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High mountain freshwater systems are particularly sensitive to the impacts of global warming and relevant environmental changes. Microorganisms contribute substantially to biogeochemical processes, yet their distribution patterns and driving mechanism in alpine streams remain understudied. Here, we examined the bacterial and fungal community compositions in stream biofilm along the elevational gradient of 745–1874 m on Mt. Kilimanjaro and explored their alpha and beta diversity patterns and the underlying environmental drivers. We found that the species richness and evenness monotonically increased towards higher elevations for bacteria, while were non-significant for fungi. However, both bacterial and fungal communities showed consistent elevational distance-decay relationships, i.e., the dissimilarity of assemblage composition increased with greater elevational differences. Bacterial alpha diversity patterns were mainly affected by chemical variables such as total nitrogen and phosphorus, while fungi were affected by physical variables such as riparian shading and stream width. Notably, climatic variables such as mean annual temperature strongly affected the elevational succession of bacterial and fungal community compositions. Our study is the first exploration of microbial biodiversity and their underlying driving mechanisms for stream ecosystems in tropical alpine regions. Our findings provide insights on the response patterns of tropical aquatic microbial community composition and diversity under climate change. [ABSTRACT FROM AUTHOR]

The benefits of hypoxia for maintaining the stemness of cultured human bone marrow-derived endothelial progenitor cells (BM EPCs) have previously been demonstrated but the mechanisms responsible remain unclear. Growing evidences suggest that cellular metabolism plays an important role in regulating stem cell fate and self-renewal. Here we aimed to detect the changes of glucose metabolism and to explore its role on maintaining the stemness of BM EPCs under hypoxia. We identified the metabolic status of BM EPCs by using extracellular flux analysis, LC–MS/MS, and 13C tracing HPLC-QE-MS, and found that hypoxia induced glucose metabolic reprogramming, which manifested as increased glycolysis and pentose phosphate pathway (PPP), decreased tricarboxylic acid (TCA) and mitochondrial respiration. We further pharmacologically altered the metabolic status of cells by employing various of inhibitors of key enzymes of glycolysis, PPP, TCA cycle and mitochondria electron transport chain (ETC). We found that inhibiting glycolysis or PPP impaired cell proliferation either under normoxia or hypoxia. On the contrary, inhibiting pyruvate oxidation, TCA or ETC promoted cell proliferation under normoxia mimicking hypoxic conditions. Moreover, promoting pyruvate oxidation reverses the maintenance effect of hypoxia on cell stemness. Taken together, our data suggest that hypoxia induced glucose metabolic reprogramming maintains the stemness of BM EPCs, and artificial manipulation of cell metabolism can be an effective way for regulating the stemness of BM EPCs, thereby improving the efficiency of cell expansion in vitro. [ABSTRACT FROM AUTHOR]

Heterogeneous, sulfate radical-based advanced oxidation processes (AOPs) have arisen in recent decades due to their high reactivity and oxidation capabilities for a wide spectrum of hazardous and refractory organic compounds. The presence of a rate-limiting step with a slow conversion rate from ≡Me(n+1)+ to ≡Men+ in transition metal oxides, on the other hand, severely limits the performance of PMS activation. Also, the activity of metal catalysts is pH-sensitive. Herein, we provide a promising strategy to solve these issues. In this paper, Cu/Mn–ZnO nanoparticles consisting of dual reaction centers (DRCs) with electron-rich/poor areas were synthesized by hydrothermal methods, which demonstrated high activity, stability, and reusability in heterogeneous catalysis. Characterization results (e.g., XPS) revealed that the catalysts present surface electron-rich Cu & oxygen vacancies (OVs) centers/deficient micro-areas, avoiding direct reaction with metal ions, while pollutants can be captured and preliminarily degraded by the electron-deficient areas as electron donors. As a result, the structure eliminated the influence of pH on activity in the range of 2.5–10.5 and exhibited significant catalytic activity. Using Rhodamine B (Rh-B) as the target pollutant, the degradation rate was up to 96% at 10 min. Moreover, the EPR analysis and quenching experiments revealed that 1O2 was the predominant reactive oxygen species (ROS) attacking the pollutants. Overall, the catalyst developed in this study has great potential for the treatment of refractory pollutants by activating peroxymonosulfate (PMS). [ABSTRACT FROM AUTHOR]

Cerebral ischemic stroke is one of the leading causes of morbidity and mortality worldwide, and rapidly increasing annually with no more effective therapeutic measures. Thus, the novel diagnostic and prognostic biomarkers are urgent to be identified for prevention and therapy of ischemic stroke. Recently, long noncoding RNAs (lncRNAs), a major family of noncoding RNAs with more than 200 nucleotides, have been considered as new targets for modulating pathological process of ischemic stroke. In this review, we summarized that the lncRNA-maternally expressed gene 3 (MEG3) played a critical role in promotion of neuronal cell death and inhibition of angiogenesis in response to hypoxia or ischemia condition, and further described the challenge of overcrossing blood–brain barrier (BBB) and determination of optimal carrier for delivering lncRNA' drugs into the specific brain regions. In brief, MEG3 will be a potential diagnostic biomarker and drug target in treatment and therapy of ischemic stroke in the future. [ABSTRACT FROM AUTHOR]

The toxicity of silver nanoparticles (AgNPs) with a single morphology to aquatic organisms has been well demonstrated in the past decade, but few studies have been carried out to evaluate the differences in toxicity among AgNPs with various microstructural morphologies. In this work, C. vulgaris was used as the tested organism to examine the differences in toxic effects among AgNSs, AgNCs, and AgPLs at concentrations of 0.5, 1.0, 2.0, and 5.0 mg/L. The results showed that the cell density and chlorophyll a content of C. vulgaris decreased when the dose of AgNPs was increased, while the inhibiting effects that were caused by AgPLs were stronger than those that were caused by AgNCs and AgNSs. Under short-term exposure to AgPLs, the ROS content was significantly higher than those under exposure to AgNCs and AgNSs, while the MDA content fluctuated without obvious regularity. The dose of AgPLs affected the antioxidative enzyme activity and lipid peroxidation more obviously than those of AgNSs and AgNCs. The superoxide dismutase and catalase contents in the former case were distinctly higher than those in the latter cases. Consequently, the cell apoptosis rate under exposure to AgPLs reached 83%, which was higher than those under exposure to AgNSs (50%) and AgNCs (71%). This work shows that the level of toxicity to C. vulgaris was in the order of AgPLs > AgNCs > AgNSs. The obtained results demonstrate that the microstructural morphologies of AgNPs determined their potential toxicity. [ABSTRACT FROM AUTHOR]

Haematopoietic stem cells (HSCs) tightly regulate their quiescence, proliferation, and differentiation to generate blood cells during the entire lifetime. The mechanisms by which these critical activities are balanced are still unclear. Here, we report that Macrophage-Erythroblast Attacher (MAEA, also known as EMP), a receptor thus far only identified in erythroblastic island, is a membrane-associated E3 ubiquitin ligase subunit essential for HSC maintenance and lymphoid potential. Maea is highly expressed in HSCs and its deletion in mice severely impairs HSC quiescence and leads to a lethal myeloproliferative syndrome. Mechanistically, we have found that the surface expression of several haematopoietic cytokine receptors (e.g. MPL, FLT3) is stabilised in the absence of Maea, thereby prolonging their intracellular signalling. This is associated with impaired autophagy flux in HSCs but not in mature haematopoietic cells. Administration of receptor kinase inhibitor or autophagy-inducing compounds rescues the functional defects of Maea-deficient HSCs. Our results suggest that MAEA provides E3 ubiquitin ligase activity, guarding HSC function by restricting cytokine receptor signalling via autophagy. Haematopoietic stem cells (HSCs) are metabolically quiescent, with balanced myeloid and lymphoid potential. Here the authors show that MAEA is required in HSCs for ubiquitination and downregulation of surface cytokine receptors via autophagy; MAEA loss leads to impaired HSC quiescence and a myeloproliferative disorder. [ABSTRACT FROM AUTHOR]

The development of phase change materials (PCMs) with high energy storage density, enhanced photothermal conversion efficiency and good form-stability is essential for practical application in utilization of solar energy. Herein, novel PCM composites (CPPCMs) with extremely high energy storage density and superb solar-thermal conversion performance were fabricated by introducing n-octacosane into three-dimensional (3D) porous cellulose nanofibril (CNF)/polypyrrole (PPy) hybrid aerogels. Due to the strong encapsulation capability of CNF/PPy hybrid aerogels (CPAs), the synthesized PCM composites maintained perfect shape stability above the melting point of n-octacosane. Further investigation showed CPPCMs exhibited extremely high latent heat in the range of 239.4–258.4 J/g and high loading rate of n-octacosane (up to 96%). The melting/cooling cycling test and thermogravimetric analysis indicated the composite PCMs possessed excellent cyclic stability and thermal stability. Moreover, simulated sunlight test showed that the photothermal conversion efficiency of CPPCMs significantly improved with the increased content of polypyrrole in the PCM composites. In conclusion, the obtained PCM composites, which exhibited excellent shape stability, superior solar-heat conversion capability and extremely high energy storage density, showed considerable potential for practical utilization and storage of solar energy. [ABSTRACT FROM AUTHOR]

The Hall–Petch relationship, according to which the strength of a metal increases as the grain size decreases, has been reported to break down at a critical grain size of around 10 to 15 nanometres1,2. As the grain size decreases beyond this point, the dominant mechanism of deformation switches from a dislocation-mediated process to grain boundary sliding, leading to material softening. In one previous approach, stabilization of grain boundaries through relaxation and molybdenum segregation was used to prevent this softening effect in nickel–molybdenum alloys with grain sizes below 10 nanometres3. Here we track in situ the yield stress and deformation texturing of pure nickel samples of various average grain sizes using a diamond anvil cell coupled with radial X-ray diffraction. Our high-pressure experiments reveal continuous strengthening in samples with grain sizes from 200 nanometres down to 3 nanometres, with the strengthening enhanced (rather than reduced) at grain sizes smaller than 20 nanometres. We achieve a yield strength of approximately 4.2 gigapascals in our 3-nanometre-grain-size samples, ten times stronger than that of a commercial nickel material. A maximum flow stress of 10.2 gigapascals is obtained in nickel of grain size 3 nanometres for the pressure range studied here. We see similar patterns of compression strengthening in gold and palladium samples down to the smallest grain sizes. Simulations and transmission electron microscopy reveal that the high strength observed in nickel of grain size 3 nanometres is caused by the superposition of strengthening mechanisms: both partial and full dislocation hardening plus suppression of grain boundary plasticity. These insights contribute to the ongoing search for ultrastrong metals via materials engineering. High-pressure diamond anvil cell experiments reveal that compression strengthening of nanocrystalline nickel increases as its grain sizes decrease to 3 nanometres, owing to dislocation hardening and suppression of grain boundary plasticity. [ABSTRACT FROM AUTHOR]

Introduction: Hypopharyngeal squamous cell carcinoma (HSCC) is among the most lethal tumors encountered in the head and neck and frequently involves regional metastasis. However, the mechanism underlying the aggressiveness of HSCC remains elusive. S100A4 is a well-established metastasis-promoting regulator in a variety of malignancies, but its role in HSCC has not yet been identified. Objectives: Our objectives were to explore the expression levels of S100A4 in HSCC tumors and its association with clinicopathological parameters and the clinical prognosis of HSCC and to confirm its role in the metastatic process of the HSCC FaDu cell line in vitro. Methods: We assessed the expression levels of S100A4 with immunohistochemistry (IHC) in HSCC tumors (n = 71) and adjacent normal tissues (n = 44). In vitro experiments were performed to explore the impact of S100A4 knockdown on biological phenotypes of human HSCC FaDu cell line, including migration, invasion, proliferation, apoptosis, and cell cycle. Results: The expression of S100A4 was elevated in HSCC tumors compared with adjacent normal tissues and positively correlated with cervical lymph node metastasis in this HSCC patient cohort. In vitro experiments showed that S100A4 knockdown significantly impaired migration and invasion and increased the proportion of cells in G0/G1 phase with no change in proliferation or apoptosis in FaDu cells. Additionally, nuclear S100A4 expression proved to be an independent prognostic indicator in patients with HSCC. Conclusion: This study demonstrated for the first time that S100A4 expression is upregulated in HSCC tumors and that this upregulation is positively correlated with cervical lymph node metastasis of this malignancy. The metastasis-promoting role of S100A4 was further validated in the HSCC FaDu cell line, indicating that S100A4 is a potential therapeutic target for HSCC. Furthermore, this study suggests that nuclear S100A4 expression could be considered a prognostic biomarker for HSCC. [ABSTRACT FROM AUTHOR]

The ubiquitin-protein ligases (E3s) directly participate in ubiquitin (Ub) transferring to the target proteins in the ubiquitination pathway. The HECT ubiquitin-protein ligase (UPL), one type of E3s, is characterized as containing a conserved HECT domain of approximately 350 amino acids in the C terminus. Some UPLs were found to be involved in trichome development and leaf senescence in Arabidopsis. However, studies on plant UPLs, such as characteristics of the protein structure, predicted functional motifs of the HECT domain, and the regulatory expression of UPLs have all been limited. Here, we present genome-wide identification of the genes encoding UPLs (HECT gene) in apple. The 13 genes (named as MdUPL1- MdUPL13) from ten different chromosomes were divided into four groups by phylogenetic analysis. Among these groups, the encoding genes in the intron-exon structure and the included additional functional domains were quite different. Notably, the F-box domain was first found in MdUPL7 in plant UPLs. The HECT domain in different MdUPL groups also presented different spatial features and three types of conservative motifs were identified. The promoters of each MdUPL member carried multiple stress-response related elements by cis-acting element analysis. Experimental results demonstrated that the expressions of several MdUPLs were quite sensitive to cold-, drought-, and salt-stresses by qRT-PCR assay. The results of this study helped to elucidate the functions of HECT proteins, especially in Rosaceae plants. [ABSTRACT FROM AUTHOR]

This work evaluated the adsorption and protection capacities of amino-functionalized mesoporous silica nanoparticles (Am-MSNs) for the recombinant DNA (rDNA), pcDNA3.1(+)-PKB-HA. The in vitro biocompatibility of Am-MSNs was also tested on HeLa and A549 cells, respectively. The results reveal that the MSNs modified with 3-aminopropyltriethoxysilane exhibit good adsorption capacity for pcDNA3.1(+)-PKB-HA at physiological conditions and the adsorption amount is higher than that of other silica nanoparticles. Moreover, the material can also protect pcDNA3.1(+)-PKB-HA from enzymatic degradation completely and presents high in vitro biocompatibility. This demonstrates that Am-MSNs may be potential nonviral vector candidates for pcDNA3.1(+)-PKB-HA. [ABSTRACT FROM AUTHOR]

Two new inorganic-organic hybrid polymers, Mn(QS)(H2O) (1) and Co(QS)(H2O)2 (2) (H2QS=8-hydroxylquinoline-5-sulfonic acid), based on 8-hydroxylquinoline-5-sulfonate ligand, have been synthesized under solvothermal conditions and their structures were solved by single-crystal X-ray diffraction analysis. Compound 1 is a three-dimensional open framework with rutile topology structure, and compound 2 is a three-dimensional supramolecular structure. These compounds were characterized by powder XRD, infrared spectroscopy, thermogravimetric analysis, fluorescence properties and magnetism properties. [ABSTRACT FROM AUTHOR]

Ten to twenty percent of the hepatocellular carcinoma (HCC) patients fulfilling the Milan criteria (MC) recurred within three years after orthotopic liver transplantation (OLT). We therefore utilize a training cohort to develop an improved prognostic model for predicting the recurrence in these patients. By univariate and multivariate analysis, AFP level [cut-off value: 321 ng/mL, area under the curve (AUC) = 0.724, 95% confidence interval (CI) = 0.604-0.843, P < 0.001] and cytokeratin-19 (CK19) and glypican-3 (GPC3) expression pattern from nine putative prognostic factors were entered in risk factor scoring model to conjecture the tumor recurrence. In the training cohort, the AUC value of the model was 0.767 (95% CI = 0.645-0.890, P < 0.001), which was the highest among all the elements. The model's performance was then assessed using a validation cohort. In the validation cohort, the AUC value of the model was 0.843 (95% CI = 0.720−0.966, P < 0.001) which was higher than any other elements. The results indicated that model had high performance with good discrimination ability and significantly improved the predictive capacity for the recurrence of HCC patients within MC after OLT. [ABSTRACT FROM AUTHOR]