Free-living amoebae (FLA) are prevalent in drinking water distribution networks (DWDNs), yet our understanding of FLA community dynamics and assembly mechanisms in DWDNs remains limited. This study characterized the occurrence patterns of amoeba communities and identified key factors influencing their assembly across four full-scale DWDNs in three Chinese cities, each utilizing different disinfectants (chlorine, chloramine, and chlorine dioxide). High-throughput sequencing of full-length 18S rRNA genes revealed highly diverse FLA communities and an array of rare FLA species in DWDNs.
View Article and Find Full Text PDFMultiple myeloma (MM), a hematological malignancy of plasma cells, has remained largely incurable owing to drug resistance and disease relapse, which requires novel therapeutic targets and treatment approaches. Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) acts as an oncoprotein linked to the development of various tumors. However, the functional consequence of Pin1 overexpression in modulating MM biology has not been established.
View Article and Find Full Text PDFMangrove forests represent important sources of methane, partly thwarting their ecosystem function as an efficient atmospheric carbon dioxide sink. Many studies have focused on the spatial and temporal variability of methane emissions from mangrove ecosystems, yet little is known about the microbial and physical controls on the release of biogenic methane from tidally influenced mangrove sediments. Here, we show that aerobic methane oxidation is a key microbial process that effectively reduces methane emissions from mangrove sediments.
View Article and Find Full Text PDFHeavy metals can impact the structure and function of coastal sediment. The dissolved organic matter (DOM) pool plays an important role in determining both the heavy metal toxicity and microbial community composition in coastal sediments. However, how heavy metals affect the interactions between microbial communities and DOM remains unclear.
View Article and Find Full Text PDFLeukemia is a widespread hematological malignancy characterized by an elevated white blood cell count in both the blood and the bone marrow. Despite notable advancements in leukemia intervention in the clinic, a large proportion of patients, especially acute leukemia patients, fail to achieve long-term remission or complete remission following treatment. Therefore, leukemia therapy necessitates optimization to meet the treatment requirements.
View Article and Find Full Text PDFMultiple myeloma (MM) is a hematological malignancy that remains incurable, primarily due to the high likelihood of relapse or development of resistance to current treatments. To explore and discover new medications capable of overcoming drug resistance in MM, we conducted cell viability inhibition screens of 1504 FDA-approved drugs. Lomitapide, a cholesterol-lowering agent, was found to exhibit effective inhibition on bortezomib-resistant MM cells in vitro and in vivo.
View Article and Find Full Text PDFRoof-harvested rainwater stored for potable and nonpotable usages represent a clean and sustainable water supply resource. However, the microbial dynamics and mechanisms of community assembly in long-termed operated rainwater storage systems remain elusive. In this study, characteristics of microbial communities in different habitats were systematically compared within rainwater and tap-water simulated storage systems (SWSSs) constructed with different tank materials (PVC, stainless steel and cement).
View Article and Find Full Text PDFNontuberculous mycobacteria (NTM) represent an emerging health concern due to their escalating infections worldwide. Although drinking water distribution systems (DWDSs) have been considered as NTM reservoirs and a potential infection route, NTM community at the species level remain largely elusive in DWDSs. This study employed high-throughput sequencing coupled with qPCR to profile NTM community and estimate their abundances at the species level in water and biofilm samples in four DWDSs using three different disinfectants (i.
View Article and Find Full Text PDFA high recurrence rate of non-Hodgkin's lymphoma (NHL) following chimeric antigen receptor T (CAR T) cell treatment remains a bottleneck, and immunosuppressive tumor microenvironment (TME) compromising CAR T cell efficacy in NHL is the primary cause of relapse. Accordingly, modifying the structure of CAR T cells to attenuate the inhibitory effect of TME thus reducing recurrence rate is a valuable research topic. CD47 has been proved to be a promising therapeutic target and is crucial in regulating macrophage function.
View Article and Find Full Text PDFSecondary water supply systems (SWSSs) are crucial water supply infrastructures for high-rise buildings in metropolitan cities. In recent years, they have garnered public attention due to increased microbial risks. However, our understanding of SWSS microbial ecology, particularly concerning the composition of eukaryotes and the underlying mechanisms driving microbial dynamics and assembly in SWSSs, remains elusive.
View Article and Find Full Text PDFB-cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological disorder with a dismal prognosis. The dysregulation of histone acetylation is of great significance in the pathogenesis and progression of B-ALL. Regarded as a fundamental acetyltransferase gene, the role of HBO1 (lysine acetyltransferase 7/KAT7) in B-ALL has not been investigated.
View Article and Find Full Text PDFEthnopharmacological Relevance: 'Xiayuxue decoction' (XYXD) is a traditional Chinese medicine compound, composing of three natural medicines: Rheum officinale Baill., Prunus persica (L.) Batsch and Eupolyphaga sinensis Walker.
View Article and Find Full Text PDFBackground: Centipedes have been used to treat tumors for hundreds of years in China. However, current studies focus on antimicrobial and anticoagulation agents rather than tumors. The molecular identities of antihepatoma bioactive components in centipedes have not yet been extensively investigated.
View Article and Find Full Text PDFThe bone marrow microenvironment supports leukocyte mobilization and differentiation and controls the development of leukemias, including acute myeloid leukemia (AML). Here, we found that the development of AML xenotransplants was suppressed in mice with osteoclasts tuberous sclerosis 1 (Tsc1) deletion. Tsc1-deficient osteoclasts released a high level of interleukin-34 (IL-34), which efficiently induced AML cell differentiation and prevented AML progression in various preclinical models.
View Article and Find Full Text PDFSelf-renewal and differentiation arrest are two features of leukaemia stem cells (LSCs) responsible for the high relapse rate of acute myeloid leukaemia (AML). To screen drugs to overcome differentiation blockade for AML, we conducted screening of 2040 small molecules from a library of United States Food and Drug Administration-approved drugs and found that the cyclin-dependent kinase (CDK)4/6 inhibitor, abemaciclib, exerts high anti-leukaemic activity. Abemaciclib significantly suppressed proliferation and promoted the differentiation of LSCs in vitro.
View Article and Find Full Text PDFBackground: Myocyte enhancer factor 2D (MEF2D) is involved in the progression of various malignant tumors. However, its impact on B-cell acute lymphoblastic leukemia (B-ALL) has not been elucidated.
Methods: In this study, the expression level of MEF2D in B-ALL patients was validated through the Gene Expression Omnibus (GEO) database and clinical specimens.
Phytoplankton is the major source of labile organic matter in the sunlit ocean, and they are therefore key players in most biogeochemical cycles. However, studies examining the heterotrophic bacterial cycling of specific phytoplankton-derived nitrogen (N)- and sulfur (S)-containing organic compounds are currently lacking at the molecular level. Therefore, the present study investigated how the addition of N-containing (glycine betaine [GBT]) and S-containing (dimethylsulfoniopropionate [DMSP]) organic compounds, as well as glucose, influenced the microbial production of new organic molecules and the microbial community composition.
View Article and Find Full Text PDFBiomed Pharmacother
October 2022
To identify therapeutic targets in acute myeloid leukemia (AML), we conducted growth inhibition screens of 2040 small molecules from a library of FDA-approved drugs using a panel of 12 AML cell lines. Tegaserod maleate, a 5-hydroxytryptamine 4 receptor partial agonist, elicits strong anti-AML effects in vitro and in vivo by targeting transient receptor potential melastatin subtype 8 (TRPM8), which plays critical roles in several important processes. However, the role of TRPM8 remains incompletely described in AML, whose treatment is based mostly on antimitotic chemotherapy.
View Article and Find Full Text PDFWorld J Gastrointest Oncol
November 2021
Background: Hepatocellular carcinoma (HCC) is characterized by dysregulation of the immune microenvironment and the development of chemoresistance. Specifically, expression of the programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis, an immune checkpoint, may lead to tumour immune escape, resulting in disease progression. The latest research shows that tumour immune escape may be caused by the upregulation of PD-L1 mediated by hypoxia-inducible factor-1 alpha (HIF-1α), and simultaneous inhibition of HIF-1α and PD-L1 has the potential to enhance the host's antitumour immunity.
View Article and Find Full Text PDFTrivalent arsenic (As) is an effective agent for treating patients with acute promyelocytic leukaemia, but its ionic nature leads to several major limitations like low effective concentrations in leukaemia cells and substantial off-target cytotoxicity, which limits its general application to other types of leukaemia. Here, building from our clinical discovery that cancerous cells from patients with different leukaemia forms featured stable and strong expression of CD71, we designed a ferritin-based As nanomedicine, As@Fn, that bound to leukaemia cells with very high affinity, and efficiently delivered cytotoxic As into a large diversity of leukaemia cell lines and patient cells. Moreover, As@Fn exerted strong anti-leukaemia effects in diverse cell-line-derived xenograft models, as well as in a patient-derived xenograft model, in which it consistently outperformed the gold standard, showing its potential as a precision treatment for a variety of leukaemias.
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