients who received vinorelbine plus cisplatin. No interstitial lung disease was noted with gefitinib. No deaths were treatment related.
Adjuvant gefitinib led to significantly longer disease-free survival compared with that for vinorelbine plus cisplatin in patients with completely resected stage II–IIIA (N1–N2) EGFR-mutant NSCLC. Based on the superior disease-free survival, reduced toxicity, and improved quality of life, adjuvant gefitinib could be a potential treatment option compared with adjuvant chemotherapy in these patients. However, the duration of benefit with gefitinib after 24 months might be limited and overall survival data are not yet mature.
Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine; National Health and Family Planning Commission of People's Republic of China; Guangzhou Science and Technology Bureau; AstraZeneca China.
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