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Polystyrene microplastics (PS) and dibutyl phthalate (DBP) are emerging pollutants widely coexisting in agroecosystems. However, the efficacies of PS as carriers for DBP and their interactive mechanisms on crop safety remain scarce. Here, this study investigated the combined exposure effects and the interacting mechanisms of PS laden with DBP on choy sum (Brassica parachinensis L.). Results showed that PS could efficiently adsorb and carry DBP, with a maximum carrying capacity of 9.91 %, facilitating the chemical translocation of DBP in choy sum and exacerbating phytotoxicity. Due to the changes in the properties of PS, DBP loading aggravated the phytotoxicity of choy sum, exhibiting synergistically toxic effects compared with individual exposure. The Trojan-horse-complexes formed by PS+DBP severely delayed the seed germination process and altered spatial growth patterns, causing disruptions in oxidative stress, osmoregulation, photosynthetic function, and elemental reservoirs of choy sum. Combined pollutants enhanced the uptake and translocation of both PS and DBP by 8.90-31.94 % and 136.81-139.37 %, respectively; while the accumulation processes for PS were more complex than for DBP. Visualization indicated that PS was intensively sequestered in roots with a strong fluorescent signal after loading DBP. This study comprehensively investigated the efficacies of PS carrying DBP on phytotoxicity, bioavailability, and their interactive mechanisms, providing significant evidence for food safety assessment of emerging contaminant interactions.
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Aminoacyl-tRNA synthetases (aaRS) are fundamental to the translation machinery with emerging roles in transcriptional regulation. Previous cellular studies have demonstrated tyrosyl-tRNA synthetase (YARS1 or TyrRS) as a stress response protein through its cytosol-nucleus translocation to maintain cellular homeostasis. Here, we established a mouse model with a disrupted TyrRS nuclear localization signal, revealing its systemic impact on metabolism. Nuclear TyrRS deficiency (YarsΔNLS) led to reduced lean mass, reflecting a mild developmental defect, and reduced fat mass, possibly due to increased energy expenditure. Consistently, YarsΔNLS mice exhibit improved insulin sensitivity and reduced insulin levels, yet maintain normoglycemia, indicative of enhanced insulin action. Notably, YarsΔNLS mice also develop progressive hearing loss. These findings underscore the crucial function of nuclear TyrRS in the maintenance of fat storage and hearing and suggest that aaRSs' regulatory roles can affect metabolic pathways and tissue-specific health. This work broadens our understanding of how protein synthesis interconnects metabolic regulation to ensure energy efficiency.
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The aminoacyl-tRNA synthetases (aaRS) are a large group of enzymes that implement the genetic code in all known biological systems. They attach amino acids to their cognate tRNAs, moonlight in various translational and non-translational activities beyond aminoacylation, and are linked to many genetic disorders. The aaRS have a subtle ontology characterized by structural and functional idiosyncrasies that vary from organism to organism, and protein to protein. Across the tree of life, the 22 coded amino acids are handled by 16 evolutionary families of Class I aaRS and 21 families of Class II aaRS. We introduce AARS Online, an interactive Wikipedia-like tool curated by an international consortium of field experts. This platform systematizes existing knowledge about the aaRS by showcasing a taxonomically diverse selection of aaRS sequences and structures. Through its graphical user interface, AARS Online facilitates a seamless exploration between protein sequence and structure, providing a friendly introduction to the material for non-experts and a useful resource for experts. Curated multiple sequence alignments can be extracted for downstream analyses. Accessible at www.aars.online, AARS Online is a free resource to delve into the world of the aaRS.
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α-Aminonitriles are not only broadly useful building blocks but also structural motifs in bioactive molecules. The Strecker reaction is one of the most widely used methods for α-aminonitrile synthesis. However, a severe drawback in Strecker reactions is the required use of a stoichiometric amount of toxic cyanation reagents. Thus, the development of a greener and widely applicable method for the synthesis of aminonitriles from readily available starting materials presents an important yet unmet challenge. We developed a general and new method for the synthesis of aminonitriles from readily available aminoacetonitrile. This method utilized off-the-shelf ammonium salts as catalysts, tolerated air and moisture, and avoided the use of cyanation reagents, which rendered it a greener alternative to the widely practiced Strecker reaction approach. We further illustrated that chiral ammonium-catalyzed asymmetric reactions of N-arylidene aminoacetonitriles could provide chiral α-tertiary and α-quaternary aminonitriles and α-aminonitriles bearing two continuous stereocenters.
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Acute oral toxicity is currently not available for most polycyclic aromatic hydrocarbons (PAHs), especially their derivatives, because it is cost-prohibitive to experimentally determine all of them. Here, quantitative structure-activity relationship (QSAR) models using machine learning (ML) for predicting the toxicity of PAH derivatives were developed, based on oral toxicity data points of 788 individual substances of rats. Both the individual ML algorithm gradient boosting regression trees (GBRT) and the stacking ML algorithm (extreme gradient boosting + GBRT + random forest regression) provided the best prediction results with satisfactory determination coefficients for both cross-validation and the test set. It was found that those PAH derivatives with fewer polar hydrogens, more large-sized atoms, more branches, and lower polarizability have higher toxicity. Software based on the optimal ML-QSAR model was successfully developed to expand the application potential of the developed model, obtaining reliable prediction of pLD50 values and reference doses for 6893 external PAH derivatives. Among these chemicals, 472 were identified as moderately or highly toxic; 10 out of them had clear environment detection or use records. The findings provide valuable insights into the toxicity of PAHs and their derivatives, offering a standard platform for effectively evaluating chemical toxicity using ML-QSAR models.
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The cell wall serves as the primary barrier against the entry of heavy metal ions into cells. However, excessive accumulation of heavy metals within plants can lead to alterations in the spatial structure and physical properties of the cell wall, thereby affecting the capacity of plants to capture heavy metals. Proline (Pro) is involved in the synthesis of the cell wall, modulating the stability and integrity of its structure. Extensins, core proteins that maintain the cell wall structure, are proline/hydroxyproline-rich glycoproteins that contain the characteristic sequence Ser-[Pro]3-5. They act as intermediates in the regulation of biological processes such as cell wall synthesis, assembly, and signal transduction, typically forming a network structure of cell wall proteins through cross-linking with pectin. This network is essential for the self-assembly expansion of the plant cell wall and plays an indispensable role in cell wall stress signal transduction through its interaction with intracellular signalling molecules. However, the mechanisms by which Pro affects the synthesis of cell wall structural proteins, cell wall assembly, and the sensing of cell wall stress under heavy metal stress remain unclear. This review, from the perspectives of biochemistry and molecular biology, comprehensively elaborates on the impact of Pro and Pro-rich proteins on the structure and function of the cell wall. These findings emphasize the mechanism by which Pro enhances the ability of the cell wall to capture heavy metals, providing new research ideas for the use of genetic engineering to manipulate cell wall synthesis and repair, thereby reducing the phytotoxicity of heavy metals.
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Pared Celular , Metales Pesados , Prolina , Pared Celular/metabolismo , Pared Celular/efectos de los fármacos , Prolina/metabolismo , Metales Pesados/toxicidad , Estrés Fisiológico/efectos de los fármacos , Proteínas de Plantas/metabolismo , Plantas/efectos de los fármacos , Plantas/metabolismo , Transducción de Señal/efectos de los fármacos , Contaminantes del Suelo/toxicidadRESUMEN
BACKGROUND AND PURPOSE: Liver cancer is the fourth leading cause of cancer-related death worldwide, with hepatocellular carcinoma (HCC) being the most common type of primary liver cancer. APG-1252 is a small molecule inhibitor targeting Bcl-2 and Bcl-xl. However, its anti-tumor effects in HCC, alone or in combination with Cabozantinib, have not been extensively studied. EXPERIMENTAL: Approach: TCGA database analysis was used to analysis the gene expression levels of Bcl-2 and Bcl-xl in HCC tissues. Western blot was employed to detect the protein expression levels. And the inhibitory effects of APG-1252 and Cabozantinib on the proliferation of HCC cell lines was detected by CCK-8. The effect on the migration and invasion of HCC cells was verified by transwell assay. Huh7 xenograft model in nude mice was used to investigate the combination antitumor effect in vivo. KEY RESULTS: Our study demonstrated that APG-1252 monotherapy inhibited the proliferation and migration ability of HCC cells, and induced HCC cells apoptosis. The combination of APG-1252 and Cabozantinib showed significant synergistic antitumor effects. Furthermore, the in vivo experiment demonstrated that the combination therapy exerted a synergistic effect in delaying tumor growth, notably downregulating MEK/ERK phosphorylation levels. In terms of mechanism, Cabozantinib treatment caused an increase in the phosphorylation levels of CREB and Bcl-xl proteins, while the combination with APG-1252 mitigated this effect, thereby enhanced the antitumor effect of Cabozantinib. CONCLUSION AND IMPLICATIONS: Our findings suggest that APG-1252 in combination with Cabozantinib offers a more effective treatment strategy for HCC patients, warranting further clinical investigation.
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Anilidas , Carcinoma Hepatocelular , Proliferación Celular , Neoplasias Hepáticas , Ratones Desnudos , Piridinas , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína bcl-X , Animales , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Anilidas/farmacología , Anilidas/uso terapéutico , Piridinas/farmacología , Piridinas/uso terapéutico , Proteína bcl-X/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ratones , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Ratones Endogámicos BALB C , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , MasculinoRESUMEN
Lettuce is one of the most widely cultivated and consumed dicotyledonous vegetables globally. Despite the availability of its reference genome sequence, lettuce gene annotation remains incomplete, impeding comprehensive research and the broad application of genomic resources. Long-read RNA isoform sequencing (Iso-Seq) offers substantial advantages for analyzing RNA alternative splicing and aiding gene annotation, yet it faces throughput limitations. We present the HIT-ISOseq method tailored for bulk sample analysis, significantly enhancing RNA sequencing throughput on the PacBio platform by concatenating cDNA. Here we show, HIT-ISOseq generates 3-4 cDNA molecules per CCS read in lettuce, yielding 15.7 million long reads per PacBio Sequel II SMRT Cell 8 M. We validate its effectiveness in analyzing six lettuce tissue samples, including roots, stems, and leaves, revealing tissue-specific gene expression patterns and RNA isoforms. Leveraging diverse tissue long-read RNA sequencing, we refine the transcript annotation of the lettuce reference genome, expanding its GO and KEGG annotation repertoire. Collectively, this study serves as a foundational reference for genome annotation and the analysis of multi-sample isoform expression, utilizing high-throughput long-read transcriptome sequencing.
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Secuenciación de Nucleótidos de Alto Rendimiento , Lactuca , Análisis de Secuencia de ARN , Lactuca/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Análisis de Secuencia de ARN/métodos , ARN de Planta/genética , Especificidad de Órganos/genética , Regulación de la Expresión Génica de las Plantas , Anotación de Secuencia Molecular , Empalme Alternativo , Isoformas de ARN/genética , Genes de PlantasRESUMEN
Tumour morphology (tumour burden score (TBS)) and liver function (albumin-to-alkaline phosphatase ratio (AAPR)) have been shown to correlate with outcomes in intrahepatic cholangiocarcinoma (ICC). This study aimed to evaluate the combined predictive effect of TBS and AAPR on survival outcomes in ICC patients. We conducted a retrospective analysis using a multicentre database of ICC patients who underwent curative surgery from 2011 to 2018. The Kaplan-Meier method was employed to examine the relationship between a new index (combining TBS and AAPR) and long-term outcomes. The predictive efficacy of this index was compared to other conventional indicators. A total of 560 patients were included in the study. Based on TBS and AAPR stratification, patients were classified into three groups. Kaplan-Meier curves demonstrated that 124 patients with low TBS and high AAPR had the best overall survival (OS) and recurrence-free survival (RFS), while 170 patients with high TBS and low AAPR had the worst outcomes (log-rank p < 0.001). Multivariate analyses identified the combined index as an independent predictor of OS and RFS. Furthermore, the index showed superior accuracy in predicting OS and RFS compared to other conventional indicators. Collectively, this study demonstrated that the combination of liver function and tumour morphology provides a synergistic effect in evaluating the prognosis of ICC patients. The novel index combining TBS and AAPR effectively stratified postoperative survival outcomes in ICC patients undergoing curative resection.
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Fosfatasa Alcalina , Neoplasias de los Conductos Biliares , Colangiocarcinoma , Carga Tumoral , Humanos , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Colangiocarcinoma/sangre , Colangiocarcinoma/mortalidad , Femenino , Masculino , Fosfatasa Alcalina/sangre , Persona de Mediana Edad , Pronóstico , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/sangre , Anciano , Estudios Retrospectivos , Estimación de Kaplan-Meier , Biomarcadores de Tumor/sangreRESUMEN
BACKGROUND: However, the connection between smoking and the prognosis of patients with bladder cancer remains unclear. AIM: To determine whether smoking is linked to the recurrence and progression of bladder cancer. METHODS: As of July 20, 2022, relevant English-language research was identified by searching PubMed, the Web of Science, and the Cochrane Library. We pooled the available data from the included studies using a random effects model. Subgroup analysis and sensitivity analysis were also conducted. RESULTS: A total of 12 studies were included in this meta-analysis. The combined analysis revealed that tobacco exposure was associated with a significantly greater recurrence rate than nonsmoking status [odd ratios (OR) = 1.76, 95%CI: 1.84-2.93], and the progression of bladder cancer was significantly greater in smokers than in nonsmokers (OR = 1.21, 95%CI: 1.02-1.44). Stratified analysis further revealed that current smokers were more likely to experience relapse than never-smokers were (OR = 1.85, 95%CI: 1.11-3.07). Former smokers also had a greater risk of relapse than did never-smokers (OR = 1.73, 95%CI: 1.09-2.73). Subgroup analysis indicated that non-Caucasians may be more susceptible to bladder cancer recurrence than Caucasians are (OR = 2.13, 95%CI: 1.74-2.61). CONCLUSION: This meta-analysis revealed that tobacco exposure may be a significant risk factor for both the recurrence and progression of bladder cancer.
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In this editorial, we comment on the article by Chen et al. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a global public health burden whose incidence has risen concurrently with overweight and obesity. Given its detrimental health impact, early identification of at-risk individuals is crucial. MAFLD diagnosis is based on evidence of hepatic steatosis indicated by liver biopsy, imaging, or blood biomarkers, and one of the following conditions: Overweight/ obesity, type 2 diabetes mellitus, or metabolic dysregulation. However, in large-scale epidemiological studies, liver biopsies are not feasible. The application of techniques such as ultrasonography, computed tomography, magnetic resonance imaging, and magnetic resonance spectroscopy is restricted by their limited sensitivity, low effectiveness, high costs, and need for specialized software. Blood biomarkers offer several advantages, particularly in large-scale epidemiological studies or clinical scenarios where traditional imaging techniques are impractical. Analysis of cumulative effects of excess high-normal blood alanine aminotransferase (ALT) levels of blood ALT levels could facilitate identification of at-risk patients who might not be detected through conventional imaging methods. Accordingly, investigating the utility of blood biomarkers in MAFLD should enhance early detection and monitoring, enabling timely intervention and management and improving patient outcomes.
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Alanina Transaminasa , Biomarcadores , Humanos , Biomarcadores/sangre , Alanina Transaminasa/sangre , Hígado/diagnóstico por imagen , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Factores de Riesgo , Obesidad/complicaciones , Obesidad/diagnóstico , Obesidad/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diagnóstico PrecozRESUMEN
Simultaneous biodegradation of multiple micropollutantslike polycyclic aromatic hydrocarbons (PAHs) and phthalates (PAEs) by microbial consortia remain unclear. Here, four distinct bacterial consortia capable of degrading PAHs and PAEs were domesticated from sludge and its composts. PAH-degrading consortium HS and PAE-degrading consortium EC2 displayed the highest degradation efficiencies for PAHs (37 %-99 %) and PAEs (98 %-99 %), respectively, being significantly higher than those of individual member strains. Consortia HS and EC2 could simultaneously degrade both PAHs and PAEs. Remarkably, a synthetic consortium Syn by co-culturing consortia HS and EC2 demonstrated proficient simultaneous biodegradation for both PAHs (65 %-98 %) and PAEs (91 %-97 %). These consortia changed their community structure with enriching pollutant-degrading genera and extracellular polymeric substance contents to promote simultaneous biodegradation of multiple pollutants. Moreover, consortium Syn significantly enhanced degradation of both PAHs and PAEs in soil and sludge. This study provides strong candidates for simultaneous bioremediation of complex polluted environments by PAHs and PAEs.
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Biodegradación Ambiental , Consorcios Microbianos , Ácidos Ftálicos , Hidrocarburos Policíclicos Aromáticos , Aguas del Alcantarillado , Contaminantes del Suelo , Aguas del Alcantarillado/microbiología , Hidrocarburos Policíclicos Aromáticos/metabolismo , Contaminantes del Suelo/metabolismo , Ácidos Ftálicos/metabolismo , Bacterias/metabolismo , Microbiología del SueloRESUMEN
We aim to investigate the effect of RVG-Lamp2b-modified exosomes (exos) loaded with neurotrophin-3 (NT-3) on facial nerve injury. Exos were collected from control cells (Ctrl Exo) or bone marrow mesenchymal stem cells co-transfected with RVG-Lamp2b and NT-3 plasmids (RVG-NT-3 Exo) by gradient centrifugation and identified by western blotting, transmission electron microscopy, and nanoparticle tracking analysis. Effect of RVG-NT-3 Exo on oxidative stress damage was determined by analysis of the morphology, viability, and ROS production of neurons. Effect of RVG-NT-3 Exo on facial nerve axotomy (FNA) was determined by detecting ROS production, neuroinflammatory reaction, microglia activation, facial motor neuron (FMN) death, and myelin sheath repair. Loading NT-3 and modifying with RVG-Lamp2b did not alter the properties of the exos. Moreover, RVG-NT-3 Exo could effectively target neurons to deliver NT-3. Treatment with RVG-NT-3 Exo lowered H2O2-induced oxidative stress damage in primary neurons and Nsc-34 cells. RVG-NT-3 Exo treatment significantly decreased ROS production, neuroinflammatory response, FMN death, and elevated microglia activation and myelin sheath repair in FNA rat models. Our findings suggested that RVG-NT-3 Exo-mediated delivery of NT-3 is effective for the treatment of facial nerve injury.
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Exosomas , Traumatismos del Nervio Facial , Células Madre Mesenquimatosas , Neurotrofina 3 , Estrés Oxidativo , Exosomas/metabolismo , Exosomas/trasplante , Neurotrofina 3/administración & dosificación , Neurotrofina 3/metabolismo , Neurotrofina 3/genética , Traumatismos del Nervio Facial/terapia , Traumatismos del Nervio Facial/metabolismo , Células Madre Mesenquimatosas/metabolismo , Animales , Ratas , Células Cultivadas , Humanos , Modelos Animales de Enfermedad , Proteínas Nogo/genética , Proteínas Nogo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ratas Sprague-Dawley , Sistemas de Liberación de Medicamentos/métodosRESUMEN
Xanthates, common mining flotation reagents, strongly bind thiophilic metals such as copper (Cu), lead (Pb), cadmium (Cd), and zinc (Zn) and consequentially change their bioavailability and mobility upon their discharge into the environment. However, accurate quantification of the metal-xanthate complexes has remained elusive. This study develops a novel and robust method that realizes the accurate quantification of the metal-xanthate complexes resulted from single and multiple reactions of three typical xanthates (ethyl, isopropyl, and butyl xanthates) and four thiophilic metals (Cu, Pb, Cd, and Zn) in water samples. This method uses sulfur (S2-) dissociation, followed by tandem solid phase extraction of C18 + PWAX and subsequent LC-MS/MS analysis. It has a wide linearity range (1-1000 µg/L, R2 ≥ 0.995), low method detection limits (0.002-0.036 µg/L), and good recoveries (70.6-107.0 %) at 0.01-10 mg/L of xanthates. Applications of this method showed ubiquitous occurrence of the metal-xanthate complexes as the primary species in flotation wastewaters, which the concentrations were 4.6-28.9-fold higher than those previously determined. It is the first quantitative method established for the analysis of metal-xanthate complexes in water samples, which is of great importance to comprehensively understand the fate and risks of xanthates in the environment.
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BACKGROUND: We compared magnetic resonance imaging (MRI) turbo spin-echo images reconstructed using a deep learning technique (TSE-DL) with standard turbo spin-echo (TSE-SD) images of the lumbar spine regarding image quality and detection performance of common degenerative pathologies. METHODS: This prospective, single-center study included 31 patients (15 males and 16 females; aged 51 ± 16 years (mean ± standard deviation)) who underwent lumbar spine exams with both TSE-SD and TSE-DL acquisitions for degenerative spine diseases. Images were analyzed by two radiologists and assessed for qualitative image quality using a 4-point Likert scale, quantitative signal-to-noise ratio (SNR) of anatomic landmarks, and detection of common pathologies. Paired-sample t, Wilcoxon, and McNemar tests, unweighted/linearly weighted Cohen κ statistics, and intraclass correlation coefficients were used. RESULTS: Scan time for TSE-DL and TSE-SD protocols was 2:55 and 5:17 min:s, respectively. The overall image quality was either significantly higher for TSE-DL or not significantly different between TSE-SD and TSE-DL. TSE-DL demonstrated higher SNR and subject noise scores than TSE-SD. For pathology detection, the interreader agreement was substantial to almost perfect for TSE-DL, with κ values ranging from 0.61 to 1.00; the interprotocol agreement was almost perfect for both readers, with κ values ranging from 0.84 to 1.00. There was no significant difference in the diagnostic confidence or detection rate of common pathologies between the two sequences (p ≥ 0.081). CONCLUSIONS: TSE-DL allowed for a 45% reduction in scan time over TSE-SD in lumbar spine MRI without compromising the overall image quality and showed comparable detection performance of common pathologies in the evaluation of degenerative lumbar spine changes. RELEVANCE STATEMENT: Deep learning-reconstructed lumbar spine MRI protocol enabled a 45% reduction in scan time compared with conventional reconstruction, with comparable image quality and detection performance of common degenerative pathologies. KEY POINTS: ⢠Lumbar spine MRI with deep learning reconstruction has broad application prospects. ⢠Deep learning reconstruction of lumbar spine MRI saved 45% scan time without compromising overall image quality. ⢠When compared with standard sequences, deep learning reconstruction showed similar detection performance of common degenerative lumbar spine pathologies.
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Aprendizaje Profundo , Vértebras Lumbares , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Vértebras Lumbares/diagnóstico por imagen , Adulto , Anciano , Relación Señal-Ruido , Enfermedades de la Columna Vertebral/diagnóstico por imagenRESUMEN
Di-n-butyl phthalate (DBP) is one of the important phthalates detected commonly in soils and crops, posing serious threat to human health. Pseudochrobactrum sp. XF203 (XF203), a new strain related with DBP biodegradation, was first identified from a natural habitat lacking human disturbance. Genomic analysis coupled with gene expression comparison assay revealed this strain harbors the key aromatic ring-cleaving gene catE203 (encoding catechol 2,3-dioxygenase/C23O) involved DBP biodegradation. Following intermediates identification and enzymatic analysis also indicated a C23O dependent DBP lysis pathway in XF203. The gene directed ribosome engineering was operated and to generate a desirable mutant strain XF203R with highest catE203 gene expression level and strong DBP degrading ability. The X203R removed DBP in soil jointly by reassembling bacterial community. These results demonstrate a great value of XF203R for the practical DBP bioremediation application, highlighting the important role of the key gene-directed ribosome engineering in mining multi-pollutants degrading bacteria from natural habitats where various functional genes are well conserved.
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Biodegradación Ambiental , Dibutil Ftalato , Ribosomas , Contaminantes del Suelo , Contaminantes del Suelo/metabolismo , Dibutil Ftalato/metabolismo , Ribosomas/metabolismo , Microbiología del Suelo , Expresión Génica , Burkholderiaceae/metabolismo , Burkholderiaceae/genéticaRESUMEN
Sepsis is a lethal systemic inflammatory disease against infection that lacks effective therapeutic approaches. Liver resident macrophage Kupffer cell (KC)-initiated bacterial clearance is crucial for the host to defend against infection. However, it remains unclear whether this process also governs the antibacterial therapy of sepsis that would be used to improve therapeutic outcomes. Here, we found that copper-doped carbon dots (Cu-CDs) exhibited superior antibacterial capabilities in vitro but displayed limited therapeutic effects in septic mice due to their limited ability to target the liver and restore KC antimicrobial capacity. Thus, we developed a composite nanodrug of copper-doped carbon dot-loaded apoVs (CC-apoVs) that combined the antibacterial ability of Cu-CDs and liver KC targeting features of apoV. Moreover, intravenous injection of CC-apoVs markedly alleviated the systemic infection and decreased the mortality of septic mice compared to Cu-CD and apoV infusion alone. Mechanistically, CC-apoV injection rescued impaired liver KCs during sepsis and enhanced their ability to capture and kill bloodborne bacteria. In addition, apoV-promoted macrophage killing of bacteria could be blocked by the inhibition of small GTPase Rab5. This study reveals a liver KC-targeted therapeutic strategy for sepsis and provides a nanodrug CC-apoV to improve the host antibacterial defense and amplify the therapeutic effect of the nanodrug.