The existence of breast cancer stem cells (BCSCs) is a major reason underlying cancer metastasis and recurrence after chemotherapy and radiotherapy. Targeting BCSCs may ameliorate breast cancer ...relapse and therapy resistance. Here we report that expression of the pseudokinase Tribble 3 (TRIB3) positively associates with breast cancer stemness and progression. Elevated TRIB3 expression supports BCSCs by interacting with AKT to interfere with the FOXO1-AKT interaction and suppress FOXO1 phosphorylation, ubiquitination, and degradation by E3 ligases SKP2 and NEDD4L. The accumulated FOXO1 promotes transcriptional expression of SOX2, a transcriptional factor for cancer stemness, which in turn, activates FOXO1 transcription and forms a positive regulatory loop. Disturbing the TRIB3-AKT interaction suppresses BCSCs by accelerating FOXO1 degradation and reducing SOX2 expression in mouse models of breast cancer. Our study provides insights into breast cancer development and confers a potential therapeutic strategy against TRIB3-overexpressed breast cancer.
Accumulating evidence indicates that circular RNAs (circRNAs) are abundant in the human transcriptome. However, their involvement in biological processes, including pluripotency, remains mostly ...undescribed. We identified a subset of circRNAs that are enriched in undifferentiated human embryonic stem cells (hESCs) and demonstrated that two, circBIRC6 and circCORO1C, are functionally associated with the pluripotent state. Mechanistically, we found that circBIRC6 is enriched in the AGO2 complex and directly interacts with microRNAs, miR-34a, and miR-145, which are known to modulate target genes that maintain pluripotency. Correspondingly, circBIRC6 attenuates the downregulation of these target genes and suppresses hESC differentiation. We further identified hESC-enriched splicing factors (SFs) and demonstrated that circBIRC6 biogenesis in hESCs is promoted by the SF ESRP1, whose expression is controlled by the core pluripotency-associated factors, OCT4 and NANOG. Collectively, our data suggest that circRNA serves as a microRNA "sponge" to regulate the molecular circuitry, which modulates human pluripotency and differentiation.
Understanding the dynamics and underlying mechanism of carbon exchange between terrestrial ecosystems and the atmosphere is one of the key issues in global change research. In this study, we ...quantified the carbon fluxes in different terrestrial ecosystems in China, and analyzed their spatial variation and environmental drivers based on the long‐term observation data of ChinaFLUX sites and the published data from other flux sites in China. The results indicate that gross ecosystem productivity (GEP), ecosystem respiration (ER), and net ecosystem productivity (NEP) of terrestrial ecosystems in China showed a significantly latitudinal pattern, declining linearly with the increase of latitude. However, GEP, ER, and NEP did not present a clear longitudinal pattern. The carbon sink functional areas of terrestrial ecosystems in China were mainly located in the subtropical and temperate forests, coastal wetlands in eastern China, the temperate meadow steppe in the northeast China, and the alpine meadow in eastern edge of Qinghai‐Tibetan Plateau. The forest ecosystems had stronger carbon sink than grassland ecosystems. The spatial patterns of GEP and ER in China were mainly determined by mean annual precipitation (MAP) and mean annual temperature (MAT), whereas the spatial variation in NEP was largely explained by MAT. The combined effects of MAT and MAP explained 79%, 62%, and 66% of the spatial variations in GEP, ER, and NEP, respectively. The GEP, ER, and NEP in different ecosystems in China exhibited ‘positive coupling correlation’ in their spatial patterns. Both ER and NEP were significantly correlated with GEP, with 68% of the per‐unit GEP contributed to ER and 29% to NEP. MAT and MAP affected the spatial patterns of ER and NEP mainly by their direct effects on the spatial pattern of GEP.
Perfluorinated alkyl substances, such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), are toxic materials that are known to globally contaminate water, air, and soil resources. ...Strategies for the simultaneous detection and removal of these compounds are desired to address this emerging health and environmental issue. Herein, we develop a type of guanidinocalix5arene that can selectively and strongly bind to PFOS and PFOA, which we use to demonstrate the sensitive and quantitative detection of these compounds in contaminated water through a fluorescent indicator displacement assay. Moreover, by co-assembling iron oxide nanoparticle with the amphiphilic guanidinocalix5arene, we are able to use simple magnetic absorption and filtration to efficiently remove PFOS and PFOA from contaminated water. This supramolecular approach that uses both molecular recognition and self-assembly of macrocyclic amphiphiles is promising for the detection and remediation of water pollution.
Tumor initiation and growth depend on its microenvironment in which cancer-associated fibroblasts （CAFs） in tumor stroma play an important role. Prostaglandin E2 （PGE2） and interleukin （IL）-6 signal ...pathways are involved in the crosstalk between tumor and stromal cells. However, how PGE2-mediated signaling modulates this crosstalk remains unclear. Here, we show that microRNA （miR）-149 links PGE2 and IL-6 signaling in mediating the crosstalk between tumor cells and CAFs in gastric cancer （GC）. miR-149 inhibited fibroblast activation by targeting IL-6 and miR-149 expression was substantially suppressed in the CAFs of GC. miR-149 negatively regulated CAFs and their effect on GC development both in vitro and in vivo. CAFs enhanced epithelial-to-mesenchymal transition （EMT） and the stem-like properties of GC cells in a miR-149-1L-6-dependent manner. In addition to IL-6, PGE2 receptor 2 （PTGER2/EP2） was revealed as another potential target of miR-149 in fibroblasts. Furthermore, H. pylori infection, a leading cause of human GC, was able to induce cyclooxygenase-2 （COX-2）/PGE2 signaling and to enhance PGE2 production, resulting in the hypermethylation of miR-149 in CAFs and increased IL-6 secretion. Our findings indicate that miR-149 mediates the crosstalk between tumor cells and CAFs in GC and highlight the potential of interfering miRNAs in stromal cells to improve cancer therapy.
Although photocatalytic hydrogen evolution (PHE) is ideal for solar-to-fuel conversion, it remains challenging to construct a highly efficient PHE system by steering the charge flow in a precise ...manner. Here we tackle this challenge by assembling 1T MoS2 monolayers selectively and chemically onto (Bi12O17) end-faces of Bi12O17Cl2 monolayers to craft two-dimensional (2D) Janus (Cl2)-(Bi12O17)-(MoS2) bilayer junctions, a new 2D motif different from van der Waals heterostructure. Electrons and holes from visible light-irradiated Bi12O17Cl2 are directionally separated by the internal electric field to (Bi12O17) and (Cl2) end-faces, respectively. The separated electrons can further migrate to MoS2 via Bi-S bonds formed between (Bi12O17) and MoS2 monolayers. This atomic-level directional charge separation endows the Janus bilayers with ultralong carrier lifetime of 3,446 ns and hence a superior visible-light PHE rate of 33 mmol h(-1) g(-1). Our delineated Janus bilayer junctions on the basis of the oriented assembly of monolayers presents a new design concept to effectively steer the charge flow for PHE.
Tumor-associated antigens (TAAs) have been tested in various clinical trials in cancer treatment but the patterns of specific T cell response to personalized TAA immunization remains to be fully ...understood. We report antigen-specific T cell responses in patients immunized with dendritic cell vaccines pulsed with personalized TAA panels. Tumor samples from patients were first analyzed to identify overexpressed TAAs. Autologous DCs were then transfected with pre-manufactured mRNAs encoding the full-length TAAs, overexpressed in the patients' tumors. Patients with glioblastoma multiforme (GBM) or advanced lung cancer received DC vaccines transfected with personalized TAA panels, in combination with low-dose cyclophosphamide, poly I:C, imiquimod and anti-PD-1 antibody. Antigen-specific T cell responses were measured. Safety and efficacy were evaluated. A total of ten patients were treated with DC vaccines transfected with personalized TAA panels containing 3–13 different TAAs. Among the seven patients tested for anti-TAA T cell responses, most of the TAAs induced antigen-specific CD4
+
and/or CD8
+
T cell responses, regardless of their expression levels in the tumor tissues. No Grade III/IV adverse events were observed among these patients. Furthermore, the treated patients were associated with favorable overall survival when compared to patients who received standard treatment in the same institution. Personalized TAA immunization-induced-specific CD4
+
and CD8
+
T cell responses without obvious autoimmune adverse events and was associated with favorable overall survival. These results support further studies on DC immunization with personalized TAA panels for combined immunotherapeutic regimens in solid tumor patients.
Trial registration
ClinicalTrials.gov, NCT02709616 (March, 2016), NCT02808364 (June 2016), NCT02808416 (June, 2016).
A controllable vacuum‐diffusion method for gradual phosphidation of carbon coated metallic Co nanoparticles into Co/CoP Janus nanoparticles is reported. Janus Co/CoP nanoparticles, as typical ...Mott–Schottky electrocatalysts, exhibit excellent hydrogen evolution reaction and oxygen evolution reaction performance in various electrolytes across wide pH range along with high durability. The Mott–Schottky Co/CoP catalyst can work as bifunctional electrode materials for overall water splitting in wide pH range and can achieve a current density of 10 mA cm−2 in neutral electrolyte at only 1.51 V.
Mott–Schottky type Janus Co/CoP nanoparticles are constructed by a proof‐of‐concept strategy, promoting the overall water splitting activity as typical Mott–Schottky electrocatalysts. The electron redistribution at the Co/CoP interface significantly and generally boosts the catalytic activity of Janus nanoparticles for both hydrogen evolution reaction and oxygen evolution reaction across a wide pH range.
Rhodiola rosea L., a worldwide botanical adaptogen, has been confirmed to possess protective effects of inflammatory injury for many diseases, including cardiovascular diseases, neurodegenerative ...diseases, diabetes, sepsis, and cancer. This paper is to review the recent clinical and experimental researches about the anti-inflammatory effects and the related mechanisms of Rhodiola rosea L. extracts, preparations, and the active compounds. From the collected information reviewed, this paper will provide the theoretical basis for its clinical application, and provide the evidences or guidance for future studies and medicinal exploitations of Rhodiola rosea L.
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