AIMS: The aim of this study was to characterize anaerobic ammonium oxidation (anammox) community in sediments of the Dongjiang River, a drinking water source of Hong Kong. METHODS AND RESULTS: The ...diversity and distribution of the anammox community were investigated based on a comparative analyses of 16S rRNA and hydrazine oxidation (hzo) genes of anammox bacteria. Candidatus Brocadia and two new anammox bacterial clusters were detected based on phylogenetic analysis of 16S rRNA genes. In contrast, the targeting of hzo genes indicated the presence of only Candidatus Jettenia with four different clusters. It was found that the sequence diversities of hzo genes were higher than those of the 16S rRNA genes. The abundance of anammox bacteria varied significantly among the sediment samples based on qPCR. Pearson correlation analysis indicated that nitrite concentration was the key factor influencing the abundance of anammox bacteria. The redundance analysis (RDA) confirmed that the combination of the contents of nitrite and nitrate, and the ratio of total nitrogen vs total carbon (TN/TC) had significant impact on the anammox bacterial community structure. CONCLUSIONS: The results revealed that the diverse anammox bacteria were present in sediments of the Dongjiang River, and the community structures were associated with varied environmental factors caused by urban pollutant invasion. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report about the distribution of anammox bacterial community in sediments of the Dongjiang River, which provides helpful information of anammox niche specificity and influencing factors in the river ecosystem.
Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent triggers. This process has been ...termed 'trained immunity', a de facto innate immune memory. Research in the past decade has pointed to the broad benefits of trained immunity for host defence but has also suggested potentially detrimental outcomes in immune-mediated and chronic inflammatory diseases. Here we define 'trained immunity' as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity.
Metastatic colonization is one of the critical steps in tumor metastasis. A pre-metastatic niche is required for metastatic colonization and is determined by tumor-stroma interactions, yet the ...mechanistic underpinnings remain incompletely understood.
PCR-based miRNome profiling, qPCR, immunofluorescent analyses evaluated the expression of exosomal miR-141 and cell-to-cell communication. LC-MS/MS proteomic profiling and Dual-Luciferase analyses identified YAP1 as the direct target of miR-141. Human cytokine profiling, ChIP, luciferase reporter assays, and subcellular fractionation analyses confirmed YAP1 in modulating GROα production. A series of in vitro tumorigenic assays, an ex vivo model and Yap1 stromal conditional knockout (cKO) mouse model demonstrated the roles of miR-141/YAP1/GROα/CXCR1/2 signaling cascade. RNAi, CRISPR/Cas9 and CRISPRi systems were used for gene silencing. Blood sera, OvCa tumor tissue samples, and tissue array were included for clinical correlations.
Hsa-miR-141-3p (miR-141), an exosomal miRNA, is highly secreted by ovarian cancer cells and reprograms stromal fibroblasts into proinflammatory cancer-associated fibroblasts (CAFs), facilitating metastatic colonization. A mechanistic study showed that miR-141 targeted YAP1, a critical effector of the Hippo pathway, reducing the nuclear YAP1/TAZ ratio and enhancing GROα production from stromal fibroblasts. Stromal-specific knockout (cKO) of Yap1 in murine models shaped the GROα-enriched microenvironment, facilitating in vivo tumor colonization, but this effect was reversed after Cxcr1/2 depletion in OvCa cells. The YAP1/GROα correlation was demonstrated in clinical samples, highlighting the clinical relevance of this research and providing a potential therapeutic intervention for impeding premetastatic niche formation and metastatic progression of ovarian cancers.
This study uncovers miR-141 as an OvCa-derived exosomal microRNA mediating the tumor-stroma interactions and the formation of tumor-promoting stromal niche through activating YAP1/GROα/CXCRs signaling cascade, providing new insight into therapy for OvCa patients with peritoneal metastases.
Significance We used massively parallel sequencing to study the size profiles of plasma DNA samples at single-base resolution and in a genome-wide manner. We used chromosome arm-level z -score ...analysis (CAZA) to identify tumor-derived plasma DNA for studying their specific size profiles. We showed that populations of aberrantly short and long DNA molecules existed in the plasma of patients with hepatocellular carcinoma. The short ones preferentially carried the tumor-associated copy number aberrations. We further showed that there were elevated amounts of mitochondrial DNA in the plasma of hepatocellular carcinoma patients. Such molecules were much shorter than the nuclear DNA in plasma. These findings have shed light on fundamental biological characteristics of plasma DNA and related diagnostic applications for cancer.
The analysis of tumor-derived circulating cell-free DNA opens up new possibilities for performing liquid biopsies for the assessment of solid tumors. Although its clinical potential has been increasingly recognized, many aspects of the biological characteristics of tumor-derived cell-free DNA remain unclear. With respect to the size profile of such plasma DNA molecules, a number of studies reported the finding of increased integrity of tumor-derived plasma DNA, whereas others found evidence to suggest that plasma DNA molecules released by tumors might be shorter. Here, we performed a detailed analysis of the size profiles of plasma DNA in 90 patients with hepatocellular carcinoma, 67 with chronic hepatitis B, 36 with hepatitis B-associated cirrhosis, and 32 healthy controls. We used massively parallel sequencing to achieve plasma DNA size measurement at single-base resolution and in a genome-wide manner. Tumor-derived plasma DNA molecules were further identified with the use of chromosome arm-level z -score analysis (CAZA), which facilitated the studying of their specific size profiles. We showed that populations of aberrantly short and long DNA molecules existed in the plasma of patients with hepatocellular carcinoma. The short ones preferentially carried the tumor-associated copy number aberrations. We further showed that there were elevated amounts of plasma mitochondrial DNA in the plasma of hepatocellular carcinoma patients. Such molecules were much shorter than the nuclear DNA in plasma. These results have improved our understanding of the size profile of tumor-derived circulating cell-free DNA and might further enhance our ability to use plasma DNA as a molecular diagnostic tool.
Heme oxygenase-1 (HO-1) is a heme-degrading enzyme anchored in the endoplasmic reticulum by a carboxyl-terminal transmembrane segment (TMS). HO-1 is highly expressed in various cancers and its ...nuclear localization is associated with the progression of some cancers. Nevertheless, the mechanism underlying HO-1 nuclear translocation and its pathological significance remain elusive. Here we show that the signal peptide peptidase (SPP) catalyzes the intramembrane cleavage of HO-1. Coexpression of HO-1 with wild-type SPP, but not a dominant-negative SPP, promoted the nuclear localization of HO-1 in cells. Mass spectrometry analysis of cytosolic HO-1 isolated from HeLa cells overexpressing HO-1 and SPP revealed two adjacent intramembrane cleavage sites located after S275 and F276 within the TMS. Mutations of S275F276 to A275L276 significantly hindered SPP-mediated HO-1 cleavage and nuclear localization. Nuclear HO-1 was detected in A549 and DU145 cancer cell lines expressing high levels of endogenous HO-1 and SPP. SPP knockdown or inhibition significantly reduced nuclear HO-1 localization in A549 and DU145 cells. The positive nuclear HO-1 stain was also evident in lung cancer tissues expressing high levels of HO-1 and SPP. Overexpression of a truncated HO-1 (t-HO-1) lacking the TMS in HeLa and H1299 cells promoted cell proliferation and migration/invasion. The effect of t-HO-1 was not affected by a mutation in the catalytic site. However, blockade of t-HO-1 nuclear localization abolished t-HO-1-mediated effect. The tumorigenic effect of t-HO-1 was also demonstrated in the mouse model. These findings disclose that SPP-mediated intramembrane cleavage of HO-1 promotes HO-1 nuclear localization and cancer progression independent of HO-1 enzymatic activity.
We explored the detection of genome-wide hypomethylation in plasma using shotgun massively parallel bisulfite sequencing as a marker for cancer. Tumor-associated copy number aberrations (CNAs) could ...also be observed from the bisulfite DNA sequencing data. Hypomethylation and CNAs were detected in the plasma DNA of patients with hepatocellular carcinoma, breast cancer, lung cancer, nasopharyngeal cancer, smooth muscle sarcoma, and neuroendocrine tumor. For the detection of nonmetastatic cancer cases, plasma hypomethylation gave a sensitivity and specificity of 74% and 94%, respectively, when a mean of 93 million reads per case were obtained. Reducing the sequencing depth to 10 million reads per case was found to have no adverse effect on the sensitivity and specificity for cancer detection, giving respective figures of 68% and 94%. This characteristic thus indicates that analysis of plasma hypomethylation by this sequencing-based method may be a relatively cost-effective approach for cancer detection. We also demonstrated that plasma hypomethylation had utility for monitoring hepatocellular carcinoma patients following tumor resection and for detecting residual disease. Plasma hypomethylation can be combined with plasma CNA analysis for further enhancement of the detection sensitivity or specificity using different diagnostic algorithms. Using the detection of at least one type of aberration to define an abnormality, a sensitivity of 87% could be achieved with a specificity of 88%. These developments have thus expanded the applications of plasma DNA analysis for cancer detection and monitoring.
Delivering isotopic tracers for metabolic studies in rodents without overt stress is challenging. Current methods achieve low label enrichment in proteins and lipids. Here, we report noninvasive ...introduction of
C
-glucose via a stress-free, ad libitum liquid diet. Using NMR and ion chromatography-mass spectrometry, we quantify extensive
C enrichment in products of glycolysis, the Krebs cycle, the pentose phosphate pathway, nucleobases, UDP-sugars, glycogen, lipids, and proteins in mouse tissues during 12 to 48 h of
C
-glucose feeding. Applying this approach to patient-derived lung tumor xenografts (PDTX), we show that the liver supplies glucose-derived Gln via the blood to the PDTX to fuel Glu and glutathione synthesis while gluconeogenesis occurs in the PDTX. Comparison of PDTX with ex vivo tumor cultures and arsenic-transformed lung cells versus xenografts reveals differential glucose metabolism that could reflect distinct tumor microenvironment. We further found differences in glucose metabolism between the primary PDTX and distant lymph node metastases.
The origin of enhanced superconductivity over 50 K in the recently discovered FeSe monolayer films grown on SrTiO
(STO), as compared to 8 K in bulk FeSe, is intensely debated. As with the ...ferrochalcogenides A
Fe
Se
and potassium-doped FeSe, which also have a relatively high-superconducting critical temperature (T
), the Fermi surface (FS) of the FeSe/STO monolayer films is free of hole-like FS, suggesting that a Lifshitz transition by which these hole FSs vanish may help increasing T
. However, the fundamental reasons explaining this increase of T
remain unclear. Here we report a 15 K jump of T
accompanying a second Lifshitz transition characterized by the emergence of an electron pocket at the Brillouin zone centre, which is triggered by high-electron doping following in situ deposition of potassium on FeSe/STO monolayer films. Our results suggest that the pairing interactions are orbital dependent in generating enhanced superconductivity in FeSe.
Abstract
Supported atomic metal sites have discrete molecular orbitals. Precise control over the energies of these sites is key to achieving novel reaction pathways with superior selectivity. Here, ...we achieve selective oxygen (O
2
) activation by utilising a framework of cerium (Ce) cations to reduce the energy of 3
d
orbitals of isolated copper (Cu) sites. Operando X-ray absorption spectroscopy, electron paramagnetic resonance and density-functional theory simulations are used to demonstrate that a Cu(I)O
2
3−
site selectively adsorbs molecular O
2
, forming a rarely reported electrophilic η
2
-O
2
species at 298 K. Assisted by neighbouring Ce(III) cations, η
2
-O
2
is finally reduced to two O
2−
, that create two Cu–O–Ce oxo-bridges at 453 K. The isolated Cu(I)/(II) sites are ten times more active in CO oxidation than CuO clusters, showing a turnover frequency of 0.028 ± 0.003 s
−1
at 373 K and 0.01 bar
P
CO
. The unique electronic structure of Cu(I)O
2
3−
site suggests its potential in selective oxidation.
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