Exosomes derived from bone marrow mesenchymal stem cells promote proliferation and migration via upregulation yes-associated protein/transcriptional coactivator with PDZ binding motif expression in breast cancer cells.

Bone marrow mesenchymal stem cells (BM-MSCs), with the properties of self-renewal and pluripotency, can migrate to the tumor sites and exert complex effects on tumor progression and communications by releasing exosomes. However, to our knowledge, only a few studies have reported the effects of BM-MSCs exosomes on breast cancer cells development. Here, utilizing exosomes isolated from in vitro BM-MSCs, we systematically investigated this issue in a breast cancer cell line. In this study, we found that BM-MSCs exosomes are actively incorporated by breast cancer cell MDA-MB-231 cells and subsequently promote MDA-MB-231 cells proliferation and migration. Mechanistically, we further found Yes-associated protein (YAP) and transcriptional coactivator with PDZ binding motif (TAZ) which are Hippo signaling components were involved in this promoting progress. Consistently, YAP and TAZ knockdown could significantly reverse breast cancer cells proliferation and migration improved by BM-MSCs exosomes. Taken together, our findings demonstrated a new mechanism through which BM-MSCs-derived exosomes may contribute to breast cancer cells proliferation and migration, which might provide an evidence for novel drug discovery based on exosomes and Hippo signaling.

Synthesis of a molecularly imprinted polymer on mSiO2 @Fe3 O4 for the selective adsorption of atrazine.

Atrazine contamination of water is of considerable concern because of the potential hazard to human health. In this study, a magnetic molecularly imprinted polymer for atrazine was prepared by the surface-imprinting technique using Fe3 O4 as the core, mesoporous silica as the carrier, atrazine as the template, and itaconic acid as the functional monomer. The magnetic molecularly imprinted polymer was characterized by Fourier-transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, and vibration-sample magnetometry. The binding properties of the magnetic molecularly imprinted polymer toward atrazine were investigated by adsorption isotherms, kinetics, and competitive adsorption. It was found that the adsorption equilibrium was achieved within 2 h, the maximum adsorption capacity of atrazine was 8.8 µmol/g, and the adsorption process could be well described by the Langmuir isotherm model and pseudo-second-order kinetic model. The magnetic molecularly imprinted polymer exhibited good adsorption selectivity for atrazine with respect to structural analogues, such as cyanazine, simetryne, and prometryn. The reusability of the magnetic molecularly imprinted polymer was demonstrated for at least five repeated cycles without a significant decrease in adsorption capacity. These results suggested that the magnetic molecularly imprinted polymer could be used as an efficient material for the selective adsorption and removal of atrazine from water samples.

STC2 suppresses triple-negative breast cancer migration and invasion by inhibition on EMT and promotion on cell apoptosis.

To investigate the effects of higher cellular stanniocalcin 2 (STC2) on suppressing the migration and invasion but promoting the apoptosis of triple-negative breast cancer (TNBC). STC2 in TNBC and the para-carcinoma tissues were analyzed by immunohistochemistry (IHC), while the mRNA level was measured by qPCR. Over-expressing or silencing STC2 was established in MDA-MB-231 cells. Epithelial mesenchymal transition (EMT) related proteins, cell migration, invasion, proliferation and apoptosis were detected. MDA-MB-231 with over-expressing or silencing STC2 were injected into nude mice to formatting tumors, and then EMT related proteins were measured by IHC. Lower STC2 expressed in TNBC tissues than in the para-carcinoma tissues. Silencing STC2 promoted EMT of TNBC cell MDA-MB-231, as well as cell migration, invasion and proliferation, but suppressed MDA-MB-231 apoptosis, while over-expressing STC2 had the opposite results, which might be related to PKC/PI3K/AKT/mTOR pathway. STC2 was the protective gene in TNBC, by suppressing migration and invasion to inhibit MDA-MB-231 cell EMT but promote cell apoptosis, in order to suppress TNBC progression.

Circ_0108942 Regulates the Progression of Breast Cancer by Regulating the MiR-1178-3p/TMED3 Axis.

BACKGROUND: Breast cancer (BC) has posed a fatal threat to women's lives and the search for new methods of diagnosis and treatment is an important way to break the bottleneck of high mortality in BC. Circular RNAs (circRNAs) have been confirmed to be aberrantly expressed in several types of cancers, and this study is intended to elucidate the role and mechanism of circ_0108942 in BC. MATERIALS AND METHODS: The levels of circ_0108942, microRNA-1178-3p (miR-1178-3p), and transmembrane p24 trafficking protein 3 (TMED3) were measured using real-time quantitative polymerase chain reaction (RT-qPCR) or western blot. Meanwhile, the cell proliferation, migration, invasion, angiopoiesis, and apoptosis were analyzed using 5-ethynyl-2'-deoxyuridine (EdU), transwell, tubule formation, and flow cytometry assays. Protein levels were determined by western blot. In addition, we used dual-luciferase reporter and RNA pull-down assays to identify the interplay between miR-1178-3p and circ_0108942 or TMED3. Lastly, the impact of circ_0108942 on the growth of BC tumors in vivo was analyzed by xenograft models. RESULTS: Circ_0108942 and TMED3 were notably upregulated in BC, and the miR-1178-3p was downregulated. Functionally, silencing circ_0108942 suppressed cell proliferation, migration, invasion and promoted apoptosis in BC cells. In mechanism, circ_0108942 regulated TMED3 expression by sponging miR-1178-3p. Meanwhile, circ_0108942 knockdown also greatly constrained tumor growth in vivo. CONCLUSION: Circ_0108942 boosted BC progression by regulating miR-1178-3p and thus upregulating TMED3.

Machine learning integrated high quantum yield blue light carbon dots for real-time and on-site detection of Cr(VI) in groundwater and drinking water.

The safety of groundwater and drinking water is directly related to the well-being of human beings and ecosystems. On-site monitoring and timely response to heavy metals in these water sources are crucial for water supply security. Fluorescent probes combined with machine learning technology have been applied to on-site detection of heavy metals. However, they were primarily focused on industrial-level detection and lacked the sensitivity required for detecting Cr(VI) in groundwater and drinking water. In this study, we developed an machine learning-integrated approach using high-quantum-yield (QY) N-doped blue-light carbon dots (N-BCDs) for instant detection of Cr(VI) in groundwater and drinking water. N-BCDs were synthesized within 3 min using a household microwave oven with citric acid and 1,2-diaminobenzene, resulting in a QY of approximately 90 %. The fluorescence of N-BCDs was quenched via the internal filter effect (IFE), enabling the detection of Cr(VI) within 1 min, with a detection limit of 0.1574 µg L-1 for Cr(VI) concentrations ranging from 0 to 60 µg L-1. We employed machine learning methods to determine Cr(VI) concentrations from simple shots, based on the red-green-blue (RGB) feature and Kmeans feature extraction. These features were input into four models (Ridge, XGB, SVR, and Linear), achieving a fitness of 95.2 %. Furthermore, the accuracies for Cr(VI) concentration identification in actual groundwater and drinking water were as high as 95.71 % and 96.81 %, respectively. Our work successfully extended the detection range of Cr(VI) to the µg level, significantly improving the practical applicability of the method and providing a new approach for on-site detection of Cr(VI) in groundwater and drinking water.

Development of a model for predicting mortality of breast cancer admitted to Intensive Care Unit.

Background: There is still not a mortality prediction model built for breast cancer admitted to intensive care unit (ICU). Objectives: We aimed to build a prognostic model with comprehensive data achieved from eICU database. Methods: Outcome was defined as all-cause in-hospital mortality. Least absolute shrinkage and selection operator (LASSO) was conducted to select important variables which were then taken into logistic regression to build the model. Bootstrap method was then conducted for internal validation. Results: 448 patients were included in this study and 79 (17.6%) died in hospital. Only 5 items were included in the model and the area under the curve (AUC) was 0.844 (95% confidence interval [CI]: 0.804-0.884). Calibration curve and Brier score (0.111, 95% CI: 0.090-0.127) showed good calibration of the model. After internal validation, corrected AUC and Brier score were 0.834 and 0.116. Decision curve analysis (DCA) also showed effective clinical use of the model. The model can be easily assessed on website of https://breastcancer123.shinyapps.io/BreastCancerICU/. Conclusions: The model derived in this study can provide an accurate prognosis for breast cancer admitted to ICU easily, which can help better clinical management.

Subspecies Classification and Comparative Genomic Analysis of Lactobacillus kefiranofaciens HL1 and M1 for Potential Niche-Specific Genes and Pathways.

(1) Background: Strains HL1 and M1, isolated from kefir grains, have been tentatively identified, based on their partial 16S rRNA gene sequences, as Lactobacillus kefiranofaciens. The two strains demonstrated different health benefits. Therefore, not only the genetic factors exerting diverse functionalities in different L. kefiranofaciens strains, but also the potential niche-specific genes and pathways among the L. kefiranofaciens strains, should be identified. (2) Methods: Phenotypic and genotypic approaches were employed to identify strains HL1 and M1 at the subspecies level. For the further characterization of the probiotic properties of both strains, comparative genomic analyses were used. (3) Results: Both strains were identified as L. kefiranofaciens subsp. kefirgranum. According to the COG function category, dTDP-rhamnose and rhamnose-containing glycans were specifically detected in the L. kefiranofaciens subsp. Kefirgranum genomes. Three unique genes (epsI, epsJ, and epsK) encoding glycosyltransferase in the EPS gene cluster, and the ImpB/MucB/SamB family protein encoding gene were found in HL1 and M1. The specific ability to degrade arginine via the ADI pathway was found in HL1. The presence of the complete glycogen metabolism (glg) operon in the L. kefiranofaciens strains suggested the importance of glycogen synthesis to enable colonization in kefir grains and extend survival under environmental stresses. (4) Conclusions: The obtained novel information on the potential genes and pathways for polysaccharide synthesis and other functionalities in our HL1 and M1 strains could be applied for further functionality predictions for potential probiotic screening.

Co-Culture Strategy of Lactobacillus kefiranofaciens HL1 for Developing Functional Fermented Milk.

Our previous studies indicated that Lactobacillus kefiranofaciens HL1, isolated from kefir grain, has strong antioxidant activities and anti-aging effects. However, this strain is difficult to use in isolation when manufacturing fermented products due to poor viability in milk. Thus, the purpose of this study was to apply a co-culture strategy to develop a novel probiotic fermented milk rich in L. kefiranofaciens HL1. Each of four selected starter cultures was co-cultured with kefir strain HL1 in different media to evaluate their effects on microbial activity and availability of milk fermentation. The results of a colony size test on de Man, Rogosa and Sharpe (MRS) agar agar, microbial viability, and acidification performance in MRS broth and skimmed milk suggested that Lactococcus lactis subsp. cremoris APL15 is a suitable candidate for co-culturing with HL1. We then co-cultured HL1 and APL15 in skimmed milk and report remarkable improvement in fermentation ability and no negative impact on the viability of strain HL1 or textural and rheological properties of the milk. Through a co-culture strategy, we have improved the viability of kefir strain HL1 in fermented skimmed milk products and successfully developed a novel milk product with a unique flavor and sufficient probiotics.

Activation of persulfate by MnOOH: Degradation of organic compounds by nonradical mechanism.

Advanced oxidation processes (AOPs) based on persulfate (PS) has attracted great attention due to its high efficiency for degradation of organic pollutants. Manganese-based materials have been considered as the desirable catalysts for in-situ chemical oxidation since they are abundant in the earth's crust and environment-friendly. In this study, manganese oxyhydroxide (MnOOH) was used as an activator for PS to degrade p-chloroaniline (PCA) from wastewater. The effects of MnOOH dosage, PS dosage and initial pH on PCA degradation performance were studied. Experimental results showed that PCA degradation efficiency was enhanced by higher MnOOH and PS addition, and the degradation efficiency was slightly inhibited as the initial pH increased from 3 to 9. MnOOH showed excellent stability and reusability when used as the activator of PS. In addition, a comprehensive study was conducted to determine the PS activation mechanism. The results revealed that PS activation by MnOOH followed a nonradical mechanism. No 1O2 was generated, and the main active substance in the reaction was the activated PS molecule on the surface of MnOOH. The hydroxyl group on the catalyst surface acted as a bridge connecting PS and the catalyst, leading to the activation of PS. The intermediates during PCA degradation were also analyzed, and three possible degradation pathways of PCA were proposed. This study expects to deepen the understanding of the PS activation mechanism by manganese oxide, and provides technical support for the practical application of AOPs of manganese-based materials for wastewater treatment.

Enhanced removal of As(â ¢) and As(â ¤) from aqueous solution using ionic liquid-modified magnetic graphene oxide.

In this study, ionic liquid (IL) 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6])-modified magnetic graphene oxide (MGO-IL) was prepared for the first time, and was used to adsorb and remove arsenic (As(Ⅲ) and As(V)) ions from aqueous solution. MGO-IL was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, and magnetization curves. Effects of ionic liquid type, solution pH, initial arsenic concentration and contact time on the adsorption performance of MGO-IL for As(Ⅲ) and As(V) were studied. The experimental results showed that the adsorption equilibrium was achieved within 30 min, with maximum adsorption capacities of 160.65 mg g-1 for As(Ⅲ) and 104.13 mg g-1 for As(V), respectively, and MGO-IL could be rapidly isolated from solution by applying a magnetic field. MGO-IL was reused for 5 times, without marked decrease in its adsorption capacities. Moreover, common coexisting anions did not interfere with the absorption of As(Ⅲ) and As(V). Compared with MGO, the sorption quantities of MGO-IL for As(Ⅲ) and As(V) were greatly enhanced, and the equilibrium time was significantly reduced. Therefore, MGO-IL can potentially serve as an excellent adsorbent for the simultaneous separation and removal of As(Ⅲ) and As(V) from water.

A novel ion-imprinted polymer based on graphene oxide-mesoporous silica nanosheet for fast and efficient removal of chromium (VI) from aqueous solution.

A novel chromium (VI) ion-imprinted polymer (Cr(VI)-IIP) was prepared using surface ion imprinting technique on graphene oxide-mesoporous silica (GO-MS) nanosheets with 3-(2-amino ethyl amino) propyl trimethoxysilane as the functional monomer. The prepared Cr(VI)-IIP was characterized by Fourier transform infrared spectroscopy, scanning electronic microscopy, X-ray diffraction and thermogravimetric analysis. The prepared Cr(VI)-IIP was then applied to remove Cr(VI) ions from aqueous solution. The influences of functional monomer amount, contact time, initial Cr(VI) concentration, solution pH and temperature, on the adsorption performance of Cr(VI)-IIP were investigated. Adsorption experiments revealed that the sorption equilibrium was achieved within 5 min with a high adsorption capacity up to 438.1 mg g-1, and the adsorption process followed pseudo-second-order kinetic model and Freundlich adsorption isotherm model. The Cr(VI)-IIP exhibited superior selectivity for Cr(VI) with respected to Cr(III), Mo(VI), PO43-, SO42- and NO3-. Moreover, Cr(VI)-IIP showed good reusability in five adsorption/desorption cycles. Results indicated that the synthesized Cr(VI)-IIP possessed excellent potential applications for the treatment of wastewaters containing Cr(VI).