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1.
Nature ; 590(7847): 600-605, 2021 02.
Article in English | MEDLINE | ID: mdl-33408412

ABSTRACT

The intensive application of inorganic nitrogen underlies marked increases in crop production, but imposes detrimental effects on ecosystems1,2: it is therefore crucial for future sustainable agriculture to improve the nitrogen-use efficiency of crop plants. Here we report the genetic basis of nitrogen-use efficiency associated with adaptation to local soils in rice (Oryza sativa L.). Using a panel of diverse rice germplasm collected from different ecogeographical regions, we performed a genome-wide association study on the tillering response to nitrogen-the trait that is most closely correlated with nitrogen-use efficiency in rice-and identified OsTCP19 as a modulator of this tillering response through its transcriptional response to nitrogen and its targeting to the tiller-promoting gene DWARF AND LOW-TILLERING (DLT)3,4. A 29-bp insertion and/or deletion in the OsTCP19 promoter confers a differential transcriptional response and variation in the tillering response to nitrogen among rice varieties. The allele of OsTCP19 associated with a high tillering response to nitrogen is prevalent in wild rice populations, but has largely been lost in modern cultivars: this loss correlates with increased local soil nitrogen content, which suggests that it might have contributed to geographical adaptation in rice. Introgression of the allele associated with a high tillering response into modern rice cultivars boosts grain yield and nitrogen-use efficiency under low or moderate levels of nitrogen, which demonstrates substantial potential for rice breeding and the amelioration of negative environment effects by reducing the application of nitrogen to crops.


Subject(s)
Adaptation, Physiological/genetics , Crops, Agricultural/genetics , Nitrogen/metabolism , Oryza/genetics , Oryza/metabolism , Plant Proteins/genetics , Soil/chemistry , Alleles , Crops, Agricultural/metabolism , Epistasis, Genetic , Gene Expression Regulation, Plant , Genetic Introgression , Genetic Variation , Genome-Wide Association Study , INDEL Mutation , Oryza/growth & development , Plant Proteins/metabolism , Promoter Regions, Genetic/genetics
2.
Development ; 150(24)2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37997706

ABSTRACT

Sperm with normal morphology and motility are essential for successful fertilization, and the strong attachment of the sperm head-tail coupling apparatus to the nuclear envelope during spermatogenesis is required to ensure the integrity of sperm for capacitation and fertilization. Here, we report that Arrdc5 is associated with spermatogenesis. The Arrdc5 knockout mouse model showed male infertility characterized by a high bent-head rate and reduced motility in sperm, which led to capacitation defects and subsequent fertilization failure. Through mass spectrometry, we found that ARRDC5 affects spermatogenesis by affecting NDC1 and SUN5. We further found that ARRDC5 might affect the vesicle-trafficking protein SEC22A-mediated transport and localization of NDC1, SUN5 and other head-tail coupling apparatus-related proteins that are responsible for initiating the attachment of the sperm head and tail. We finally performed intracytoplasmic sperm injection as a way to explore therapeutic strategies. Our findings demonstrate the essential role and the underlying molecular mechanism of ARRDC5 in anchoring the sperm head to the tail during spermatogenesis.


Subject(s)
Infertility, Male , Semen , Humans , Animals , Mice , Male , Semen/metabolism , Spermatogenesis/genetics , Spermatozoa/metabolism , Sperm Head/metabolism , Proteins/metabolism , Infertility, Male/genetics , Infertility, Male/metabolism , Mice, Knockout , Membrane Proteins/metabolism
3.
Development ; 150(12)2023 06 15.
Article in English | MEDLINE | ID: mdl-37218508

ABSTRACT

The accumulation and storage of maternal mRNA is crucial for oocyte maturation and embryonic development. PATL2 is an oocyte-specific RNA-binding protein, and previous studies have confirmed that PATL2 mutation in humans and knockout mice cause oocyte maturation arrest or embryonic development arrest, respectively. However, the physiological function of PATL2 in the process of oocyte maturation and embryonic development is largely unknown. Here, we report that PATL2 is highly expressed in growing oocytes and couples with EIF4E and CPEB1 to regulate maternal mRNA expression in immature oocytes. The germinal vesicle oocytes from Patl2-/- mice exhibit decreasing maternal mRNA expression and reduced levels of protein synthesis. We further confirmed that PATL2 phosphorylation occurs in the oocyte maturation process and identified the S279 phosphorylation site using phosphoproteomics. We found that the S279D mutation decreased the protein level of PATL2 and led to subfertility in Palt2S279D knock-in mice. Our work reveals the previously unrecognized role of PATL2 in regulating the maternal transcriptome and shows that phosphorylation of PATL2 leads to the regulation of PATL2 protein levels via ubiquitin-mediated proteasomal degradation in oocytes.


Subject(s)
Eukaryotic Initiation Factor-4E , Nuclear Proteins , RNA, Messenger, Stored , RNA-Binding Proteins , Animals , Female , Humans , Mice , Pregnancy , Eukaryotic Initiation Factor-4E/metabolism , Homeostasis , Mice, Knockout , mRNA Cleavage and Polyadenylation Factors/metabolism , Nuclear Proteins/metabolism , Oocytes/metabolism , RNA, Messenger/metabolism , RNA, Messenger, Stored/metabolism , RNA-Binding Proteins/metabolism , Transcription Factors/metabolism
4.
Hum Mol Genet ; 32(14): 2326-2334, 2023 07 04.
Article in English | MEDLINE | ID: mdl-37133443

ABSTRACT

Fertilization is a fundamental process of development, and the blocking mechanisms act at the zona pellucida (ZP) and plasma membrane of the egg to prevent any additional sperm from binding, permeating and fusing after fertilization. In clinical practice, some couples undergoing recurrent IVF failures that mature oocytes had abnormal fertilization for unknown reason. Ovastacin encoded by ASTL cleave the ZP protein ZP2 and play a key role in preventing polyspermy. Here, we identified bi-allelic variants in ASTL that are mainly characterized by fertilization problems in humans. All four independent affected individuals had bi-allelic frameshift variants or predicted damaging missense variants, which follow a Mendelian recessive inheritance pattern. The frameshift variants significantly decreased the quantity of ASTL protein in vitro. And all missense variants affected the enzymatic activity that cleaves ZP2 in mouse egg in vitro. Three knock-in female mice (corresponding to three missense variants in patients) all show subfertility due to low embryo developmental potential. This work presents strong evidence that pathogenic variants in ASTL cause female infertility and provides a new genetic marker for the diagnosis of fertilization problems.


Subject(s)
Infertility, Female , Semen , Humans , Male , Female , Mice , Animals , Zona Pellucida Glycoproteins/genetics , Zona Pellucida Glycoproteins/metabolism , Semen/metabolism , Oocytes/metabolism , Infertility, Female/genetics , Fertilization/genetics , Metalloproteases/genetics
5.
Genome Res ; 32(7): 1285-1297, 2022 07.
Article in English | MEDLINE | ID: mdl-35835565

ABSTRACT

Heat shock is a common environmental stress, although the response of the nucleus to it remains controversial in mammalian cells. Acute reaction and chronic adaptation to environmental stress may have distinct internal rewiring in the gene regulation networks. However, this difference remains largely unexplored. Here, we report that chromatin conformation and chromatin accessibility respond differently in short- and long-term heat shock in human K562 cells. We found that chromatin conformation in K562 cells was largely stable in response to short-term heat shock, whereas it showed clear and characteristic changes after long-term heat treatment with little alteration in chromatin accessibility during the whole process. We further show in silico and experimental evidence strongly suggesting that changes in chromatin conformation may largely stem from an accumulation of cells in the M stage of the cell cycle in response to heat shock. Our results represent a paradigm shift away from the controversial view of chromatin response to heat shock and emphasize the necessity of cell cycle analysis when interpreting bulk Hi-C data.


Subject(s)
Chromatin , Heat-Shock Response , Animals , Cell Cycle Checkpoints/genetics , Chromatin/genetics , Genomics , Heat-Shock Response/genetics , Humans , K562 Cells , Mammals/genetics
6.
Brief Bioinform ; 24(1)2023 01 19.
Article in English | MEDLINE | ID: mdl-36575569

ABSTRACT

Single-cell ribonucleic acid (RNA) sequencing (scRNA-seq) has been a powerful technology for transcriptome analysis. However, the systematic validation of diverse computational tools used in scRNA-seq analysis remains challenging. Here, we propose a novel simulation tool, termed as Simulation of Cellular Heterogeneity (SimCH), for the flexible and comprehensive assessment of scRNA-seq computational methods. The Gaussian Copula framework is recruited to retain gene coexpression of experimental data shown to be associated with cellular heterogeneity. The synthetic count matrices generated by suitable SimCH modes closely match experimental data originating from either homogeneous or heterogeneous cell populations and either unique molecular identifier (UMI)-based or non-UMI-based techniques. We demonstrate how SimCH can benchmark several types of computational methods, including cell clustering, discovery of differentially expressed genes, trajectory inference, batch correction and imputation. Moreover, we show how SimCH can be used to conduct power evaluation of cell clustering methods. Given these merits, we believe that SimCH can accelerate single-cell research.


Subject(s)
RNA , Single-Cell Analysis , RNA/genetics , Sequence Analysis, RNA/methods , Single-Cell Analysis/methods , Gene Expression Profiling/methods , Cluster Analysis , Gene Expression
7.
Cell Mol Life Sci ; 81(1): 174, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38597936

ABSTRACT

Mature spermatozoa with normal morphology and motility are essential for male reproduction. The epididymis has an important role in the proper maturation and function of spermatozoa for fertilization. However, factors related to the processes involved in spermatozoa modifications are still unclear. Here we demonstrated that CCDC28A, a member of the CCDC family proteins, is highly expressed in testes and the CCDC28A deletion leads to male infertility. We found CCDC28A deletion had a mild effect on spermatogenesis. And epididymal sperm collected from Ccdc28a-/- mice showed bent sperm heads, acrosomal defects, reduced motility and decreased in vitro fertilization competence whereas their axoneme, outer dense fibers, and fibrous sheath were all normal. Furthermore, we found that CCDC28A interacted with sperm acrosome membrane-associated protein 1 (SPACA1) and glycogen synthase kinase 3a (GSK3A), and deficiencies in both proteins in mice led to bent heads and abnormal acrosomes, respectively. Altogether, our results reveal the essential role of CCDC28A in regulating sperm morphology and motility and suggesting a potential marker for male infertility.


Subject(s)
Infertility, Male , Sperm Motility , Male , Animals , Mice , Humans , Sperm Motility/genetics , Semen , Infertility, Male/genetics , Sperm Head , Spermatozoa
8.
J Proteome Res ; 23(3): 916-928, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38367214

ABSTRACT

Myopia accounts for a significant proportion of visual lesions worldwide and has the potential to progress toward pathological myopia. This study aims to reveal the difference in protein content in aqueous humor between high myopic and nonhigh myopic patients, as well as better understand the dysregulation of proteins in myopic eyes. Aqueous humor was collected for liquid chromatograph mass spectrometer (LC/MS) analysis from 30 individual eyes that underwent phacoemulsification and intraocular lens (IOL) implantation. Results showed that a total of 190 differentially expressed proteins were identified, which revealed their involvement in cell metabolism, immune and inflammatory response, and system and anatomical structure. Further analysis focused on 15 intensively interacted hub proteins, encompassing functions related to complement cascades, lipoprotein metabolism, and fibrin biological function. Subsequent validations demonstrated elevated levels of APOE (apolipoprotein E), C3 (complement 3), and AHSG (α-2-HS-glycoprotein) in the high myopia group (31 eyes of cataracts and 45 eyes of high myopia with cataracts). AHSG had a significant positive correlation with axial length in high myopic patients, with good efficacy in distinguishing between myopic and nonmyopic groups. AHSG may be a potential indicator of the pathological severity and participator in the pathological progress of high myopia. This study depicted differential expression characteristics of aqueous humor in patients with high myopia and provided optional information for further experimental research on exploring the molecular mechanisms and potential therapeutic targets for high myopia. Data are available via ProteomeXchange with the identifier PXD047584.


Subject(s)
Cataract Extraction , Cataract , Myopia , Humans , Aqueous Humor , Proteomics
9.
Hum Genet ; 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38252283

ABSTRACT

Preimplantation embryonic arrest is an important pathogenesis of female infertility, but little is known about the genetic factors behind this phenotype. MEI4 is an essential protein for DNA double-strand break formation during meiosis, and Mei4 knock-out female mice are viable but sterile, indicating that MEI4 plays a crucial role in reproduction. To date, MEI4 has not been found to be associated with any human reproductive diseases. Here, we identified six compound heterozygous and homozygous MEI4 variants-namely, c.293C > T, p.(Ser98Leu), c.401C > G, p.(Pro134Arg), c.391C > G, p.(Pro131Ala), c.914A > T, p.(Tyr305Phe), c.908C > G, p.(Ala303Gly), and c.899A > T, p.(Gln300Leu)-in four independent families that were responsible for female infertility mainly characterized by preimplantation embryonic arrest. In vitro, we found that these variants reduced the interaction between MEI4 and DNA. In vivo, we generated a knock-in mouse model and demonstrated that female mice were infertile and were characterized by developmental defects during oogenesis. Our findings reveal the important roles of MEI4 in human reproduction and provide a new diagnostic marker for genetic counseling of clinical infertility patients.

10.
J Neuroinflammation ; 21(1): 2, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38178103

ABSTRACT

BACKGROUND: Some studies have shown that gut microbiota may be associated with dementia. However, the causal effects between gut microbiota and different types of dementia and whether cytokines act as a mediator remain unclear. METHODS: Gut microbiota, cytokines, and five dementia types, including Alzheimer's disease (AD), frontotemporal dementia (FTD), dementia with Lewy body (DLB), vascular dementia (VD), and Parkinson's disease dementia (PDD) were identified from large-scale genome-wide association studies (GWAS) summary data. We used Mendelian randomization (MR) to investigate the causal relationships between gut microbiota, cytokines, and five types of dementia. Inverse variance weighting (IVW) was used as the main statistical method. In addition, we explored whether cytokines act as a mediating factor in the pathway from gut microbiota to dementia. RESULTS: There were 20 positive and 16 negative causal effects between genetic liability in the gut microbiota and dementia. Also, there were five positive and four negative causal effects between cytokines and dementias. Cytokines did not act as mediating factors. CONCLUSIONS: Gut microbiota and cytokines were causally associated with five types of dementia, and cytokines seemed not to be the mediating factors in the pathway from gut microbiota to dementia.


Subject(s)
Alzheimer Disease , Frontotemporal Dementia , Gastrointestinal Microbiome , Parkinson Disease , Humans , Gastrointestinal Microbiome/genetics , Cytokines/genetics , Genome-Wide Association Study , Mendelian Randomization Analysis
11.
Small ; 20(16): e2307366, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38039446

ABSTRACT

Restoring immune tolerance is the ultimate goal for rheumatoid arthritis (RA) treatment. The most reported oral or intravenous injection routes for the immunization of autoantigens cause gastrointestinal side effects, low patient compliance, and unsatisfied immune tolerance induction. Herein, the use of a transdermal microneedle patch is for the first time investigated to codeliver CII peptide autoantigen and rapamycin for reversing immune disorders of RA. The immunized microneedles efficiently recruit antigen-presenting cells particularly Langerhans cells, and induce tolerogenic dendritic cells at the administration skin site. The tolerogenic dendritic cells further homing to lymph nodes to activate systemic Treg cell differentiation, which upregulates the expression of anti-inflammatory mediators while inhibiting the polarization of Th1/2 and Th17 T cell phenotypes and the expression of inflammatory profiles. As a result, the optimized microneedles nearly completely eliminate RA symptoms and inflammatory infiltrations. Furthermore, it is demonstrated that a low dose of rapamycin is crucial for the successful induction of immune tolerance. The results indicate that a rationally designed microneedle patch is a promising strategy for immune balance restoration with increased immune tolerance induction efficiency and patient compliance.


Subject(s)
Arthritis, Rheumatoid , Langerhans Cells , Humans , Th17 Cells , Arthritis, Rheumatoid/therapy , Immune Tolerance , Sirolimus/pharmacology
12.
Brief Bioinform ; 23(1)2022 01 17.
Article in English | MEDLINE | ID: mdl-34875002

ABSTRACT

As the basal bricks, the dynamics and arrangement of nucleosomes orchestrate the higher architecture of chromatin in a fundamental way, thereby affecting almost all nuclear biology processes. Thanks to its rather simple protocol, assay for transposase-accessible chromatin using sequencing (ATAC)-seq has been rapidly adopted as a major tool for chromatin-accessible profiling at both bulk and single-cell levels; however, to picture the arrangement of nucleosomes per se remains a challenge with ATAC-seq. In the present work, we introduce a novel ATAC-seq analysis toolkit, named decoding nucleosome organization profile based on ATAC-seq data (deNOPA), to predict nucleosome positions. Assessments showed that deNOPA outperformed state-of-the-art tools with ultra-sparse ATAC-seq data, e.g. no more than 0.5 fragment per base pair. The remarkable performance of deNOPA was fueled by the short fragment reads, which compose nearly half of sequenced reads in the ATAC-seq libraries and are commonly discarded by state-of-the-art nucleosome positioning tools. However, we found that the short fragment reads enrich information on nucleosome positions and that the linker regions were predicted by reads from both short and long fragments using Gaussian smoothing. Last, using deNOPA, we showed that the dynamics of nucleosome organization may not directly couple with chromatin accessibility in the cis-regulatory regions when human cells respond to heat shock stimulation. Our deNOPA provides a powerful tool with which to analyze the dynamics of chromatin at nucleosome position level with ultra-sparse ATAC-seq data.


Subject(s)
Chromatin Immunoprecipitation Sequencing , Nucleosomes , Chromatin/genetics , High-Throughput Nucleotide Sequencing/methods , Humans , Nucleosomes/genetics , Sequence Analysis, DNA
13.
Biometals ; 37(1): 211-222, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37792258

ABSTRACT

A chronic disease, hypertension (HTN) is prevalent among the elderly. Exploring the factors that influence HTN and blood pressure (BP) changes is of great public health significance. However, mixed exposure to multiple serum metals has had less research on the effects on BP and HTN for the elderly. From April to August 2019, 2372 people participated in the community physical examination program for the elderly in Tongling City, Anhui Province. We measured BP and serum levels of 10 metals and collected basic demographic information. We analyzed the relationship between metal levels and changes in BP and HTN by the least absolute shrinkage and selection operator regression, Bayesian kernel machine regression model, and generalized linear model. In multiple models, lead (Pb) and cadmium (Cd) were still significantly associated with HTN occurrence after adjusting for potential confounders (Pb: ORquartile 4 VS quartile 1 = 1.20, 95% CI 1.01-1.43; Cd: ORquartile 4 VS quartile 1 = 1.37, 95% CI 1.16-1.62). In the male subgroup, results were similar to those of the general population. In the female group, Cd was positively correlated with HTN and systolic blood pressure, while Pb was not. According to this study, Pb and Cd were correlated with BP and HTN positively, and there was a certain joint effect. To some extent, our findings provide clues for the prevention of hypertension in the elderly.


Subject(s)
Cadmium , Hypertension , Humans , Male , Female , Aged , Blood Pressure , Cadmium/toxicity , Bayes Theorem , Lead/pharmacology , Hypertension/chemically induced , Hypertension/epidemiology
14.
Exp Cell Res ; 429(1): 113649, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37225012

ABSTRACT

BACKGROUND: Fibrotic scar is a severe side effect of trabeculectomy, resulting in unsatisfactory outcomes for glaucoma surgery. Accumulating evidence showed human Tenon's fibroblasts (HTFs) play an important role in fibrosis formation. We previously reported that the aqueous level of secreted protein acidic and rich in cysteine (SPARC) was higher in the patients with primary angle closure glaucoma, which was associated with the failure of trabeculectomy. In this study, the potential effect and mechanism of SPARC in promoting fibrosis were explored by using HTFs. METHODS: HTFs were employed in this study and examined under a phase-contrast microscope. Cell viability was determined by CCK-8. The expressions of SPARC-YAP/TAZ signaling and the fibrosis-related markers were examined with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), Western blot, and immunofluorescence, subcellular fractionation was conducted to further determined the variation of YAP and phosphorylated YAP. The differential gene expressions were analyzed with RNA sequencing (RNAseq), followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. RESULTS: Exogenous SPARC induced HTFs-myofibroblast transformation, as evidenced by the increased expression of α-SMA, collagen I and fibronectin in both protein and mRNA levels. SPARC knockdown decreased the expressions of the above genes in TGF-ß2-treated HTFs. KEGG analysis showed that the Hippo signaling pathway was mostly enriched. SPARC treatment increased the expressions of YAP, TAZ, CTGF and CYR61 as well as enhanced YAP translocation from cytoplasm to nucleus, and decreased the phosphorylation of YAP and LAST1/2, which was reversed by SPARC knockdown. Knockdown of YAP1 decreased the fibrosis-related markers, such as α-SMA, collagen I and Fibronectin, in SPARC-treated HTFs. CONCLUSIONS: SPARC induced HTFs-myofibroblast transformation via activating YAP/TAZ signaling. Targeting SPARC-YAP/TAZ axis in HTFs might provide a novel strategy for inhibiting fibrosis formation after trabeculectomy.


Subject(s)
Fibronectins , Myofibroblasts , Humans , Myofibroblasts/metabolism , Fibronectins/metabolism , Osteonectin/genetics , Osteonectin/metabolism , Fibroblasts/metabolism , Collagen Type I/metabolism , Fibrosis , Cells, Cultured
15.
Appl Microbiol Biotechnol ; 108(1): 315, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38689185

ABSTRACT

The plant microbes are an integral part of the host and play fundamental roles in plant growth and health. There is evidence indicating that plants have the ability to attract beneficial microorganisms through their roots in order to defend against pathogens. However, the mechanisms of plant microbial community assembly from below- to aboveground compartments under pathogen infection remain unclear. In this study, we investigated the bacterial and fungal communities in bulk soil, rhizosphere soil, root, stem, and leaf of both healthy and infected (Potato virus Y disease, PVY) plants. The results indicated that bacterial and fungal communities showed different recruitment strategies in plant organs. The number and abundance of shared bacterial ASVs between bulk and rhizosphere soils decreased with ascending migration from below- to aboveground compartments, while the number and abundance of fungal ASVs showed no obvious changes. Field type, plant compartments, and PVY infection all affected the diversity and structures of microbial community, with stronger effects observed in the bacterial community than the fungal community. Furthermore, PVY infection, rhizosphere soil pH, and water content (WC) contributed more to the assembly of the bacterial community than the fungal community. The analysis of microbial networks revealed that the bacterial communities were more sensitive to PVY infection than the fungal communities, as evidenced by the lower network stability of the bacterial community, which was characterized by a higher proportion of positive edges. PVY infection further increased the bacterial network stability and decreased the fungal network stability. These findings advance our understanding of how microbes respond to pathogen infections and provide a rationale and theoretical basis for biocontrol technology in promoting sustainable agriculture. KEY POINTS: • Different recruitment strategies between plant bacterial and fungal communities. • Bacterial community was more sensitive to PVY infection than fungal community. • pH and WC drove the microbial community assembly under PVY infection.


Subject(s)
Bacteria , Fungi , Plant Diseases , Plant Roots , Rhizosphere , Soil Microbiology , Fungi/physiology , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Bacteria/metabolism , Plant Diseases/microbiology , Plant Roots/microbiology , Microbiota , Plant Leaves/microbiology , Hydrogen-Ion Concentration , Mycobiome , Plants/microbiology
16.
Clin Lab ; 70(3)2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38469780

ABSTRACT

BACKGROUND: Acute myeloid leukemia (AML) with t(8;21)(q22;q22.1); RUNX1::RUNX1T1 has a relatively favorable prognosis with a high complete remission rate and long disease-free survival. METHODS AND RESULTS: Here we describe a patient who had AML with t(8;21)(q22;q22.1); RUNX1::RUNX1T1. Cooperating mutations including KRAS and ASXL1, and with other abnormal karyotype del(17) and with a myelomonocytic differentiation. CONCLUSIONS: The patient relapsed despite achieving a morphologic complete remission (CR).


Subject(s)
Leukemia, Myeloid, Acute , Translocation, Genetic , Humans , Core Binding Factor Alpha 2 Subunit/genetics , RUNX1 Translocation Partner 1 Protein/genetics , Leukemia, Myeloid, Acute/genetics , Mutation
17.
Clin Lab ; 70(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38747919

ABSTRACT

BACKGROUND: For many years it has been postulated that the immune system controls the progress of multiple myeloma (MM). However, the phenotypes of T cells in MM remain to be elucidated. In this study, we compared the phenotypes of T cells, which were obtained from the peripheral blood, in MM patients with those in healthy donors (HD). The expression of CCR7, CD57, CD28, HLA-DR, CD38, CD45RA, and CD45RO were assessed on T cells from MM patients and HDs using multicolor flow cytometry (MFC). METHODS: For this study, 17 newly diagnosed MM patients were selected, and 20 healthy people were selected as a control group. MFC was used to detect the markers on T cells. RESULTS: We detected significant increases in the expression levels of HLA-DR, CD38, and CD57on CD8+ T cells, significant decreases in the expression levels of CD28 and CD45RA on CD8+ T cells, and a decrease of CD4+ effec-tor T cells in MM patients, compared to the HD group. CONCLUSIONS: Our study shows that the accumulation of peripheral CD8+CD57+T cells, CD8+CD38high T cells, and CD8+HLA-DR+CD38high T cells is reflective of an ongoing antitumor T cell response and a progressive immune dysfunction in MM. During chemotherapy, the recovery of immune function can be monitored by detecting the proportion of activated molecules of T lymphocytes.


Subject(s)
ADP-ribosyl Cyclase 1 , CD28 Antigens , Flow Cytometry , HLA-DR Antigens , Leukocyte Common Antigens , Multiple Myeloma , Humans , Multiple Myeloma/immunology , CD28 Antigens/immunology , CD28 Antigens/metabolism , ADP-ribosyl Cyclase 1/metabolism , HLA-DR Antigens/immunology , HLA-DR Antigens/metabolism , HLA-DR Antigens/blood , Leukocyte Common Antigens/metabolism , Male , Middle Aged , Female , Aged , CD57 Antigens/metabolism , Case-Control Studies , Immunophenotyping/methods , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Adult , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Membrane Glycoproteins/immunology
18.
Environ Toxicol ; 39(3): 1481-1493, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37994612

ABSTRACT

BACKGROUND: Matrine has been identified to have anticancer activity in hepatocellular carcinoma (HCC). Circ_0055976 was highly expressed in HCC. Here, we investigated the function and relationship of Matrine and circ_0055976 in HCC tumorigenesis. METHODS: Cell proliferation and invasion were detected using Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine (EdU), colony formation and transwell assays, respectively. Cell aerobic glycolysis was evaluated by detecting glucose consumption, lactate production, and the ratios of ATP/ADP. Levels of genes and proteins were detected by quantitative real-time polymerase chain reaction and Western blotting. The target relationship between miR-1179 and circ_0055976 or lactate dehydrogenase A (LDHA) was analyzed by dual-luciferase reporter assay. The mouse xenograft model was established to conduct the in vivo assay. RESULTS: Matrine suppressed HCC cell proliferation, invasion and anaerobic glycolysis in vitro. Circ_0055976 was highly expressed in HCC tissues and cells, and was reduced by Matrine treatment. Moreover, overexpression of circ_0055976 reversed the anticancer effects of Matrine in HCC cells. Mechanistically, circ_0055976/miR-1179/LDHA formed an axis. Circ_0055976 knockdown or miR-1179 overexpression impaired HCC cell proliferation, invasion, and anaerobic glycolysis, which were reversed by miR-1179 inhibition or LDHA overexpression. Meanwhile, forced expression of LDHA abolished the regulatory effects of Matrine on HCC cells. In the clinic, Matrine impeded HCC tumor growth in vivo, and this effect was boosted after circ_0055976 silencing. CONCLUSION: Matrine suppressed HCC cell proliferation, invasion, and anaerobic glycolysis via circ_0055976/miR-1179/LDHA axis, providing a new insight into the clinical application of Matrine in HCC treatment.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , Humans , Animals , Mice , Lactate Dehydrogenase 5 , Matrines , Cell Transformation, Neoplastic , Carcinogenesis , Cell Proliferation , Disease Models, Animal , Cell Line, Tumor
19.
Ren Fail ; 46(2): 2359642, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38860328

ABSTRACT

OBJECTIVES: Most functional magnetic resonance research has primarily examined alterations in the affected kidney, often neglecting the contralateral kidney. Our study aims to investigate whether imaging parameters accurately depict changes in both the renal cortex and medulla in a unilateral ureteral obstruction rat model, thereby showcasing the utility of intravoxel incoherent motion (IVIM) in evaluating contralateral renal changes. METHODS: Six rats underwent MR scans and were subsequently sacrificed for baseline histological examination. Following the induction of left ureteral obstruction, 48 rats were scanned, and the histopathological examinations were conducted on days 3, 7, 10, 14, 21, 28, 35, and 42. The apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudodiffusion (D*), and perfusion fraction (f) values were measured using IVIM. RESULTS: On the 10th day of obstruction, both cortical and medullary ADC values differed significantly between the UUO10 group and the sham group (p < 0.01). The cortical D values showed statistically significant differences between UUO3 group and sham group (p < 0.01) but not among UUO groups at other time point. Additionally, the cortical and medullary f values were statistically significant between the UUO21 group and the sham group (p < 0.01). Especially, the cortical f values exhibited significant differences between the UUO21 group and the UUO groups with shorter obstruction time (at time point of 3, 7, 10, 14 day) (p < 0.01). CONCLUSIONS: Significant hemodynamic alterations were observed in the contralateral kidney following renal obstruction. IVIM accurately captures changes in the unobstructed kidney. Particularly, the cortical f value exhibits the highest potential for assessing contralateral renal modifications.


Subject(s)
Diffusion Magnetic Resonance Imaging , Disease Models, Animal , Rats, Sprague-Dawley , Ureteral Obstruction , Animals , Ureteral Obstruction/diagnostic imaging , Ureteral Obstruction/physiopathology , Rats , Diffusion Magnetic Resonance Imaging/methods , Male , Kidney Cortex/diagnostic imaging , Kidney Cortex/pathology , Kidney/diagnostic imaging , Kidney/pathology , Kidney Medulla/diagnostic imaging , Kidney Medulla/pathology
20.
Angew Chem Int Ed Engl ; : e202407892, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38945831

ABSTRACT

The commercialization of all-solid-state Li batteries (ASSLBs) demands solid electrolytes with strong cost-competitiveness, low density (for enabling satisfactory energy densities), and decent anode compatibility (the need for cathode compatibility can be circumvented by the cathode coating techniques that are widely applied in sulfide-based ASSLBs). However, none of the reported oxide, sulfide, or chloride solid electrolytes meets these requirements simultaneously. Here, we design a Li7P3S7.5O3.5 (LPSO) solid electrolyte, which shows a combination of all the aforementioned characteristics. The synthesis of this material does not need the expensive Li2S, so the raw materials cost is only $14.42/kg, which, unlike most solid electrolytes, lies below the $50/kg threshold for commercialization. The density of LPSO is 1.70 g cm-3, considerably lower than those of the oxide (typically above 5 g cm-3) and chloride (around 2.5 g cm-3) solid electrolytes. Besides, LPSO also shows excellent anode compatibility. The Li | LPSO | Li cell cycles stably with a potential of ~50 mV under 0.1 mA cm-2 for over 4200 h at 25 °C, and the all-solid-state pouch cell with the Si anode shows a capacity retention of 89.29% after 200 cycles under 88.6 mA g-1 at 60 °C.

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