Labyrinthulomycetes thrives in organic matter-rich waters with ecological partitioning in the Pearl River Estuary.

Labyrinthulomycetes play an important role in marine biogeochemical cycles, but their diversity, distribution patterns, and key regulatory factors remain unclear. This study measured the abundance and diversity of Labyrinthulomycetes in the Pearl River Estuary (PRE) to understand its distribution pattern and relationship with environmental and biological factors. The abundance of Labyrinthulomycetes ranged from 24 to 500 cells·mL-1, with an average of 144.37 ± 94.65 cells·mL-1, and its community composition showed obvious ecological partitioning in the PRE. The results of statistical analysis indicated that CDOM, salinity, and chlorophyll a contributed significantly (P < 0.01) to the community composition, explaining 46.59%, 11.34%, and 4.38% of the variance, respectively. The Labyrinthulomycetes distribution pattern combined with the niches of dominant species was revealed; low-salinity species mainly use terrigenous organic matter occupied dominant positions in the upper estuary and showed the highest abundance; moderate-salinity species that can use phytoplankton-derived resources thrived in the middle estuary; and seawater species dominated the lower estuary with the highest diversity but the lowest abundance. In addition, the results of phylogenetic tree analysis indicated that the existence of a novel lineage, and further study on the diversity and ecological functions of Labyrinthulomycetes is needed.IMPORTANCELabyrinthulomycetes play important roles in organic matter remineralization, carbon sinks, and food webs. However, the true diversity of Labyrinthulomycetes is still unclear due to limitations in isolation and culture methods. In addition, previous studies on their relationship with environmental factors are inconsistent and even contradictory, and it is speculated that their community composition may have spatial heterogeneity along the environmental gradient. In this study, the distribution pattern and key regulators of Labyrinthulomycetes in the PRE were revealed. Combining the niche of dominant species, it is suggested that salinity determines the spatial differences in Labyrinthulomycetes diversity, and the resources of substrate (terrestrial input or phytoplankton-derived) determine the dominant species, and its abundance is mainly determined by organic matter concentrations. Our study provided new information on the Labyrinthulomycetes diversity and verified the spatial heterogeneity of Labyrinthulomycetes community composition, providing reliable explanations for the inconsistencies in previous studies.

Dissolved organic phosphorus promotes Cyclotella growth and adaptability in eutrophic tropical estuaries.

Dissolved organic phosphorus (DOP) is an important nutrient for phytoplankton growth in oligotrophic oceans. However, little is known about the impact of DOP on phytoplankton growth in eutrophic waters. In the present study, we conducted field monitoring as well as in situ and laboratory experiments in the Pearl River estuary (PRE). Field observations showed an increase in the nitrogen-to-phosphorus ratio and DOP in recent years in the PRE. The phytoplankton community was dominated by nanophytoplankton Cyclotella in the upper and middle estuary, with high concentrations of DOP and light limitation during the ebb stage of the spring to neap tide in summer. The relative abundance of Cyclotella in natural waters was higher after enrichment with estuarine water with a background of 0.40-0.46 µM DOP, even when dissolved inorganic phosphorus was sufficient (0.55-0.76 µM). In addition, the relative abundance of Cyclotella in natural waters was higher after enrichment with phosphoesters. Laboratory culture results also confirmed that phosphoesters can enhance the growth rate of Cyclotella cryptica. Our study highlights that Cyclotella can become the dominant species in estuaries with increased levels of phosphoesters and low and fluctuating light adaptability and under the joint effect of dynamic processes such as upwelling and tides. Our results provide new insights into the role of Cyclotella in biogeochemical cycles affected by DOP utilization and potential applications in relieving the hypoxia of tropical eutrophic estuaries.IMPORTANCEThis study provides evidence that Cyclotella can become the dominant species in estuaries with increased levels of phosphoesters and low and fluctuating light adaptability and under the joint effect of dynamic processes such as upwelling and tides. Our study provides new insights into the role of Cyclotella in biogeochemical cycles affected by dissolved organic phosphorus utilization, especially affected by anthropogenic inputs and climate change. Potential applications include relieving the hypoxia of tropical eutrophic estuaries.

Insights into ecological effects of fish and shellfish mariculture on microeukaryotic community.

To better understand the ecological effects of mariculture, the diversity distribution, determinant and interaction of microeukaryote communities from fish cage and suspended shellfish farming were investigated in three bays of South China Coast. Our alpha and beta diversity analyses showed that the difference of the microeukaryote community between fish and shellfish farming was more significant at local than regional scale, and microeukaryotes respond more to spatial effect than mariculture effect at regional scale. Mantel test, variation partitioning analysis and co-occurrence network analysis revealed that the environmental factors especially chemical and biotic factors contributed more to community assembly in fish than shellfish farming. Based on the comparisons of community composition and determinant between fish and shellfish farming, the effect mechanisms of the two farming types on microeukaryote community were proposed. Fish farming brings significant environmental variation and thus has strong bottom-up impacts on microeukaryotes, while shellfish farming exerts a grazing pressure on microeukaryotes by filter-feeding and has top-down control to them. Furthermore, the network stability analyses revealed weaker community stability in fish than shellfish farming, suggesting that the microeukaryote community was more sensitive to environmental change deduced by fish than shellfish farming. Overall, this study revealed the different influencing mechanisms of fish and shellfish mariculture on microeukaryotes, which will improve the understanding of the ecological effects of mariculture and provide guidance for the management of mariculture under future environmental pressures.

Measurable residual disease detected by flow cytometry independently predicts prognoses of NPM1-mutated acute myeloid leukemia.

Acute myeloid leukemia (AML) with NPM1 mutation is a distinct genetic entity with favorable outcomes. Nevertheless, emerging evidence suggests that NPM1-mutated AML is still a highly heterogeneous disorder. In this study, 266 patients with AML with NPM1 mutations were retrospectively analyzed to evaluate the associations between variant allele frequency (VAF) of NPM1 mutations, co-mutated genes, measurable residual disease (MRD), and patient outcomes. Multiparameter flow cytometry (MFC) and real-time quantitative polymerase chain reaction (RT-PCR) were used for monitoring MRD. Ultimately, 106 patients were included in the long-term follow-up period. Patients with high NPM1 VAF (≥ 42.43%) had poorer 2-year relapse-free survival (RFS) (55.7% vs. 70.2%, P = 0.017) and overall survival (OS) (63.7% vs. 82.0%, P = 0.027) than those with low VAF. DNMT3A mutations negatively influenced the outcomes of patients with NPM1 mutations. Patients with high DNMT3A VAF or NPM1/DNMT3A/FLT3-ITD triple mutations had shorter RFS and significantly lower OS than that in controls. After two cycles of chemotherapy, patients with positive MFC MRD results had lower RFS (MRD+ vs. MRD-:44.9% vs. 67.6%, P = 0.007) and OS (61.5% vs. 76.6%, P = 0.011) than those without positive MFC MRD results. In multivariate analysis, high NPM1 VAF (hazard ratio [HR] = 2.045; P = 0.034) and positive MRD after two cycles of chemotherapy (HR = 3.289; P = 0.003) were independent risk factors for RFS; MRD positivity after two cycles of chemotherapy (HR = 3.293; P = 0.008) independently predicted the OS of the patients. These results indicate that VAF of both NPM1 gene itself or certain co-occurring gene pre-treatment and MRD post-treatment are potential markers for restratifying the prognoses of patients AML having NPM1 mutations.

Cyclosporine plus eltrombopag in the treatment of aplastic anemia with or without antithymocyte immunoglobulin: A multicenter real-world retrospective study.

AIMS: To compare cyclosporine (CSA) combining eltrombopag (EPAG) with or without antithymocyte globulin (ATG) in aplastic anemia (AA) patients in the real world. METHODS: AA patients who received ATG combining CSA and EPAG (Group A) and CSA + EPAG (Group B) as front-line treatment in 13 medical centers in China were enrolled. The efficacy and safety were compared. RESULTS: A total of 89 patients were enrolled with 51 patients in Group A and 38 patients in Group B. The 6-month overall response (OR)/complete response (CR) was 73.3%/24.4% and 60.6%/27.3% in Groups A and B (p > .1). For severe AA patients, the 6-month OR was 74.1% versus 50% and 6-month CR was 25.9% versus 20% in Groups A and B (p > 0.1). Multivariate analysis showed gender affects the 6-month OR with females better OR (p = .017, OR 6.045, 95% CI: 1.377-26.546) and time from disease onset to treatment affected the 12-month CR (p = .026, OR 0.263, 95% CI: 0.081-0.852). No difference was found in side effects except ATG infusion reaction and serum sickness. Mortality was 7.8% in Group A and no patient died in Group B. CONCLUSIONS: CSA + EPAG had a similar response and less side effects compared with standard immunosuppressive therapy + EPAG in newly diagnosed AA.

Rising temperature contributed to the outbreak of a macrozooplankton Creseis acicula by enhancing its feeding and assimilation for algal food nearby the coastal Daya Bay Nuclear Power Plant.

An outbreak of a macrozooplankton Creseis acicula occurred in the summer of 2020 nearby the Daya Bay Nuclear Power Plant located on the coast of the Daya Bay in the South China Sea. The outbreaks of C. acicula often threaten human health, the marine environment, and other human activities including the safe operation of coastal nuclear power plants. Seawater temperature has been suggested as an important factor influencing such outbreaks. However, the underlying mechanisms through which temperature influences C. acicula remains unknown. Here, we studied the effects of temperature on the ingestion and assimilation of algal food by feeding radiocarbon-labeled algae Chlorella sp. at simulated field temperatures (19-31 °C) to C. acicula collected during the outbreak in the Daya Bay. We also quantified the allocation of the food carbon to dissolved organic carbon (DOC), CO2, and fecal pellets. The results showed that the zooplankton during the same feeding time ingested doubled or tripled algal food at higher temperatures, and it produced and released significantly more DOC, CO2, and fecal pellets with more ingested food carbon. Meanwhile, the assimilation efficiency for the ingested food carbon slightly increased from 48% to 54% with rising temperature. As a result, higher assimilation rates indicating faster growth of C. acicula were observed at higher temperatures. In addition, the high activation energy of 0.908 eV indicated that the assimilation rate was very sensitive to temperature rising. Our results show that relatively rising temperature can enhance C. acicula's ingestion and assimilation rates for algal food, benefit its growth and metabolism, and contribute to its outbreak. This study provides a mechanistic interpretation for the relationship between rising temperature and the outbreaks of C. acicula and suggests that such outbreaks may occur more frequently and widely in the warming ocean.

Prognostic role and clinicopathological features of SMAD4 gene mutation in colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Approximately 5.0-24.2% of colorectal cancers (CRCs) have inactivating mutations in SMAD4, making it one of the frequently mutated genes in CRC. We thus carried out a comprehensive system review and meta-analysis investigating the prognostic significance and clinicopathological features of SMAD4 gene mutation in CRC patients. METHODS: A detailed literature search was conducted in PubMed, Web of Science and Embase databases to study the relationship between SMAD4 mutations and the demographic and clinicopathological characteristics in CRC patients. The hazard ratios (HRs) with 95% confidence intervals (CI) were used to evaluate the effect of SMAD4 mutations on overall survival (OS) and progression-free survival (PFS)/recurrence-free survival (RFS). RESULTS: Ten studies enrolling 4394 patients were eligible for inclusion. Data on OS were available from 5 studies and data on PFS/RFS were available from 3 studies. Comparing SMAD4-mutated CRC patients with SMAD4 wild-type CRC patients, the summary HR for OS was 1.46 (95% CI 1.28-1.67, P = 0.001), the summary HR for PFS/RFS was 1.59 (95% CI 1.14-2.22, P = 0.006). In terms of clinicopathology parameters, 9 studies have data that can be extracted, SMAD4 mutations were associated with tumor location (odds ratio [OR] = 1.15, colon/rectum, 95% CI 1.01-1.31, P = 0.042), TNM stage (OR = 1.28, stage IV/I-III, 95% CI 1.03-1.58, P = 0.025), lymph node metastasis (OR = 1.42, N1 + N2/N0, 95% CI 1.20-1.67, P < 0.001), mucinous differentiation (OR = 2.23, 95% CI 1.85-2.70, P < 0.001) and rat sarcoma viral oncogene homolog (RAS) mutation status (OR = 2.13, 95% CI 1.37-3.34, P = 0.001). No connection was found with age, gender, tumor grade, microsatellite instability status and b-viral oncogene homolog B1 mutation status. Besides, publication bias was not observed in any study. CONCLUSIONS: This meta-analysis suggests that SMAD4 mutation was associated with OS, PFS/RFS, and clinicopathological parameters, including tumor site, disease stage, RAS status, lymph node metastasis and mucinous differentiation. Our meta-analysis indicated that SMAD4 mutations could predict the poor prognosis and aggressive clinicopathological characteristics of CRC. More large-sample cohort studies are needed to confirm this conclusion. Since SMAD4 mutations are closely related to RAS mutations, their relationship warrants further investigation.

Bacterioplankton Metacommunity Processes across Thermal Gradients: Weaker Species Sorting but Stronger Niche Segregation in Summer than in Winter in a Subtropical Bay.

Thermal effluents from nuclear power plants greatly change the environmental and ecological conditions of the receiving marine water body, but knowledge about their impact on microbial ecology is limited. Here we used high-throughput sequencing of the 16S rRNA gene to examine marine bacterioplankton metacommunity assembly across thermal gradients in two representative seasons (i.e., winter and summer) in a subtropical bay located on the northern coast of the South China Sea. We found high heterogeneity in bacterioplankton community compositions (BCCs) across thermal gradients and between seasons. The spatially structured temperature gradient created by thermal effluents was the key determinant of BCCs, but its influence differed by season. Using a metacommunity approach, we found that in the thermal discharge area, i.e., where water is frequently exchanged with surrounding seawater and thermal effluent water, the BCC spatial patterns were shaped by species sorting rather than by mass effects from surrounding seawater or by dilution of thermal effluent water by surrounding seawater. However, this effect of species sorting was weaker in summer than in winter seawater. In both seasons, the bacterioplankton community structure was predominately determined by niche sharing; however, the relative importance of niche segregation was enhanced in summer seawater. Our findings suggest that for the seasonal differences in metacommunity processes, the BCCs of subtropical summer seawater were more sensitive to temperature and were more difficult to predict than those of winter seawater in the face of different intensities of thermal impacts.IMPORTANCE Understanding the mechanisms of bacterial community assembly across environmental gradients is one of the major goals of marine microbial ecology. Thermal effluents from two nuclear power plants have been present in the subtropical Daya Bay for more than 20 years and have generated a comparatively stable and long thermal gradient (a temperature increase from 0 to 10°C). The environmental patches across thermal gradients are heterogeneous and very strongly interconnected on a microbial scale; thus, this is a useful model for the study of the metacommunity processes (i.e., patch dynamics, species sorting, mass effects, and neutral processes) that underlie marine bacterioplankton assembly. The significance of our research is to reveal how environmental conditions and dispersal-related processes interact to influence bacterioplankton metacommunity processes and their seasonal differences across thermal gradients. Our results may advance the understanding of marine microbial ecology under future conditions of global warming.

Analysis of nifH DNA and RNA reveals a disproportionate contribution to nitrogenase activities by rare plankton-associated diazotrophs.

BACKGROUND: Holobionts comprising nitrogen-fixing diazotrophs and phytoplankton or zooplankton are ubiquitous in the pelagic sea. However, neither the community structure of plankton-associated diazotrophs (PADs) nor their nitrogenase transcriptional activity are well-understood. In this study, we used nifH gene Illumina sequencing and quantitative PCR to characterize the community composition and nifH expression profile of PADs with > 100 µm size fraction in the euphotic zone of the northern South China Sea. RESULTS: The results of DNA- and RNA-derived nifH gene revealed a higher alpha-diversity in the active than in the total community. Moreover, the compositional resemblance among different sites was less for active than for total communities of PADs. We characterized the 20 most abundant OTUs by ranking the sum of sequence reads across 9 sampling stations for individual OTUs in both nifH DNA and RNA libraries, and then assessed their phylogenetic relatedness. Eight of the 20 abundant OTUs were phylogenetically affiliated with Trichodesmium and occurred in approximately equal proportion in both the DNA and RNA libraries. The analysis of nifH gene expression level showed uneven attribute of the abundance and nitrogenase activities by the remaining 12 OTUs. Taxa belonging to cluster III and Betaproteobacteria were present at moderate abundance but exhibited negligible nitrogenase transcription activity. Whereas, the abundances of Richelia, Deltaproteobacteria and Gammaproteobacteria were low but the contribution of these groups to nitrogenase transcription was disproportionately high. CONCLUSIONS: The substantial variation in community structure among active dizatrophic fractions compared to the total communities suggests that the former are better indicators of biological response to environmental changes. Altogether, our study highlights the importance of rare PADs groups in nitrogen fixation in plankton holobionts, evidenced by their high level of nitrogenase transcription.

CSF3R mutations were associated with an unfavorable prognosis in patients with acute myeloid leukemia with CEBPA double mutations.

The aim of this study was to explore the clinical features and prognostic significance of CSF3R mutations in AML patients with CEBPA double mutations (CEBPAdm). One hundred one AML patients with CEBPAdm were retrospectively analyzed in this study. Mutation status of CSF3R gene, clinical features, and long-term outcomes were analyzed. The frequency of CSF3R mutations in patients with CEBPAdm was 19.80% (20/101). Patients with CSF3R mutations were associated with a lower platelet (u = 2.728, P = 0.006) and higher leukocytes (u = 3.178, P = 0.001) compared with those with wide-type CSF3R gene. The 5-year relapse-free survival (RFS) was 18.7% in patients with CSF3R mutations, which was significantly lower than those with wide-type CSF3R (31.8%) (P = 0.015). The 5-year overall survival (OS) was also significantly different between patients with and without CSF3R mutations (17.5% versus 57.4%, P = 0.019). The prevalence of CSF3R mutations was high in AML patients with CEBPAdm, which indicated a poor prognosis, and CSF3R mutations may be a new potential candidate for prognostically re-stratifying AML patients with CEBPAdm.

Uptake and subcellular distribution of aluminum in a marine diatom.

Aluminum (Al) is widespread in the environment including the ocean. The effects of Al on marine organisms have attracted more and more attention in recent years. However, the mechanisms of uptake of Al by marine organisms and the subcellular distribution of Al once assimilated are unknown. Here we report the uptake and subcellular distribution of Al in a marine diatom Thalassiosira weissflogii. Short-term (< 120 min) uptake experiments showed that the Al uptake rate by the diatom was 0.033 ±â€¯0.013 fmol-1 cell-1 min-1 (internalization flux normalized to the exposure Al concentration of 2 µM = 0.034 ±â€¯0.013 nmol m-2 min-1 nM-1). Subcellular fractionation experiments showed that the internalized Al was partitioned to subcellular components in the following order: granules (69 ±â€¯5%) > debris (17 ±â€¯4%) > organelles (12 ±â€¯2%) > heat-stable peptides (HSP) (~2%) > heat-denaturable proteins (HDP) (< 1%), indicating that the majority of intracellular Al was detoxified and stored in inorganic forms. The subcellular distribution of Al in the diatom is different from that of Al in freshwater green algae, in which most of the internalized Al is partitioned to organelles. We also evaluated an artificial seawater-based EDTA rinse solution to remove Al adsorbed on the diatom cell surface. Overall, our study provides new information to understand the mechanisms of uptake of Al by marine diatoms, and the mechanisms responsible for the biological effects (both toxic and beneficial) of Al on the growth of marine phytoplankton, especially diatoms.

Is phosphorus a limiting factor to regulate the growth of phytoplankton in Daya Bay, northern South China Sea: a mesocosm experiment.

Previous field investigations implied a potential phosphorus (P)-limitation on the growth of phytoplankton in Daya Bay, a mesotrophic bay in the northern South China Sea. Using a total of 15 mesocosms (3 × 3 × 1.5 m, with ~10.8 m3 natural seawater containing phytoplankton assemblages for each), we found P-enrichment caused no obvious effect on phytoplankton (Chl a) growth across 8-day's cultivation in neither winter nor summer, while nitrogen (N)-enrichment greatly increased Chl a in both seasons. N plus P-enrichment further increased Chl a content. The N- or N plus P-enrichments increased the allocation of nano-Chl a but decreased micro-Chl a in most cases, with no obvious effect by P-alone. Coincided with nutrients effect on Chl a content, N- or N plus P-enrichments significantly enhanced the maximum photochemical quantum yield of Photosystem II (FV/FM) and maximum relative electron transport rate (rETRmax), but declined the non-photochemical quenching (NPQ), as well as the threshold for light saturation of electron transport (EK); again, P-enrichment had no significant effect. Moreover, the absorption cross section for PSII photochemistry (σPSII) and electron transport efficiency (α) increased due to N- or N plus P-enrichments, indicating the increased nutrients enhance the light utilization efficiency through promoting PSII light harvesting ability, and thus to enhance phytoplankton growth. Our findings indicate that N- or N plus P-enrichments rigorously fuel phytoplankton blooms regardless of N:P ratios, making a note of caution on the expected P-deficiency or P-limitation on the basis of Redfield N:P ratios in Daya Bay.

Bacterial growth efficiency in a partly eutrophicated bay of South China Sea: Implication for anthropogenic impacts and potential hypoxia events.

Bacterial metabolism plays a dual role [bacterial production (BP) and bacterial respiration (BR)] in the aquatic ecosystem and potentially leads to hypoxia in the coastal eutrophic area. Bacterial growth efficiency (BGE) is an important index showing the contribution of bacterial metabolism to marine biological production and carbon budget in the pelagic ecosystem. In this study, the spatial and seasonal variety as well as diurnal variation dynamics of BGE and associated ecological characteristics were investigated in a partly eutrophicated subtropical bay (the Daya Bay) located in the northern South China Sea. Furthermore, the relationship between bacterial metabolism and potential hypoxia event was analyzed. The average BGE was 0.14 and 0.22 in summer and winter, respectively, which was lower than the mean value ever reported in other coastal and estuarine waters. The diurnal variations of BGE and BP were widely fluctuated in the Daya Bay, with approximately 3-8 fold variation of BP and 2-3 fold variation of BR in different seasons, suggesting the importance of short-term ecological dynamics on evaluating the long-term ecological processes in the coastal waters. BR was the predominant contributor to the bacterial carbon demand; however, the variation of BGE was controlled by BP in both seasons. BGE was always high in the near-shore waters with higher eutrophic level and more active BP and BR. The bacterial metabolism could deplete dissolved oxygen (DO) in the Daya bay within about 9 days when the water body was enclosed and photosynthesis was prohibited. Therefore, low DO concentration and potential hypoxia was more likely to be found in the near-shore waters of the Daya Bay in summer, since the water was stratified and enclosed with poor water exchange capacity in this area. While in winter, hypoxia seldom occurred due to vertical mixing throughout the water column. Further biological-physical coupling research is recommended to find out the detailed formation mechanism of hypoxia in the bay, and to predict the potential hypoxia events and their environmental impacts in the future.

The surface molecular signature of leukemic cells is associated with NPM1 mutations and FLT3 -ITD in patients with de novo acute myeloid leukemia.

Certain molecular mutations are associated with signs of cell morphology and differentiation in acute myeloid leukemia (AML). However, only limited data are available for the detailed analysis of such correlations. In this study, AML patients were classified into 4 subsets according to CD34, HLA-DR and CD11c expression levels. Significantly low CD34 antigen expression was observed in nucleophosmin (NPM1)-mutated patients and in those with FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD). No correlations were observed among NPM1 mutations, FLT3-ITD and monocytic morphology in patients without CD34 expression. Both NPM1 mutations and FLT3-ITD were absent in cluster IIb patients (CD34(+)CD11c(-)). The associations among NPM1 mutations, FLT3-ITD and the surface molecular signature of leukemic cells may offer beneficial information about the pathogenesis of AML.

Olverembatinib combined with inotuzumab ozogamicin in relapsed refractory Philadelphia chromosome-positive acute lymphoblastic leukemia: A case report.

RATIONALE: Patients with relapsed and refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with the T315I mutation are at higher risk of relapse and have shorter overall survival. PATIENT CONCERNS: A 31-year-old man presented to the hematology department with intermittent fever and pancytopenia. He was diagnosed with Ph+ acute lymphoblastic leukemia and experienced 2 relapses during treatment. A drug-resistant T315I mutation was detected in the ABL kinase region during review. DIAGNOSES: Morphological examination of the bone marrow revealed approximately 93.5% lymphoid blast. Flow cytometric analysis confirmed the diagnosis of common B-cell ALL with the following phenotype: CD34, CD45dim, CD19, CD10, cCD79a, CD58dim, CD81dim, cTdT, HLA-DR, CD22dim, CXCR4, CD33dim, CD20, CD25, CD13, CD123. The examination of the ABL kinase region mutation suggested a T315I mutation. INTERVENTIONS: Olverembatinib, a third-generation TKI drug, was administered in combination with inotuzumab ozogamicin to treat the disease. OUTCOMES: The patient achieved morphological remission with a negative flow cytometry MRD test, and the quantification of BCR-ABL transcripts was 0% after 1 cycle of therapy. LESSONS: The third-generation TKI olverembatinib has been proven to be effective in CML patients with the T315I mutation, and it may also be effective in Ph+ acute lymphoblastic leukemia. Some new immune drugs have also shown improvement in the remission rate. Combination therapy with olverembatinib and Ino can achieve a complete molecular response in patients with relapsed and refractory Ph+ ALL with the T315I mutation.

Insights into prokaryotic communities and their potential functions in biogeochemical cycles in cold seep.

Microorganisms are significant drivers of organic matter mineralization and are essential in marine biogeochemical cycles. However, the variations and influencing factors in prokaryotic communities from cold-seep sediments to the water column and the specific role of these microorganisms in biogeochemical cycles in the water column above cold seep remain unclear. Here, we investigated prokaryotic communities and their roles in nitrogen/sulfur cycling processes and conducted in situ dissolved organic matter (DOM) enrichment experiments to explore the effects of diverse sources of DOM on prokaryotic communities. Field investigations showed that the prokaryotic communities in the near-bottom water were more similar to those in the deep layer of the euphotic zone (44.60%) and at a depth of 400 m (50.89%) than those in the sediment (18.00%). DOM enrichment experiments revealed that adding dissolved organic nitrogen (DON) and phosphorus DOP caused a notable increase in the relative abundances of Rhodobacterales and Vibrionales, respectively. A remarkable increase was observed in the relative abundance of Alteromonadales and Pseudomonadales after the addition of dissolved organic sulfur (DOS). The metagenomic results revealed that Proteobacteria served as the keystone taxa in mediating the biogeochemical cycles of nitrogen, phosphorus, and sulfur in the Haima cold seep. This study highlights the responses of prokaryotes to DOM with different components and the microbially driven elemental cycles in cold seeps, providing a foundational reference for further studies on material energy metabolism and the coupled cycling of essential elements mediated by deep-sea microorganisms. IMPORTANCE: Deep-sea cold seeps are among the most productive ecosystems, sustaining unique fauna and microbial communities through the release of methane and other hydrocarbons. Our study revealed that the influence of seepage fluid on the prokaryotic community in the water column is surprisingly limited, which challenges conventional views regarding the impact of seepage fluids. In addition, we identified that different DOM compositions play a crucial role in shaping the prokaryotic community composition, providing new insights into the factors driving microbial diversity in cold seeps. Furthermore, the study highlighted Proteobacteria as key and multifaceted drivers of biogeochemical cycles in cold seeps, emphasizing their significant contribution to complex interactions and processes. These findings offer a fresh perspective on the dynamics of cold-seep environments and their microbial communities, advancing our understanding of the biogeochemical functions in deep-sea environments.

Mechanisms underlying therapeutic resistance of tyrosine kinase inhibitors in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a malignant clonal disease involving hematopoietic stem cells that is characterized by myeloid cell proliferation in bone marrow and peripheral blood, and the presence of the Philadelphia (Ph) chromosome with BCR-ABL fusion gene. Treatment of CML has dramatically improved since the advent of tyrosine kinase inhibitors (TKI). However, there are a small subset of CML patients who develop resistance to TKI. Mutations in the ABL kinase domain (KD) are currently recognized as the leading cause of TKI resistance in CML. In this review, we discuss the concept of resistance and summarize recent advances exploring the mechanisms underlying CML resistance. Overcoming TKI resistance appears to be the most successful approach to reduce the burden of leukemia and enhance cures for CML. Advances in new strategies to combat drug resistance may rapidly change the management of TKI-resistant CML and expand the prospects for available therapies.

Cold seep nitrogen fixation and its potential relationship with sulfur cycling.

Dinitrogen (N2) fixation is a crucial source of bioavailable nitrogen in carbon-dominated cold seep systems. Previous studies have shown that diazotrophy is not necessarily dependent on sulfate-dependent anaerobic oxidation of methane for energy, and diverse catabolism can fuel the high-energy-demanding process in sediments. However, it remains unclear whether diazotroph can obtain energy by sulfur oxidation in sulfur-rich cold seep water column. Here, field investigations and in situ experiments were conducted in Haima cold seep to examine the effects of diverse sources of dissolved organic matter (DOM) on N2 fixation, specifically containing sulfur, carbon, nitrogen, and phosphorus. We found that active N2 fixation occurred in the water column above the Haima cold seep, with the Dechloromonas genus dominating the diazotroph community as revealed by nifH gene using high-throughput sequencing. In situ experiments showed an increased rate of N2 fixation (1.15- to 12.70-fold compared to that in control group) and a greater relative abundance of the Dechloromonas genus following enrichment with sulfur-containing organic matter. Furthermore, metagenomic assembly and binning revealed that Dechloromonas sp. carried genes related to N2 fixation (nifDHK) and sulfur compound oxidation (fccAB and soxABCXYZ), implying that the genus potentially serves as a multifunctional mediator for N2 fixation and sulfur cycling. Our results provide new insights regarding potential coupling mechanism associated with sulfur-driven N2 fixation in methane- and sulfide-rich environments. IMPORTANCE: N2 fixation is an important source of biologically available in carbon-dominated cold seep systems as little nitrogen is released by hydrocarbon seepage, thereby promoting biological productivity and the degradation of non-nitrogenous organic matter. Cold seeps are rich in diverse sources of dissolved organic matter (DOM) derived from the sinking of photosynthetic products in euphotic layer and the release of chemosynthesis products on the seafloor. However, it remains unclear whether N2 fixation is coupled to the metabolic processes of DOM, as determined by e.g., carbon, nitrogen, phosphorus, and sulfur content, for energy acquisition in sulfur-rich cold seeps. In this study, diazotroph community structure and its response to DOM compositions were revealed. Moreover, the metagenomics analysis suggested that Dechloromonas genus plays a dominant role in potential coupling N2 fixation and sulfur oxidation. Our study highlighted that sulfur oxidation in deep-sea cold seeps may serve as an energy source to drive N2 fixation.

Regime shift in a coastal pelagic ecosystem with increasing human-induced nutrient inputs over decades.

Human-induced nutrient inputs to global coastal waters are leading to increasing nutrients and escalating eutrophication. However, how aquatic ecosystem functioning responds to these changes remains insufficiently studied. Here we report the long-term changes in the nutrient regime and planktonic ecosystem functioning in the Daya Bay, a typical subtropical semi-enclosed bay experiencing rapid economic and social development for several decades. Time-series (from 1991 to 2018) data with a mostly quarterly resolution were collected to depict long-term changes in dissolved inorganic nutrients and plankton abundances, based on which we constructed simplified abundance size spectra (SASS) and plankton abundance ratios to describe the functioning of the planktonic ecosystem. The results revealed a long-term increase in system productivity but a decrease in integrated energy transfer efficiency of the planktonic ecosystem, with rising concentrations of dissolved inorganic nitrogen (DIN). Shifts in the nutrient regime and planktonic ecosystem functioning were detected at a tipping point or threshold around 2006-2007. The shifts were characterized by abrupt changes in the trends of nutrient (phosphate, ammonia, nitrite) concentrations, nutrient ratios (DIN/phosphate, silicate/phosphate), plankton abundance, and total plankton biomass. Compared to the nutrient regime, the planktonic ecosystem functioning shifted several years later. Overall, this study indicates that the pelagic ecosystem regime can shift significantly in response to long-term increasing input of human-induced nutrients in coastal waters such as the Daya Bay. The regime shifts may have profound implications for fishery production, and ecosystem management in the bay.

Linking coral fluorescence phenotypes to thermal bleaching in the reef-building Galaxea fascicularis from the northern South China Sea.

Coral fluorescence phenotypes have been suggested as an adaptation to a broad range of environmental conditions, yet the mechanisms linking thermal bleaching tolerance in reef-building coral populations, associated with fluorescence phenotypes due to GFP-like proteins, remains unclear. In this study, the relationship between the thermal sensitivity and phenotypic plasticity of corals was investigated using two phenotypes of Galaxea fascicularis, green and brown. The results reveal that brown G. fascicularis was more susceptible to bleaching than green G. fascicularis when exposed to a higher growth temperature of 32 °C. Both phenotypes of G. fascicularis were associated with the thermotolerant Symbiodiniaceae symbiont, Durusdinium trenchii. However, the brown G. fascicularis showed a significant decrease in Symbiodiniaceae cell density and a significant increase in pathogenic bacteria abundance when the growth temperature was raised from 29 to 32 °C. The physiological traits and transcriptomic profiles of Symbiodiniaceae were not notably affected, but there were differences in the transcriptional levels of certain genes between the two phenotype hosts of G. fascicularis. Under heat stress of 32 °C, the gene encoding green fluorescent protein (GFP)-like and chromosome-associated proteins, as well as genes related to oxidative phosphorylation, cell growth and death showed lower transcriptional levels in the brown G. fascicularis compared to the green G. fascicularis. Overall, the results demonstrate that the green form of G. fascicularis is better able to tolerate ocean warming and defend against pathogenic bacteria, likely due to higher gene transcription levels and defense ability. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00190-1.