Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.420
Filtrar
1.
Autophagy ; : 1-18, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38597182

RESUMO

Non-structural protein 2 (nsp2) exists in all coronaviruses (CoVs), while its primary function in viral pathogenicity, is largely unclear. One such enteric CoV, porcine epidemic diarrhea virus (PEDV), causes high mortality in neonatal piglets worldwide. To determine the biological role of nsp2, we generated a PEDV mutant containing a complete nsp2 deletion (rPEDV-Δnsp2) from a highly pathogenic strain by reverse genetics, showing that nsp2 was dispensable for PEDV infection, while its deficiency reduced viral replication in vitro. Intriguingly, rPEDV-Δnsp2 was entirely avirulent in vivo, with significantly increased productions of IFNB (interferon beta) and IFN-stimulated genes (ISGs) in various intestinal tissues of challenged newborn piglets. Notably, nsp2 targets and degrades TBK1 (TANK binding kinase 1), the critical kinase in the innate immune response. Mechanistically, nsp2 induced the macroautophagy/autophagy process and recruited a selective autophagic receptor, NBR1 (NBR1 autophagy cargo receptor). NBR1 subsequently facilitated the K48-linked ubiquitination of TBK1 and delivered it for autophagosome-mediated degradation. Accordingly, the replication of rPEDV-Δnsp2 CoV was restrained by reduced autophagy and excess productions of type I IFNs and ISGs. Our data collectively define enteric CoV nsp2 as a novel virulence determinant, propose a crucial role of nsp2 in diminishing innate antiviral immunity by targeting TBK1 for NBR1-mediated selective autophagy, and pave the way to develop a new type of nsp2-based attenuated PEDV vaccine. The study also provides new insights into the prevention and treatment of other pathogenic CoVs.Abbreviations: 3-MA: 3-methyladenine; Baf A1: bafilomycin A1; CoV: coronavirus; CQ: chloroquine; dpi: days post-inoculation; DMVs: double-membrane vesicles; GABARAP: GABA type A receptor-associated protein; GFP: green fluorescent protein; GIGYF2: GRB10 interacting GYF protein 2; hpi: hours post-infection; IFA: immunofluorescence assay; IFIH1: interferon induced with helicase C domain 1; IFIT2: interferon induced protein with tetratricopeptide repeats 2; IFITM1: interferon induced transmembrane protein 1; IFNB: interferon beta; IRF3: interferon regulatory factor 3; ISGs: interferon-stimulated genes; mAb: monoclonal antibody; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAVS: mitochondrial antiviral signaling protein; NBR1: NBR1 autophagy cargo receptor; nsp2: non-structural protein 2; OAS1: 2'-5'-oligoadenylate synthetase 1; PEDV: porcine epidemic diarrhea virus; PRRs: pattern recognition receptors; RIGI: RNA sensor RIG-I; RT-qPCR: reverse transcription quantitative polymerase chain reaction; SQSTM1: sequestosome 1; TBK1: TANK binding kinase 1; TCID50: 50% tissue culture infectious doses; VSV: vesicular stomatitis virus.

2.
Inorg Chem ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38620065

RESUMO

Herein, three In(III)-based metal-organic frameworks (In-MOFs) with different degrees of interpenetration (DOI), namely In-MOF-1, In-MOF-2, and In-MOF-3, constructed by In3+ and Y-shaped ligands 4,4',4″-s-triazine-2,4,6-triyltribenzoate (H3TATB), are successfully synthesized through the ionothermal/solvothermal method. Subsequently, three novel In-MOFs, including noninterpenetration polycatenation, 2-fold interpenetrated, and 4-fold interpenetrated structure, are employed as the platform for systematically investigating the separation efficiency of CO2/N2, CO2/CH4, and CO2/CH4/N2 mixture gas system. Among them, In-MOF-2 shows the highest CO2 uptake capacities at 298 K and simultaneously possesses the low adsorption enthalpy of CO2 (26.4 kJ/mol at low coverage), a feature desirable for low-energy-cost adsorbent regeneration. The CO2/N2 (v: v = 15/85) selectivity of In-MOF-2 reaches 37.6 (at 298 K and 1 bar), also revealing outstanding selective separation ability from flue gases and purifying natural gas, affording a unique robust separation material as it has moderate DOI and pore size. In-MOF-2 shows exceptional stability and feasibility to achieve reproducibility. Aperture adjustment makes In-MOF-2 a versatile platform for selectively capturing CO2 from flue gases or purifying natural gas.

3.
Cell Prolif ; : e13646, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623945

RESUMO

Transglutaminase 2 (Tgm2) plays an essential role in hepatic repair following prolonged toxic injury. During cholestatic liver injury, the intrahepatic cholangiocytes undergo dynamic tissue expansion and remodelling, referred to as ductular reaction (DR), which is crucial for liver regeneration. However, the molecular mechanisms governing the dynamics of active cells in DR are still largely unclear. Here, we generated Tgm2-knockout mice (Tgm2-/-) and Tgm2-CreERT2-Rosa26-mTmG flox/flox (Tgm2CreERT2-R26T/Gf/f) mice and performed a three-dimensional (3D) collagen gel culture of mouse hepatocytes to demonstrate how Tgm2 signalling is involved in DR to remodel intrahepatic cholangiocytes. Our results showed that the deletion of Tgm2 adversely affected the functionality and maturity of the proliferative cholangiocytes in DR, thus leading to more severe cholestasis during DDC-induced liver injury. Additionally, Tgm2 hepatocytes played a crucial role in the regulation of DR through metaplasia. We unveiled that Tgm2 regulated H3K4me3Q5ser via serotonin to promote BMP signalling activation to participate in DR. Besides, we revealed that the activation or inhibition of BMP signalling could promote or suppress the development and maturation of cholangiocytes in DDC-induced DR. Furthermore, our 3D collagen gel culture assay indicated that Tgm2 was vital for the development of cholangiocytes in vitro. Our results uncovered a considerable role of BMP signalling in controlling metaplasia of Tgm2 hepatocytes in DR and revealed the phenotypic plasticity of mature hepatocytes.

4.
BMC Biol ; 22(1): 82, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609969

RESUMO

BACKGROUND: As an endemic shrub of the Qinghai-Tibetan Plateau (QTP), the distribution of Hippophae tibetana Schlecht. ranges between 2800 and 5200 m above sea level. As the most basal branch of the Hippophae genus, H. tibetana has an extensive evolutionary history. The H. tibetana is a valuable tree for studying the ecological evolution of species under extreme conditions. RESULTS: Here, we generated a high-quality chromosome-level genome of H. tibetana. The total size of the assembly genome is 917 Mb. The phylogenomic analysis of 1064 single-copy genes showed a divergence between 3.4 and 12.8 Mya for H. tibetana. Multiple gene families associated with DNA repair and disease resistance were significantly expanded in H. tibetana. We also identified many genes related to DNA repair with signs of positive selection. These results showed expansion and positive selection likely play important roles in H. tibetana's adaptation to comprehensive extreme environments in the QTP. A comprehensive genomic and transcriptomic analysis identified 49 genes involved in the flavonoid biosynthesis pathway in H. tibetana. We generated transgenic sea buckthorn hairy root producing high levels of flavonoid. CONCLUSIONS: Taken together, this H. tibetana high-quality genome provides insights into the plant adaptation mechanisms of plant under extreme environments and lay foundation for the functional genomic research and molecular breeding of H. tibetana.


Assuntos
Hippophae , Humanos , Altitude , Reparo do DNA , Flavonoides , Cromossomos
5.
Environ Sci Technol ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578665

RESUMO

Carbon neutral or negative mining can potentially be achieved by integrating carbon mineralization processes into the mine design, operations, and closure plans. Brucite [Mg(OH)2] is a highly reactive mineral present in some ultramafic mine tailings with the potential to be rapidly carbonated and can contain significant amounts of ferrous iron [Fe(II)] substituted for Mg; however, the influence of this substitution on carbon mineralization reaction products and efficiency has not been thoroughly constrained. To better assess the efficiency of carbon storage in brucite-bearing tailings, we performed carbonation experiments using synthetic Fe(II)-substituted brucite (0, 6, 23, and 44 mol % Fe) slurries in oxic and anoxic conditions with 10% CO2. Additionally, the carbonation process was evaluated using different background electrolytes (NaCl, Na2SO4, and Na4SiO4). Our results indicate that carbonation efficiency decreases with increasing Fe(II) substitution. In oxic conditions, precipitation of ferrihydrite [Fe10IIIO14(OH)2] and layered double hydroxides {e.g., pyroaurite [Mg6Fe2III(OH)16CO3·4H2O]} limited carbonation efficiency. Carbonation in anoxic environments led to the formation of Fe(II)-substituted nesquehonite (MgCO3·3H2O) and dypingite [Mg5(CO3)4(OH)2·âˆ¼5H2O], as well as chukanovite [Fe2IICO3(OH)2] in the case of 23 and 44 mol % Fe(II)-brucite carbonation. Carbonation efficiencies were consistent between chloride- and sulfate-rich solutions but declined in the presence of dissolved Si due to the formation of amorphous SiO2·nH2O and Fe-Mg silicates. Overall, our results indicate that carbonation efficiency and the long-term fate of stored CO2 may depend on the amount of substituted Fe(II) in both feedstock minerals and carbonate products.

7.
Angew Chem Int Ed Engl ; : e202405314, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602843

RESUMO

Ice has been suggested to have played a significant role in the origin of life partly owing to its ability to concentrate organic molecules and promote reaction efficiency. However, the techniques for studying organic molecules in ice are absorption-based, which limits the sensitivity of measurements. Here we introduce an emission-based method to study organic molecules in water ice: the phosphorescence displays high sensitivity depending on the hydration state of an organic salt probe, acridinium iodide (ADI). The designed ADI aqueous system exhibits phosphorescence that can be severely perturbed when the temperature is higher than 110 K at a concentration of the order of 10-5M, indicating changes in hydration for ADI. Using the ADI phosphorescent probe, it is found that the microstructures of water ice, i.e., crystalline vs. glassy, can be strongly dictated by a trace amount (as low as 10-5M) of water-soluble organic molecules. Consistent with cryoSEM images and temperature-dependent Raman spectral data, the ADI is dehydrated in more crystalline ice and hydrated in more glassy ice. The current investigation serves as a starting point for using more sensitive spectroscopic techniques for studying water-organics interactions at a much lower concentration and wider temperature range.

8.
Microbiol Spectr ; : e0009724, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38606996

RESUMO

Mycoplasma pneumoniae (MP) is commonly detected in children. However, the epidemiological trends of MP in Northeast (NE) China are unclear. This retrospective study aimed to investigate the prevalence of MP infections in this understudied region. The clinical manifestations and bronchoscopic findings observed in hospitalized patients with severe Mycoplasma pneumoniae pneumonia (SMPP) were collected from comprehensive data obtained from six tertiary hospitals in NE and Inner Mongolian (IM) China, from 1 January 2017 to 31 December 2023. A total of 5,593,530 children who visited the outpatient and emergency departments, and 412,480 inpatient hospitalized children were included in the study. The positivity rate of MP immunoglobulin M (IgM) in the children who visited the outpatient and emergency departments varied from 7.80% to 10.12%, whereas that of MP infection in hospitalized children ranged from 27.18% to 30.10%. Children hospitalized for MP infection were mainly concentrated in the 1- to 4-year (41.39%) and 4- to 7-year (24.25%) age groups. Before 2020, the season with the highest incidence of MP was winter. After the implementation of non-pharmaceutical interventions (NPIs), the MP epidemic season changed, and the number of children with MP infections decreased; however, the proportion of MP infections in hospitalized children did not change significantly. Starting from August 2023, the MP infection rate in outpatient, emergency, and hospitalized children increased sharply, with SMPP and its complications (e.g., plastic bronchitis and pleural effusion) increasing significantly. MP is prevalent in NE and IM, China. When the NPIs ended, MP infection showed a delayed outbreak trend, and the number of children with severe infection increased significantly. IMPORTANCE: In Northeastern (NE) and Inner Mongolia (IM), the incidence of Mycoplasma pneumoniae (MP) infections, including severe Mycoplasma pneumoniae pneumonia (SMPP), is high, posing health risks and imposing substantial economic burdens on the local population. Therefore, it is imperative to prioritize the study of MP prevalence and address the research gaps in MP epidemiology in these areas of China. We obtained a comprehensive collection of pediatric outpatient, emergency, and inpatient data from six public Grade III hospitals. We believe that our study makes a significant contribution to the literature because understanding regional variations in MP infections can help healthcare professionals tailor prevention and treatment strategies, and studying bronchoscopic manifestations can provide insights into the impact of the disease on the respiratory system, potentially leading to a more effective clinical management.

9.
Environ Sci Technol ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38588505

RESUMO

The energy transition will have significant mineral demands and there is growing interest in recovering critical metals, including rare earth elements (REE), from secondary sources in aqueous and sedimentary environments. However, the role of clays in REE transport and deposition in these settings remains understudied. This work investigated REE adsorption to the clay minerals illite and kaolinite through pH adsorption experiments and extended X-ray absorption fine structure (EXAFS). Clay type, pH, and ionic strength (IS) affected adsorption, with decreased adsorption under acidic pH and elevated IS. Illite had a higher adsorption capacity than kaolinite; however, >95% adsorption was achieved at pH ∼7.5 regardless of IS or clay. These results were used to develop a surface complexation model with the derived binding constants used to predict REE speciation in the presence of competing sorbents. This demonstrated that clays become increasingly important as pH increases, and EXAFS modeling showed that REE can exist as both inner- and outer-sphere complexes. Together, this indicated that clays can be an important control on the transport and enrichment of REE in sedimentary systems. These findings can be applied to identify settings to target for resource extraction or to predict REE transport and fate as a contaminant.

10.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(2): 253-259, 2024 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-38595241

RESUMO

OBJECTIVE: To treat the Crohn's disease (CD) patients with ustekinumab (UST), to eva-luate their clinical and endoscopic remission, and to evaluate their transmural response (TR) and transmural healing (TH) condition using intestinal ultrasonography (IUS). METHODS: Retrospective analysis was made on patients diagnosed with CD in Peking University People's Hospital from January 2020 to August 2022, who were treated with UST for remission induction and maintenance therapy. All the patients were evaluated on both week 8 and week 16/20 after treatment, including clinical, biochemical indicators, colonoscopy and IUS examination. RESULTS: A total of 13 patients were enrolled in this study, including 11 males and 2 females. The minimum age was 23 years, the maximum age was 73 years and the mean age was 36.92 years. All the patients were in the active stage of disease before treatment, and the average Best Crohn's disease activity index (Best CDAI) score was 270.12±105.55. In week 8, the Best CDAI score of the patients decreased from 270.12±105.55 to 133.16±48.66 (t=4.977, P < 0.001). Eight patients achieved clinical remission while 5 patients remained in the active stage. Nine patients underwent colonoscopy evaluation. The average simple endoscopic score for Crohn's disease (SES-CD) score decreased from 10.71±7.14 before treatment to 6.00±7.81(t=2.483, P=0.048) in week 16/20. Four patients achieved endoscopic remission while 5 patients did not. In week 8, 5 patients achieved TR, 2 patients achieved TH, the other 6 patients did not get TR or TH. In week 16/20, 6 patients achieved TR, 3 patients achieved TH while the other 4 patients did not get TR or TH. There was no significant statistical difference in the TR effect of UST between small intestine and colon lesions (Fisher test, P > 0.999). The rate of UST transmural response in the patients who had had previous biological agent therapy was lower than those with no previous biological agent therapy, but there was no significant statistical difference (Fisher test, P=0.491). CONCLUSION: After treatment of UST, the clinical and endoscopic conditions of the CD patients had been improved, and some patients could achieve clinical remission and endoscopic remission. UST had good TR and TH effects on CD. TR might appear in week 8, and the TR effect increased in week 16/20. There was no significant statistical difference in the TR effect between small intestine and colon lesions. TR effect of UST was better in the patients who had no previous biological agent therapy than those who had had other biological agents, but the result had no significant statistical difference.


Assuntos
Doença de Crohn , Masculino , Feminino , Humanos , Adulto , Adulto Jovem , Idoso , Doença de Crohn/tratamento farmacológico , Doença de Crohn/patologia , Ustekinumab/uso terapêutico , Estudos Retrospectivos , Colonoscopia , Indução de Remissão , Resultado do Tratamento
11.
J Neural Eng ; 21(2)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38588700

RESUMO

Objective. The instability of the EEG acquisition devices may lead to information loss in the channels or frequency bands of the collected EEG. This phenomenon may be ignored in available models, which leads to the overfitting and low generalization of the model.Approach. Multiple self-supervised learning tasks are introduced in the proposed model to enhance the generalization of EEG emotion recognition and reduce the overfitting problem to some extent. Firstly, channel masking and frequency masking are introduced to simulate the information loss in certain channels and frequency bands resulting from the instability of EEG, and two self-supervised learning-based feature reconstruction tasks combining masked graph autoencoders (GAE) are constructed to enhance the generalization of the shared encoder. Secondly, to take full advantage of the complementary information contained in these two self-supervised learning tasks to ensure the reliability of feature reconstruction, a weight sharing (WS) mechanism is introduced between the two graph decoders. Thirdly, an adaptive weight multi-task loss (AWML) strategy based on homoscedastic uncertainty is adopted to combine the supervised learning loss and the two self-supervised learning losses to enhance the performance further.Main results. Experimental results on SEED, SEED-V, and DEAP datasets demonstrate that: (i) Generally, the proposed model achieves higher averaged emotion classification accuracy than various baselines included in both subject-dependent and subject-independent scenarios. (ii) Each key module contributes to the performance enhancement of the proposed model. (iii) It achieves higher training efficiency, and significantly lower model size and computational complexity than the state-of-the-art (SOTA) multi-task-based model. (iv) The performances of the proposed model are less influenced by the key parameters.Significance. The introduction of the self-supervised learning task helps to enhance the generalization of the EEG emotion recognition model and eliminate overfitting to some extent, which can be modified to be applied in other EEG-based classification tasks.


Assuntos
Emoções , Reconhecimento Psicológico , Reprodutibilidade dos Testes , Aprendizado de Máquina Supervisionado , Eletroencefalografia
12.
Plant J ; 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38491869

RESUMO

The sex of dioecious plants is mainly determined by genetic factors, but it can also be converted by environmental cues such as exogenous phytohormones. Gibberellic acids (GAs) are well-known inducers of flowering and sexual development, yet the pathway of gibberellin-induced sex conversion in dioecious spinach (Spinacia oleracea L.) remains elusive. Based on sex detection before and after GA3 application using T11A and SSR19 molecular markers, we confirmed and elevated the masculinization effect of GA on a single female plant through exogenous applications of GA3 , showing complete conversion and functional stamens. Silencing of GIBBERELLIC ACID INSENSITIVE (SpGAI), a single DELLA family protein that is a central GA signaling repressor, results in similar masculinization. We also show that SpGAI can physically interact with the spinach KNOX transcription factor SHOOT MERISTEMLESS (SpSTM), which is a homolog of the flower meristem identity regulator STM in Arabidopsis. The silencing of SpSTM also masculinized female flowers in spinach. Furthermore, SpSTM could directly bind the intron of SpPI to repress SpPI expression in developing female flowers. Overall, our results suggest that GA induces a female masculinization process through the SpGAI-SpSTM-SpPI regulatory module in spinach. These insights may help to clarify the molecular mechanism underlying the sex conversion system in dioecious plants while also elucidating the physiological basis for the generation of unisexual flowers so as to establish dioecy in plants.

13.
Water Res ; 255: 121523, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38554632

RESUMO

The paddy field is a hot area of biogeochemical process. The paddy water has a large capacity in photo-generation of reactive intermediates (RIs) due to abundant photosensitive dissolved organic matter (DOM), which is influenced by the spatial heterogeneity of paddy soils but rarely been explored. Our work presents the first investigation of the role of soil properties on photochemistry in paddy water. Soil organic matter (SOM), determined by the temperature, was the dominant factor for the photo-generation of RIs in paddy water of main rice producing areas. The RI concentrations generated with abundant SOM from cool regions are 0.05-8.71 times higher than those for the warm regions in China. The humic-like substance and aromatic-like compounds of DOM plays an essential role in RIs generation, which is abundant in paddy soils rich in SOM from Chinese cool regions. In addition, RIs can efficiently accelerate the photo-ammonification of urea and free amino acids by 15.2 %-164 %, leading to 0.13-0.17 mmol/L/d photo-produced ammonium after fertilization, which is preferentially absorbed by rice. The findings of this study will extend our knowledge of the geochemistry of global paddy field ecosystem. The potential role of RIs in nitrogen cycle should be highlighted in the agroecosystem.

14.
Cell Death Dis ; 15(3): 233, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521813

RESUMO

AURKA is an established target for cancer therapy; however, the efficacy of its inhibitors in clinical trials is hindered by differential response rates across different tumor subtypes. In this study, we demonstrate AURKA regulates amino acid synthesis, rendering it a vulnerable target in KEAP1-deficient non-small cell lung cancer (NSCLC). Through CRISPR metabolic screens, we identified that KEAP1-knockdown cells showed the highest sensitivity to the AURKA inhibitor MLN8237. Subsequent investigations confirmed that KEAP1 deficiency heightens the susceptibility of NSCLC cells to AURKA inhibition both in vitro and in vivo, with the response depending on NRF2 activation. Mechanistically, AURKA interacts with the eIF2α kinase GCN2 and maintains its phosphorylation to regulate eIF2α-ATF4-mediated amino acid biosynthesis. AURKA inhibition restrains the expression of asparagine synthetase (ASNS), making KEAP1-deficient NSCLC cells vulnerable to AURKA inhibitors, in which ASNS is highly expressed. Our study unveils the pivotal role of AURKA in amino acid metabolism and identifies a specific metabolic indication for AURKA inhibitors. These findings also provide a novel clinical therapeutic target for KEAP1-mutant/deficient NSCLC, which is characterized by resistance to radiotherapy, chemotherapy, and targeted therapy.


Assuntos
Aurora Quinase A , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Asparagina , Aurora Quinase A/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Neoplasias Pulmonares/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo
15.
Sci Total Environ ; 926: 171777, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38499094

RESUMO

The transport and deposition pathways of anthropogenic radionuclides at the global scale, particularly volatile 129I, remain somewhat elusive due to a dearth of comprehensive investigations. To gain a better understanding of the transport dynamics and deposition mechanism of anthropogenic 129I in the terrestrial environment, one hundred surface soil samples collected from northeast China were analyzed for 129I and 127I concentrations in this study. Our findings reveal that 129I/127I atomic ratios in the mid-eastern Inner Mongolia (MIM) were approximately an order of magnitude higher than the rest of the investigated area. This is, besides the global fallout and the long-range transport of 129I released from the European nuclear reprocessing plants via westerly winds, possibly attributed to the dust with high 129I levels from the East Asian arid regions. In addition to the significant dust-induced 129I input, the unique meteorological conditions and topographical features in the MIM synergistically contribute to the pronounced accumulation and deposition of 129I in this region. This study will provide novel insights into the transport and deposition mechanism of anthropogenic radionuclides, which is significant for the assessment of anthropogenic nuclear activities on the environment in the future.

16.
Sheng Wu Gong Cheng Xue Bao ; 40(3): 799-811, 2024 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-38545978

RESUMO

Pseudouridine is the most abundant modified nucleoside found in non-coding RNA and is widely used in biological and pharmaceutical fields. However, current methods for pseudouridine production suffer from drawbacks such as complex procedures, low efficiency and high costs. This study presents a novel enzymatic cascade reaction route in Escherichia coli, enabling the whole-cell catalytic synthesis of pseudouridine from uridine. Initially, a metabolic pathway was established through plasmid-mediated overexpression of endogenous pseudouridine-5-phosphase glycosidase, ribokinase, and ribonucleoside hydrolase, resulting in the accumulation of pseudouridine. Subsequently, highly active endogenous ribonucleoside hydrolase was screened to enhance uridine hydrolysis and provide more precursors for pseudouridine synthesis. Furthermore, modifications were made to the substrates and products transport pathways to increase the pseudouridine yield while avoiding the accumulation of by-product uridine. The resulting recombinant strain Ψ-7 catalyzed the conversion of 30 g/L uridine into 27.24 g/L pseudouridine in 24 h, achieving a conversion rate of 90.8% and a production efficiency of 1.135 g/(L·h). These values represent the highest reported yield and production efficiency achieved by enzymatic catalysis methods to date.


Assuntos
Escherichia coli , Pseudouridina , Pseudouridina/genética , Pseudouridina/química , Pseudouridina/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Uridina/genética , Uridina/química , Uridina/metabolismo , Catálise , Hidrolases/metabolismo
18.
J Am Heart Assoc ; 13(7): e033779, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38533964

RESUMO

BACKGROUND: This study aimed to investigate the predictive value of parameters of every precordial lead and their combinations in differentiating between idiopathic ventricular arrhythmias (IVAs) from the right ventricular outflow tract and aortic sinus of Valsalva (ASV). METHODS AND RESULTS: Between March 1, 2018, and December 1, 2021, consecutive patients receiving successful ablation of right ventricular outflow tract or ASV IVAs were enrolled. The amplitude and duration of the R wave and S wave were measured in every precordial lead during IVAs. These parameters were either summed, subtracted, multiplied, or divided to create different indexes. The index with the highest area under the curve to predict ASV IVAs was developed, compared with established indexes, and validated in an independent prospective multicenter cohort. A total of 150 patients (60 men; mean age, 45.3±16.4 years) were included in the derivation cohort. The RV1+RV3 index (summed R-wave amplitude in leads V1 and V3) had the highest area under the curve (0.942) among the established indexes. An RV1+RV3 index >1.3 mV could predict ASV IVAs with a sensitivity of 95% and a specificity of 83%. Its predictive performance was maintained in the validation cohort (N=109). In patients with V3 R/S transition, an RV1+RV3 index >1.3 mV could predict ASV IVAs, with an area under the curve of 0.892, 93% sensitivity, and 75% specificity. CONCLUSIONS: The RV1+RV3 index is a simple and novel criterion that accurately differentiates between right ventricular outflow tract and ASV IVAs. Its performance outperformed established indexes, making it a valuable tool in clinical practice.


Assuntos
Ablação por Cateter , Seio Aórtico , Taquicardia Ventricular , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Estudos Prospectivos , Seio Aórtico/diagnóstico por imagem , Seio Aórtico/cirurgia , Eletrocardiografia/métodos , Ablação por Cateter/métodos , Arritmias Cardíacas , Ventrículos do Coração , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/cirurgia
19.
Genes (Basel) ; 15(3)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38540386

RESUMO

Nitrogen (N) is one of the essential nutrients for the growth and development of crops. The adequate application of N not only increases the yield of crops but also improves the quality of agricultural products, but the excessive application of N can cause many adverse effects on ecology and the environment. In this study, genome-wide association analysis (GWAS) was performed under low- and high-N conditions based on 788,396 SNPs and phenotypic traits relevant to N uptake and utilization (N content and N accumulation). A total of 75 QTLs were obtained using GWAS, which contained 811 genes. Of 811 genes, 281 genes showed different haplotypes, and 40 genes had significant phenotypic differences among different haplotypes. Of these 40 genes, 5 differentially expressed genes (Os01g0159250, Os02g0618200, Os02g0618400, Os02g0630300, and Os06g0619000) were finally identified as the more valuable candidate genes based on the transcriptome data sequenced from Longjing31 (low-N-tolerant variety) and Songjing 10 (low-N-sensitive variety) under low- and high-N treatments. These new findings enrich the genetic resources for N uptake and utilization in rice, as well as lay a theoretical foundation for improving the efficiency of N uptake and utilization in rice.


Assuntos
Oryza , Plântula , Plântula/genética , Mapeamento Cromossômico , Oryza/genética , Estudo de Associação Genômica Ampla , Nitrogênio , Produtos Agrícolas/genética
20.
Clin Chim Acta ; 557: 117877, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38537675

RESUMO

This study focuses on recent advances in proteomics and provides an up-to-date use of this technology in identifying cardiovascular disease (CVD) biomarkers. A total of eight electronic databases (PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang, Vip, Sinomed, and CNKI) were searched and five were used for integrative analysis of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR) and 1 secondary indicator area under the curve (AUC). This systematic review and integrative analysis summarized potential biomarkers previously identified by proteomics. The integrative analysis suggested that proteomics technology had high clinical value in CVD diagnosis. The findings provided new possible directions for the prevention or diagnosis of CVD.


Assuntos
Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/diagnóstico , Proteômica , Biomarcadores , Sensibilidade e Especificidade , Curva ROC
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...