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Integrated fixed-film activated sludge (IFAS) is a hybrid wastewater treatment process that combines suspended and attached growth. The current review provides an overview of the effect of operating parameters on the performance of IFAS and their implications for wastewater treatment. The operating parameters examined include hydraulic retention time (HRT), solids retention time (SRT), dissolved oxygen (DO) levels, temperature, nutrient loading rates, and aeration. Proper control and optimization of these parameters significantly enhance the treatment efficiency and pollutant removal. Longer HRT and appropriate SRT contribute to improved organic matter and nutrient removal. DO levels promote the growth of aerobic microorganisms, leading to enhanced organic matter degradation. Temperature influences microbial activity and enzymatic reactions, impacting treatment efficiency. Nutrient loading rates must be carefully managed to avoid system overload or inhibition. Effective aeration ensures uniform distribution of wastewater and biofilm carriers, optimizing contact between microorganisms and pollutants. IFAS has been used in water reuse applications, providing a sustainable and reliable water source for non-potable uses. Overall, IFAS has proven to be an effective and efficient treatment process that can provide high-quality effluent suitable for discharge or reuse. Understanding the effects of these operating parameters helps to optimize the design and operation for efficient wastewater treatment. Further research is needed to explore the interactions between different parameters, evaluate their impact under varying wastewater characteristics, and develop advanced control strategies for improved performance and sustainability.

Haematopoietic stem cells (HSCs) can reside as dormant cells in endosteal niches in the bone marrow, where they are resistant to certain types of chemotherapy. In this article, the authors suggest that by first awakening dormant HSCs to become actively self-renewing cells, this resistance to chemotherapy could be overcome. Haematopoietic stem cells (HSCs) in mouse bone marrow are located in specialized niches as single cells. During homeostasis, signals from this environment keep some HSCs dormant, which preserves long-term self-renewal potential, while other HSCs actively self renew to maintain haematopoiesis. In response to haematopoietic stress, dormant HSCs become activated and rapidly replenish the haematopoietic system. Interestingly, three factors — granulocyte colony-stimulating factor, interferon-α and arsenic trioxide — have been shown to efficiently activate dormant stem cells and thereby could break their resistance to anti-proliferative chemotherapeutics. Thus, we propose that two-step strategies could target resistant leukaemic stem cells by priming tumours with activators of dormancy followed by chemotherapy or targeted therapies.

Recent studies have revealed that long non-coding RNAs (lncRNAs) play important roles in cancer biology and that lncRNA gas5 (growth arrest-specific 5) regulates breast cancer cell growth. However, the role of gas5 in pancreatic cancer progression remains largely unknown. In the current study, we assay the expression level of gas5 in pancreatic cancer tissues and define the role of gas5 in the regulation of pancreatic cancer cell proliferation. We verify that the expression level of gas5 is significantly decreased in pancreatic cancer tissues compared with normal control. Overexpression of gas5 in pancreatic cancer cells inhibits cell proliferation, whereas gas5 inhibition induces a significant decrease in G0/G1 phase and an increase in S phase. We further demonstrate that gas5 negatively regulates CDK6 (cyclin-dependent kinase 6) expression in vitro and in vivo. More importantly, knockdown of CDK6 partially abrogates gas5-siRNA-induced cell proliferation. These data suggest an important role of gas5 in the molecular etiology of pancreatic cancer and implicate the potential application of gas5 in pancreatic cancer therapy.

Background: Epithelial–mesenchymal transition (EMT) is a crucial process in cancer progression that provides cancer cells with the ability to escape from the primary focus, invade stromal tissues and migrate to distant regions. Cell lines that lack E-cadherin show increased tumorigenesis and metastasis, and the expression levels of E-cadherin and Snail correlate inversely with the prognosis of patients suffering from breast cancer or oral squamous cell carcinoma (OSCC). Moreover, recent studies have shown that most EMT cases are regulated by soluble growth factors or cytokines. Among these factors, fibroblast growth factors (FGFs) execute diverse functions by binding to and activating members of the FGF receptor (FGFR) family, including FGFR1–4. Fibroblast growth factor receptor 1 is an oncoprotein that is involved in tumorigenesis, and PD173074 is known to be a selective inhibitor of FGFR1. However, the roles of FGFR1 and FGFR1 inhibitors have not yet been examined in detail. Methods: Here, we investigated the expression of FGFR1 in head and neck squamous cell carcinoma (HNSCC) and the role of the FGFR1 inhibitor PD173074 in carcinogenesis and the EMT process. Results: Fibroblast growth factor receptor 1 was highly expressed in 54% of HNSCC cases and was significantly correlated with malignant behaviours. Nuclear FGFR1 expression was also observed and correlated well with histological differentiation, the pattern of invasion and abundant nuclear polymorphism. Fibroblast growth factor receptor 1 was also overexpressed in EMT cell lines compared with non-EMT cell lines. Furthermore, treatment of HOC313 cells with PD173074 suppressed cellular proliferation and invasion and reduced ERK1/2 and p38 activation. These cells also demonstrated morphological changes, transforming from spindle- to cobble stone-like in shape. In addition, the expression levels of certain matrix metalloproteinases (MMPs), whose genes contain activator protein-1 (AP-1) promoter sites, as well as Snail1 and Snail2 were reduced following PD173074 treatment. Conclusion: Taken together, these data suggest that PD173074 inhibits the MAPK pathway, which regulates the activity of AP-1 and induces MET. Furthermore, this induction of MET likely suppresses cancer cell growth and invasion.

Spatial and temporal control of cell growth is central for the morphogenesis of multicellular organisms. For some cell types that undergo extensive post‐mitotic cell growth, such as neurons and hair cells, orchestrating the extent of post‐mitotic cell growth with development is vital for their physiology and function. Previous studies suggested that the extent of cell growth is linked with an increase in ploidy by endoreduplication but how developmental signals control endocycling and cell growth is not understood in both animals and plants. In this study we show that a trihelix transcription factor, GT2‐LIKE 1 (GTL1), actively terminates ploidy‐dependent cell growth and its developmentally regulated expression is one of the key determinants of cell size in Arabidopsis leaf hair cells (trichomes). Through genome‐wide chromatin‐binding studies (ChIP‐chip) coupled with transcriptional profiling, we further demonstrate that GTL1 directly represses the transcription of CDH1/FZR/CCS52 , an activator of the anaphase‐promoting complex/cyclosome (APC/C), to stop the endocycle progression and ploidy‐dependent cell growth. Thus, our findings uncover a previously uncharacterised key molecular link between developmental programming and cell‐size control, highlighting the central role of APC/C in post‐mitotic cell growth. How are endoreduplication and growth coordinated in development? The transcription factor GTL1 acts as a master regulator of the endocycle program in Arabidopsis by repressing APC/C.

Abstract Rationale Patients with asthma exhibit variable response to inhaled corticosteroids (ICS). Vitamin D is hypothesized to exert effects on phenotype and glucocorticoid (GC) response in asthma. Objectives To determine the effect of vitamin D levels on phenotype and GC response in asthma. Methods Nonsmoking adults with asthma were enrolled in a study assessing the relationship between serum 25(OH)D (vitamin D) concentrations and lung function, airway hyperresponsiveness (AHR), and GC response, as measured by dexamethasone-induced expression of mitogen-activated protein kinase phosphatase (MKP)-1 by peripheral blood mononuclear cells. Measurements and Main Results A total of 54 adults with asthma (FEV1, 82.9 ± 15.7% predicted [mean ± SD], serum vitamin D levels of 28.1 ± 10.2 ng/ml) were enrolled. Higher vitamin D levels were associated with greater lung function, with a 22.7 (±9.3) ml (mean ± SE) increase in FEV1 for each nanogram per milliliter increase in vitamin D (P = 0.02). Participants with vitamin D insufficiency (<30 ng/ml) demonstrated increased AHR, with a provocative concentration of methacholine inducing a 20% fall in FEV1 of 1.03 (±0.2) mg/ml versus 1.92 (±0.2) mg/ml in those with vitamin D of 30 ng/ml or higher (P = 0.01). In ICS-untreated participants, dexamethasone-induced MKP-1 expression increased with higher vitamin D levels, with a 0.05 (±0.02)-fold increase (P = 0.02) in MKP-1 expression observed for each nanogram per milliliter increase in vitamin D, a finding that occurred in the absence of a significant increase in IL-10 expression. Conclusions In asthma, reduced vitamin D levels are associated with impaired lung function, increased AHR, and reduced GC response, suggesting that supplementation of vitamin D levels in patients with asthma may improve multiple parameters of asthma severity and treatment response. Clinical trials registered with www.clinicaltrials.gov (NCT00495157, NCT00565266, and NCT00557180).

Resveratrol (Res; 3,4′,5-trihydroxy-trans-stilbene), which is a polyphenol found in grapes, can block cell proliferation and induce growth arrest and/or cell death in several types of cancer cells. However, the precise mechanisms by which Res exerts anticancer effects remain poorly understood. Res blocked both anchorage-dependent and -independent growth of HT-29 and COLO 201 human colon cancer cells in a dose- and time-dependent manner. Annexin V staining and Western blot analysis revealed that Res induced apoptosis accompanied by an increase in Caspase-8 and Caspase-3 cleavage. In HT-29 cells, Res caused autophagy as characterized by the appearance of autophagic vacuoles by electron microscopy and elevation of microtubule-associated protein 1 light chain 3 (LC3)-II by immunoblotting, which was associated with the punctuate pattern of LC3 detected by fluorescein microscopy. Inhibition of Res-induced autophagy by the autophagy inhibitor 3-methyladenine caused a significant decrease in apoptosis accompanied by decreased cleavage of Casapse-8 and Caspase-3, indicating that Res-induced autophagy was cytotoxic. However, inhibition of Res-induced apoptosis by the pan-caspase inhibitor Z-VAD(OMe)-FMK did not decrease autophagy but elevated LC3-II levels. Interestingly, Res increased the intracellular reactive oxygen species (ROS) level, which correlated to the induction of Casapse-8 and Caspase-3 cleavage and the elevation of LC3-II; treatment with ROS scavenger N-acetyl cysteine diminished this effect. Therefore, the effect of Res on the induction of apoptosis via autophagy is mediated through ROS in human colon cancer cells.

Traditionally, vaccines have been utilized to generate immune responses to a pathogen in a naive population. In the setting of congenital cytomegalovirus (CMV) infection, a vaccine that, when administered to women already infected with CMV, could boost the mother's immunity to CMV would most likely be beneficial in diminishing in utero transmission of CMV. However, the ability to boost an immune response in a population of individuals seropositive for a pathogen of interest is not well studied. This study examines the ability of a recombinant CMV glycoprotein  vaccine with MF59 adjuvant to boost both antibody (neutralizing and enzyme-linked immunosorbent assay end point dilution titer) and CD4+ T-cell responses in previously CMV-seropositive women by way of natural infection. These data suggest that this vaccine is capable of boosting immunity in a population of CMV-infected women and warrants additional evaluation to determine whether these boosted responses may prevent mother to child transmission of CMV.

Gastric cancer (GC) develops through deregulation of gene expression and accumulation of epigenetic abnormalities, leading to tumor cell acquisition of malignant features. MicroRNAs (miRNAs) play a critical role in cancer development where they can act as oncogenes or oncosuppressors. To identify miRNAs that are associated with some clinicopathologic features of GC and/or participate in tumor progression, miRNA expression in 20 GC tissues and five corresponding non‐neoplastic gastric mucosa was examined by miRNA microarray. Oligonucleotide array analysis was carried out for miRNA target prediction. The functions of candidate miRNAs and their target genes were also analyzed by quantitative RT‐PCR, Western blotting, reporter gene assay, and cell invasion assay. Comparison of miRNA expression profiles revealed that downregulation of miR‐148a was identified in most of the GC tissues. Downregulation of miR‐148a was significantly correlated with an advanced clinical stage, lymph node metastasis, and poor clinical outcome. Custom oligonucleotide array analysis revealed that MMP7 expression was markedly downregulated in miR‐148a‐overexpressing GC cells; MMP7 was found to be a direct and functional target of miR‐148a, participating in cell invasion. These results suggest that miR‐148a contributes to the maintenance of homeostasis in normal stomach tissue and plays an important role in GC invasion by regulating MMP7 expression. miR‐148a expression was significantly downregulated in gastric cancer, and its downregulation was significantly correlated with an worse clinico‐pathologic characters. MMP7 was found to be a direct and functional target of miR‐148a, participating in cell invasion.