Responses of Attached Bacterial Communities to Blooms of the Swimming Shelled Pteropod Creseis acicula in Daya Bay, Southern China.

The shelled pteropod Creseis acicula is a marine pelagic shellfish widely distributed from temperate to tropical seas around the world. From June to July 2020, a C. acicula bloom first happened in the Daya Bay, southern China, and its density reached the highest value (5600 ind. m-3) ever recorded around the world. However, few studies have investigated the responses of bacterial communities to the C. acicula bloom. In the present study, we examined the community profiles of three communities of bacteria including the free-living and particle-attached bacteria in the blooming and reference waters, and bacteria attached to the whole body and shell of C. acicula using a high-throughput sequencing method. The results indicated that the C. acicula bloom had a greater impact on particle-attached bacteria than free-living bacteria. Among the bloom-sensitive particle-attached bacteria, the predominant bacterial phyla were Pseudomonadota, Bacteroidota, and Verrucomicrobiota in the blooming areas, whereas, they were Actinomycetota and Planctomycetota in the reference areas. Specifically, fecal bacteria Haloferula and Halioglobus sp. were significantly enriched in the blooming waters and accumulated on C. acicula shells. Conversely, the significantly lower relative abundance of Nocardioides sp. in the blooming area and accumulated on the whole body of C. acicula indicated their attachment to particles consumed by C. acicula. Overall, our results suggested that the C. acicula bloom influenced marine bacteria, particularly particle-attached bacteria by increasing (e.g. providing shells and feces) or decreasing (e.g. filter-feeding the suspended particles) the abundance of available substances.

Responses of microeukaryotic community structure to a Phaeocystis globosa bloom in a semi-enclosed subtropical bay.

The occurrence of Phaeocystis globosa, a harmful algal bloom species in Chinese coastal waters, has significant impacts on marine organisms and poses a threat to the safety of coastal nuclear power plants. Although previous studies have established a close association between P. globosa blooms and the bacterial community, the relationship between the microeukaryotic community and P. globosa blooms remains poorly understood. In this study, the variations in the microeukaryotic community resulting from a P. globosa bloom were analyzed using 18S rRNA gene amplicon sequencing. The results indicated that the diversity of the microeukaryotic community during the bloom phase was significantly higher than that during the dissipation phase. The microeukaryotic community compositions varied significantly between the two phases of the P. globosa bloom. During the bloom phase, the dominant microeukaryotic was Viridiplantae, which was then replaced by Dinoflagellata during the dissipation phase. Co-occurrence network analysis showed that the relationship among the microeukaryotic community during the bloom phase was more complex than that during the dissipation phase, and the keystone taxa varied as the bloom progressed. Additionally, microeukaryotic community assembly was primarily driven by stochastic processes during the bloom phase based on the ß-nearest taxon distance, whereas it was driven by both deterministic processes and stochastic processes during the dissipation phase. Overall, our findings provide novel insight into the mechanisms and interactions involved in microeukaryotic community dynamics in environments disturbed by P. globosa blooms.

Cationic Starch Nanoparticles for Enhancing CpG Oligodeoxynucleotide-Mediated Antitumor Immunity.

CpG ODNs demonstrate a significant promise for immunotherapy. However, their application is limited owing to quick DNase digestion and inadequate cellular internalization. Transportation of CpG ODNs into immune cells is crucial. Although viral vectors exhibit high transfection efficiency, safety risks, high cost, and low carrying capacity remain big obstacles. Herein, a novel CpG ODNs vector was fabricated by using starch. Starch was ultrasonicated and simply aminated (NH2-St) through grafting with diethylenetriamine, which was spherical with a diameter of 50 nm. NH2-St possessed good biocompatibility. Cationic NH2-St encapsulated CpG ODNs well and possessed a high loading capacity of 317 µg/mg. NH2-St protected CpG ODNs from nuclease digestion and significantly enhanced their cellular uptake. NH2-St/CpG induced the potent secretion of antitumor cytokines from macrophages and effectively suppressed the growth of tumor cells. This work highlights the promise of starch for CpG ODNs delivery, which brings new hope for cancer immunotherapy.

Diffuse large B-cell lymphoma with continuously elevated immunoglobulin M following treatment: a case report with pathologic, immunophenotypic, and molecular analyses.

A rare subtype of diffuse large B-cell lymphoma (DLBCL) has been reported to be accompanied by elevated immunoglobulin M (IgM) paraprotein in the serum at diagnosis, called as IgMs-DLBCL. The monoclonal IgM paraprotein disappears soon after treatment in most of these patients. Here, we described a DLBCL patient with continuously elevated IgM following therapy. A 59-year-old male was diagnosed with DLBCL (GCB subtype per Hans algorithm, stage IA) with involvement of the right cervical lymph node. After six cycles of immuno-chemotherapy with the R-CHOP regimen, complete metabolic remission was achieved, but an elevated level of serum IgM persisted. To investigate the origin of elevated IgM, pathologic, immunophenotypic, and molecular analyses of lymph node and bone marrow (BM) samples were performed pre- and post-treatment. BM infiltration of lymphoplasmacytic cells, and a typical immunophenotypic profile by flow cytometry supported the diagnosis of Waldenström macroglobulinemia (WM). The MCD subtype of DLBCL was identified by next-generation sequencing of the lymph node at initial diagnosis characterized by co-occurring point mutations in MYD88 L265P and CD79B. Additionally, two different dominant clonotypes of the immunoglobulin heavy chain (IGH) were detected in the lymph node and BM by IGH sequencing, which was IGHV 3-11*06/IGHJ 3*02 and IGHV 3-11*06/IGHJ 6*02, respectively, speculating to be two independent clonal origins. This study will provide a panoramic understanding of the origin or biological characteristics of DLBCL co-occurring with WM.

The anthropogenic effects on organic matter in sediment core based on Bayesian mixing model: a case study of Daya Bay.

Sediment is an important carrier of evidence about environmental evolution which receives huge volumes of organic material originated from both anthropogenic and natural sources. In this study, based on sedimentary chronology, the vertical trends of particle size distribution, total organic carbon (TOC), total nitrogen (TN), and their stable isotopes (δ13C, δ15N) in the sediment core of the nuclear power sea in southwest Daya Bay were analyzed, and the distribution characteristics and contribution ratios of different sources of organic matter in the sedimentary environment over the past 70 years were resolved using a Bayesian mixing model (MixSIAR). TOC, TN, δ13C, and δ15N ranged from 0.89 to 1.56%, 0.09 to 0.2%, - 22.3 to - 20.6‰, and 4.38 to 6.51‰, respectively. The organic matter in the sediment is controlled by a mixture of terrestrial input and marine autochthonous, the proportion of organic matter from terrestrial sources increases, while that from marine sources decreases in the sediment core, which persists from 1960 to 2000, yet organic matter from marine sources still dominates. The first signs of increased primary productivity occurred in 1960, and it was primarily due to agricultural activity. After the 1980s, the rapid increase in population around Daya Bay, the construction of nuclear power plants, the rise of aquaculture, and the quick expansion of industrial bases were all major factors that changed the ecological environment of Daya Bay.

Bisabolane-type sesquiterpenoids and bacillibactin from the marine-derived fungus Aspergillus sydowii SCSIO 41041 and their enzyme inhibiting activity.

Twelve compounds, including eleven bisabolane-type sesquiterpenoids (1 - 11), and one bacillibactin (12) were identified from marine-derived fungus Aspergillus sydowii SCSIO 41041 isolated from Creseis acicula. The chemical structures were elucidated by the basis of spectroscopic evidences, including HRESIMS, NMR and optical rotation. Biologically, all compounds were evaluated for their acetyl cholin-esterase (AChE) enzyme, pancreatic lipase (PL) enzyme, neuraminidase (NA) and phosphodiesterase 4 (PDE4) inhibitory activities. Compound 12 displayed significant inhibitory activity against neuraminidase (NA) with an IC50 value of 24.0 µM, which was equivalent to the positive drug oseltamivir phosphate (IC50 value of 20.0 µM). And the NA inhibitory activity was confirmed by molecular docking analysis.

C-reactive protein impairs immune response of CD8+ T cells via FcγRIIb-p38MAPK-ROS axis in multiple myeloma.

BACKGROUND: C-reactive protein (CRP) is a prototypical acute phase protein in humans with the function of regulating immune cells. Serum CRP levels are elevated in multiple myeloma (MM), associated with MM cell proliferation and bone destruction. However, its direct effects on T lymphocytes in MM have not been elucidated. METHODS: Public data sets were used to explore the correlation of CRP levels with immune cell infiltration and cytotoxicity score of CD8+ T cells in MM. In vitro, repeated freeze-thaw myeloma cell lines were taken as tumor antigens to load dendritic cells (DCs) derived from HLA-A*0201-positive healthy donors. MM-specific cytotoxic T cells (MM-CTL) were obtained from T lymphocytes of the corresponding donors pulsed with these DCs. B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T cells were manipulated by transfecting with lentivirus encoding an anti-BCMA single-chain variable fragment. Then T cells from healthy controls, MM-CTLs and BCMA CAR-T cells were exposed to CRP and analyzed for cell proliferation, cytotoxicity, immunophenotypes. CRP binding capacity to T cells before and after Fc gamma receptors IIb (FcγRIIb) blockage, p38 mitogen-activated protein kinase (MAPK) pathway and the downstream molecules were also detected. In vivo, both normal C57BL/6J mice and the Vk*MYC myeloma mouse models were applied to confirm the impact of CRP on T cells. RESULTS: CRP levels were negatively correlated with cell-infiltration and cytotoxicity score of CD8+ T cells in MM. In vitro experiments showed that CRP inhibited T-cell proliferation in a dose-dependent manner, impaired the cytotoxic activity and upregulated expression of senescent markers in CD8+ T cells. In vivo results validated the suppressive role of CRP in CD8+ T cells. CRP could bind to CD8+ T cells, mainly to the naïve T subset, while the binding was dramatically decreased by FcγRIIb blockage. Furthermore, CRP resulted in increased phosphorylation of p38 MAPK, elevated levels of reactive oxygen species and oxidized glutathione in CD8+ T cells. CONCLUSIONS: We found that CRP impaired immune response of CD8+ T cells via FcγRIIb-p38MAPK-ROS signaling pathway. The study casted new insights into the role of CRP in anti-myeloma immunity, providing implications for future immunotherapy in MM.

Transcriptome Responses to Different Environments in Intertidal Zones in the Peanut Worm Sipunculus nudus.

The peanut worm (Sipunculus nudus) is an important intertidal species worldwide. Species living in the same aquaculture area might suffer different environmental impacts. To increase knowledge of the molecular mechanisms underlying the response to environmental fluctuations, we performed a transcriptome analysis of S. nudus from different intertidal zones using a combination of the SMRT platform and the Illumina sequencing platform. (1) A total of 105,259 unigenes were assembled, and 23,063 unigenes were perfectly annotated. The results of the PacBio Iso-Seq and IIIumina RNA-Seq enriched the genetic database of S. nudus. (2) A total of 830 DEGs were detected in S. nudus from the different groups. In particular, 33 DEGs had differential expression in the top nine KEGG pathways related to pathogens, protein synthesis, and cellular immune response and signaling. The results indicate that S. nudus from different zones experience different environmental stresses. (3) Several DEGs (HSPA1, NFKBIA, eEF1A, etc.) in pathways related to pathogens (influenza A, legionellosis, measles, and toxoplasmosis) had higher expression in groups M and L. HSPA1 was clearly enriched in most of the pathways, followed by NFKBIA. The results show that the peanut worms from the M and L tidal flats might have suffered more severe environmental conditions. (4) Some DEGs (MKP, MRAS, and HSPB1) were upregulated in peanut worms from the H tidal flat, and these DEGs were mainly involved in the MAPK signaling pathway. These results indicate that the MAPK pathway may play a vital role in the immune response of the peanut worm to the effects of different intertidal flats. This study provides a valuable starting point for further studies to elucidate the molecular basis of the response to different environmental stresses in S. nudus.

Effect and mechanism of microplastics exposure against microalgae: Photosynthesis and oxidative stress.

The occurrence of microplastics (MPs) within aquatic ecosystems attracts a major environmental concern. It was demonstrated MPs could cause various ecotoxicological effects on microalgae. However, existing data on the effects of MPs on microalgae showed great variability among studies. Here, we performed a meta-analysis of the latest studies on the effects of MPs on photosynthesis and oxidative stress in microalgae. A total of 835 biological endpoints were investigated from 55 studies extracted, and 37 % of them were significantly affected by MPs. In this study, the impact of MPs against microalgae was concentration-dependent and size-dependent, and microalgae were more susceptible to MPs stress in freshwater than marine. Additionally, we summarized the biological functions of microalgae that are primarily affected by MPs. Under MPs exposure, the content of chlorophyll a (Chl-a) was reduced and electron transfer in the photosynthetic system was hindered, causing electron accumulation and oxidative stress damage, which may also affect biological processes such as energy production, carbon fixation, lipid metabolism, and nucleic acid metabolism. Finally, our findings provide important insights into the effects of MPs stress on photosynthesis and oxidative stress in microalga and enhance the current understanding of the potential risk of MPs pollution on aquatic organisms.

Human activities contributing to the accumulation of high-risk trace metal(loid)s in soils of China's five major urban agglomerations.

Rapid urbanization has accelerated the accumulation of trace metal(loid)s (TMs) in soils, but the relationship between this accumulation and human activities remains largely unknown. Therefore, based on 775 published literatures (2001-2020), this study aimed to identify the influence of human activities on TM accumulation. Results showed that all soil TM concentrations were higher than their corresponding Chinese soil background values. The pollution risk assessment indicated that the soil TMs in the study area were at moderate levels, and the value of Pollution load index was 2.10. According to the assessment of health risks, the non-carcinogenic risks for adults were at the "Negligible risk" level; while the carcinogenic risk was not negligible for all populations, with children being more susceptible than adults. Meanwhile, six high-risk TMs were identified based on the grading of Contaminating factors (CF ≥ 3) and contribution to health risk (≥ 75%), including four high pollution risk TMs (Cd, Hg, Cu, and Pb) and two high health risk TMs (Cr and As) . In addition, in accordance with the results of the Random forest model, the accumulation of soil high-risk TMs was closely related to influencing factors associated with human activities. The accumulation of Hg and Cr among five major urban agglomerations had the same influencing factors (the number of industrial companies and the amount of industrial wastewater discharge for Hg; the amount of pesticide application and highway mileage for Cr). However, there were significant differences in the factors influencing the accumulation of the other four high-risk TMs (including Cd, As, Cu and Pb), due to the different characteristics of each urban agglomeration. Our results provide new insights into the relationship between human activities and soil TM accumulation.

Unravelling the imbalanced Th17-like cell differentiation by single-cell RNA sequencing in multiple myeloma.

Multiple myeloma (MM) is a bone marrow resident hematological malignancy. T helper (Th) cells play an essential role in maladjustment of immune function and promotion of myeloma cell proliferation and survival, which has not been fully elucidated. Here, we compared transcriptome profiles of CD4+ T cells in bone marrow samples of 3 healthy individuals and 10 MM patients before and after treatment using single-cell RNA sequencing. CD4+ T cells were divided into 7 clusters. Imbalanced Th17-like cell differentiation was indicated in MM based on bioinformation analyses, which involved IL2-STAT5 pathways and transcription factors NKFB1, RELA, STAT3, and GTF2A2. Pseudotime trajectory analysis of CD4+ T cell clusters further uncovered the enhanced transition of Th17-like to regulatory T (Treg) cells in MM, which was featured by expression changes of PLAC8, NKFB1, RELA, STAT3, and STAT1 along with the developmental path. Reduced cell-cell interaction between MM cells and CD4+ naïve/recently activated naïve T cells via CD74-APP might lead to imbalanced Th17-like cell differentiation. Checkpoints via TIGIT-NECTIN3 and LGALS9-CD47 in Treg and MM cells were also identified. Our study reveals imbalanced differentiation pattern of Th17-like cells and the immunosuppressive profiles in connection with MM cells, which might help to shed light on CD4+ T cell function in MM.

Coastal sediment heavy metal(loid) pollution under multifaceted anthropogenic stress: Insights based on geochemical baselines and source-related risks.

Contamination and risk assessments generally ignore the potential bias in results caused by the variation of background values at different spatial scales due to the spatial heterogeneity of sediments. This study aims to perform quantitative source-ecological risk assessment via establishing geochemical baselines values (GBVs) of heavy metal(loid)s (HMs) in Daya Bay, China. Cumulative frequency distribution (CFD) curves determined the GBVs of 12.44 (Cu), 30.88 (Pb), 69.89 (Zn), 0.06 (Cd), 47.85 (Cr), 6.80 (As), and 0.056 mg kg-1 (Hg), which were comparable to the background values of Guangdong Province surface soils, and implied a potential terrestrial origin of the coastal sediments. Principal component analysis (PCA) and positive matrix factorization (PMF) identified three sources (F1: natural processes; F2: anthropogenic impacts; F3: specific sources) with contributions of 51.7%, 29.2%, and 19.1%, respectively. The source-specific risk assessment revealed an ecological risk contribution potential of 73.8% for the mixed anthropogenic sources (F2 + F3) and only 26.2% for natural processes. Cd and Hg were the priority management of metallic elements, occupying 63.5% and 72.5% of the contribution weights of F2 and F3, respectively, which showed multi-level pollution potentials and ecological risk levels. The spatial distribution patterns demonstrated the hotspot features of HM pollution, and priority concerns should be given to the management of marine traffic and industrial point source pollution in Daya Bay. The results of the study provide a scientific approach and perspective for pollution treatment and risk management in the coastal environment.

Bortezomib, Melphalan, and Prednisone With or Without Daratumumab in Transplant-ineligible Asian Patients With Newly Diagnosed Multiple Myeloma: The Phase 3 OCTANS Study.

INTRODUCTION: In the global phase 3 ALCYONE trial, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) improved outcomes versus VMP in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. Here, we report the primary analysis of the phase 3 OCTANS trial of D-VMP versus VMP in transplant-ineligible Asian NDMM patients. PATIENTS AND METHODS: In total, 220 patients were randomized (2:1) to receive 9 cycles of VMP (bortezomib 1.3 mg/m2 subcutaneously twice weekly in Cycle 1 and weekly in Cycles 2 to 9; melphalan 9 mg/m2 orally; and prednisone 60 mg/m2 orally on Days 1 to 4 of each cycle) ± daratumumab 16 mg/kg intravenously weekly in Cycle 1, every 3 weeks in Cycles 2 to 9, and every 4 weeks thereafter until disease progression. RESULTS: After a median follow-up of 12.3 months, very good partial response or better rates (primary endpoint) were 74.0% versus 43.2% with D-VMP versus VMP (odds ratio, 3.57; 95% confidence interval [CI], 1.99-6.43; P < .0001). Median progression-free survival (PFS) with D-VMP versus VMP was not reached versus 18.2 months (hazard ratio, .43; 95% CI, .24-.77; P = .0033); 12-month PFS rates were 84.2% versus 64.6%. The most frequent grade 3/4 treatment-emergent adverse events with D-VMP/VMP were thrombocytopenia (46.5%/45.1%), neutropenia (39.6%/50.7%), and leukopenia (31.3%/36.6%). CONCLUSION: D-VMP demonstrated a favorable benefit/risk profile in transplant-ineligible Asian NDMM patients. This trial was registered at www. CLINICALTRIALS: gov as #NCT03217812.

Distinct mechanisms of dysfunctional antigen-presenting DCs and monocytes by single-cell sequencing in multiple myeloma.

Multiple myeloma (MM) is an incurable plasma cell malignancy with the hallmark of immunodeficiency, including dysfunction of T cells, NK cells, and APCs. Dysfunctional APCs have been reported to play a key role in promoting MM progression. However, the molecular mechanisms remain elusive. Here, single-cell transcriptome analysis of dendritic cells (DC) and monocytes from 10 MM patients and three healthy volunteers was performed. Both DCs and monocytes were divided into five distinct clusters, respectively. Among them, monocyte-derived DCs (mono-DC) were shown to develop from intermediate monocytes (IM) via trajectory analysis. Functional analysis showed that, compared with healthy controls, conventional DC2 (cDC2), mono-DC, and IM of MM patients exhibited impaired antigen processing and presentation capacity. Moreover, reduced regulon activity of interferon regulatory factor 1 (IRF1) was found in cDC2, mono-DC and IM of MM patients according to single-cell regulatory network inference and clustering (SCENIC) analysis, while the downstream mechanisms were distinct. Specifically in MM patients, cathepsin S (CTSS) was markedly downregulated in cDC2, major histocompatibility complex (MHC) class II transactivator (CIITA) was significantly decreased in IM, in addition both CTSS and CIITA were downregulated in mono-DC based on differentially expressed genes analysis. In vitro study validated that knockdown of Irf1 downregulated Ctss and Ciita respectively in mouse DC cell line DC2.4 and mouse monocyte/macrophage cell line RAW264.7, which ultimately inhibited proliferation of CD4+ T cells after being cocultured with DC2.4 or RAW264.7 cells. This current study unveils the distinct mechanisms of cDC2, IM, and mono-DC function impairment in MM, offering new insight into the pathogenesis of immunodeficiency.

Single-cell RNA sequencing reveals XBP1-SLC38A2 axis as a metabolic regulator in cytotoxic T lymphocytes in multiple myeloma.

The mechanisms underlying the functional impairment and metabolic reprogramming of T lymphocytes in multiple myeloma (MM) have not been fully elucidated. In this study, single-cell RNA sequencing was used to compare gene expression profiles in T cells in bone marrow and peripheral blood of 10 newly diagnosed MM patients versus 3 healthy donors. Unbiased bioinformatics analysis revealed 9 cytotoxic T cell clusters. All 9 clusters in MM had higher expression of senescence markers (e.g., KLRG1 and CTSW) than the healthy control; some had higher expression of exhaustion-related markers (e.g., LAG3 and TNFRSF14). Pathway enrichment analyses showed downregulated amino acid metabolism and upregulated unfolded protein response (UPR) pathways, along with absent expression of glutamine transporter SLC38A2 and increased expression of UPR hallmark XBP1 in cytotoxic T cells in MM. In vitro studies revealed that XBP1 inhibited SLC38A2 by directly binding to its promoter, and silencing SLC38A2 resulted in decreased glutamine uptake and immune dysfunction of T cells. This study provided a landscape description of the immunosuppressive and metabolic features in T lymphocytes in MM, and suggested an important role of XBP1-SLC38A2 axis in T cell function.

Source apportionment and human health risk of PAHs accumulated in edible marine organisms: A perspective of "source-organism-human".

Most PAHs produced by human activities can be absorbed and accumulated by edible organisms and pose a potential hazard to human health. However, the source apportionment and human health risk of PAHs accumulated in edible organisms remains largely unknown. Therefore, we conducted source analysis and health risk assessment based on the PAH concentrations in ten marine fish from coastal areas of Guangdong, China. Results showed that the pollution of PAHs in fish organisms was at "Minimally polluted" level, and that all marine fish had the ability to accumulate PAHs. Risk assessment indicated Carcinogenic risk of PAHs in four populations was at a "Cautionary risk" level, with urban children suffered the highest risk. Petroleum pollution, Coal and biomass combustion, and Marine transport emissions were identified as the main anthropogenic sources for PAHs in organisms, and Marine transport emissions accounted for the highest Carcinogenic risk. The Acceptable daily intake for all populations were far below their actual daily intake without causing "Cautionary risk". Our findings provide new insights into the source apportionment and health risk of PAHs from a "source-organism-human" perspective, and suggested that joint management of three anthropogenic sources would be an effective way to prevent the health risks of PAHs.

Machine Learning Model Based on Optimized Radiomics Feature from 18F-FDG-PET/CT and Clinical Characteristics Predicts Prognosis of Multiple Myeloma: A Preliminary Study.

OBJECTS: To evaluate the prognostic value of radiomics features extracted from 18F-FDG-PET/CT images and integrated with clinical characteristics and conventional PET/CT metrics in newly diagnosed multiple myeloma (NDMM) patients. METHODS: We retrospectively reviewed baseline clinical information and 18F-FDG-PET/CT imaging data of MM patients with 18F-FDG-PET/CT. Multivariate Cox regression models involving different combinations were constructed, and stepwise regression was performed: (1) radiomics features of PET/CT alone (Rad Model); (2) Using clinical data (including clinical/laboratory parameters and conventional PET/CT metrics) only (Cli Model); (3) Combination radiomics features and clinical data (Cli-Rad Model). Model performance was evaluated by C-index and Net Reclassification Index (NRI). RESULTS: Ninety-eight patients with NDMM who underwent 18F-FDG-PET/CT between 2014 and 2019 were included in this study. Combining radiomics features from PET/CT with clinical data showed higher prognostic performance than models with radiomics features or clinical data alone (C-index 0.790 vs. 0.675 vs. 0.736 in training cohort; 0.698 vs. 0.651 vs. 0.563 in validation cohort; AUC 0.761, sensitivity 56.7%, specificity 85.7%, p < 0.05 in training cohort and AUC 0.650, sensitivity 80.0%, specificity78.6%, p < 0.05 in validation cohort) When clinical data was combined with radiomics, an increase in the performance of the model was observed (NRI > 0). CONCLUSIONS: Radiomics features extracted from the PET and CT components of baseline 18F-FDG-PET/CT images may become an effective complement to provide prognostic information; therefore, radiomics features combined with clinical characteristic may provide clinical value for MM prognosis prediction.

Nonmetric multidimensional scaling and probabilistic ecological risk assessment of trace metals in surface sediments of Daya Bay (China) using diffusive gradients in thin films.

This research is one main objective to assess combined toxicity of trace metal mixtures in aquatic biota in coastal sediments. Coastal sediments around the world are a major reservoir of trace metals from industrial wastewater discharge. Our case study site, Daya Bay in southern China, was selected because it has been under severe man-made impacts. Diffusive gradients in thin films (DGT) technique has proven to be a good method for measuring the bioavailability of trace metals. The bioavailability and distribution of trace metals in surface sediments were investigated along with their possible biological risks. The average bioavailable (DGT-labile) concentrations (µg/L) were 0.44 (V), 0.51 (Cr), 52.49 (Mn), 0.10 (Co), 1.36 (Ni), 0.74 (Cu), 14.53 (Zn), 0.97 (As), 0.14 (Se), 6.73 (Mo), 0.17 (Cd), 0.27 (Sb), 0.10 (W), and 1.32 (Pb). Nonmetric multidimensional scaling (NMS) is a robust multivariate ordination method that makes no assumptions about the distribution of the underlying data. NMS was used to explore that DGT-labile concentrations of trace metals were influenced by sediment properties. NMS results indicated that most DGT- labile trace metals influenced by sediment properties. Risk assessment of single trace metal toxicity revealed that risk quotient (RQ) values for Mn, Cu, Zn and Pb significantly exceeded 1, demonstrating that the toxic effects of these trace metals should be not ignored. The probabilistic ecological risk assessment for integral toxicity of one mixture of 14 trace metals revealed that Daya Bay surface sediments had a low probability (9.04 %) of adverse effects on aquatic biota.

Dynamic single-cell RNA-seq analysis reveals distinct tumor program associated with microenvironmental remodeling and drug sensitivity in multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is a hematological malignancy characterized by clonal proliferation of malignant plasma cells. Despite extensive research, molecular mechanisms in MM that drive drug sensitivity and clinic outcome remain elusive. RESULTS: Single-cell RNA sequencing was applied to study tumor heterogeneity and molecular dynamics in 10 MM individuals before and after 2 cycles of bortezomib-cyclophosphamide-dexamethasone (VCD) treatment, with 3 healthy volunteers as controls. We identified that unfolded protein response and metabolic-related program were decreased, whereas stress-associated and immune reactive programs were increased after 2 cycles of VCD treatment. Interestingly, low expression of the immune reactive program by tumor cells was associated with unfavorable drug response and poor survival in MM, which probably due to downregulation of MHC class I mediated antigen presentation and immune surveillance, and upregulation of markers related to immune escape. Furthermore, combined with immune cells profiling, we uncovered a link between tumor intrinsic immune reactive program and immunosuppressive phenotype in microenvironment, evidenced by exhausted states and expression of checkpoint molecules and suppressive genes in T cells, NK cells and monocytes. Notably, expression of YBX1 was associated with downregulation of immune activation signaling in myeloma and reduced immune cells infiltration, thereby contributed to poor prognosis. CONCLUSIONS: We dissected the tumor and immune reprogramming in MM during targeted therapy at the single-cell resolution, and identified a tumor program that integrated tumoral signaling and changes in immune microenvironment, which provided insights into understanding drug sensitivity in MM.