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1.
Sci Total Environ ; 926: 171923, 2024 May 20.
Article En | MEDLINE | ID: mdl-38522523

The detrimental effects of heavy metal accumulation on both ecosystems and public health have raised widespread concern. Source-specific risk assessment is crucial for developing effective strategies to prevent and control heavy metal contamination in surface water. This study aims to investigate the contamination characteristics of heavy metals in the Yangtze River Basin, identifying the pollution sources, assessing the risk levels, and further evaluating the health risks to humans. The results indicated that the average concentrations of heavy metals were ranked as follows: zinc (Zn) > arsenic (As) > copper (Cu) > chromium (Cr) > cadmium (Cd) > nickel (Ni) > lead (Pb), with average concentrations of 38.02 µg/L, 4.34 µg/L, 2.53 µg/L, 2.10 µg/L, 1.17 µg/L, 0.84 µg/L, and 0.32 µg/L, respectively, all below the WHO 2017 standards for safe drinking water. The distribution trend indicates higher concentrations in the upper and lower reaches and lower concentrations in the mid-reaches of the river. By integrating the Absolute Principal Component Scores-Multiple Linear Regression (APCS-MLR) receptor model and Positive Matrix Factorization (PMF) model, the main sources of heavy metals were identified as industrial activities (APCS-MLR: 41.3 %; PMF: 42.1 %), agricultural activities (APCS-MLR: 30.1 %; PMF: 27.4 %), and unknown mix sources (APCS-MLR: 29.1 %; PMF: 30.4 %). The calculation of the hazard index (HI) for both children and adults was <1, indicating no non-carcinogenic or carcinogenic risks. Based on the source-specific risk assessment, agricultural activities contribute the most to non-carcinogenic risks, while industrial activities pose the greatest contribution to carcinogenic risks. This study offers a reference for monitoring heavy metals and controlling health risks to residents, and provides crucial evidence for the utilization and protection of surface water in the Yangtze River Basin.


Drinking Water , Metals, Heavy , Adult , Child , Humans , Rivers , Ecosystem , Environmental Monitoring , Metals, Heavy/analysis , Cadmium , Risk Assessment , China
2.
Biomark Med ; 17(14): 623-634, 2023 07.
Article En | MEDLINE | ID: mdl-37812024

Background: Cancer is one of the top causes of mortality worldwide. The matrix metalloproteinase MMP12 is highly expressed in some cancers, but there is a lack of meta-analyses proving the correlation between MMP12 and cancer. Materials & methods: A literature search was performed using Web of Science, PubMed and other databases. Quantitative meta-analysis of the data was carried out. The Cancer Genome Atlas was further used to validate our results. Results: High MMP12 expression was associated with poorer overall survival and poorer 5-year overall survival. Elevated expression of MMP12 predicted shorter overall survival in six cancers and worse disease-free survival in four malignancies based on validation using the Gene Expression Profiling Interactive Analysis online analysis tool. Conclusion: Elevated MMP12 expression is likely a marker of poor prognosis in various cancers.


What is this summary about? This study looked at how a gene called MMP12 affects the survival time and health of cancer patients. The MMP12 gene makes a protein that helps cancer cells grow. We studied information from 38 research studies involving 9582 patients. We wanted to learn how the gene MMP12 is connected to the prognosis and survival of people who have cancer. What was the result? The study found that patients with less MMP12 tended to live longer. Based on this, we can say that having less of the protein MMP12 may be better for patients. By contrast, high levels of MMP12 were linked to more advanced cancer stages, so this protein may aid cancer growth. What do these results mean? These findings can help doctors diagnose cancer and predict what might happen to patients. If we can control this gene, we might find new treatments to stop cancer from growing and help people live longer. However, we need to do more research to be sure about these findings and to understand this gene better.


Matrix Metalloproteinase 12 , Neoplasms , Humans , Prognosis , Matrix Metalloproteinase 12/genetics , Neoplasms/diagnosis , Neoplasms/genetics , Disease-Free Survival , Gene Expression Profiling
3.
Sci Total Environ ; 903: 166252, 2023 Dec 10.
Article En | MEDLINE | ID: mdl-37574059

Tropospheric ozone (O3), which is one of the main pollutants impeding air quality compliance, has received considerable attention in China. As maritime transportation continues to expand, the effect of ship emissions on air quality is becoming increasingly important. In this study, the Weather Research and Forecast model (WRF), the Community Multiscale Air Quality model (CMAQ), and the integrated process rate (IPR) module provided in the CMAQ are applied to evaluate the impacts of ship emissions on O3 concentration at a national scale in China, including the spatiotemporal characteristics and influencing pathways. Ship emissions can increase or decrease O3 concentrations, with varying effects in different seasons and regions. In the winter, spring, and fall, ship emissions were predicted to decrease O3 concentrations in most areas, whereas in the summer, they increase the O3 concentration, even in regions far away from the coastline, thus adversely affecting the Yangtze River Delta (YRD) and Pearl River Delta (YRD). Additionally, owing to differences in the emissions of volatile organic compounds and nitrogen oxides, the northern and southern regions of the YRD respond differently to ship emissions. Additionally, the influence of ship emissions on the diurnal variation of O3 in the summer was investigated, where significant differences were indicated between cities. The IPR was used to investigate the individual processes contributing to changes in the O3 concentration caused by ship emissions. The transport process appears to be the primary contributor to O3 production, whereas chemistry and dry deposition played key roles in O3 loss. This study provides an in-depth insight into the impacts of ship emissions on O3 in China, which can facilitate the formulation of corresponding environmental policies.

4.
Medicine (Baltimore) ; 102(23): e34012, 2023 Jun 09.
Article En | MEDLINE | ID: mdl-37335642

BACKGROUND: Tripartite motif-containing protein 21 (TRIM21), a member of the ubiquitin ligase family, makes a significant contribution to the ubiquitination of multiple tumor marker proteins associated with tumor cell proliferation, metastasis and selective apoptosis. As the research further develops, an increasing number of studies have manifested that the TRIM21 expression level can be considered an indicator of cancer prognosis. However, the interrelationship between TRIM21 and multiple forms of carcinogens has not been demonstrated in a meta-analysis. METHODS: We performed a systematic literature retrieval in various electronic databases including PubMed, Embase, Web of Science, Wanfang and China National Knowledge Infrastructure. Besides, the hazard ratio (HR) and the pooled relative risk (RR) were integrated in the assessment of cancer incidence and cancer mortality by Stata SE15.1. Additionally, we used an online database based on The Cancer Genome Atlas (TCGA) to further validate our results. RESULTS: A total of 17 studies were included, totaling 7239 participants. High expression of TRIM21 was significantly correlated with better OS (HR = 0.74; 95% CI: 0.57-0.91; P < .001) and progression-free survival (PFS) (HR = 0.66; 95% CI: 0.42-0.91; P < .001). We found that high TRIM21 expression predicted significant impact on clinical characteristics like decreased lymph node metastasis (RR = 1.12; 95% CI: 0.97-1.30; P < .001), tumor stage (RR = 1.06; 95% CI: 0.82-1.37; P < .001) and tumor grade (RR = 1.07; 95% CI: 0.56-2.05; P < .001). However, TRIM21 expression had no significant impact on other clinical characteristics such as age (RR = 1.06; 95% CI: 0.91-1.25; P = .068), sex (RR = 1.04; 95% CI: 0.95-1.12; P = .953), or tumor size (RR = 1.14; 95% CI: 0.97-1.33; P = .05). Based on the Gene Expression Profiling Interactive Analysis (GEPIA) online analysis tool, TRIM21 was significantly downregulated in 5 cancers while significantly upregulated in 2 cancers, and the descending expression of TRIM21 predicted shorter OS in 5 cancers, worse PFS in 2 malignancies, while the elevated expression of TRIM21 predicted shorter OS and worse PFS in 2 carcinomas. CONCLUSIONS: TRIM21 could serve as a new biomarker for patients with solid malignancies and could be a potential therapeutic target for patients.


Carcinoma , Neoplasms , Humans , Prognosis , Proportional Hazards Models , Biomarkers, Tumor/metabolism , Progression-Free Survival , Neoplasm Proteins
5.
Sci Data ; 10(1): 309, 2023 05 20.
Article En | MEDLINE | ID: mdl-37210394

The Belt and Road (B&R) Initiative is considered as closely aligned with the UN's Sustainable Development Goals by 2030 and could have a huge global impact. Its sustainable development issues have attracted worldwide attention. However, both the existing research and data accumulation on this aspect are seriously insufficient. Starting from the logic of the ultimate goal of sustainable development (namely within the ecological limitations, maximizing human well-being with minimum ecological consumption and minimizing the planetary pressures with maximum resource utilization efficiency), we have constructed a comprehensive evaluation method on sustainable development, namely the Consumption-Pressure-Output-Efficiency method in our previous study. Based on it, we provide a database with five datasets, which includes four core datasets (ecological consumption, planetary pressures, human well-being outputs and ecological well-being output efficiency) and a related dataset (biocapacity, ecological surplus/deficit, population), covering 61 B&R countries, B&R regional average and global average from 1990 to 2018. It can be used for further comprehensive research on sustainable development under planetary pressures and others of B&R.

6.
Pathol Res Pract ; 245: 154474, 2023 May.
Article En | MEDLINE | ID: mdl-37119730

BACKGROUND: P4HB (prolyl 4-hydroxylase, beta polypeptide) is a human chromosomal gene that encodes an endoplasmic reticulum (ER) molecular chaperone protein with oxidoreductase, chaperone and isomerase activities. Recent studies indicated that P4HB may have clinical significance, with elevated P4HB expression reported in cancer patients, but its impact on tumor prognosis is not yet clear. To our knowledge, this is the first meta-analysis to show an association between P4HB expression and the prognosis of various cancers. METHODS: We conducted a systematic literature search in the PubMed, PubMed Central, Web of Science, Embase, CNKI, Wanfang and Weipu databases, followed by a quantitative meta-analysis using Stata SE14.0 and R statistics software 4.2.1. The hazard ratio (HR) and relative risk (RR) were analyzed to evaluate the relationships of P4HB expression levels with overall survival (OS), disease-free survival (DFS), and clinicopathological parameters of cancer patients. Subsequently, P4HB expression in various cancer types was validated using the Gene Expression Profiling Interactive Analysis (GEPIA) online database. RESULTS: Ten articles containing the data of 4121 cancer patients were included in the analysis, and a significant correlation of high P4HB expression with apparently shorter OS was found (HR, 1.90; 95% CI, 1.50-2.40; P < 0.01), while there was no significant correlation with gender (RR, 1.06; 95% CI, 0.91-1.22; P = 0.084), or age. Additionally, GEPIA online analysis revealed significant upregulation of P4HB in 13 types of cancer. Among them, P4HB overexpression was associated with shorter OS in 9 and worse DFS in 11 cancer types. CONCLUSIONS: Upregulation of P4HB is correlated with worse prognosis in various cancers, which could provide new ideas for the development of P4HB-related diagnostic biomarkers and new therapeutic targets.


Biomarkers, Tumor , Neoplasms , Humans , Biomarkers, Tumor/metabolism , Neoplasms/pathology , Prognosis , Proportional Hazards Models , Disease-Free Survival , Procollagen-Proline Dioxygenase , Protein Disulfide-Isomerases/metabolism
7.
Int Immunopharmacol ; 116: 109826, 2023 Mar.
Article En | MEDLINE | ID: mdl-36764269

Reduced Na+/K+-ATPase (NKA) activity and NKAα1 expression are engaged in the pathologies of renal diseases. NKA-mediated Src activation is not the only reason for NKA-related renal fibrosis. In this study, we found that genetic reduction of NKAα1 exhibited exacerbated tubulointerstitial lesions and fibrosis in the UUO mice model. Activation of NKAα1 with an antibody against the extracellular DR region of the NKAα1 subunit (DRm217) prevented UUO-induced tubulointerstitial lesions, preserved kidney function, and decrease renal fibrosis. Further studies revealed that NKAα1 deficiency mice exhibited high inflammation factors expression when they suffered UUO surgery, compared with NKAα1+/+ (WT) mice. DRm217 alleviated inflammatory cell infiltration, suppress NF-κB phosphorylation, and decreased inflammatory factors expression in the UUO mice model. Released HMGB1 can trigger the inflammatory response and contribute to renal fibrosis. Knockdown of NKA in renal tubular cells or in NKAα1+/- mice was associated with more susceptibility to HMGB1 release in the UUO mice model. DRm217 exerted its antifibrotic effect via inhibiting HMGB1 release. Furthermore, AMPK activation participates in the effect of DRm217 on inhibiting HMGB1 release. Our findings suggest that NKAα1 is a regulator of renal fibrosis and its DR-region is a novel target on it.


HMGB1 Protein , Kidney Diseases , Ureteral Obstruction , Mice , Animals , HMGB1 Protein/genetics , HMGB1 Protein/metabolism , Sodium-Potassium-Exchanging ATPase/genetics , Sodium-Potassium-Exchanging ATPase/metabolism , Kidney/pathology , Kidney Diseases/pathology , Antibodies, Monoclonal/pharmacology , Fibrosis
8.
Environ Sci Pollut Res Int ; 30(11): 29442-29457, 2023 Mar.
Article En | MEDLINE | ID: mdl-36417062

Nitrogen pollution in groundwater is an environmental issue of global concern. Identifying nitrogen pollution sources and determining migration and transformation processes are the major ways to prevent and control nitrogen pollution in the groundwater on a regional scale. In this study, groundwater in the lower Wei River was investigated by combining multi-isotope tracing techniques with the SIAR hybrid model (source resolution) to trace the nitrate sources and their contribution rate to nitrogen pollution in groundwater of different geomorphological units, considering types of geomorphology as the units. The multi-isotope tracing technique allows dynamic analysis of nitrate sources, and the combination of this technology can improve the accuracy of nitrogen source traceability. The results indicated that the pH of the water bodies in the study area ranged from 6.83 to 8.01, which is neutral and weakly alkaline. The nitrogen pollution was mainly due to nitrates. The significant factors affecting nitrogen migration in groundwater are the geomorphological type, the chemical characteristics of the groundwater, and the age of the groundwater. Nitrogen migration and transformation processes in the study area were dominated by nitrification, and sources of nitrate pollution were mainly animal manure and domestic sewage (32.6%), followed by atmospheric deposition (26.8%), soil nitrogen (20.9%), and chemical fertilizer (19.7%). The main sources of nitrate in groundwater from river flats, alluvial plains, and loess tableland were animal manure and domestic sewage (43.7%), animal manure and domestic sewage (59.1%), and atmospheric deposition (55.5%), respectively. The result is mainly related to the different structural characteristics of various geomorphic units and the intensity of human activities. This study can provide a theoretical basis for the relevant agencies to develop plans to combat groundwater pollution.


Groundwater , Water Pollutants, Chemical , Animals , Humans , Nitrogen/analysis , Nitrates/analysis , Nitrogen Isotopes/analysis , Rivers/chemistry , Manure/analysis , Sewage/chemistry , Water Pollutants, Chemical/analysis , Environmental Monitoring/methods , Groundwater/chemistry , China
9.
Front Immunol ; 13: 898925, 2022.
Article En | MEDLINE | ID: mdl-35865532

Molecular classification based on transcriptional characteristics is often used to study tumor heterogeneity. Human cancer has different cell populations with distinct transcription in tumors, and their heterogeneity is the focus of tumor therapy. Our purpose was to explore the tumor heterogeneity of uveal melanoma (UM) through RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq). Based on the consensus clustering assays of the prognosis-related immune gene set, the immune subtype (IS) of UM and its corresponding immune characteristics were comprehensively analyzed. The heterogeneous cell groups and corresponding marker genes of UM were identified from GSE138433 using scRNA-seq analysis. Pseudotime trajectory analysis and SCENIC analysis were conducted to explore the trajectory of cell differentiation and the regulatory network of single-cell transcription factors (TFs). Based on 37 immune gene sets, UM was divided into two different immune subtypes (IS1 and IS2). The two kinds of ISs have different characteristics in prognosis, immune-related molecules, immune score, and immune cell infiltration. According to 11,988 cells of scRNA-seq data from six UM samples, 11 cell clusters and 10 cell types were identified. The subsets of C1, C4, C5, C8, and C9 were related to the prognosis of UM, and different TF-target gene regulatory networks were involved. These five cell subsets differentiated into 3 different states. Our results provided valuable information about the heterogeneity of UM tumors and the expression patterns of TFs in different cell types.


Melanoma , Uveal Neoplasms , Gene Regulatory Networks , Humans , Melanoma/pathology , Sequence Analysis, RNA/methods , Uveal Neoplasms/genetics , Uveal Neoplasms/metabolism , Uveal Neoplasms/pathology
10.
Sci Rep ; 11(1): 22244, 2021 11 15.
Article En | MEDLINE | ID: mdl-34782661

Cutaneous melanoma could be treated by immunotherapy, which only has limited efficacy on uveal melanoma (UM). UM immunotyping for predicting immunotherapeutic responses and guiding immunotherapy should be better understood. This study identified molecular subtypes and key genetic markers associated with immunotherapy through immunosignature analysis. We screened a 6-immune cell signature simultaneously correlated with UM prognosis. Three immune subtypes (IS) were determined based on the 6-immune cell signature. Overall survival (OS) of IS3 was the longest. Significant differences of linear discriminant analysis (LDA) score were detected among the three IS types. IS3 with the highest LDA score showed a low immunosuppression. IS1 with the lowest LDA score was more immunosuppressive. LDA score was significantly negatively correlated with most immune checkpoint-related genes, and could reflect UM patients' response to anti-PD1 immunotherapy. Weighted correlation network analysis (WGCNA) identified that salmon, purple, yellow modules were related to IS and screened 6 prognostic genes. Patients with high-expressed NME1 and TMEM255A developed poor prognosis, while those with high-expressed BEX5 and ROPN1 had better prognosis. There was no notable difference in OS between patients with high-expressed LRRN1 and ST13 and those with low-expressed LRRN1 and ST13. NME1, TMEM255A, Bex5 and ROPN1 showed potential prognostic significance in UM.


Biomarkers, Tumor/genetics , Immunomodulation/genetics , Melanoma/etiology , Melanoma/mortality , Transcriptome , Uveal Neoplasms/etiology , Uveal Neoplasms/mortality , Cluster Analysis , Computational Biology/methods , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Humans , Immune Checkpoint Proteins/genetics , Immune Checkpoint Proteins/metabolism , Melanoma/metabolism , Melanoma/therapy , Molecular Sequence Annotation , Molecular Targeted Therapy , Proportional Hazards Models , ROC Curve , Signal Transduction , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Uveal Neoplasms/metabolism , Uveal Neoplasms/therapy
11.
Article En | MEDLINE | ID: mdl-34335838

Subchondral bone lesions, as the crucial inducement for accelerating cartilage degeneration, have been considered as the initiating factor and the potential therapeutic target of knee osteoarthritis (KOA). Acupotomy, the biomechanical therapy guided by traditional Chinese meridians theory, alleviates cartilage deterioration by correcting abnormal mechanics. Whether this mechanical effect of acupotomy inhibits KOA subchondral bone lesions is indistinct. This study aimed to investigate the effects of acupotomy on inhibiting subchondral bone resorption and to define the possible mechanism in immobilization-induced KOA rabbits. After KOA modeling, 8 groups of rabbits (4w/6w acupotomy, 4w/6w electroacupuncture, 4w/6w model, and 4w/6w control groups) received the indicated intervention for 3 weeks. Histological and bone histomorphometry analyses revealed that acupotomy prevented both cartilage surface erosion and subchondral bone loss. Further, acupotomy suppressed osteoclast activity and enhanced osteoblast activity in KOA subchondral bone, showing a significantly decreased expression of tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinases-9 (MMP-9), and cathepsin K (Ctsk) and a significantly increased expression of osteocalcin (OCN); this regulation may be mediated by blocking the decrease in osteoprotegerin (OPG) and the increase in NF-κB receptor activated protein ligand (RANKL). These findings indicated that acupotomy inhibited osteoclast activity and promoted osteoblast activity to ameliorate hyperactive subchondral bone resorption and cartilage degeneration in immobilization-induced KOA rabbits, which may be mediated by the OPG/RANKL signaling pathway. Taken together, our results indicate that acupotomy may have therapeutic potential in KOA by restoring the balance between bone formation and bone resorption to attenuate subchondral bone lesions.

12.
Mater Sci Eng C Mater Biol Appl ; 110: 110687, 2020 May.
Article En | MEDLINE | ID: mdl-32204115

Electronic structure and bioactivity of calcium phosphate (CaP) coatings on Ti-based anodic nanotubes are investigated. Nanotubes on pure Ti and Ti-6Al-4V alloy, respectively, are used as substrates for CaP deposition. The CaP coatings are formed by first growing a seeding CaP layer using alternative immersion (AIM) treatment followed by crystallization in Dulbecco's phosphate-buffered saline (DPBS). CaP coatings formed on both Ti and Ti-6Al-4V substrates are found containing a variety of bioactive CaP species, such as hydroxyapatite (HA), amorphous CaP (ACP), octacalcium phosphate (OCP), and dicalcium phosphate dihydrate (DCPD). The compositions of the coatings during the nucleation and crystallization processes are tracked and analyzed using X-ray absorption near-edge structure (XANES). The variation of CaP species in the resulted coatings are found strongly dependent on the choice of metal substrates, which leads to different bioactivities. By comparing the proliferation and differentiation of osteoblast cells (MC3T3-E1) on the CaP coatings, correlations between CaP species and their bioactivities are established.


Calcium Phosphates/chemistry , Coated Materials, Biocompatible/chemistry , Nanotubes/chemistry , Oxides/chemistry , Titanium/chemistry , 3T3 Cells , Alloys , Animals , Calcium Phosphates/pharmacology , Cell Differentiation/drug effects , Cell Line , Cell Proliferation/drug effects , Crystallization/methods , Durapatite/chemistry , Materials Testing/methods , Mice , Osteoblasts/drug effects , Surface Properties/drug effects , Tensile Strength/drug effects
13.
Sci Total Environ ; 708: 134636, 2020 Mar 15.
Article En | MEDLINE | ID: mdl-31791755

A large amount of NOX and SO2 emitted from ships may elevate atmospheric N and S and eventually aggravate the deposition of N and S. The understanding of N and S deposition due to ship emissions is still limited, especially for China because it has a long coastline, busy shipping routes, and several large ports. To fill this gap, a comprehensive air quality model was employed in this study to quantify the contributions of ship emissions to N and S deposition on a national scale in China. Both the spatial and temporal variations of N and S deposition, as well as the major N and S species from ship traffic, were investigated. The results indicate that ship emissions contributed significantly to the deposition of N and S, especially in coastal and offshore areas, where the largest ship contribution to both N and S deposition could exceed 15 kg·ha-1·yr-1. For N deposition, ship emissions caused an increase in the total N deposition, not only in port areas and along shipping routes but also far inland, with evident seasonal variations. The contribution from dry N deposition was evidently larger than wet N deposition, especially over the coastal areas. S deposition, however, was generally higher along shipping routes but exhibited distinct seasonal variations. The total S deposition was dominated by dry deposition, especially over offshore areas. Ship-caused dry S deposition occurred mainly in offshore areas, while wet S deposition could be found over wider inland regions and inland waterways, although with a markedly smaller magnitude.

14.
J Biol Chem ; 294(16): 6562-6577, 2019 04 19.
Article En | MEDLINE | ID: mdl-30814255

The proteasome holoenzyme is a molecular machine that degrades most proteins in eukaryotes. In the holoenzyme, its heterohexameric ATPase injects protein substrates into the proteolytic core particle, where degradation occurs. The heterohexameric ATPase, referred to as 'Rpt ring', assembles through six ATPase subunits (Rpt1-Rpt6) individually binding to specific chaperones (Rpn14, Nas6, Nas2, and Hsm3). Here, our findings suggest that the onset of Rpt ring assembly can be regulated by two alternative mechanisms. Excess Rpt subunits relative to their chaperones are sequestered into multiple puncta specifically during early-stage Rpt ring assembly. Sequestration occurs during stressed conditions, for example heat, which transcriptionally induce Rpt subunits. When the free Rpt pool is limited experimentally, Rpt subunits are competent for proteasome assembly even without their cognate chaperones. These data suggest that sequestration may regulate amounts of individual Rpt subunits relative to their chaperones, allowing for proper onset of Rpt ring assembly. Indeed, Rpt subunits in the puncta can later resume their assembly into the proteasome. Intriguingly, when proteasome assembly resumes in stressed cells or is ongoing in unstressed cells, excess Rpt subunits are recognized by an alternative mechanism-degradation by the proteasome holoenzyme itself. Rpt subunits undergo proteasome assembly until the holoenzyme complex is generated at a sufficient level. The fully-formed holoenzyme can then degrade any remaining excess Rpt subunits, thereby regulating its own Rpt ring assembly. These two alternative mechanisms, degradation and sequestration of Rpt subunits, may help control the onset of chaperone-mediated Rpt ring assembly, thereby promoting proper proteasome holoenzyme formation.


Molecular Chaperones/metabolism , Proteasome Endopeptidase Complex/metabolism , Proteolysis , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Holoenzymes/genetics , Holoenzymes/metabolism , Molecular Chaperones/genetics , Proteasome Endopeptidase Complex/genetics , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae Proteins/genetics
15.
Proc Natl Acad Sci U S A ; 115(52): 13246-13251, 2018 12 26.
Article En | MEDLINE | ID: mdl-30530678

In the proteasome holoenzyme, the hexameric ATPases (Rpt1-Rpt6) enable degradation of ubiquitinated proteins by unfolding and translocating them into the proteolytic core particle. During early-stage proteasome assembly, individual Rpt proteins assemble into the hexameric "Rpt ring" through binding to their cognate chaperones: Nas2, Hsm3, Nas6, and Rpn14. Here, we show that Rpt ring assembly employs a specific ubiquitination-mediated control. An E3 ligase, Not4, selectively ubiquitinates Rpt5 during Rpt ring assembly. To access Rpt5, Not4 competes with Nas2 until the penultimate step and then with Hsm3 at the final step of Rpt ring completion. Using the known Rpt-chaperone cocrystal structures, we show that Not4-mediated ubiquitination sites in Rpt5 are obstructed by Nas2 and Hsm3. Thus, Not4 can distinguish a Rpt ring that matures without these chaperones, based on its accessibility to Rpt5. Rpt5 ubiquitination does not destabilize the ring but hinders incorporation of incoming subunits-Rpn1 ubiquitin receptor and Ubp6 deubiquitinase-thereby blocking progression of proteasome assembly and ubiquitin regeneration from proteasome substrates. Our findings reveal an assembly checkpoint where Not4 monitors chaperone actions during hexameric ATPase ring assembly, thereby ensuring the accuracy of proteasome holoenzyme maturation.


Adenosine Triphosphatases/metabolism , Molecular Chaperones/metabolism , Proteasome Endopeptidase Complex/metabolism , Repressor Proteins/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Ubiquitin-Protein Ligases/metabolism , Ubiquitin/metabolism , Binding Sites , Models, Molecular , Protein Binding , Protein Conformation , Saccharomyces cerevisiae/growth & development , Ubiquitinated Proteins/metabolism
16.
Int J Ophthalmol ; 8(5): 904-9, 2015.
Article En | MEDLINE | ID: mdl-26558199

AIM: To expose rat retinal Müller cells to 530 nm monochromatic light and investigate the influence of varying light illumination times on basic fibroblast growth factor (bFGF) and transforming growth factor-ß1 (TGF-ß1) expression. METHODS: Three groups of rat retinal Müller cells cultured in vitro under a 530 nm monochromatic light were divided into 6, 12 and 24h experimental groups, while cells incubated under dark conditions served as the control group. The bFGF and TGF-ß1 mRNA expression, protein levels and fluorescence intensity of the Müller cells were analyzed. RESULTS: The bFGF mRNA expression and protein levels were significantly upregulated in Müller cells in all three experimental groups compared with the control group (P<0.05), while that of TGF-ß1 was downregulated (P<0.05). Also, bFGF expression was positively correlated, but TGF-ß1 expression was negatively correlated with illumination time. The largest changes for both cytokines were seen in the 24h group. The changes in bFGF and TGF-ß1 fluorescence intensity were highest in the 24h group, and significant differences were observed among the experimental groups (P<0.05). CONCLUSION: The expressions of bFGF and TGF-ß1 changed in a time-dependent manner in Müller cells exposed to 530 nm monochromatic light with 250 lx illumination intensity. Müller cells might play a role in the development of myopia by increasing bFGF expression or decreasing TGF-ß1 expression. Changes in cytokine expression in retinal Müller cells may affect monochromatic light-induced myopia.

17.
Inorg Chem ; 54(9): 4268-78, 2015 May 04.
Article En | MEDLINE | ID: mdl-25871285

A series of new alkaline-earth metal diphosphonate frameworks were successfully synthesized under solvothermal reaction condition (160 °C, 3 d) using 1-hydroxyethylidene-1,1-diphosphonic acid (CH3C(OH)(H2PO3)2, hedpH4) as a diphosphonate building block and Mg(II), Ca(II), Sr(II), or Ba(II) ions as alkaline-earth metal ion centers in water, dimethylformamide, and/or EtOH media. These diphosphonate frameworks, (H2NMe2)4[Mg(hedpH2)3]·3H2O (1), (H2NMe2)2[Ca(hedpH2)2] (2), (H2NMe2)2[Sr3(hedpH2)4(H2O)2] (3), and [Ba3(hedpH2)3]·H2O (4) exhibited interesting structural topologies (zero-, one-, two-, and three-dimensional (0D, 1D, 2D, and 3D, respectively)), which are mainly depending on the metal ions and the solvents used in the synthesis. The single-crystal analysis of these newly synthesized compounds revealed that 1 was a 0D molecule, 2 has 1D chains, 3 was a 3D molecule, and 4 has 2D layers. All compounds were further characterized using thermogravimetric analysis, solid-state (31)P NMR, powder X-ray diffraction analysis, UV-vis spectra, and infrared spectroscopy. In addition, Eu(III)- and Tb(III)-doped compounds of 1-4, namely, (H2NMe2)4[Ln(x)Mg(1-x)(hedpH2)2(hedpH(2-x))]·3H2O (1Ln), (H2NMe2)2[Ln(x)Ca(1-x)(hedpH2)(hedpH(2-x))] (2Ln), (H2NMe2)2[Ln(x)Sr(3-x)(hedpH2)3(hedpH(2-x))(H2O)2] (3Ln), and [Ln(x)Ba(3-x)(hedpH2)2(hedpH(2-x))]·H2O (4Ln) (where Ln = Eu, Tb), were synthesized, and their photoluminescence properties were studied. The quantum yield of 1Eu-4Eu was measured with reference to commercial red phosphor, Y2O2S:Eu(3+) (YE), and the quantum yield of terbium-doped compounds 1Tb-4Tb was measured with reference to commercial green-emitting phosphor CeMgAl10O17:Tb(3+). Interestingly, the compound 2Eu showed very high quantum yield of 92.2%, which is better than that of the reference commercial red phosphor, YE (90.8%).

18.
J Acoust Soc Am ; 137(3): 1551-6, 2015 Mar.
Article En | MEDLINE | ID: mdl-25786965

Underwater vehicles are often equipped with anechoic coatings to absorb the sound waves of active sonar and attenuate the noise emitted from the vessels. Rubber layers with periodically distributed air cavities are widely used as anechoic coatings. In this paper, the sound absorption of anechoic coatings embedded with doubly periodic cavities and backed with periodically rib-stiffened plates is investigated using a finite element method (FEM) with Bloch-periodic boundary conditions. Numerical results given by the FEM are compared with those of a simplified transfer impedance approach to explain the shifting of the main absorption peak. Further a simplified FEM approach, which reduces calculation time significantly and maintains the reasonable accuracy, is proposed for a comparison. The results indicate that the plate and the ribs can have significant impacts on the absorption performance of anechoic coatings, especially at low frequencies.

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