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1.
Mol Plant ; 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35524410

RESUMO

Chinese sprangletop (Leptochloa chinensis (L.) Nees), belonging to the grass subfamily Chloridoideae, is one of the most notorious weeds in the rice ecosystems. Here we report a chromosome-scale reference genome assembly and a genomic variation map of the tetraploid L. chinensis. The L. chinensis genome is contributed by two diploid progenitors that diverged ∼10.9 million years ago, and its two subgenomes display neither fractionation bias nor overall gene expression dominance. Comparative genomic analyses reveal substantial genome rearrangements in L. chinensis after its divergence from the common ancestor of Chloridoideae, and together with and transcriptome profiling, demonstrate the important contribution of the tetraploidization to the gene sources for the L. chinensis herbicide resistance. Population genomic analyses of 89 accessions from China uncover that L. chinensis collected from southern/southwestern provinces have substantially higher nucleotide diversity than those from the middle and lower reaches of the Yangtze River, suggesting the spread route of L. chinensis in China from the southern/southwestern provinces to the middle and lower reaches of the Yangtze River. During this spread, L. chinensis shows significantly increased herbicide resistance, accompanied by the selection of numerous genes involved in herbicide resistance. Together, our study provides valuable genomic resources for the management of L. chinensis and insights into the herbicide resistance as well as the origin and adaptive evolution of L. chinensis.

2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(2): 286-289, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35538764

RESUMO

Objective To evaluate the safety and effectiveness of laparoscopic common bile duct exploration in the treatment of common bile duct stones. Methods A retrospective analysis was conducted for 158 patients with cholecystolithiasis and choledocholithiasis admitted to the Number One Hospital of Zhangjiakou from January 2015 to December 2019.The patients were assigned into three groups according to the diameters of cystic duct and common bile duct,degrees of abdominal infection and tissue edema,and operation method.Group A(16 cases):laparoscopic cholecystectomy,transcystic choledochoscopic exploration for stone removal;Group B(94 cases):laparoscopic cholecystectomy,common bile duct incision exploration combined with choledochoscopy for stone removal,T tube drainage;Group C(48 cases):laparoscopic cholecystectomy,common bile duct incision exploration combined with choledochoscopy for stone removal,primary closure of the common bile duct.The operation time,residual rate of stones,and complication(bleeding,bile leakage,and wound infection) rate were compared between groups. Results The operation time of groups A,B,and C was(95.1±14.7),(102.2±18.1),(110.1±16.4) minutes,respectively,which showed no statistical difference between each other(F=0.020,P=0.887).One case in group A had residual stones,while no residual stone appeared in groups B and C.The overall stone clearance rate was 99.4% and the overall complication rate was 1.9%.There was no perioperative death. Conclusion It is generally safe and effective to carry out laparoscopic cholecystectomy and common bile duct exploration for stone removal in suitable populations.

3.
Adv Mater ; : e2201575, 2022 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-35526115

RESUMO

Here an ultrasonic motor built with a contactless meta engine block (MEB) is designed and experimentally demonstrated for twisting the linear momentum of sound emanating a Helmholtz resonator-based metasurface into orbital angular momentum (OAM). The MEB is capable to host high-efficient excitations of eigenmodes carrying desired OAM whose Bessel acoustic intensity patterns are enhanced by over 10 times compared to the incident wave. Thanks to this efficiency, bidirectional ultrasonic OAM is capable to drive loads at speeds up to 1000 rpm at 4 Watts and remarkable sound radiation torque levels. Moreover, we also demonstrate the possibility of using arbitrarily shaped MEBs by engineering its physical boundary condition based on an analytically derived criterion to guarantee high twisting efficiency of man-made OAM. Our results show how noninvasive driving of an ultrasonic motor can be made possible through appropriately-designed momentum twisting, which opens the door to a new class of integrated mechanical devices solely powered by sound. This article is protected by copyright. All rights reserved.

4.
Radiat Oncol ; 17(1): 82, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35443714

RESUMO

BACKGROUND: Robotic linac is ideally suited to deliver hypo-fractionated radiotherapy due to its compact head and flexible positioning. The non-coplanar treatment space improves the delivery versatility but the complexity also leads to prolonged optimization and treatment time. METHODS: In this study, we attempted to use the deep learning (pytorch) framework for the plan optimization of circular cone based robotic radiotherapy. The optimization problem was topologized into a simple feedforward neural network, thus the treatment plan optimization was transformed into network training. With this transformation, the pytorch toolkit with high-efficiency automatic differentiation (AD) for gradient calculation was used as the optimization solver. To improve the treatment efficiency, plans with fewer nodes and beams were sought. The least absolute shrinkage and selection operator (lasso) and the group lasso were employed to address the "sparsity" issue. RESULTS: The AD-S (AD sparse) approach was validated on 6 brain and 6 liver cancer cases and the results were compared with the commercial MultiPlan (MLP) system. It was found that the AD-S plans achieved rapid dose fall-off and satisfactory sparing of organs at risk (OARs). Treatment efficiency was improved by the reduction in the number of nodes (28%) and beams (18%), and monitor unit (MU, 24%), respectively. The computational time was shortened to 47.3 s on average. CONCLUSIONS: In summary, this first attempt of applying deep learning framework to the robotic radiotherapy plan optimization is promising and has the potential to be used clinically.


Assuntos
Radioterapia de Intensidade Modulada , Procedimentos Cirúrgicos Robóticos , Humanos , Órgãos em Risco , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos
5.
Sci Total Environ ; 835: 155522, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35489501

RESUMO

Ibuprofen (IBU) and naproxen (NPX) are commonly used non-steroidal anti-inflammatory drugs (NSAIDs) with high-risk quotients and are frequently detected in various aquatic environments. A weak electrostimulated biofilm not only had improved removal efficiencies to IBU and NPX, but also transformed different enantiomers with comparable efficiency and without configuration inversion. IBU was transformed mainly by oxidation (hydroxyl-IBU, carboxy-IBU), while NPX was mainly detoxified. The microbial analysis of IBU and NPX biofilm showed that the shared core consortia (> 1%) contained typical electro-active bacteria (Geobacter, Desulfovibrio), fermenters (Petrimonas, Acetobacterium) and potential degraders (Pandoraea, Nocardiaceae), which exhibited synergistic interactions by exchanging the additional electrons, H+, coenzyme NAD(H) or NAD(P) (H) and energy. The fungal community has a significant correlation to those core bacteria and they may also play transformation roles with their diverse enzymes. Plenty of nonspecific oxidoreductase, decarboxylase, hydrolase, cytochrome P450, and other enzymes relating to xenobiotic degradation were high-abundance encoded by the core consortia and could potentially participate in IBU and NPX biotransformation. This study offers new insights into the functional microbes and enzymes working on complex NSAIDs biotransformation and provided a feasible strategy for the enhanced removal of NSAIDs (especially IBU and NPX).

6.
Chemosphere ; 301: 134549, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35405189

RESUMO

Excessive input of nitrogen(N) fertilizer and improper selection of fertilizer types in the greenhouse vegetable production process will lead to a large amount of N loss. In order to relieve the environmental pollution caused by N loss, a planting experiment was carried out in a solar greenhouse in Shouguang, Shandong, China, to investigate the effects of N-reducing fertilizer and straw application on greenhouse vegetable yield and soil N loss, and to explore the fate of N after fertilizer application using the 15N isotope tracing technique. The experiment was planted for two seasons from July 2017 to June 2018 with four treatments: control (CK), conventional fertilizer (CN), reduced N topdressing (SN), and reduced N topdressing + straw (SNS). The results indicated that N reduction fertilizer and straw application resulted in a 35.25%-35.49% reduction in total N2O emissions and 15.76%-41.77% reduction in mineral N leaching losses. 15N isotopes as tracers showed that the maximum abundance in N2O was reduced by 58.5% and 55.68% for SN and SNS, respectively, and cumulative N2O emissions were reduced by 80.44% and 81.67%, respectively, and mineral N leaching was reduced by 74.4% and 70.48%, respectively, after fertilization compared to CN treatment. There was no significant difference in tomato yield between the three fertilizer treatments in the two growing seasons. Therefore, in greenhouse vegetable production, the amount of N fertilizer was reduced by 40.7% and the addition of straw reduced N2O emissions and N leaching without affecting tomato yields.

7.
Sci Total Environ ; 835: 155420, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35469873

RESUMO

Small changes in soil aggregates-associated organic carbon (OC) can induce huge fluctuations in greenhouse gas emissions. However, there is a knowledge gap on the responses to nitrogen (N) fertilization under plastic film mulching, especially in long-term continuous rotation systems. This study assessed the impacts of plastic film mulching and N fertilization on the soil aggregate distribution and associated OC and N fractions in a 10-year continuous cucumber-cabbage rotation soil (0-40 cm). The impacts also were further quantified using the design of experiment (DOE) method. Plastic film mulching alleviated the impact of N fertilization on soil aggregate stability, which declined under higher N doses. Plastic film mulching coupled with N fertilization resulted in higher contents of soil OC and dissolved OC in macroaggregates but lower contents in silt+clay- aggregates. The total N and dissolved organic N (DON) contents in different aggregates varied significantly with N application doses, and the alternations were impacted by plastic film mulching, which improved the DON distribution in larger agglomerates, especially at medium and high N doses. Soil aggregate distribution and associated OC and N fractions did not show consistent trends in different soil depths, which was attributed to the contributions of plastic film mulching, N fertilization and their interactions. The study suggests that N fertilizer should be applied under plastic film mulches at appropriate levels to improve C assimilation and soil fertility and promote the sustainable development of long-term vegetable rotation systems.

8.
Artigo em Inglês | MEDLINE | ID: mdl-35439142

RESUMO

The powerful learning ability of deep neural networks enables reinforcement learning (RL) agents to learn competent control policies directly from continuous environments. In theory, to achieve stable performance, neural networks assume identically and independently distributed (i.i.d.) inputs, which unfortunately does not hold in the general RL paradigm where the training data are temporally correlated and nonstationary. This issue may lead to the phenomenon of ``catastrophic interference'' and the collapse in performance. In this article, we present interference-aware deep Q-learning (IQ) to mitigate catastrophic interference in single-task deep RL. Specifically, we resort to online clustering to achieve on-the-fly context division, together with a multihead network and a knowledge distillation regularization term for preserving the policy of learned contexts. Built upon deep Q networks (DQNs), IQ consistently boosts the stability and performance when compared to existing methods, verified with extensive experiments on classic control and Atari tasks. The code is publicly available at https://github.com/Sweety-dm/Interference-aware-Deep-Q-learning.

9.
Acta Biomater ; 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35405327

RESUMO

Selective BCL2 inhibitor ABT-199 has been approved to treat hematological malignancies including acute myeloid leukemia (AML). However, acquired drug resistance and severe side effects occur after extended treatment limiting the clinical usage of ABT-199. Here, we successfully encapsulated pure ABT-199 in amphiphilic mPEG-b-PTMC169 block copolymer, forming mPEG-b-PTMC169@ABT-199 nanoparticles (abbreviated as PEG-ABT-199), which presented better aqueous dispersion and higher efficiency of loading and encapsulation than pure ABT-199. We then compared the anti-leukemic ability of pure ABT-199 and PEG-ABT-199 in vitro and in vivo. PEG-ABT-199 had a lower IC50 value compared with pure ABT-199 in MV4-11 and MOLM-13 cell lines. In addition, PEG-ABT-199 significantly induced apoptosis and decreased colony number than pure ABT-199. Most importantly, PEG-ABT-199 markedly reduced leukemic burden, inhibited the infiltration of leukemic blasts in the spleen, and extended the overall survival (OS) in MLL-AF9-transduced murine AML compared with free ABT-199. Meanwhile, the blank PEG169 NP was non-toxic to normal hematopoiesis in vitro and in vivo, suggesting that PEG169 NP is a safe carrier. Mechanistically, PEG-ABT-199 enhanced mitochondria-targeted delivery of ABT-199 to trigger the collapse of mitochondrial membrane potential (MMP), the release of cytochrome c (cyt-c), and mitochondria-based apoptosis. In conclusion, our results suggest that PEG-ABT-199 has more vital anti-leukemic ability than pure ABT-199. PEG-ABT-199 has potential application in clinical trials to alleviate side effects and improve anti-leukemia ability. STATEMENT OF SIGNIFICANCE: ATB-199, an orally selective inhibitor for BCL2 protein, presents marked activity in relapsed or refractory AML, T-ALL, and CLL patients. However, ABT-199 resistance severely limits the further clinical usage because of off-target effects, non-specific toxicities, and low delivery of drugs. To reduce the side-effects and improve the solubility and bioavailability, ABT-199 was encapsulated into the amphiphilic mPEG-b-PTMC block copolymer by co-assembly method to obtain mPEG-b-PTMC@ABT-199 nanoparticles (PEG-ABT-199). PEG-ABT-199 has several advantages compared with pure ABT-199. 1.PEG-ABT-199 presents better aqueous dispersion and higher efficiencies of loading and encapsulation than pure ABT-199. 2. PEG-ABT-199 substantially enhances the anti-leukemic ability in vitro and in vivo compared with pure ABT-199. 3. PEG-ABT-199 has little effects on normal cells. 4. PEG-ABT-199 can reduce treatment cost.

11.
Transl Res ; 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35460889

RESUMO

Dysferlin (DYSF) has drawn much attention due to its involvement in dysferlinopathy and was reported to affect monocyte functions in recent studies. However, the role of DYSF in the pathogenesis of atherosclerotic cardiovascular diseases (ASCVD) and the regulation mechanism of DYSF expression have not been fully studied. In this study, Gene Expression Omnibus (GEO) database and epigenome-wide association study (EWAS) literatures were searched to find the DNA methylation-driven genes (including DYSF) of ASCVD. The hub genes related to DYSF were also identified through weighted correlation network analysis (WGCNA). Regulation of DYSF expression through its promoter methylation status was verified using peripheral blood leucocytes (PBLs) from ASCVD patients and normal controls, and experiments on THP1 cells and Apoe-/- mice. Similarly, the expressions of DYSF related hub genes, mainly contained SELL, STAT3 and TMX1, were also validated. DYSF functions were then evaluated by phagocytosis, transwell and adhesion assays in DYSF knock-down and overexpressed THP1 cells. The results showed that DYSF promoter hypermethylation up-regulated its expression in clinical samples, THP1 cells and Apoe-/- mice, confirming DYSF as a DNA methylation-driven gene. The combination of DYSF expression and methylation status in PBLs had a considerable prediction value for ASCVD. Besides, DYSF could enhance the phagocytosis, migration and adhesion ability of THP1 cells. Among DYSF related hub genes, SELL was proven to be the downstream target of DYSF by wet experiments. In conclusion, DYSF promoter hypermethylation upregulated its expression and promoted monocytes activation, which further participated in the pathogenesis of ASCVD.

13.
Zhongguo Yi Liao Qi Xie Za Zhi ; 46(2): 181-186, 2022 Mar 30.
Artigo em Chinês | MEDLINE | ID: mdl-35411747

RESUMO

As an important auxiliary tool for amputees to gain abled limb functions, prosthetic limbs with decoration or feedforward control channel could not meet the needs. In order to enable the prosthesis to deliver the information, includes temperature, pressure, position, shape and so on, a variety of sensory feedback methods have been integrated into the prosthesis. According to the position of the feedback terminal on the human body, the perceptual feedback systems include invasive and noninvasive sensory feedback. This review presents the research progress of these perceptual feedback techniques, and summarizes the problems in the application in artificial limbs. Finally, the development trend of sensory feedback technology in prostheses is prospected.


Assuntos
Amputados , Membros Artificiais , Retroalimentação Sensorial , Humanos , Desenho de Prótese , Tecnologia
14.
Clin Epigenetics ; 14(1): 32, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35227297

RESUMO

BACKGROUND: Recent studies have suggested that folic acid can restore abnormal DNA methylation and monocyte subset shifts caused by hyperhomocysteinemia (HHcy) and hyperlipidemia (HL). However, the exact mechanism of action is still not fully understood. In this study, we further investigated the reversal effect and underlying mechanism of folic acid on the shift in monocyte subsets induced by aberrant lipids and Hcy metabolism via DNA methylation in vitro and in vivo. RESULTS: Our results showed that intermediate monocytes were significantly increased but had the lowest global 5-methylcytosine (5-mC) levels in coronary artery disease (CAD) patients, which might lead to a decrease in the global 5-mC levels of peripheral blood leukocytes (PBLs). We also discovered that ARID5B might mediate the increased proportion of intermediate monocytes, as this factor was related to the proportion of monocyte subsets and the expression of CCR2. The expression of ARID5B was inversely associated with the hypermethylated cg25953130 CpG site, which was induced by HL and HHcy. ARID5B could also regulate monocyte CCR2, MCP-1, and TNF-α expression, adhesion and migration, macrophage polarization, and monocyte/macrophage apoptosis, which might explain the regulatory effect of ARID5B on monocyte subset shifting. Folic acid reversed HL- and HHcy-mediated aberrant global and cg25953130 DNA methylation, reduced the proportion of intermediate monocytes, and inhibited the formation of atherosclerotic plaques. CONCLUSION: Folic acid plays a protective role against atherosclerosis through the regulation of DNA methylation, ARID5B expression, and monocyte subsets.


Assuntos
Aterosclerose , Placa Aterosclerótica , Aterosclerose/genética , Aterosclerose/metabolismo , Metilação de DNA , Ácido Fólico/metabolismo , Ácido Fólico/farmacologia , Humanos , Monócitos/metabolismo , Placa Aterosclerótica/genética
15.
J Genet Genomics ; 49(4): 338-349, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35240304

RESUMO

Liver fibrosis is a key transformation stage and also a reversible pathological process in various types of chronic liver diseases. However, the pathogenesis of liver fibrosis still remains elusive. Here, we report that the calcium binding protein A11 (S100A11) is consistently upregulated in the integrated data from GSE liver fibrosis and tree shrew liver proteomics. S100A11 is also experimentally activated in liver fibrosis in mouse, rat, tree shrew, and human with liver fibrosis. While overexpression of S100A11 in vivo and in vitro exacerbates liver fibrosis, the inhibition of S100A11 improves liver fibrosis. Mechanistically, S100A11 activates hepatic stellate cells (HSCs) and the fibrogenesis process via the regulation of the deacetylation of Smad3 in the TGF-ß signaling pathway. S100A11 physically interacts with SIRT6, a deacetylase of Smad2/3, which may competitively inhibit the interaction between SIRT6 and Smad2/3. The subsequent release and activation of Smad2/3 promote the activation of HSCs and fibrogenesis. Additionally, a significant elevation of S100A11 in serum is observed in clinical patients. Our study uncovers S100A11 as a novel profibrogenic factor in liver fibrosis, which may represent both a potential biomarker and a promising therapy target for treating liver fibrosis and fibrosis-related liver diseases.


Assuntos
Transdução de Sinais , Sirtuínas , Animais , Humanos , Fígado/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Camundongos , Ratos , Transdução de Sinais/fisiologia , Sirtuínas/metabolismo , Fator de Crescimento Transformador beta/metabolismo
16.
Front Immunol ; 13: 731500, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35237256

RESUMO

Pleckstrin homology-like domain, family A, member 1 (PHLDA1) has been reported to be expressed in many mammalian tissues and cells. However, the functions and exact mechanisms of PHLDA1 remain unclear. In this study, we found that PHLDA1 expression was significantly altered in macrophages after exposure to lipopolysaccharide (LPS) in vitro, suggesting that PHLDA1 may be involved in the regulation of TLR4 signaling pathway activated by LPS. PHLDA1 attenuated the production of LPS-stimulated proinflammatory cytokines (TNF-α, IL-6, and IL-1ß). Further research showed that the phosphorylation levels of some important signal molecules in TLR4/MyD88-mediated MAPK and NF-κB signaling pathways were reduced by PHLDA1, which in turn impaired the transcription factors NF-κB and AP1 nuclear translocation and their responsive element activities. Furthermore, we found that PHLDA1 repressed LPS-induced proinflammatory cytokine production via binding to Tollip which restrained TLR4 signaling pathway. A mouse model of endotoxemia was established to confirm the above similar results. In brief, our findings demonstrate that PHLDA1 is a negative regulator of LPS-induced proinflammatory cytokine production by Tollip, suggesting that PHLDA1 plays an anti-inflammatory role through inhibiting the TLR4/MyD88 signaling pathway with the help of Tollip. PHLDA1 may be a novel therapeutic target in treating endotoxemia.


Assuntos
Endotoxemia , Lipopolissacarídeos , Animais , Citocinas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lipopolissacarídeos/farmacologia , Mamíferos/metabolismo , Camundongos , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Fatores de Transcrição
17.
Ying Yong Sheng Tai Xue Bao ; 33(2): 415-422, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35229515

RESUMO

The phospholipid fatty acid (PLFA) technique was used to investigate the effects of fertilization on soil characteristics and microbial community of tomato in a solar greenhouse in Shouguang, Shandong Province, China, based on a long-term (12-year) fertilization experiment. The experiment involved a control (CK) and five fertilization treatments, namely, traditional nitrogen application (CN), traditional nitrogen application+straw return (CNS), optimized nitrogen application (SN), optimized nitrogen application+straw return (SNS), and organic manure nitrogen application+straw return (MNS). Results showed that the contents of soil organic matter and avai-lable P and K under all fertilization treatments were significantly higher than that of CK, but no significant difference among fertilization treatments. The traditional nitrogen application (i.e., CN and CNS) significantly decreased soil pH. The reduction of nitrogen fertilizer (i.e., SN, SNS and MNS) did not affect soil pH. Compared with CK, no straw treatment (i.e., CN and SN) and MNS did not affect the content of soil available N, but nitrogen combined with straw returned (i.e., CNS and SNS) significantly increased soil available N content. The optimized N with straw return (i.e., SNS) treatment resulted in the highest soil available N. Compared with CK and treatments without straw (i.e., CN, SN), treatments with straw (i.e., MNS, CNS and SNS) substantially changed soil microbial community structure and increased the biomass of soil bacteria, fungi, actinomycetes, mycorrhizal fungi, and the total amount of PLFA. SNS treatment had the highest soil microbial diversity, the highest biomass of soil bacteria, fungi, and actinomycetes, the highest total amount of PLFA, the highest ratios of fungi/bacteria and monounsaturated fatty acids/saturated fatty acids (MONO/SAT), the two indicators for soil ecosystem stability. Further, it had the lowest ratios of iso/anteiso fatty acids (i/a) and gram-positive/gram-negative bacteria (G+/G-), the indicators for nutritional stress. Redundancy and correlation analysis revealed that soil organic matter was the main factor affecting soil microbial community structure, with a significant positive correlation with actinomycetes and gram-positive bacteria. In conclusion, straw returning combined with optimized nitrogen application (i.e., SNS, 8 t·hm-2 of wheat straw with N fertilizer reduced by 58.3%) could improve soil nutrient status, soil microbial biomass, soil microbial community structure, and soil ecological environment. It would be an effective measure for reducing fertilizer application and improving efficiency.


Assuntos
Lycopersicon esculentum , Microbiota , Agricultura , Fertilização , Fertilizantes , Nitrogênio/análise , Nutrientes , Solo/química , Microbiologia do Solo
18.
Aging Cell ; 21(4): e13595, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35343058

RESUMO

Although it is well known that metabolic control plays a crucial role in regulating the health span and life span of various organisms, little is known for the systems metabolic profile of centenarians, the paradigm of human healthy aging and longevity. Meanwhile, how to well characterize the system-level metabolic states in an organism of interest remains to be a major challenge in systems metabolism research. To address this challenge and better understand the metabolic mechanisms of healthy aging, we developed a method of genome-wide precision metabolic modeling (GPMM) which is able to quantitatively integrate transcriptome, proteome and kinetome data in predictive modeling of metabolic networks. Benchmarking analysis showed that GPMM successfully characterized metabolic reprogramming in the NCI-60 cancer cell lines; it dramatically improved the performance of the modeling with an R2 of 0.86 between the predicted and experimental measurements over the performance of existing methods. Using this approach, we examined the metabolic networks of a Chinese centenarian cohort and identified the elevated fatty acid oxidation (FAO) as the most significant metabolic feature in these long-lived individuals. Evidence from serum metabolomics supports this observation. Given that FAO declines with normal aging and is impaired in many age-related diseases, our study suggests that the elevated FAO has potential to be a novel signature of healthy aging of humans.


Assuntos
Envelhecimento Saudável , Longevidade , Idoso de 80 Anos ou mais , Envelhecimento/genética , Envelhecimento/metabolismo , Humanos , Longevidade/genética , Metabolômica , Transcriptoma/genética
19.
Front Immunol ; 13: 773001, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35154100

RESUMO

Objective: Limiting purine intake, inhibiting xanthine oxidoreductase (XOR) and inhibiting urate reabsorption in proximal tubule by uricosuric drugs, to reduce serum uric acid (UA) levels, are recognized treatments for gout. However, the mechanism of increased how XOR expression and activity in hyperuricemia and gout remains unclear. This study aims to explore whether exogenous purines are responsible for increased XOR expression and activity. Methods: HepG2 and Bel-7402 human hepatoma cells were stimulated with exogenous purine, or were exposed to conditioned growth medium of purine-stimulated Jurkat cells, followed by measurement of XOR expression and UA production to determine the effect of lymphocyte-secreted cytokines on XOR expression in hepatocytes. The expression of STAT1, IRF1 and CBP and their binding on the XDH promoter were detected by western blotting and ChIP-qPCR. The level of DNA methylation was determined by bisulfite sequencing PCR. Blood samples from 117 hyperuricemia patients and 119 healthy individuals were collected to analyze the correlation between purine, UA and IFN-γ concentrations. Results: Excess of purine was metabolized to UA in hepatocyte metabolism by XOR that was induced by IFN-γ secreted in the conditioned growth medium of Jurkat cells in response to exogenous purine, but it did not directly induce XOR expression. IFN-γ upregulated XOR expression due to the enhanced binding of STAT1 to IRF1 to further recruit CBP to the XDH promoter. Clinical data showed positive correlation of serum IFN-γ with both purine and UA, and associated risk of hyperuricemia. Conclusion: Purine not only acts as a metabolic substrate of XOR for UA production, but it induces inflammation through IFN-γ secretion that stimulates UA production through elevation of XOR expression.


Assuntos
Hepatócitos/efeitos dos fármacos , Interferon gama/imunologia , Purinas/metabolismo , Purinas/farmacologia , Regulação para Cima , Ácido Úrico/metabolismo , Xantina Desidrogenase/genética , Carcinoma Hepatocelular , Linhagem Celular Tumoral , Humanos , Inflamação , Interferon gama/biossíntese , Células Jurkat , Neoplasias Hepáticas
20.
Chemosphere ; 295: 133935, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35149011

RESUMO

The co-existence of volatile chlorinated hydrocarbons (VCHs) and nitrate pollution in groundwater is prominent, but how nitrate exposure affects weak-electrical stimulated bio-dechlorination activity of VCH is largely unknown. Here, by establishing weak-electrical stimulated trichloroethylene (TCE) dechlorination systems, the influence on TCE dechlorination by exposure to the different concentrations (25-100 mg L-1) of nitrate was investigated. The existence of nitrate in general decreased TCE dechlorination efficiency to varying degrees, and the higher nitrate concentration, the stronger the inhibitory effects, verified by the gradually decreased transcription levels of tceA. Although the TCE dechlorination kinetic rate constant decreased by 36% the most, under all nitrate concentration ranges, TCE could be completely removed within 32 h and no difference in generated metabolites was found, revealing the well-maintained dechlorination activity. This was due to the quickly enriched bio-denitrification activity, which removed nitrate completely within 9 h, and thus relieved the inhibition on TCE dechlorination. The obvious bacterial community structure succession was also observed, from dominating with dechlorination genera (e.g., Acetobacterium, Eubacterium) to dominating with both dechlorination and denitrification genera (e.g., Acidovorax and Brachymonas). The study proposed the great potential for the in situ simultaneous denitrification and dehalogenation in groundwater contaminated with both nitrate and VCHs.


Assuntos
Água Subterrânea , Hidrocarbonetos Clorados , Tricloroetileno , Biodegradação Ambiental , Estimulação Elétrica , Água Subterrânea/química , Nitratos , Tricloroetileno/química
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