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.
Although clinical studies have shown promise for targeting programmed cell death protein-1 (PD-1) and ligand (PD-L1) signaling in non-small cell lung cancer (NSCLC), the factors that predict which ...subtype patients will be responsive to checkpoint blockade are not fully understood.
We performed an integrated analysis on the multiple-dimensional data types including genomic, transcriptomic, proteomic, and clinical data from cohorts of lung adenocarcinoma public (discovery set) and internal (validation set) database and immunotherapeutic patients. Gene set enrichment analysis (GSEA) was used to determine potentially relevant gene expression signatures between specific subgroups.
We observed that
mutation significantly increased expression of immune checkpoints and activated T-effector and interferon-γ signature. More importantly, the
comutated subgroup manifested exclusive increased expression of PD-L1 and a highest proportion of
Meanwhile,
or
-mutated tumors showed prominently increased mutation burden and specifically enriched in the transversion-high (TH) cohort. Further analysis focused on the potential molecular mechanism revealed that
or
mutation altered a group of genes involved in cell-cycle regulating, DNA replication and damage repair. Finally, immunotherapeutic analysis from public clinical trial and prospective observation in our center were further confirmed that
or
mutation patients, especially those with co-occurring
mutations, showed remarkable clinical benefit to PD-1 inhibitors.
This work provides evidence that
and
mutation in lung adenocarcinoma may be served as a pair of potential predictive factors in guiding anti-PD-1/PD-L1 immunotherapy.
.
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.
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.
Halide perovskite like methylammonium lead iodide perovskite (MAPbI3) with its prominent optoelectronic properties has triggered substantial concerns in photocatalytic H2 evolution. In this work, to ...attain preferable photocatalytic performance, a MAPbI3/cobalt phosphide (CoP) hybrid heterojunction is constructed by a facile in situ photosynthesis approach. Systematic investigations reveal that the CoP nanoparticle can work as co‐catalyst to not only extract photogenerated electrons effectively from MAPbI3 to improve the photoinduced charge separation, but also facilitate the interfacial catalytic reaction. As a result, the as‐achieved MAPbI3/CoP hybrid displays a superior H2 evolution rate of 785.9 µmol h−1 g−1 in hydroiodic acid solution within 3 h, which is ≈8.0 times higher than that of pristine MAPbI3. Furthermore, the H2 evolution rate of MAPbI3/CoP hybrid can reach 2087.5 µmol h−1 g−1 when the photocatalytic reaction time reaches 27 h. This study employs a facile in situ photosynthesis strategy to deposit the metal phosphide co‐catalyst on halide perovskite nanocrystals to conduct photocatalytic H2 evolution reaction, which may stimulate the intensive investigation of perovskite/co‐catalyst hybrid systems for future photocatalytic applications.
A methylammonium lead iodide perovskite (MAPbI3)/ cobalt phosphide (CoP) hybrid heterojunction for photocatalytic H2 evolution is synthesized by a facile in situ photosynthesis approach. In this hybrid, CoP nanoparticles can work as a co‐catalyst to not only extract photogenerated electrons effectively from MAPbI3 to improve the photoinduced charge separation, but also facilitate the interfacial catalytic reaction, which further contributes to an enhanced H2 evolution activity.
In this research, the antifungal role of hydrogen sulfide (H2S) on the postharvest pathogens Aspergillus niger and Penicillium italicum growing on fruits and under culture conditions on defined media ...was investigated. Our results show that H2S, released by sodium hydrosulfide (NaHS) effectively reduced the postharvest decay of fruits induced by A. niger and P. italicum. Furthermore, H2S inhibited spore germination, germ tube elongation, mycelial growth, and produced abnormal mycelial contractions when the fungi were grown on defined media in Petri plates. Further studies showed that H2S could cause an increase in intracellular reactive oxygen species (ROS) in A. niger. In accordance with this observation we show that enzyme activities and the expression of superoxide dismutase (SOD) and catalase (CAT) genes in A. niger treated with H2S were lower than those in control. Moreover, H2S also significantly inhibited the growth of Saccharomyces cerevisiae, Rhizopus oryzae, the human pathogen Candida albicans, and several food-borne bacteria. We also found that short time exposure of H2S showed a microbicidal role rather than just inhibiting the growth of microbes. Taken together, this study suggests the potential value of H2S in reducing postharvest loss and food spoilage caused by microbe propagation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Increasing evidence has confirmed that the antimicrobial and anti‐inflammatory effects of cinnamon essential oil (CEO) contribute to protection against inflammatory bowel disease (IBD). The dextran ...sodium sulfate (DSS)‐induced colitis mouse model was established to investigate the correlation between the protective effects of CEO and the regulation of intestinal microflora. The symptoms of IBD were assessed by measuring the hemoglobin content, myeloperoxidase activity, histopathological observation, cytokines, and toll‐like receptor (TLR4) expression. The alteration of the fecal microbiome composition was analyzed by 16S rRNA gene sequencing. The results indicated that the oral administration of CEO enriched with cinnamaldehyde effectively alleviated the development of DSS‐induced colitis. In contrast to the inability of antibiotics to regulate flora imbalance, the mice fed with CEO had an improved diversity and richness of intestinal microbiota, and a modified community composition with a decrease in Helicobacter and Bacteroides and an increase in Bacteroidales_S24‐7 family and short‐chain fatty acids (SCFA)‐producing bacteria (Alloprevotella and Lachnospiraceae_NK4A136_group). Moreover, the correlation analysis showed that TLR4 and tumor necrosis factor‐α was positively correlated with Helicobacter, but inversely correlated with SCFA‐producing bacteria. These findings indicated from a new perspective that the inhibitory effect of CEO on IBD was closely related to improving the intestinal flora imbalance.
In order to investigate the physiological effects of exogenous γ-aminobutyric acid (GABA) on drought tolerance in white clover (Trifolium repens), GABA shunt, polyamines (PAs), and proline (Pro) ...metabolism were examined after plants pretreated with or without GABA (8 mM) and then exposed to water or 15% PEG-induced drought stress in growth chamber. In this study, exogenous application of GABA effectively alleviated drought-induced damage in leaves, as reflected by significantly higher relative water content, lower electrolyte leakage, lipid peroxidation, and leaf wilt. Exogenous GABA further promoted drought-induced increases in GABA transaminase and alpha ketone glutarate dehydrogenase activities, but inhibited glutamate decarboxylase activity under both control and drought conditions, resulting in an increase in endogenous glutamate (Glu) and GABA content. Besides, exogenous GABA could well accelerated PAs synthesis and suppressed PAs catabolism, which lead to the extremely enhanced different types of PAs content (free Put and Spd, insoluble bound Spd and Spm, soluble conjugated Spd and Spm, and total Put, Spd and Spm) under drought stress. In addition, exogenous GABA application further activated drought-induced Δ
-pyrroline-5-carboxylate synthetase and proline dehydrogenase activities, but suppressed drought-facilitated ornithine -δ-amino transferase activities, leading to a higher Pro accumulation and metabolism in GABA-pretreated plants in the middle and last period of drought. The results suggested that increased endogenous GABA by exogenous GABA treatment could improve drought tolerance of white clover associated with a positive regulation in the GABA-shunt, PAs and Pro metabolism.
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.
PDF
