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The PICALM::MLLT10 fusion is a rare but recurrent cytogenetic abnormality in acute leukemia, with limited clinicopathologic and outcome data available. Herein, we analyzed 156 acute leukemia patients with PICALM::MLLT10 fusion, including 12 patients from our institutions and 144 patients from the literature. The PICALM::MLLT10 fusion preferentially manifested in pediatric and young adult patients, with a median age of 24 years. T-lymphoblastic leukemia/lymphoma (T-ALL) constituted 65% of cases, acute myeloid leukemia (AML) 27%, and acute leukemia of ambiguous lineage (ALAL) 8%. About half of T-ALL were classified as an early T-precursor (ETP)-ALL. In our institutions' cohort, mediastinum was the most common extramedullary site of involvement. Eight of 12 patients were diagnosed with T-ALL exhibiting a pro-/pre-T stage phenotype (CD4/CD8-double negative, CD7-positive), and frequent CD79a expression. NGS revealed pathogenic mutations in 5 of 6 tested cases, including NOTCH1, and genes in RAS and JAK-STAT pathways and epigenetic modifiers. Of 138 cases with follow-up, pediatric patients (<18 years) had 5-year overall survival (OS) of 71%, significantly better than adults at 33%. The 5-year OS for AML patients was 25%, notably shorter than T-ALL patients at 54%; this distinction was observed in both pediatric and adult populations. Furthermore, adult but not pediatric ETP-ALL patients demonstrated inferior survival compared to non-ETP-ALL patients. Neither karyotype complexity nor transplant status had a discernible impact on OS. In conclusion, PICALM::MLLT10 fusion is most commonly seen in T-ALL patients, particularly those with an ETP phenotype. AML and adult ETP-ALL patients had adverse prognosis. PICALM::MLTT10 fusion testing should be considered in T-ALL, AML, and ALAL patients.
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Leucemia Mieloide Aguda , Proteínas de Fusión Oncogénica , Humanos , Masculino , Femenino , Adulto , Adulto Joven , Adolescente , Proteínas de Fusión Oncogénica/genética , Niño , Persona de Mediana Edad , Preescolar , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Anciano , Fenotipo , Predisposición Genética a la Enfermedad , Lactante , Factores de Transcripción/genéticaRESUMEN
The acidification of the marginal seawater was a more intricate process than the ocean. Although some studies have been done on seasonal acidification in the bottom water of Chinese marginal seas, research on surface water acidification has still been insufficient. We analyzed the acidification properties and controlling factors in the Bohai Sea (BS) and Yellow Sea (YS) surface water during April 2023. The observation showed that the average surface water pH of the BS, North Yellow Sea (NYS), and South Yellow Sea (SYS) were 8.09 ± 0.06, 8.13 ± 0.05, and 8.15 ± 0.05. Phytoplankton significantly impacted pH and Ωarag, while riverine inputs and biological activity played a vital role in controlling DIC and TA. The Yellow River significantly impacted the BS. The North Yellow Sea Cold Water Mass had a limited impact on acidification, while the South Yellow Sea Cold Water Mass significantly affected the SYS. Regarding seasonal fluctuations, Ωarag was significantly higher in summer than in other seasons. DIC and TA showed different patterns in both the BS and YS, with a minimal fluctuation in pH. Over the last two decades, the pH in the BS showed a slight annual decline, and the rate of change was (-1.45 ± 2.19) × 10-5 yr-1. In contrast, the NYS and SYS have slightly risen, with rates of change of (2.39 ± 1.24) × 10-5 and (1.23 ± 0.76) × 10-5 yr-1. We believed that surface water acidification in the BS and YS did not follow the expected trend of significant acidification observed in open oceanic regions. Instead, the acidification process in these marginal seas was dominated by local factors such as riverine inputs, biological activity, and cold water masses, resulting in minimal pH changes over the last two decades.
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Estaciones del Año , Agua de Mar , Concentración de Iones de Hidrógeno , Agua de Mar/química , China , Océanos y Mares , Fitoplancton , Monitoreo del AmbienteRESUMEN
The oxygen minimum zone (OMZ) is an important representative of marine hypoxia in the open ocean, and it is developing rapidly under the context of global warming. However, the research on OMZ in the Western Pacific is still deficient. This study focused on its basic characteristics and impact on the degradation of particulate matters in the M4 seamount of Western Pacific. The results showed that the OMZ is located at 290-1100 m, just below the high-salinity area and thermocline. The M4 seamount has a weak impact on the OMZ, and only the bottom waters contacting with the seamount have a weak decrease in dissolved oxygen (DO). With the increase of water depth, particulate nitrogen and phosphorus decrease first above and in the OMZ and then increase below the OMZ, while particulate organic carbon (POC) gradually decreases. The low-DO environment in the OMZ is not conducive to the degradation of particulate matters, which promotes the transport of particulate matters to the deep sea, and most particulate matters have the lowest degradation rate here. The waters above the OMZ have the fastest change rate of particulate matters, in which particulate organic phosphorus (POP) and particulate inorganic phosphorus (PIP) are preferentially degraded, and the degradation rate of them is significantly higher than particulate organic nitrogen (PON) and particulate inorganic nitrogen (PIN). The particulate nitrogen and phosphorus in the waters below the OMZ continue to increase, while PON/total particulate nitrogen (TPN) and POP/total particulate phosphorus (TPP) increase significantly, and the increase rate of PIN and PIP is far lower than PON and POP, indicating that the increase of organic matters in particulate matters is more significant. It is speculated that this phenomenon might be related to the input of Antarctic Bottom Water or the in-situ production by microorganisms. This study revealed the relationship between OMZ and different particulate matters, which may provide a valuable pathway for the biogeochemical effects of OMZ in the Western Pacific.
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Monitoreo del Ambiente , Nitrógeno , Oxígeno , Material Particulado , Fósforo , Agua de Mar , Material Particulado/análisis , Oxígeno/análisis , Oxígeno/metabolismo , Fósforo/análisis , Agua de Mar/química , Nitrógeno/análisis , Océano Pacífico , Contaminantes Químicos del Agua/análisisRESUMEN
Tunable-lifetime room-temperature phosphorescence (RTP) materials have been widely studied due to their broad applications. However, only few reports have achieved wide-range lifetime modulation. In this work, ultra-wide range tunable-lifetime efficient dark blue RTP materials were realized by doping methyl benzoate derivatives into polyvinyl alcohol (PVA) matrix. The phosphorescence lifetimes of the doped films can be increased from 32.8â ms to 1925.8â ms. Such wide range of phosphorescence lifetime modulation is extremely rare in current reports. Moreover, the phosphorescence emission of the methyl 4-hydroxybenzoate-doped film is located in the dark blue region and the phosphorescence quantum yield reaches as high as 15.4 %, which broadens their applications in organic optoelectronic information. Further studies demonstrated that the reason for the tunable lifetime was that the magnitude of the electron-donating ability of the substituent group modulates the HOMO-LUMO and singlet-triplet energy gap of methyl benzoate derivatives, as well as the ability to non-covalent interactions with PVA. Moreover, the potential applications of luminescent displays and optical anti-counterfeiting of these high-performance dark blue RTP materials have been conducted.
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The process of atmospheric organic carbon (OC) entering the ocean through wet deposition plays a crucial role in the global carbon cycle. To gain insights into the biogeochemical dynamics of OC at the land-sea margin, we conducted an extensive four-year investigation on precipitation OC in Jiaozhou Bay (JZB). The results showed that the volume-weighted mean concentration of particulate OC (POC) and dissolved OC (DOC) in precipitation were 0.38 and 2.06 mg C L-1 with an average wet deposition flux of OC for 2666.5 mg C m-2 yr-1. The source of POC in precipitation is predominantly by the C3 plant emission and burning and fossil fuel combustion. Wet deposition contributed 986.6 t yr-1 of OC of which 506.3 t yr-1 of bioavailable DOC, which could have significant implications for carbon cycle in the JZB. This study could enhance the understanding of the marine atmospheric OC in coastal areas.
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Bahías , Carbono , Carbono/análisis , Monitoreo del Ambiente , China , PolvoRESUMEN
Nutrients directly control the level of primary productivity and are crucial for the stability of marine ecosystems. Focusing on the survey results in August 2020 of the Yangtze River Estuary, this study elucidated the distribution characteristics and controlling factors of three nutrients: NO3-N, PO4-P, SiO3-Si. The results showed that the concentrations of NO3-N, PO4-P, SiO3-Si in the study area were generally higher near the shore than far shore, with average concentrations of 11.40, 0.70, and 23.73 µmol/L, respectively. The ocean currents drove the distribution of nutrients, and the transport of CDW and YSCC increased the nutrient levels. The resuspension of sediment caused by factors such as terrain and weather may lead to an abnormal increase in nutrients in the bottom waters. The main controlling factors of the three nutrients were different. NO3-N was significantly affected by human activities, PO4-P and SiO3-Si were mainly affected by natural factors.
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Estuarios , Ríos , Humanos , Ecosistema , Estaciones del Año , Nutrientes , China , Monitoreo del AmbienteRESUMEN
Simultaneously achieving room-temperature phosphorescence (RTP) and multiple-stimuli responsiveness in a single-component system is of significance but remains challenging. Crystallization has been recognized to be a workable strategy to fulfill the above task. However, how the molecular packing mode affects the intersystem crossing and RTP lifetime concurrently remains unclear so far. Herein, four economic small-molecular compounds, analogues of the famous drug raloxifene (RALO), are facilely synthesized and further explored as neat single-component and stimuli-responsive RTP emitters via crystallization engineering. Thanks to their simple structures and high ease to crystallize, these raloxifene analogues function as models to clarify the important role of molecular packing in the RTP and stimuli-responsiveness properties. Thorough combination of the single-crystal structure analysis and theoretical calculations clearly manifests that the tight antiparallel molecular packing mode is the key point to their RTP behaviors. Interestingly, harnessing the controllable and reversible phase transitions of the two polymorphs of RALO-OAc driven by mechanical force, solvent vapor, and heat, a single-component multilevel stimuli-responsive platform with tunable emission color is established and further exploited for optical information encryption. This work would shed light on the rational design of multi-stimuli responsive RTP systems based on single-component organics.
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In an anaerobic sequential batch reactor (SBR), marine anammox bacteria (MAB) were able to enhance microbial activity in nitrogen-rich saline wastewater and it was significantly affected by influent substrate composition and loading strength. This study therefore enhanced nitrogen removal efficiency by adjusting the influent nitrogen loading strength of MAB-inoculated anaerobic SBRs and assessed the correlation with the bacterial community. The results displayed that the system obtained optimal nitrogen removal efficiency (TN = 83.52%, NH4-N = 90.14%, and NO2-N = 83.57%) as the strength of influent nitrogen loading was increased to 201.35 mg L-1 for NH4-N and 266.42 mg L-1 for NO2-N. Moreover, the increase in the strength of influent nitrogen loading also enhanced the anammox 16S rRNA abundance (4.09 × 108 copies g-1) and ladderanes content (22.49 ng g-1dw). Analysis of 15N isotope further illustrated that all systems were dominated by anammox (average ra = 95.22%). In conclusion, these findings provide scientific guidance for the management of eutrophic seawater and contribute to the realization of industrial applications for the treatment of nitrogen-rich saline wastewater.
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Nitrógeno , Aguas Residuales , Nitrógeno/análisis , Desnitrificación , Oxidación Anaeróbica del Amoníaco , Dióxido de Nitrógeno , ARN Ribosómico 16S , Reactores Biológicos/microbiología , Bacterias , Oxidación-ReducciónRESUMEN
ABSTRACT: Acute myeloid leukemia (AML) is a heterogeneous malignancy with outcomes largely predicted by genetic abnormalities. Mutations of NPM1 are common in AML, occurring in â¼30% of cases, and generally considered a favorable risk factor. Mutations highly specific for secondary AML (sMut) have been shown to confer poor prognosis, but the overall impact of these mutations in the setting of favorable-risk AML defined by mutant NPM1 remains unclear. In this multicenter study of patients with AML (n = 233) with NPM1 mutation at diagnosis, we observed that patients with sMut had worse overall survival (OS) than those without sMut (15.3 vs 43.7 months; P = .002). Importantly, this finding persisted in the European LeukemiaNet (ELN) 2017-defined favorable risk subset (14.7 months vs not reached; P < .0001). Among patients who achieved NPM1 measurable residual disease (MRD) negativity, longer OS was observed in the entire cohort (P = .015) as well as in both the sMut subset (MRD negative: median OS (mOS) 73.9 months vs MRD positive: 12.3 months; P = .0170) and sMut ELN 2017-favorable subset (MRD negative: mOS 27.3 vs MRD positive: 10.5 months; P = .009). Co-occurrence of sMut and mutant NPM1 confers a poor prognosis in AML.
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Leucemia Mieloide Aguda , Neoplasias Primarias Secundarias , Humanos , Leucemia Mieloide Aguda/patología , Mutación , Proteínas Nucleares/genética , Nucleofosmina , PronósticoRESUMEN
Bacterial infections from chronic wounds affect about 175 million people each year and are a significant clinical problem. Through the integration of photodynamic therapy (PDT) and chemotherapy, a new photosensitizer consisting of ammonium salt N,N-bis-(2-hydroxyethyl)-N-(6-(4-(10,15,20-trimesitylporphyrin-5-yl) phenoxy) hexane)-N-methanaminium bromide, TMP(+) was successfully synthesized with a total reaction yield of 10%. The novel photosensitizer consists of two parts, a porphyrin photosensitizer part and a quaternary ammonium salt part, to achieve the synergistic effect of photodynamic and chemical antibacterial activity. With the increase of TMP(+) concentration, the diameter of the PCT fiber membranes (POL/COL/TMP(+); POL, polycaprolactone; COL, collagen) gradually increased, which was caused by the charge of the quaternary ammonium salt. At the same time, the antibacterial properties were gradually improved. We finally selected the PCT 0.5% group for the antibacterial experiment, with excellent performance in fiber uniformity, hydrophobicity and biosafety. The antibacterial experiment showed that the modified porphyrin TMP(+) had a better antibacterial effect than others. In vivo chronic wound healing experiments proved that the antibacterial and anti-inflammatory effect of the PCTL group was the best, further confirmed by H&E histological analysis, immunofluorescence and immunohistochemistry mechanism experiments. This research lays the foundation for the manufacture of novel molecules that combine chemical and photodynamic strategies.
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Standardized morphological evaluation in pathology is usually qualitative. Classifying and qualitatively analyzing the nucleated cells in the bone marrow aspirate images based on morphology is crucial for the diagnosis of acute myoid leukemia (AML), acute lymphoblastic leukemia (ALL), and Myelodysplastic syndrome (MDS), etc. However, it is time-consuming and difficult to accurately identify nucleated cells and calculate the percentage of the cells because of the complexity of bone marrow aspirate images. This paper proposed a deep learning analysis model of bone marrow aspirate images, termed Cell Detection and Confirmation Network (CDC-NET), for the aided diagnosis of AML by improving the accuracy of cell detection and recognition. Specifically, we take the nucleated cells in the bone marrow aspirate images as the detection objects to establish the model. Since some cells from different categories have similar morphology, classification error is inevitable. We design a confirmation network in which multiple trained classifiers work as pathologists to confirm the cell category by a voting method. To demonstrate the effectiveness of the proposed approach, experiments on clinical microscopic datasets are conducted. The Recall and Precision of CDC-NET are 78.54% and 91.74% respectively, and the missed rate of our method is lower than those of the other popular methods. The experimental results demonstrated that the proposed model has the potential for the pathological analysis of aspirate smears and the aided diagnosis of AML.
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Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Estados Unidos , Médula Ósea/diagnóstico por imagen , Médula Ósea/patología , Leucemia Mieloide Aguda/diagnóstico , Enfermedad Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Centers for Disease Control and Prevention, U.S.RESUMEN
The mobilization of arsenic (As) at the sediment-water interface (SWI) is crucial for determining the accumulation of dissolved As to potentially toxic levels. However, the specific impacts of redox processes involving iron (Fe) and sulfur (S), as well as microbial activities occurring in sediments, on As mobilization at the marine SWI remain poorly understood. In this study, we investigated As mobilization at the SWI in the Changjiang Estuary during three different seasons with different benthic redox conditions. The preferential reduction of arsenate (As(V)) to arsenite (As(III)) and subsequent re-adsorption onto newly formed crystalline Fe oxides restricted As release in the As(V) reduction layer. Enhanced Fe(III) reduction in the Fe(III) reduction layer contributed to As release, while the presence of low As-high Fe-high SO42- levels resulted in As removal through adsorption onto pyrite in the sulfate reduction layer. Analysis of functional genes indicated that As(V) in sediments was released into porewater through the reductive dissolution of As(V)-bearing Fe(III) oxides by Geobacter species, followed by microbial reduction of the liberated As(V) to As(III) by microbes carrying the arrA gene. The dominant pathway governing As mobilization at the SWI in the Changjiang Estuary shifted from microbial reduction control during the hypoxic summer to Fe redox control during the aerobic autumn and winter. These findings provide valuable insights into the complex mechanisms driving As mobilization and highlight the importance of considering seasonal variations in understanding As dynamics at the marine SWI.
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Arsénico , Arsénico/análisis , Compuestos Férricos/química , Estaciones del Año , Agua/análisis , Oxidación-Reducción , Sedimentos Geológicos , ÓxidosRESUMEN
Mast cell disorders range from benign proliferations to systemic diseases that cause anaphylaxis and other diverse symptoms to mast cell neoplasms with varied clinical outcomes. Mastocytosis is the pathologic process of the accumulation of abnormal mast cells in different organs, mostly driven by KIT mutations, and can present as cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma. The WHO 5th edition classification divides systemic mastocytosis into bone marrow mastocytosis, indolent systemic mastocytosis, smoldering systemic mastocytosis, aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast cell leukemia. The new ICC classifies SM slightly differently. The diagnosis of SM requires the integration of bone marrow morphologic, immunophenotypic, and molecular findings, as well as clinical signs and symptoms. Moreover, understanding the wide range of clinical presentations for patients with mast cell disorders is necessary for accurate and timely diagnosis. This review provides an updated overview of mast cell disorders, with a special emphasis on SM, including the latest approaches to diagnosis, prognostic stratification, and management of this rare disease.
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Fluoroquinolone antibiotics (FQs) are one of the most widely used antibiotics, which are new pollutants with 'pseudo persistence' in the environment, causing great ecological risks. FQs could change the structure and function of microbial communities and affect nitrogen cycling mediated by microorganisms. Consequently, FQs would change the composition of various types of nitrogen in the environment and exert a significant impact on the global nitrogen cycling. We encapsulated the distribution of FQs in the environment and its impacts on nitrogen cycling mediated by microorganisms, explained the role of FQs in each key process of nitrogen cycling, aiming to provide an important reference for revealing the ecological effects of FQs. Generally, FQs could be detected in various environmental media, with significant differences in the concentration and types of FQs in different environments. Ofloxacin, norfloxacin, ciprofloxacin, and enrofloxacin are the four types of FQs with the highest detection frequency and concentration. The effect of FQs on nitrogen cycling deeply depends on typical characteristics of concentration and species. FQs mainly inhibit nitrification by reducing the abundance of amoA gene related to ammoxidation process and the abundance and composition of ammoxidation bacteria. FQs inhibits nitrification by reducing the abundance and composition of microbial communities. The denitrification process is mainly inhibited due to the reduction of the activity of related enzymes and the abundance of genes such as narG, nirS, norB, and nosZ genes, as well as the abundance and composition of denitrifying functional microorganisms. The process of anammox is restricted due to the reduction of the abundance, composition and hzo gene abundance of anaerobic anammox bacteria. FQs lead to the reduction of active nitrogen removal and the increase of N2O release in the environment, with further environmental problems such as water eutrophication and greenhouse effect. In the future, we should pay attention to the effects of low concentration FQs and complex antibiotics on the nitrogen cycling, and focus on the effects of FQs on the changes of nitrogen cycle-related microbial monomers and communities.
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Fluoroquinolonas , Ciclo del Nitrógeno , Fluoroquinolonas/química , Antibacterianos/farmacología , Antibacterianos/química , Contaminación Ambiental , Nitrógeno , DesnitrificaciónRESUMEN
Metals are crucial to the stability of marine ecosystems, and it is important to analyze their spatial heterogeneity. This study examined the distribution and influencing factors of six metals such as manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu) and cadmium (Cd) in M4 seamount of the Western Pacific. The results showed that the factors affecting the distribution of metals are complex. The concentration ranges of Mn, Fe, Co, Ni, Cu, and Cd in the M4 seamount were 0-0.05, 0-0.44, 0-0.0014, 0-0.082, 0.12-0.16, and 0-0.013 µg/L, respectively, roughly equivalent to those of other open seas, however, there were also some differences. Specifically, the distribution of ferromanganese nodules and Co-rich crusts, resulted in a significant increase in the concentration of metals such as Mn, Fe, and Co in the bottom. This study will significantly contribute to our understanding of the spatial heterogeneity of metals in seamount areas.
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Cadmio , Metales Pesados , Ecosistema , Metales , Cobre , Agua de Mar , Cobalto , NíquelRESUMEN
Fluorescence analysis is a fast and sensitive method, and has great potential application in trace detection of environmental toxins. However, many important environmental toxins are non-fluorescent substances, and it is still a challenge to construct a fluorescence detection method for non-fluorescent substances. Here, by means of charge transfer effect and smart molecular imprinting technology, we report a sensitive indirect fluorescent sensing mechanism (IFSM) and microcystin (MC-RR) is selected as a model target. A molecular imprinted thin film is immobilized on the surface of zinc ferrite nanoparticles (ZnFe2O4 NPs) by using arginine, a dummy fragment of MC-RR. By implementation of IFSM on the paper-based microfluidic chip, a versatile platform for the quantitative assay of MC-RR is developed at trace level (the limit of detection of 0.43 µg/L and time of 20 min) in real water samples without any pretreatment. Importantly, the proposed IFSM can be easily modified and extended for the wide variety of species which lack direct interaction with the fluorescent substrate. This work offers the potential possibility to meet the requirements for the on-site analysis and may explore potential applications of molecularly imprinted fluorescent sensors.
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Impresión Molecular , Nanopartículas , Impresión Molecular/métodos , Microcistinas/análisis , Nanopartículas/química , Colorantes Fluorescentes/químicaRESUMEN
Sulfonamides (SAs) are the first broad-spectrum synthetic antimicrobial agents used in human health and veterinary medicine. The majority of SAs entering human body is discharged into aquatic environment in the form of parent material or metabolites. The residues of SAs and their metabolites in the aquatic environment and the development of drug resistance can be serious threats to ecosystems and human health. We summarized recent advances in the research of SAs. The main metabolite types of SAs and the distribution characteristics of metabolites in different aquatic environments were introduced. The ecotoxicology of SAs metabolites, especially the distribution and hazards of sulfonamide resistance genes (sul-ARGs), were discussed with emphasis. Finally, the future research works were proposed. This paper could provide basic information for further research on SAs.
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Ecosistema , Ecotoxicología , Humanos , Sulfanilamida , Sulfonamidas/toxicidadRESUMEN
Synthetic fluoroquinolones (FQs) are the third most commonly used antibiotics in the world and play an extremely important role in antibacterial drugs. The excessive use and discharge will alter ecological environment, with consequence on human health and global sustainable development. It is therefore of great significance for scientific use and management of FQs to systematically understand their biogeochemical behavior and eco-environmental effects. After drug administration in humans and animals, only a small part of FQs are transformed in vivo. The main transformation processes include formylation, acetylation, oxidation and cleavage of piperazine ring, defluorination and decarboxylation of aromatic core ring, etc. About 70% of the original drug and a small amount of transformed products would be migrated to the environment through excretion. After entering the environment, FQs and their transformation products mainly exist in environmental media such as water, soil and sediment, and undergo migration and transformation processes such as adsorption, photolysis and biodegradation. Adsorption facilitates transfer of FQs from medium to another. The photolysis mainly affects the C7-amine substituents of FQs, whereas the core structure of FQs remains intact. Biodegradation mainly refers to the degradation of FQs by microorganisms and microalgae, including piperazine modification of the piperazine ring such as acetylation and formylation, partial or complete ring cleavage, core structure decarboxylation, defluorination and conjugation formation. The migration and transformation processes of FQs cannot completely eliminate them from the environment. Instead, they would become "pseudo-persistent" pollutants, which seriously affect the behavior, growth and reproduction of algae, crustaceans and fish, change biogeochemical cycle, destroy aquatic environment, and stimulate microbial resistance and the generation of resistance genes. In the future, more in-depth studies should be conducted on the environmental behavior of FQs and their impacts on ecological environment, the risk assessment of microbial resistance and resistance genes of FQs, and the mechanism and effect of micro-biodegradation of FQs.
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Clima , Fluoroquinolonas , Animales , Humanos , Antibacterianos , Biodegradación Ambiental , PiperazinasRESUMEN
Myelodysplastic syndromes (MDS) are myeloid neoplasms that are driven by genetic mutations. Generally, it is thought that a higher number of mutations is associated with worse prognosis. However, the impact of genetic mutations when they occur in the same functional class has not been well studied. Here we investigated the impact of multiple spliceosome mutations on prognosis in MDS patients, hypothesizing that multiple mutations in the same class are biologically redundant and would not affect prognosis. Departmental Next Generation Sequencing (NGS) database (>6000 cases) was queried and the data was analyzed to identify cases with spliceosome mutations (SF3B1, SRSF2, U2AF1, ZRSR2, U2AF1). Overall, 71 patients met criteria for the study. Cases with single spliceosome mutations (i.e., no other co-mutations whatsoever) were as follows: SF3B1 (38), SRSF2 (5), U2AF2 (11), and ZRSR2 (1). Cases with concurrent spliceosome mutations were as follows: SF3B1 + SRSF2 (5), SF3B1 + U2AF1 (1), SF3B1 + ZRSR2 (3), SRSF2 + U2AF1 (2), SRSF2 + ZRSR2 (1), U2AF1 + ZRSR2 (4). Four of 55 (7.3%) of patients in the single mutation group vs. 4 of 16 (25%) of patients in the concurrent mutation group progressed to acute myeloid leukemia (AML). Mean OS in the single mutation group was 103.5 months vs. 71.6 months in the multiple concurrent mutation group (χ2= 2.404; p= 0.12). Our results challenge the current dogma that increased mutation in MDS portend worse survival. We demonstrate that multiple mutations bear no impact on clinical prognosis when the additional mutations occur in same spliceosome class.