Start-up of a full-scale two-stage partial nitritation/anammox (PN/A) process treating reject water from high solid anaerobic sludge digestion (HSAD).

High solid anaerobic digestion (HSAD) achieves the benefits of high volumetric loading rates and lower reject water production, which, however, results in much more concentrated reject water with a remarkable increase in organics and nitrogen compared with that from conventional AD with low solid content. The high concentrations of ammonium (2000-3500 mg/L) and COD (3000-4000 mg/L) were reported to exert inhibition on anammox bacteria (AnAOB), posing challenges to the application of the partial nitritation/anammox (PN/A). To date, no cases of PN/A process start-up for sludge HSAD reject water were reported.

Four new chromone derivatives from the Arctic fungus Phoma muscivora CPCC 401424 and their antiviral activities.

The crude extract of the Arctic fungus Phoma muscivora CPCC 401424 displayed anti-influenza A virus activities which led us to investigated their secondary metabolites. Four new chromone derivatives, phomarcticones A-D (1-4) and five known chromone analogs (5-9) have been isolated from Arctic fungus Phoma muscivora CPCC 401424. Compounds 3 and 4 possess rare sulfoxide groups in chromone derivatives.

New dimeric chromanone derivatives from the mutant strains of and their bioactivities.

Three new chromanone dimer derivatives, paecilins F-H (1-3) and ten known compounds (4-13), were obtained from the mutant strains of 114-2. Their structures were elucidated by extensive analysis of spectroscopic data and comparison with reported data, and the configurations of 1-3 were resolved by quantum chemical calculations of NMR shifts and ECD spectra. Compounds 5 and 11 showed significant anti-influenza A virus activities with IC values of 5.

New phenol and chromone derivatives from the endolichenic fungus species and their antiviral activities.

Three new phenolic metabolites, daldispols A-C (1-3), two new chromone derivatives, (5,7)-5,7-dihydroxy-2-methyl-5,6,7,8-tetrahydro-4-chromen-4-one (9) and (5,7)-5,7-dihydroxy-2-propyl-5,6,7,8-tetrahydro-4-chromen-4-one (10), together with five known phenolic compounds (4-8) and two known chromone compounds (11 and 12) were isolated from the endolichenic fungus sp. CPCC 400770. Their structures were elucidated on the basis of spectroscopic methods, electronic circular dichroism (ECD), and comparison with reported data.

Optimizing granular anammox retention via hydrocycloning during two-stage deammonification of high-solid sludge anaerobic digester supernatant.

High-solid sludge anaerobic digestion leads to increased organic matters in digester supernatant, which promotes heterotrophic competition and reduces anaerobic ammonium oxidation (anammox) retention. This research demonstrated effective anammox retention by hydrocycloning during a two-stage deammonification. Anammox retention was evaluated by dividing large (>0.

Microbial Transformation of -Clerodane Diterpenoid, Scutebarbatine F, by sp. CPCC 205437.

Biotransformation of the -clerodane diterpene, scutebarbatine F (), by sp. CPCC 205437 was investigated for the first time, which led to the isolation of nine new metabolites, scutebarbatine F-F (-). Their structures were determined by extensive high-resolution electrospray ionization mass spectrometry (HRESIMS) and NMR data analyses.

Hormonal modulation of ESR1 mutant metastasis.

Estrogen receptor alpha gene (ESR1) mutations occur frequently in ER-positive metastatic breast cancer, and confer clinical resistance to aromatase inhibitors. Expression of the ESR1 Y537S mutation induced an epithelial-mesenchymal transition (EMT) with cells exhibiting enhanced migration and invasion potential in vitro. When small subpopulations of Y537S ESR1 mutant cells were injected along with WT parental cells, tumor growth was enhanced with mutant cells becoming the predominant population in distant metastases.

RON signalling promotes therapeutic resistance in ESR1 mutant breast cancer.

Background: Oestrogen Receptor 1 (ESR1) mutations are frequently acquired in oestrogen receptor (ER)-positive metastatic breast cancer (MBC) patients who were treated with aromatase inhibitors (AI) in the metastatic setting. Acquired ESR1 mutations are associated with poor prognosis and there is a lack of effective therapies that selectively target these cancers.

Methods: We performed a proteomic kinome analysis in ESR1 Y537S mutant cells to identify hyperactivated kinases in ESR1 mutant cells.

Daldispones A and B, two new cyclopentenones from Daldinia sp. CPCC 400770.

Two new cyclopentenone derivatives, daldispones A (1) and B (2) were isolated from the fungus Daldinia sp. CPCC 400770. Their structures and absolute configurations were elucidated by extensive spectroscopic analyses and calculated electronic circular dichroism (ECD).

Estrogen-induced transcription at individual alleles is independent of receptor level and active conformation but can be modulated by coactivators activity.

Steroid hormones are pivotal modulators of pathophysiological processes in many organs, where they interact with nuclear receptors to regulate gene transcription. However, our understanding of hormone action at the single cell level remains incomplete. Here, we focused on estrogen stimulation of the well-characterized GREB1 and MYC target genes that revealed large differences in cell-by-cell responses, and, more interestingly, between alleles within the same cell, both over time and hormone concentration.

ESR1 mutations in breast cancer.

The acquisition of ligand-independent ESR1 mutations during aromatase inhibitor therapy in metastatic estrogen receptor (ER)-positive breast cancer is a common mechanism of hormonal therapy resistance. Preclinical and clinical studies have demonstrated that ESR1 mutations can preexist in primary tumors and can be enriched during metastasis. Furthermore, ESR1 mutations express a unique transcriptional profile that favors tumor progression, suggesting that selected ESR1 mutations may influence metastasis.

Proteomic profiling identifies key coactivators utilized by mutant ERα proteins as potential new therapeutic targets.

Approximately 75% of breast cancers are estrogen receptor alpha (ERα)-positive and are treatable with endocrine therapies, but often patients develop lethal resistant disease. Frequent mutations (10-40%) in the ligand-binding domain (LBD) codons in the gene encoding ERα (ESR1) have been identified, resulting in ligand-independent, constitutively active receptors. In addition, ESR1 chromosomal translocations can occur, resulting in fusion proteins that lack the LBD and are entirely unresponsive to all endocrine treatments.

The Impact of ESR1 Mutations on the Treatment of Metastatic Breast Cancer.

After nearly 20 years of research, it is now established that mutations within the estrogen receptor (ER) gene, ESR1, frequently occur in metastatic breast cancer and influence response to hormone therapy. Though early studies presented differing results, sensitive sequencing techniques now show that ESR1 mutations occur at a frequency between 20 and 40% depending on the assay method. Recent studies have focused on several "hot spot mutations," a cluster of mutations found in the hormone-binding domain of the ESR1 gene.

Targeted therapy for breast cancer and molecular mechanisms of resistance to treatment.

In recent years, clinical trials investigating new drugs and therapeutic combinations have led to promising advances in breast cancer therapy. Subtyping breast cancers into hormone receptor (HR) positive, epidermal growth factor receptor (HER2) positive, and triple negative breast cancer (TNBC) is currently the basis of diagnosing and treating this disease. In addition to endocrine and HER2-targeted therapies in their respective subtypes, evidence from recent preclinical studies have shown several targetable pathways that overcome resistance in the clinical setting.

ESR1 mutations affect anti-proliferative responses to tamoxifen through enhanced cross-talk with IGF signaling.

The purpose of this study was to address the role of ESR1 hormone-binding mutations in breast cancer. Soft agar anchorage-independent growth assay, Western blot, ERE reporter transactivation assay, proximity ligation assay (PLA), coimmunoprecipitation assay, silencing assay, digital droplet PCR (ddPCR), Kaplan-Meier analysis, and statistical analysis. It is now generally accepted that estrogen receptor (ESR1) mutations occur frequently in metastatic breast cancers; however, we do not yet know how to best treat these patients.

ESR1 Mutations in Breast Cancer: Proof-of-Concept Challenges Clinical Action.

Wang and colleagues demonstrate that digital droplet PCR (ddPCR) identified ESR1 mutations in 7% of primary breast cancers. ESR1 mutations were also readily detected in metastatic tissues and circulating tumor DNA in the blood. These results suggest that ddPCR may be amendable for monitoring tumor burden, and to predict relapse.

Androgen receptor promotes tamoxifen agonist activity by activation of EGFR in ERα-positive breast cancer.

Tamoxifen (Tam) resistance represents a significant clinical problem in estrogen receptor (ER) α-positive breast cancer. We previously showed that decreased expression of Rho guanine nucleotide dissociation inhibitor (Rho GDI) α, a negative regulator of the Rho GTPase pathway, is associated with Tam resistance. We now discover that androgen receptor (AR) is overexpressed in cells with decreased Rho GDIα and seek to determine AR's contribution to resistance.

Targeting thyroid hormone receptor beta in triple-negative breast cancer.

The purpose of this study was to discover novel nuclear receptor targets in triple-negative breast cancer. Expression microarray, Western blot, qRT-PCR analyses, MTT growth assay, soft agar anchorage-independent growth assay, TRE reporter transactivation assay, and statistical analysis were performed in this study. We performed microarray analysis using 227 triple-negative breast tumors, and clustered the tumors into five groups according to their nuclear receptor expression.

The SMRT coregulator enhances growth of estrogen receptor-α-positive breast cancer cells by promotion of cell cycle progression and inhibition of apoptosis.

The SMRT coregulator functions as a dual coactivator and corepressor for estrogen receptor-α (ERα) in a gene-specific manner, and in several studies its elevated expression correlates with poor outcome for breast cancer patients. A specific role of SMRT in breast cancer progression has not been elucidated, but SMRT knock-down limits estradiol-dependent growth of MCF-7 breast cancer cells. In this study, small-interfering RNA (siRNA) and short-hairpin RNA (shRNA) approaches were used to determine the effects of SMRT depletion on growth of ERα-positive MCF-7 and ZR-75-1 breast cancer cells, as well as the ERα-negative MDA-MB-231 breast cancer line.

Estrogen receptor (ER) α mutations in breast cancer: hidden in plain sight.

The idea that somatic ERα mutations could play an important role in the evolution of hormone-dependent breast cancers was proposed some years ago (Fuqua J Mammary Gland Biol Neoplasia 6(4):407-417, 2001; Dasgupta et al. Annu Rev Med 65:279-292, 2013), but has remained controversial until recently. A significant amount of new data has confirmed these initial observations and shown their significance, along with much additional work relevant to the treatment of breast cancer.