Organic carbon in wet deposition of an urbanized coastal bay, North China: Flux, sources and biogeochemical implications.

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.

Nutrient characteristics driven by multiple factors in large estuaries during summer: A case study of the Yangtze River Estuary.

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.

Achieving Efficient Dark Blue Room-Temperature Phosphorescence with Ultra-Wide Range Tunable-Lifetime.

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 32.8 ms to 1925.8 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.

Tailoring raloxifene into single-component molecular crystals possessing multilevel stimuli-responsive room-temperature phosphorescence.

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.

Enhanced nitrogen removal performance of nitrogen-rich saline wastewater by marine anammox bacteria: Based on different influent loading strengths.

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.

Mutations highly specific for secondary AML are associated with poor outcomes in ELN favorable risk NPM1-mutated AML.

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 ∼30% 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.

Novel porphyrin derivative containing cations as new photodynamic antimicrobial agent with high efficiency.

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.

CDC-NET: a cell detection and confirmation network of bone marrow aspirate images for the aided diagnosis of AML.

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.

Unraveling seasonal shifts in microbial and geochemical mediated arsenic mobilization at the estuarine sediment-water interface under redox changes.

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.

Review and Updates on Systemic Mastocytosis and Related Entities.

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.

Environmental pollution of fluoroquinolones and its relationship with nitrogen cycling mediated by microorganisms.

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.

Molecular imprinting-based indirect fluorescence detection strategy implemented on paper chip for non-fluorescent microcystin.

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.

Distribution patterns of six metals and their influencing factors in M4 seamount seawater of the Western Pacific.

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.

Behavioral and ecotoxicology of sulfonamide metabolites in the aquatic environment.

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.

Biogeochemical behavior and ecological environmental effects of fluoroquinolones.

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.

Impact of single versus multiple spliceosome mutations on myelodysplastic syndrome.

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.

Structural biology and functional features of phage-derived depolymerase Depo32 on Klebsiella pneumoniae with K2 serotype capsular polysaccharides.

Hypervirulent Klebsiella pneumoniae with capsular polysaccharides (CPSs) causes severe nosocomial- and community-acquired infections. Phage-derived depolymerases can degrade CPSs from K. pneumoniae to attenuate bacterial virulence, but their antimicrobial mechanisms and clinical potential are not well understood. In the present study, Klebsiella phage GH-K3-derived depolymerase Depo32 (encoded by gene gp32) was identified to exhibit high efficiency in specifically degrading the CPSs of K2 serotype K. pneumoniae. The cryo-electron microscopy structure of trimeric Depo32 at a resolution up to 2.32 Å revealed potential catalytic centers in the cleft of each of the two adjacent subunits. K. pneumoniae subjected to Depo32 became more sensitive to phagocytosis by RAW264.7 cells and activated the cells by the mitogen-activated protein kinase signaling pathway. In addition, intranasal inoculation with Depo32 (a single dose of 200 µg, 20 µg daily for 3 days, or in combination with gentamicin) rescued all C57BL/6J mice infected with a lethal dose of K. pneumoniae K7 without interference from its neutralizing antibody. In summary, this work elaborates on the mechanism by which Depo32 targets the degradation of K2 serotype CPSs and its potential as an antivirulence agent. IMPORTANCE Depolymerases specific to more than 20 serotypes of Klebsiella spp. have been identified, but most studies only evaluated the single-dose treatment of depolymerases with relatively simple clinical evaluation indices and did not reveal the anti-infection mechanism of these depolymerases in depth. On the basis of determining the biological characteristics, the structure of Depo32 was analyzed by cryo-electron microscopy, and the potential active center was further identified. In addition, the effects of Depo32 on macrophage phagocytosis, signaling pathway activation, and serum killing were revealed, and the efficacy of the depolymerase (single treatment, multiple treatments, or in combination with gentamicin) against acute pneumonia caused by Klebsiella pneumoniae was evaluated. Moreover, the roles of the active sites of Depo32 were also elucidated in the in vitro and in vivo studies. Therefore, through structural biology, cell biology, and in vivo experiments, this study demonstrated the mechanism by which Depo32 targets K2 serotype K. pneumoniae infection.

Role of marine algal blooms in the release of arsenic at the sediment-seawater interface: Evidence from microcosm experiments.

Algal blooms can aggravate arsenic (As) release from sediments and thus pose a pollution risk in the marine environment. However, the driving mechanism of algal blooms on sedimentary As cycling remains unclear. This study undertakes the first comprehensive examination of As release mechanisms under algal bloom conditions based on the evidence provided by temporal and depth profile changes of As species in the overlying water column, porewater and sediment, as well as As-related functional genes over the course of a 30-day incubation experiment using algal addition. The higher rate of increase of dissolved total As (dTAs) concentrations in a high biomass algal group (HAG) than an experimental control group (CG) suggested that algal degradation promoted the release of sedimentary As. The solid phase in all experimental groups remained rich in As(V), while in porewater As(III) and As(V) were the dominant As species during the initial rapid and subsequent slow degradation phases of organic matter, respectively, indicating that microbial reduction of As(V) and Fe(III) controlled the release of As during these two periods. A pronounced increase in arrA gene copies, and not a corresponding increase in the Geobacter copies, in HAG relative to CG supported the notion that algal blooms promoted microbial As(V) reduction. Additionally, the lower concentration of dissolved As(III) and cumulative dTAs flux in the sterilized-HAG treatment than in the sterilized-CG one further suggested that geochemically-mediated processes were not the main pathways of As release. Finally, it is estimated that summer algal blooms in the Changjiang Estuary can cause the release of 1440 kg of sedimentary As into the overlying water.

Case report: Co-existing chronic myeloid leukemia and chronic myelomonocytic leukemia-A clinically important but challenging scenario.

Chronic myeloid leukemia (CML) and chronic myelomonocytic leukemia (CMML) are two common myeloid neoplasms with overlapping morphologic features. We report a patient initially diagnosed with CML and treated with Tyrosine kinase inhibitor (TKI) but who then developed persistent monocytosis and worsening thrombocytopenia one year later. Repeat bone marrow biopsies only showed CML at the molecular level. However, markedly hypercellular bone marrow, megakaryocytic dysplasia, and SRSF2, TET2, and RUNX1 mutations by NextGen sequencing pointed to a diagnosis of CMML. For CML patients with persistent monocytosis and cytopenia, a mutational profile by NGS is helpful to exclude or identify the coexisting CMML.