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1.
Nat Immunol ; 22(3): 358-369, 2021 03.
Article in English | MEDLINE | ID: mdl-33432230

ABSTRACT

CD8+ T cell exhaustion dampens antitumor immunity. Although several transcription factors have been identified that regulate T cell exhaustion, the molecular mechanisms by which CD8+ T cells are triggered to enter an exhausted state remain unclear. Here, we show that interleukin-2 (IL-2) acts as an environmental cue to induce CD8+ T cell exhaustion within tumor microenvironments. We find that a continuously high level of IL-2 leads to the persistent activation of STAT5 in CD8+ T cells, which in turn induces strong expression of tryptophan hydroxylase 1, thus catalyzing the conversion to tryptophan to 5-hydroxytryptophan (5-HTP). 5-HTP subsequently activates AhR nuclear translocation, causing a coordinated upregulation of inhibitory receptors and downregulation of cytokine and effector-molecule production, thereby rendering T cells dysfunctional in the tumor microenvironment. This molecular pathway is not only present in mouse tumor models but is also observed in people with cancer, identifying IL-2 as a novel inducer of T cell exhaustion.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors/metabolism , CD8-Positive T-Lymphocytes/drug effects , Interleukin-2/metabolism , Lymphocytes, Tumor-Infiltrating/drug effects , Neoplasms/metabolism , Receptors, Aryl Hydrocarbon/metabolism , Tumor Microenvironment , 5-Hydroxytryptophan/metabolism , Animals , Antibodies, Neutralizing/pharmacology , Antineoplastic Agents/pharmacology , Basic Helix-Loop-Helix Transcription Factors/deficiency , Basic Helix-Loop-Helix Transcription Factors/genetics , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Gene Expression Regulation, Neoplastic , HCT116 Cells , HEK293 Cells , Humans , Interleukin-2/antagonists & inhibitors , Interleukin-2/genetics , Jurkat Cells , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , MCF-7 Cells , Melanoma, Experimental/drug therapy , Melanoma, Experimental/immunology , Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , NIH 3T3 Cells , Neoplasms/drug therapy , Neoplasms/immunology , Neoplasms/pathology , Receptors, Aryl Hydrocarbon/deficiency , Receptors, Aryl Hydrocarbon/genetics , Signal Transduction , Tryptophan Hydroxylase/metabolism , Xenograft Model Antitumor Assays
2.
Mol Cell ; 67(5): 733-743.e4, 2017 Sep 07.
Article in English | MEDLINE | ID: mdl-28844863

ABSTRACT

Nuclear receptors recruit multiple coactivators sequentially to activate transcription. This "ordered" recruitment allows different coactivator activities to engage the nuclear receptor complex at different steps of transcription. Estrogen receptor (ER) recruits steroid receptor coactivator-3 (SRC-3) primary coactivator and secondary coactivators, p300/CBP and CARM1. CARM1 recruitment lags behind the binding of SRC-3 and p300 to ER. Combining cryo-electron microscopy (cryo-EM) structure analysis and biochemical approaches, we demonstrate that there is a close crosstalk between early- and late-recruited coactivators. The sequential recruitment of CARM1 not only adds a protein arginine methyltransferase activity to the ER-coactivator complex, it also alters the structural organization of the pre-existing ERE/ERα/SRC-3/p300 complex. It induces a p300 conformational change and significantly increases p300 HAT activity on histone H3K18 residues, which, in turn, promotes CARM1 methylation activity on H3R17 residues to enhance transcriptional activity. This study reveals a structural role for a coactivator sequential recruitment and biochemical process in ER-mediated transcription.


Subject(s)
CARD Signaling Adaptor Proteins/metabolism , E1A-Associated p300 Protein/metabolism , Estrogen Receptor alpha/metabolism , Guanylate Cyclase/metabolism , Nuclear Receptor Coactivator 3/metabolism , Transcription, Genetic , Acetylation , Binding Sites , CARD Signaling Adaptor Proteins/chemistry , CARD Signaling Adaptor Proteins/genetics , Cryoelectron Microscopy , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , E1A-Associated p300 Protein/chemistry , E1A-Associated p300 Protein/genetics , Estrogen Receptor alpha/chemistry , Estrogen Receptor alpha/genetics , Guanylate Cyclase/chemistry , Guanylate Cyclase/genetics , HEK293 Cells , HeLa Cells , Histones/chemistry , Histones/metabolism , Humans , MCF-7 Cells , Methylation , Models, Molecular , Multiprotein Complexes , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Nuclear Receptor Coactivator 3/chemistry , Nuclear Receptor Coactivator 3/genetics , Promoter Regions, Genetic , Protein Binding , Protein Interaction Domains and Motifs , Structure-Activity Relationship , Time Factors , Transcription Factors , Transcriptional Activation , Transfection
3.
Mol Cell Probes ; 73: 101944, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38049041

ABSTRACT

Ubiquitin specific protease 5 (USP5) is a vital deubiquitinating enzyme that regulates various physiological functions by removing ubiquitin chains from target proteins. This review provides an overview of the structural and functional characteristics of USP5. Additionally, we discuss the role of USP5 in regulating diverse cellular processes, including cell proliferation, apoptosis, DNA double-strand damage, methylation, heat stress, and protein quality control, by targeting different substrates. Furthermore, we describe the involvement of USP5 in several pathological conditions such as tumors, pathological pain, developmental abnormalities, inflammatory diseases, and virus infection. Finally, we introduce newly developed inhibitors of USP5. In conclusion, investigating the novel functions and substrates of USP5, elucidating the underlying mechanisms of USP5-substrate interactions, intensifying the development of inhibitors, and exploring the upstream regulatory mechanisms of USP5 in detail can provide a new theoretical basis for the treatment of various diseases, including cancer, which is a promising research direction with considerable potential. Overall, USP5 plays a critical role in regulating various physiological and pathological processes, and investigating its novel functions and regulatory mechanisms may have significant implications for the development of therapeutic strategies for cancer and other diseases.


Subject(s)
Endopeptidases , Neoplasms , Humans , Cell Proliferation , Endopeptidases/genetics , Endopeptidases/metabolism , Neoplasms/genetics , Ubiquitin/genetics , Ubiquitin/metabolism
4.
Endocr J ; 71(6): 623-633, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38644219

ABSTRACT

Interleukin 17A (IL-17A) is a key cytokine promoting osteoblast formation, which contributes to osteogenesis. IL-17A functions in autophagy inhibition within osteoblasts. Metallothionein-2 (MT-2), as an important reactive oxygen species (ROS)-scavenging molecule, prevents oxidative stress from damaging osteoblast formation. The relationship between IL-17A-regulated autophagy and MT-2 production under oxidative stress deserves further exploration. In this study, we first investigated the roles of IL-17A in osteoblastic differentiation and ROS production in osteoblast precursors in the presence of hydrogen peroxide (H2O2). Next, we explored the effects of IL-17A on autophagic activity and MT-2 protein expression in osteoblast precursors in the presence of H2O2. Ultimately, by using autophagic pharmacological agonist (rapamycin) and lentiviral transduction technology, the relationship between autophagy, IL-17A-regulated MT-2 protein expression and IL-17A-regulated ROS production was further elucidated. Our results showed that in the presence of H2O2, IL-17A promoted osteoblastic differentiation and inhibited ROS production. Moreover, in the presence of H2O2, IL-17A inhibited autophagic activity and promoted MT-2 protein expression in osteoblast precursors. Importantly, IL-17A-promoted MT-2 protein levels and -inhibited ROS production were reversed by autophagy activation with rapamycin. Furthermore, IL-17A-inhibited ROS production were blocked by MT-2 silencing. In conclusion, IL-17A promotes ROS clearance by inhibiting autophagic degradation of MT-2, thereby protecting osteoblast formation from oxidative stress.


Subject(s)
Autophagy , Cell Differentiation , Hydrogen Peroxide , Interleukin-17 , Metallothionein , Osteoblasts , Osteogenesis , Oxidative Stress , Reactive Oxygen Species , Oxidative Stress/drug effects , Osteoblasts/drug effects , Osteoblasts/metabolism , Interleukin-17/metabolism , Interleukin-17/pharmacology , Autophagy/drug effects , Metallothionein/metabolism , Metallothionein/genetics , Animals , Mice , Cell Differentiation/drug effects , Hydrogen Peroxide/pharmacology , Osteogenesis/drug effects , Reactive Oxygen Species/metabolism , Cells, Cultured
5.
Int Ophthalmol ; 44(1): 258, 2024 Jun 23.
Article in English | MEDLINE | ID: mdl-38909343

ABSTRACT

PURPOSE: To analyze the hotspots and trends in artificial intelligence (AI) research in the field of cataracts. METHODS: The Science Citation Index Expanded of the Web of Science Core Collection was used to collect the research literature related to AI in the field of cataracts, which was analyzed for valuable information such as years, countries/regions, journals, institutions, citations, and keywords. Visualized co-occurrence network graphs were generated through the library online analysis platform, VOSviewer, and CiteSpace tools. RESULTS: A total of 222 relevant research articles from 41 countries were selected. Since 2019, the number of related articles has increased significantly every year. China (n = 82, 24.92%), the United States (n = 55, 16.72%) and India (n = 26, 7.90%) were the three countries with the most publications, accounting for 49.54% of the total. The Journal of Cataract and Refractive Surgery (n = 13, 5.86%) and Translational Vision Science & Technology (n = 10, 4.50%) had the most publications. Sun Yat-sen University (n = 25, 11.26%), the Chinese Academy of Sciences (n = 17, 7.66%), and Capital Medical University (n = 16, 7.21%) are the three institutions with the highest number of publications. We discovered through keyword analysis that cataract, diagnosis, imaging, classification, intraocular lens, and formula are the main topics of current study. CONCLUSIONS: This study revealed the hot spots and potential trends of AI in terms of cataract diagnosis and intraocular lens power calculation. AI will become more prevalent in the field of ophthalmology in the future.


Subject(s)
Artificial Intelligence , Bibliometrics , Cataract , Humans , Artificial Intelligence/trends , Cataract Extraction/trends , Cataract Extraction/statistics & numerical data , Ophthalmology/trends , Biomedical Research/trends , Biomedical Research/statistics & numerical data
6.
J Cell Physiol ; 238(10): 2481-2498, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37750538

ABSTRACT

The mechanism of aging has always been the focus of research, because aging is related to disease susceptibility and seriously affects people's quality of life. The diseases also accelerate the aging process, especially the pathological changes of substantive organs, such as cardiac hypertrophy, severely shortened lifespan. So, lesions in organs are both a consequence and a cause of aging. However, the disease in a given organ is not in isolation but is a systemic problem. Our previous study found that thyrotoxicosis mice model has aging characteristics including immunosenescence, lipotoxicity, malnutrition. But all these characteristics will lead to organ senescence, therefore, this study continued to study the aging changes of important organs such as heart, liver, and kidney in thyrotoxicosis mice using tandem mass tags (TMT) proteomics method. The results showed that the excess thyroxine led to cardiac hypertrophy. In the liver, the ability to synthesize functional proteins, detoxify, and metabolism were declined. The effect on the kidney was the decreased ability of detoxify and metabolism. The main finding of the present study was that the acceleration of organ senescence by excess thyroxine was due to proteotoxicity. The shared cause of proteotoxicity in the three organs included the intensify of oxidative phosphorylation, the redundancy production of ribosomes, and the lack of splicing and ubiquitin proteasome system function. Totally, proteotoxicity was another parallel between thyrotoxicosis and aging in addition to lipotoxicity. Our research provided a convenient and appropriate animal model for exploring aging mechanism and antiaging drugs.

7.
Plant Mol Biol ; 113(1-3): 59-74, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37634200

ABSTRACT

Leaves are the primary photosynthetic organs, providing essential substances for tree growth. It is important to obtain an anatomical understanding and regulatory network analysis of leaf development. Here, we studied leaf development in Populus Nanlin895 along a development gradient from the newly emerged leaf from the shoot apex to the sixth leaf (L1 to L6) using anatomical observations and RNA-seq analysis. It indicated that mesophyll cells possess obvious vascular, palisade, and spongy tissue with distinct intercellular spaces after L3. Additionally, vacuoles fuse while epidermal cells expand to form pavement cells. RNA-seq analysis indicated that genes highly expressed in L1 and L2 were related to cell division and differentiation, while those highly expressed in L3 were enriched in photosynthesis. Therefore, we selected L1 and L3 to integrate ATAC-seq and RNA-seq and identified 735 differentially expressed genes (DEGs) with changes in chromatin accessibility regions within their promoters, of which 87 were transcription factors (TFs), such as ABI3VP1, AP-EREBP, MYB, NAC, and GRF. Motif enrichment analysis revealed potential regulatory functions for the DEGs through upstream TFs including TCP, bZIP, HD-ZIP, Dof, BBR-BPC, and MYB. Overall, our research provides a potential molecular foundation for regulatory network exploration in leaf development during photosynthesis establishment.

8.
J Org Chem ; 88(18): 12935-12948, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37673796

ABSTRACT

An electrochemical or photoelectrochemical regioselective polyfluoroalkylation/cyclization cascade of 3-aza-1,5-dienes with sodium fluoroalkanesulfinates is presented. This protocol proceeds with a broad substrate scope and good functional group tolerance under mild, oxidant-free, transition-metal-free, and electrolyte-free conditions to provide 3-polyfluoroalkylated 4-pyrrolin-2-ones in one step from readily available N-vinylacrylamides, and it is readily scalable to the Gram scale.

9.
Inorg Chem ; 62(51): 21416-21423, 2023 Dec 25.
Article in English | MEDLINE | ID: mdl-38061059

ABSTRACT

The design of unsaturated nonprecious metal complexes with high catalytic performance for photochemical CO2 reduction is still an important challenge. In this paper, four coordinatively unsaturated Co-salen complexes 1-4 were explored in situ using o-phenylenediamine derivatives and 5-methylsalicylaldehyde as precursors of the ligands in 1-4. It was found that complex 4, bearing a nitro substituent (-NO2) on the aromatic ring of the salen ligand, exhibits the highest photochemical performance for visible-light-driven CO2-to-CO conversion in a water-containing system, with TONCO and CO selectivity values of 5300 and 96%, respectively. DFT calculations and experimental results revealed that the promoted photocatalytic activity of 4 is ascribed to the electron-withdrawing effect of the nitro group in 4 compared to 1-3 (with -CH3, -F, and -H groups, respectively), resulting in a lower reduction potential of active metal centers CoII and lower barriers for CO2 coordination and C-O cleavage steps for 4 than those for catalysts 1-3.

10.
BMC Cardiovasc Disord ; 23(1): 111, 2023 03 06.
Article in English | MEDLINE | ID: mdl-36879196

ABSTRACT

BACKGROUND: Charlson Comorbidity Index (CCI) is positively associated with all-cause readmission in patients with heart failure (HF) in western countries. However, there is a scarcity of strong scientific evidence supporting the correlation in China. This study aimed at testing this hypothesis in Chinese.   METHODS: We conducted a secondary analysis of 1,946 patients with HF in Zigong Fourth People's Hospital in China between December 2016 to June 2019. Logistic regression models were used to study the hypotheses, with adjustments for the four regression models. We also explore the linear trend and possible nonlinear relationship between CCI and readmission within six months. We further conducted subgroup analysis and tests for interaction to examine the possible interaction between CCI and the endpoint. Additionally, CCI alone and several combinations of variables based on CCI were used to predict the endpoint. Under the curve (AUC), sensitivity and specificity were reported to evaluate the performance of the predicted model. RESULTS: In the adjusted II model, CCI was an independent prognostic factor for readmission within six months in patients with HF (OR = 1.14, 95% CI: 1.03-1.26, P = 0.011). Trend tests revealed that there was a significant linear trend for the association. A nonlinear association was identified between them and the inflection point of CCI was 1. Subgroup analyses and tests for interaction indicated that cystatin played an interactive role in the association. ROC analysis indicated neither CCI alone nor combinations of variables based on CCI were adequate for prediction. CONCLUSION: CCI was independently positively correlated with readmission within six months in patients with HF in Chinese population. However, CCI has limited value on predicting readmission within six months in patients with HF.


Subject(s)
Heart Failure , Patient Readmission , Humans , Retrospective Studies , Heart Failure/diagnosis , Heart Failure/epidemiology , Heart Failure/therapy , China/epidemiology , Comorbidity
11.
Acta Pharmacol Sin ; 44(11): 2331-2341, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37225846

ABSTRACT

Liver metastasis of colorectal cancer (CRC) is the critical cause of CRC-related death due to its unique immunosuppressive microenvironment. In this study we generated a gemcitabine-loaded synthetic high-density lipoprotein (G-sHDL) to reverse immunosuppression in livers with CRC metastases. After intravenous injection, sHDL targeted hepatic monocyte-derived alternatively activated macrophages (Mono-M2) in the livers of mice bearing both subcutaneous tumors and liver metastases. The G-sHDL preferentially eradicated Mono-M2 in the livers with CRC metastases, which consequently prevented Mono-M2-mediated killing of tumor antigen-specific CD8+ T cells in the livers and thus improved the densities of tumor antigen-specific CD8+ T cells in the blood, tumor-draining lymph nodes and subcutaneous tumors of the treated mice. While reversing the immunosuppressive microenvironment, G-sHDL also induced immunogenic cell death of cancer cells, promoted maturation of dendritic cells, and increased tumor infiltration and activity of CD8+ T cells. Collectively, G-sHDL inhibited the growth of both subcutaneous tumors and liver metastases, and prolonged the survival of animals, which could be further improved when used in conjunction with anti-PD-L1 antibody. This platform can be a generalizable platform to modulate immune microenvironment of diseased livers.


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Mice , Animals , Gemcitabine , CD8-Positive T-Lymphocytes/metabolism , Lipoproteins, HDL , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Colorectal Neoplasms/drug therapy , Macrophages/metabolism , Antigens, Neoplasm , Tumor Microenvironment , Cell Line, Tumor
12.
Mol Cell ; 57(6): 1047-1058, 2015 Mar 19.
Article in English | MEDLINE | ID: mdl-25728767

ABSTRACT

Estrogen receptor (ER/ESR1) is a transcription factor critical for development, reproduction, metabolism, and cancer. ER function hinges on its ability to recruit primary and secondary coactivators, yet structural information on the full-length receptor-coactivator complex to complement preexisting and sometimes controversial biochemical information is lacking. Here, we use cryoelectron microscopy (cryo-EM) to determine the quaternary structure of an active complex of DNA-bound ERα, steroid receptor coactivator 3 (SRC-3/NCOA3), and a secondary coactivator (p300/EP300). Our structural model suggests the following assembly mechanism for the complex: each of the two ligand-bound ERα monomers independently recruits one SRC-3 protein via the transactivation domain of ERα; the two SRC-3s in turn bind to different regions of one p300 protein through multiple contacts. We also present structural evidence for the location of activation function 1 (AF-1) in a full-length nuclear receptor, which supports a role for AF-1 in SRC-3 recruitment.


Subject(s)
E1A-Associated p300 Protein/chemistry , Estrogen Receptor alpha/chemistry , Nuclear Receptor Coactivator 3/chemistry , Binding Sites , Cryoelectron Microscopy , DNA/chemistry , DNA/metabolism , E1A-Associated p300 Protein/metabolism , Estrogen Receptor alpha/metabolism , Histone Acetyltransferases/metabolism , Humans , Multiprotein Complexes/chemistry , Multiprotein Complexes/metabolism , Nuclear Receptor Coactivator 3/metabolism , Protein Conformation , Protein Structure, Tertiary , Response Elements
13.
Hereditas ; 160(1): 33, 2023 Jul 31.
Article in English | MEDLINE | ID: mdl-37518006

ABSTRACT

BACKGROUND: HMGB1 (high mobility group box B-1) exhibits crucial role in tumor genesis and development, including lung cancer. Whereas, more HMGB1-related details in non-small cell lung cancer (NSCLC) are still largely unclear. METHODS: The HMGB1 and inflammatory factors in malignant (MPE) and non-malignant pleural effusion (BPE) were determined by ELISA. Additionally, qRT-PCR, western blot, or immunohistochemistry were used to determine HMGB1, drug-resistant and apoptotic proteins' expressions in NSCLC A549, A549-DDP cell lines, and xenograft model. Cell viability, migration/ invasion, and apoptosis were analyzed using MTT, Transwell, and flow cytometry assays, respectively. RESULTS: Inflammatory factors and HMGB1 expressions in MPE were significantly higher than BPE of NSCLC. Compared with preoperative and adjacent tissues, significantly higher HMGB1, drug-resistant protein, and anti-apoptotic protein expressions were observed in recurrent tissues. Overexpressed HMGB1 induced NSCLC cells to exhibit stronger aggressive, proliferative, and drug-resistant features. The related abilities were reversed when HMGB1 was interfered. Overexpressed HMGB1 showed a similar co-localization with drug resistant protein P-gp in cytoplasm in xenograft model, while low HMGB1 expression localized in cell nucleus. CONCLUSIONS: HMGB1 overexpression significantly promoted the malignant progression and cisplatin resistance of NSCLC in vitro and in vivo.


Subject(s)
Carcinoma, Non-Small-Cell Lung , HMGB1 Protein , Lung Neoplasms , MicroRNAs , Humans , Apoptosis , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Cell Line, Tumor , Cisplatin/pharmacology , Cisplatin/therapeutic use , Drug Resistance, Neoplasm/genetics , HMGB1 Protein/genetics , HMGB1 Protein/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , MicroRNAs/metabolism , Animals
14.
Zhongguo Zhong Yao Za Zhi ; 48(5): 1176-1185, 2023 Mar.
Article in Zh | MEDLINE | ID: mdl-37005801

ABSTRACT

Salvianolic acid B(Sal B) is the main water-soluble component of Salvia miltiorrhiza Bunge. Studies have found that Sal B has a good protective effect on blood vessels. Sal B can protect endothelial cells by anti-oxidative stress, inducing autophagy, inhibiting endoplasmic reticulum stress(ERS), inhibiting endothelial inflammation and adhesion molecule expression, inhibiting endothelial cell permeability, anti-thrombosis, and other ways. In addition, Sal B can alleviate endothelial cell damage caused by high glucose(HG). For vascular smooth muscle cell(VSMC), Sal B can reduce the synthesis and secretion of inflammatory factors by inhibiting cyclooxygenase. It can also play a vasodilatory role by inhibiting Ca~(2+) influx. In addition, Sal B can inhibit VSMC proliferation and migration, thereby alleviating vascular stenosis. Sal B also inhibits lipid deposition in the subendothelium, inhibits macrophage conversion to foam cells, and reduces macrophage apoptosis, thereby reducing the volume of subendothelial lipid plaques. For some atherosclerosis(AS) complications, such as peripheral artery disease(PAD), Sal B can promote angiogenesis, thereby improving ischemia. It should be pointed out that the conclusions obtained from different experiments are not completely consistent, which needs further research. In addition, previous pharmacokinetics showed that Sal B was poorly absorbed by oral administration, and it was unstable in the stomach, with a large first-pass effect in the liver. Sal B had fast distribution and metabolism in vivo and short drug action time. These affect the bioavailability and biological effects of Sal B, and the development of clinically valuable Sal B non-injectable delivery systems remains a great challenge.


Subject(s)
Benzofurans , Endothelial Cells , Oxidative Stress , Benzofurans/pharmacology , Lipids
15.
Zhongguo Yi Liao Qi Xie Za Zhi ; 47(1): 93-98, 2023 Jan 30.
Article in Zh | MEDLINE | ID: mdl-36752015

ABSTRACT

Three different preclinical evaluation methods of MTF through-frequency response, MTF through-focus-response and expected visual acuity were used to compare and analyze the imaging differences of IOLs with four different optical designs. The research work could be used in the simultaneous vision IOLs in the optical design stage and verify the optical quality of the IOLs, the results can predict the visual representation of the patients better. The evaluation results can provide reference for IOL manufacturers and users in product design, development, validation and application selection.


Subject(s)
Lenses, Intraocular , Humans , Prosthesis Design , Vision, Ocular , Visual Acuity
16.
Planta ; 255(5): 101, 2022 Apr 09.
Article in English | MEDLINE | ID: mdl-35397691

ABSTRACT

MAIN CONCLUSION: PdeHCA2 regulates the transition from primary to secondary growth, plant architecture, and affects photosynthesis by targeting PdeBRC1 and controlling the anatomy of the mesophyll, and intercellular space, respectively. Branching, secondary growth, and photosynthesis are vital developmental processes of woody plants that determine plant architecture and timber yield. However, the mechanisms underlying these processes are unknown. Here, we report that the Populus transcription factor High Cambium Activity 2 (PdeHCA2) plays a role in the transition from primary to secondary growth, vascular development, and branching. In Populus, PdeHCA2 is expressed in undifferentiated provascular cells during primary growth, in phloem cells during secondary growth, and in leaf veins, which is different from the expression pattern of its homolog in Arabidopsis. Overexpression of PdeHCA2 has pleiotropic effects on shoot and leaf development; overexpression lines showed delayed growth of shoots and leaves, reduced photosynthesis, and abnormal shoot branching. In addition, auxin-, cytokinin-, and photosynthesis-related genes were differentially regulated in these lines. Electrophoretic mobility shift assays and transcriptome analysis indicated that PdeHCA2 directly up-regulates the expression of BRANCHED1 and the MADS-box gene PdeAGL9, which regulate plant architecture, by binding to cis-elements in the promoters of these genes. Taken together, our findings suggest that HCA2 regulates several processes in woody plants including vascular development, photosynthesis, and branching by affecting the proliferation and differentiation of parenchyma cells.


Subject(s)
Arabidopsis , Populus , Arabidopsis/metabolism , Biomass , Cambium , Gene Expression Regulation, Plant , Photosynthesis , Plant Proteins/genetics , Plant Proteins/metabolism , Populus/metabolism
17.
Plant Biotechnol J ; 20(4): 646-659, 2022 04.
Article in English | MEDLINE | ID: mdl-34726307

ABSTRACT

MicroRNAs (miRNAs) play vital roles in plant development and defence responses against various stresses. Here, we show that blocking miR1871 improves rice resistance against Magnaporthe oryzae and enhances grain yield simultaneously. The transgenic lines overexpressing miR1871 (OX1871) exhibit compromised resistance, suppressed defence responses and reduced panicle number resulting in slightly decreased yield. In contrast, the transgenic lines blocking miR1871 (MIM1871) show improved resistance, enhanced defence responses and significantly increased panicle number leading to enhanced yield per plant. The RNA-seq assay and defence response assays reveal that blocking miR1871 resulted in the enhancement of PAMP-triggered immunity (PTI). Intriguingly, miR1871 suppresses the expression of LOC_Os06g22850, which encodes a microfibrillar-associated protein (MFAP1) locating nearby the cell wall and positively regulating PTI responses. The mutants of MFAP1 resemble the phenotype of OX1871. Conversely, the transgenic lines overexpressing MFAP1 (OXMFAP1) or overexpressing both MFAP1 and miR1871 (OXMFAP1/OX1871) resemble the resistance of MIM1871. The time-course experiment data reveal that the expression of miR1871 and MFAP1 in rice leaves, panicles and basal internode is dynamic during the whole growth period to manipulate the resistance and yield traits. Our results suggest that miR1871 regulates rice yield and immunity via MFAP1, and the miR8171-MFAP1 module could be used in rice breeding to improve both immunity and yield.


Subject(s)
Magnaporthe , Oryza , Ascomycota , Disease Resistance/genetics , Gene Expression Regulation, Plant/genetics , Magnaporthe/physiology , Oryza/metabolism , Plant Breeding , Plant Diseases/genetics , Plant Proteins/genetics , Plant Proteins/metabolism
18.
J Transl Med ; 20(1): 114, 2022 03 07.
Article in English | MEDLINE | ID: mdl-35255924

ABSTRACT

BACKGROUND: Once malignancy tumors were diagnosed, the determination of tissue origin and tumor type is critical for clinical management. Although the significant advance in imaging techniques and histopathological approaches, the diagnosis remains challenging in patients with metastatic and poorly differentiated or undifferentiated tumors. Gene expression profiling has been demonstrated the ability to classify multiple tumor types. The present study aims to assess the performance of a 90-gene expression test for tumor classification (i.e. the determination of tumor tissue of origin) in real clinical settings. METHODS: Formalin-fixed paraffin-embedded samples and associated clinicopathologic information were collected from three cancer centers between January 2016 and January 2021. A total of 1417 specimens that met quality control criteria (RNA quality, tumor cell content ≥ 60% and so on) were analyzed by the 90-gene expression test to identify the tumor tissue of origin. The performance was evaluated by comparing the test results with histopathological diagnosis. RESULTS: The 1417 samples represent 21 main tumor types classified by common tissue origins and anatomic sites. Overall, the 90-gene expression test reached an accuracy of 94.4% (1338/1417, 95% CI: 0.93 to 0.96). Among different tumor types, sensitivities were ranged from 74.2% (head&neck tumor) to 100% (adrenal carcinoma, mesothelioma, and prostate cancer). Sensitivities for the most prevalent cancers of lung, breast, colorectum, and gastroesophagus are 95.0%, 98.4%, 93.9%, and 90.6%, respectively. Moreover, specificities for all 21 tumor types are greater than 99%. CONCLUSIONS: These findings showed robust performance of the 90-gene expression test for identifying the tumor tissue of origin and support the use of molecular testing as an adjunct to tumor classification, especially to those poorly differentiated or undifferentiated tumors in clinical practice.


Subject(s)
Gene Expression Profiling , Head and Neck Neoplasms , Biomarkers, Tumor/genetics , Gene Expression , Gene Expression Profiling/methods , Humans , Male , Oligonucleotide Array Sequence Analysis/methods
19.
New Phytol ; 236(6): 2216-2232, 2022 12.
Article in English | MEDLINE | ID: mdl-36101507

ABSTRACT

Rice production is threatened by multiple pathogens. Breeding cultivars with broad-spectrum disease resistance is necessary to maintain and improve crop production. Previously we found that overexpression of miR160a enhanced rice blast disease resistance. However, it is unclear whether miR160a also regulates resistance against other pathogens, and what the downstream signaling pathways are. Here, we demonstrate that miR160a positively regulates broad-spectrum resistance against the causative agents of blast, leaf blight and sheath blight in rice. Mutations of miR160a-targeted Auxin Response Factors result in different alteration of resistance conferred by miR160a. miR160a enhances disease resistance partially by suppressing ARF8, as mutation of ARF8 in MIM160 background partially restores the compromised resistance resulting from MIM160. ARF8 protein binds directly to the promoter and suppresses the expression of WRKY45, which acts as a positive regulator of rice immunity. Mutation of WRKY45 compromises the enhanced blast resistance and bacterial leaf blight resistance conferred by arf8 mutant. Overall, our results reveal that a microRNA coordinates rice broad-spectrum disease resistance by suppressing multiple target genes that play different roles in disease resistance, and uncover a new regulatory pathway mediated by the miR160a-ARF8 module. These findings provide new resources to potentially improve disease resistance for breeding in rice.


Subject(s)
Magnaporthe , Oryza , Disease Resistance/genetics , Magnaporthe/metabolism , Oryza/metabolism , Plant Diseases/microbiology , Plant Proteins/metabolism , Plant Breeding
20.
Opt Express ; 30(15): 26544-26556, 2022 Jul 18.
Article in English | MEDLINE | ID: mdl-36236843

ABSTRACT

A multifunctional design based on vanadium dioxide (VO2) metamaterial structure is proposed. Broadband absorption, linear-to-linear (LTL) polarization conversion, linear-to-circular (LTC) polarization conversion, and total reflection can be achieved based on the insulator-to-metal transition (IMT) of VO2. When the VO2 is in the metallic state, the multifunctional structure can be used as a broadband absorber. The results show that the absorption rate exceeds 90% in the frequency band of 2.17 - 4.94 THz, and the bandwidth ratio is 77.8%. When VO2 is in the insulator state, for the incident terahertz waves with a polarization angle of 45°, the structure works as a polarization converter. In this case, LTC polarization conversion can be obtained in the frequency band of 0.1 - 3.5 THz, and LTL polarization conversion also can be obtained in the frequency band of 3.5 - 6 THz, especially in the 3.755 - 4.856 THz band that the polarization conversion rate is over 90%. For the incident terahertz waves with a polarization angle of 0°, the metamaterial structure can be used as a total reflector. Additionally, impacts of geometrical parameters, incidence angle and polarization angle on the operating characteristics have also been investigated. The designed switchable multifunctional metasurfaces are promising for a wide range of applications in advanced terahertz research and smart applications.

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