The effects of polystyrene microplastics on feeding, growth, and trophic upgrading of protozoan grazers.

Microplastics have become ubiquitous in the global marine environment, posing substantial influences on marine organism health, food web function and marine ecosystem structure. Protozoan grazers are known for their ability to improve the biochemical constituents of poor-quality algae for subsequent use by higher trophic levels. However, the effects of microplastics on the trophic upgrading of protozoan grazers remain unknown. To address this knowledge gap, the ciliate Euplotes vannus and the heterotrophic dinoflagellate Oxyrrhis marina were exposed to microplastic particles (5 µm) for four days with various concentrations (1-20 mg/L). Both O. marina and E. vannus ingested microplastics. At the exposure level of 20 mg/L, the ingestion rate, growth rate, biovolume, and carbon biomass of E. vannus were significantly decreased by 28.18 %, 32.01 %, 30.46 %, and 82.27 %, respectively, while such effects were not observed for O. marina. The contents of highly unsaturated fatty acids in O. marina and E. vannus on a mixed diet of microplastic particles and green algae significantly reduced by 8.66 % and 41.49 % relative to feeding only on green algae, respectively. Besides, we also observed an increase in the composition of C18:3 (ω-3) and C20:3 (ω-3) concurrence with a significant decrease in C16:0 and C18:0 in E. vannus after 96 h exposure at 20 mg/L. These results indicate that microplastics can weaken trophic upgrading of the nutritional quality by protozoan grazers, which may consequently alter the function of food webs.

IMPeTUs parameters correlate with clinical features in newly diagnosed multiple myeloma.

Objectives: To investigate the correlations between IMPeTUs-based 18 F-FDG PET/CT parameters and clinical features in patients with newly diagnosed multiple myeloma (MM). Materials and methods: PET/CT were analysed according to the IMPeTUs criteria. We correlated these PET/CT parameters with known clinically relevant features, bone marrow plasma cell (BMPC) infiltration rate and the presence of cytogenetic abnormalities. Results: A total of 149 patients (86 males, 63 females; mean age, 59.9 ± 9.7 years) were included. Bone marrow metabolic state correlated with the most clinical features including hemoglobin (rho=-0.23, p=0.004), FLC ratio (rho=0.24, p=0.005), ß2 M (rho=0.28, p=0.001), CRP (rho=0.25, p=0.003), serum calcium (rho=0.22, p=0.02), serum creatinine (rho=0.24, p=0.004) and BMPC (rho=0.21, p=0.003). Besides, the level of hemoglobin was significant lower (0.043), and the levels of FLC ratio (0.037), ß2 M (p=0.024), CRP (p=0.05), and BMPC (p=0.043) were significant higher in patients having hypermetabolism in limbs and ribs. Hottest bone lesion Deauville criteria had a moderate correlation with CRP (rho=0.27, p=0.001) and serum calcium (rho=0.25, p=0.01). Conclusion: Several IMPeTUs-based PET/CT parameters showed significant correlations with clinical features reflecting disease burden and biology, suggesting that these new criteria can be used in the risk stratification in MM patients.

Machine learning based on biological context facilitates the identification of microvascular invasion in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma is a rare disease associated with a poor prognosis, primarily due to early recurrence and metastasis. An important feature of this condition is microvascular invasion (MVI). However, current predictive models based on imaging have limited efficacy in this regard. This study employed a random forest model to construct a predictive model for MVI identification and uncover its biological basis. Single-cell transcriptome sequencing, whole exome sequencing, and proteome sequencing were performed. The area under the curve of the prediction model in the validation set was 0.93. Further analysis indicated that MVI-associated tumor cells exhibited functional changes related to epithelial-mesenchymal transition and lipid metabolism due to alterations in the nuclear factor-kappa B and mitogen-activated protein kinase signaling pathways. Tumor cells were also differentially enriched for the interleukin-17 signaling pathway. There was less infiltration of SLC30A1+ CD8+ T cells expressing cytotoxic genes in MVI-associated intrahepatic cholangiocarcinoma, whereas there was more infiltration of myeloid cells with attenuated expression of the major histocompatibility complex II pathway. Additionally, MVI-associated intercellular communication was closely related to the SPP1-CD44 and ANXA1-FPR1 pathways. These findings resulted in a brilliant predictive model and fresh insights into MVI.

Artificial intelligence improves microvascular invasion (MVI) recognition. Multi-omics studies reveal malignant features associated with MVI. Tumors with MVI have disrupted lipid metabolism. MVI indicates a suppressive immune microenvironment. MVI can serve as a foundation for immunotherapy selection.

Differential isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2 mutation-related landscape in intrahepatic cholangiocarcinoma.

BACKGROUND: Patients with intrahepatic cholangiocarcinoma (ICC) are prone to recurrence and poor survival. Targeted therapy related to isocitrate dehydrogenase (IDH) is an extremely important treatment. IDH1 and IDH2 mutations are generally thought to have similar effects on the tumor landscape. However, it is doubtful whether these 2 mutations have exactly the same effects on tumor cells and the tumor microenvironment. METHODS: All collected tumor samples were subjected to simultaneous whole-exon sequencing and proteome sequencing. RESULTS: IDH1 mutations accounted for 12.2%, and IDH2 mutations accounted for 5.5%, all missense mutations. Tumors with IDH mutations had lower proportions of KRAS and TP53 mutations. Mutated genes were obviously enriched in the kinase pathway in the tumors with IDH2 mutations. The signaling pathways were mainly enriched in the activation of cellular metabolic activities and an increase of inhibitory immune cells in the tumors with IDH mutations. Moreover, tumors had unique enrichment in DNA repair in IDH1 mutants and secretion of biological molecules in IDH2 mutants. Inhibitory immune cells might be more prominent in IDH2 mutants, and the expression of immune checkpoints PVR and HLA-DQB1 was more prominent in IDH1 mutants. IDH mutants were more related to metabolism-related and inflammation-immune response clusters, and some belonged to the DNA replication and repair cluster. CONCLUSIONS: These results revealed the differential IDH1 and IDH2 mutation-related landscapes, and we have provided an important reference database to guide ICC treatment.

Biochemical changes in lumbar facet joint and disc degeneration by T2* mapping.

BACKGROUND: To investigate the biochemical changes in lumbar facet joint (LFJ) and intervertebral disc (IVD) with different degenerative grade by T2* mapping. METHODS: Sixty-eight patients with low back pain (study group) and 20 volunteers (control group) underwent standard MRI protocols and axial T2* mapping. Morphological evaluation of LFJ and IVD were performed on T2-weighted imaging according to Weishaupt and Pfirrmann grading system, respectively. T2* values of LFJ and of AF (anterior annulus fibrosus), NP (nucleus pulposus), and PF (posterior annulus fibrosus) in IVD were measured. Kruskal-Wallis test and Wilcoxon rank-sum test were used to compare T2* values of subjects with different degenerative grade. RESULTS: The mean T2* value of grade 0 LFJ (21.68[17.77,26.13]) was higher than those of grade I (18.42[15.68,21.8], p < 0.001), grade II (18.98[15.56,22.76], p = 0.011) and grade III (18.38[16.05,25.07], p = 0.575) LFJ in study group, and a moderate correlation was observed between T2* value and LFJ grade (rho=-0.304, p < 0.001) in control group. In the analysis of IVD, a moderate correlation was observed between AF T2* value and IVD grade (rho=-0.323, p < 0.001), and between NP T2* value and IVD grade (rho=-0.328, p < 0.001), while no significant difference was observed between the T2* values of PF in IVD of different grade in study group. CONCLUSIONS: Downward trend of T2* values can be found in LFJ, AF and NP as the degenerative grade rised. But in elderly patients with low back pain, no change trend was found in LFJ due to increased fluid accumulation in the joint space.

Recovery of 1887 metagenome-assembled genomes from the South China Sea.

The South China Sea (SCS) is a marginal sea characterized by strong land-sea biogeochemical interactions. SCS has a distinctive landscape with a multitude of seamounts in its basin. Seamounts create "seamount effects" that influence the diversity and distribution of planktonic microorganisms in the surrounding oligotrophic waters. Although the vertical distribution and community structure of marine microorganisms have been explored in certain regions of the global ocean, there is a lack of comprehensive microbial genomic surveys for uncultured microorganisms in SCS, particularly in the seamount regions. Here, we employed a metagenomic approach to study the uncultured microbial communities sampled from the Xianbei seamount region to the North Coast waters of SCS. A total of 1887 non-redundant prokaryotic metagenome-assembled genomes (MAGs) were reconstructed, of which, 153 MAGs were classified as high-quality MAGs based on the MIMAG standards. The community structure and genomic information provided by this dataset could be used to analyze microbial distribution and metabolism in the SCS.

Shenqi formula delayed Alzheimer's disease-like symptoms by skn-1 pathway in Caernorhabditis elegans.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenqi formula is composed of Codonopsis pilosula (Cp) and Lycium barbarum (Lb), and it is traditionally used for promoting qi and nourishing the spleen, liver and kidney. Cp and Lb have been reported to improve cognitive performance in APP/PS1 mice, prevent the accumulation of Aß, and reduce the neurotoxicity of Aß to achieve the anti-Alzheimer's disease (AD) effect. AIM OF THE STUDY: Shenqi formula was explored the therapeutic effect on Caenorhabditis elegans AD pathological model and the underlying mechanism of action. MATERIALS AND METHODS: Paralysis assay and serotonin sensitivity assay was used to detect whether Shenqi formula can alleviate AD paralysis phenotype, and then DPPH, ABTS, NBT and Fenton methods were applied to investigate the scavenging capacity to free radical, ROS, ·O2- and ·OH of Shenqi formula in vitro. H2DCF-DA and MitoSOX™ Red were employed to measure ROS and .O2- accumulation, respectively. RNAi was used to knock down the expression of skn-1 and daf-16 related to oxidative stress resistance signalling pathway. Fluorescence microscopy was used to record the expression of SOD-3::GFP, GST-4::GFP, SOD-1::YFP, and the nuclear translocation of SKN-1 and DAF-16. Western blot assay was carried out to test Aß monomers and oligomers. RESULTS: Shenqi formula delayed the AD-like pathological characteristics in C. elegans, and the complete Shenqi formula was more effective than Cp or Lb alone. The effect of Shenqi formula on delaying worm paralysis was partially eliminated by skn-1 RNAi, but not daf-16 RNAi. Shenqi formula significantly inhibited the abnormal deposition of Aß protein, decreased Aß protein monomers and oligomers. It increased the expressions of gst-4, sod-1, and sod-3 similar to paraquat, companied by rise then fall of ROS and .O2- in AD worms. CONCLUSIONS: Shenqi formula at least partially depended on SKN-1 signalling pathway to exert its anti-AD effect, and it is potential to be used as a kind of health food to prevent the progress of AD.

Complete Genome Sequence of Stutzerimonas stutzeri Strain SOCE 002, a Marine Bacterium Isolated from the Surface Seawater of Dapeng Bay.

We report the complete genome sequence of Stutzerimonas stutzeri strain SOCE 002, obtained from Illumina and Oxford Nanopore sequencing. The genome is 4.68 Mb long, with a GC content of 63.5%, and contains 4,334 protein-coding genes, 60 tRNAs, and 12 rRNAs. We expect that this complete genome sequence will provide a reference for both genomic and metabolic analyses of S. stutzeri.

A corpus of CO2 electrocatalytic reduction process extracted from the scientific literature.

The electrocatalytic CO2 reduction process has gained enormous attention for both environmental protection and chemicals production. Thereinto, the design of new electrocatalysts with high activity and selectivity can draw inspiration from the abundant scientific literature. An annotated and verified corpus made from massive literature can assist the development of natural language processing (NLP) models, which can offer insight to help guide the understanding of these underlying mechanisms. To facilitate data mining in this direction, we present a benchmark corpus of 6,086 records manually extracted from 835 electrocatalytic publications, along with an extended corpus with 145,179 records in this article. In this corpus, nine types of knowledge such as material, regulation method, product, faradaic efficiency, cell setup, electrolyte, synthesis method, current density, and voltage are provided by either annotating or extracting. Machine learning algorithms can be applied to the corpus to help scientists find new and effective electrocatalysts. Furthermore, researchers familiar with NLP can use this corpus to design domain-specific named entity recognition (NER) models.

Combination Effect of Microcystins and Arsenic Exposures on CKD: A Case-Control Study in China.

Evidence has shown that exposure to environmental pollutants such as microcystins (MCs), arsenic (As), and cadmium (Cd) can lead to the occurrence and development of chronic kidney disease (CKD). There is a synergistic effect between MCs and Cd. However, the combined effect of MCs and As exposures on CKD remains unclear. In Hunan province, China, 135 controls and 135 CKD cases were enrolled in a case-control study. Serum MCs, plasma As and Cd concentrations were measured for all participants. We investigated the association between MCs/As and CKD risk using conditional logistic regression. The additive model explored the interaction effect, and the Bayesian kernel machine regression (BKMR) models investigated the combined effects of MCs, As, and Cd on CKD. The results showed that MCs and As were significantly associated with CKD risk. Participants in the highest MCs concentration had a 4,81-fold increased risk of CKD compared to those in the lowest quartile (95% confidence interval [CI]: 1,96 to 11,81). The highest quartile of As concentrations corresponded to an adjusted odds ratio of 3.40 (95% CI: 1.51, 7.65) relative to the lowest quartile. MCs/As and CKD risk exhibited significant dose-response correlations (all p for trend < 0.01). In addition, a positive interaction effect of MCs and As on CKD was also reported. The CKD risk due to interaction was 2.34 times (95% CI: 0.14, 4.54) relative to the CKD risk without interaction, and the attributable proportion of CKD due to interaction among individuals with both exposures was 56% (95% CI: 0.22, 0.91). In the BKMR, the combined effect of MCs, As, and Cd was positively associated with CKD. In conclusion, both MCs and As are independent risk factors for CKD, exerting a synergistic effect between them. Combined exposure to MCs, As, and Cd can increase the risk of CKD.

Diversity and Distribution of Harmful Algal Bloom Species from Seamount to Coastal Waters in the South China Sea.

Mount Xianbei is one of the largest shallow seamounts located in the middle of the South China Sea (SCS), which might play a role in shaping the biodiversity of surrounding continental coastal waters, particularly the diversity of phytoplankton species causing frequent harmful algal blooms (HABs) in northern SCS. However, the diversity, composition, and distribution of phytoplankton species in the seamount regions of Xianbei remain largely unexplored. In this study, samples around and outside the seamount regions were collected during a late summer cruise of 2021 to test whether seamounts play a role in HAB species propagation. In total, we identified 19 HAB species across all samples using the ASV-based DNA metabarcoding approach, 6 of which had not been reported previously in the SCS, suggesting a diverse HAB species in the SCS. Specifically, 16 HAB species were found in the seamount region of Xianbei, and 5 of them were also found in the coastal waters, indicating a close connection between seamount and coastal waters. This study was the first attempt to explore HAB species' spatial diversity and vertical distribution in the seamount region of Xianbei at single-nucleotide resolution, which provides a novel explanation for the coastal HAB occurrence in the northern SCS. IMPORTANCE There are a number of seamounts under the water of the South China Sea (SCS). The seamounts might play a role in shaping the biodiversity of surrounding continental coastal waters. However, there is no direct evidence revealing the relationship of the biodiversity of phytoplankton between seamounts and coastal waters in the SCS, especially those species having the potential to form harmful algal blooms (HABs). Some HAB species might proliferate in certain geographic locations, while others may be broadly distributed across oceanic provinces. In this study, we provided a detailed analysis of phytoplankton composition and molecular detection of HAB species from seamount to coastal waters in the SCS, which suggested a strong interaction in the HAB species between the two areas. This finding provides new insights into the diversity and distribution of HABs in seamounts and their role in shaping the composition and the occurrence of HABs in coastal water.

Proteomic and single-cell landscape reveals novel pathogenic mechanisms of HBV-infected intrahepatic cholangiocarcinoma.

Despite the epidemiological association between intrahepatic cholangiocarcinoma (ICC) and hepatitis B virus (HBV) infection, little is known about the relevant oncogenic effects. A cohort of 32 HBV-infected ICC and 89 non-HBV-ICC patients were characterized using whole-exome sequencing, proteomic analysis, and single-cell RNA sequencing. Proteomic analysis revealed decreased cell-cell junction levels in HBV-ICC patients. The cell-cell junction level had an inverse relationship with the epithelial-mesenchymal transition (EMT) program in ICC patients. Analysis of the immune landscape found that more CD8 T cells and Th2 cells were present in HBV-ICC patients. Single-cell analysis indicated that transforming growth factor beta signaling-related EMT program changes increased in tumor cells of HBV-ICC patients. Moreover, ICAM1+ tumor-associated macrophages are correlated with a poor prognosis and contributed to the EMT in HBV-ICC patients. Our findings provide new insights into the behavior of HBV-infected ICC driven by various pathogenic mechanisms involving decreased cell junction levels and increased progression of the EMT program.

Complete Genome Sequence of a Cognatishimia activa Strain Assembled from the Phycosphere of the Marine Diatom Skeletonema tropicum.

Cognatishimia activa, previously known as Thalassobius activus, has been frequently isolated from marine environments. Here, we present the complete genome sequence of C. activa strain SOCE 004, assembled from the phycosphere of a long-term laboratory-maintained culture of the diatom Skeletonema tropicum. The complete genome is 3,211,994 bp long, with an average G+C content of 53.69%. The genome contains 3,195 genes, including 3,133 protein-coding genes, 50 tRNAs, and 3 copies each of 5S, 16S, and 23S rRNA genes.

Diagnostic Significance of 18F-FDG PET/CT Imaging Coupled with Magnetic Resonance Imaging of the Entire Body for Bone Metastases.

Objective: To see if 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging paired with MR diffusion imaging can help doctors diagnose bone metastases. Methods: From September 2020 to December 2021, a total of 30 individuals with probable bone metastases were recruited for the trial. With an average interval of four days, MAGNETIC resonance whole-body diffusion imaging (MR whole-body diffusion imaging) was performed on each of the 30 patients who had 18F-FDG PET/CT. The SUVmax values of the group with bone metastases were compared to those of the group without bone metastases. In this study, 18F-FDG PET/CT imaging, MR whole-body diffusion imaging, and their combination were examined. The researchers compared the results when 18F-FDG PET/CT imaging, whole-body MRI diffusion scans, and their combination indicated abnormal bone lesions. By comparing the diagnostic efficacy of 18F-FDG PET/CT imaging, MR whole-body diffusion imaging, and their combination, as well as accuracy, sensitivity, and specificity, the three techniques for diagnosing bone metastases will be evaluated for diagnostic usefulness. Results: the SUV max values of patients with bone metastases were significantly different from those of patients without bone metastases, as determined by 18F-FDG PET/CT imaging (P < 0.05). Using 18F-FDG PET/CT imaging, MR whole-body diffusion imaging, and their combined detection of aberrant bone lesions in various areas, we found statistically significant differences. Conclusion: The use of 18F-FDG PET/CT imaging in conjunction with MR whole-body diffusion imaging in the diagnosis of bone metastases can be very helpful.

Microcystin-LR Combined with Cadmium Exposures and the Risk of Chronic Kidney Disease: A Case-Control Study in Central China.

Increasing evidence indicates that exposure to microcystin-LR (MC-LR) can cause kidney damage. However, the association between MC-LR exposure and chronic kidney disease (CKD) risk in humans has not been studied. Therefore, we conducted a population-based case-control study involving 135 CKD cases and 135 matched controls in central China and analyzed the effects of MC-LR alone as well as combined with the known risk factor cadmium (Cd). Compared to the lowest quartile of MC-LR exposure, the highest quartile had a 6.56-fold (95% confidence interval [CI]: 2.46, 17.51) significantly increased risk for CKD, displaying a dose-response relationship (ptrend < 0.001). Our animal study also showed that MC-LR exposure induced kidney injury via the PI3K/AKT/mTOR signaling pathway. Comparing the highest Cd quartile to the lowest, the adjusted odds ratio for CKD was 3.88 (95% CI: 1.47, 10.28), exhibiting a dose-response relationship (ptrend < 0.006). Furthermore, a positive additive interaction was observed between MC-LR and Cd (relative excess risk due to interaction = 1.81, 95% CI: 0.42, 3.20; attributable proportion of interaction = 0.70, 95% CI: 0.35, 1.05). Our study firstly revealed that MC-LR exposure is an independent risk factor for CKD and has a synergistic relationship with Cd. MC-LR and Cd exposures are associated with CKD risk in a dose-response manner.

EMLI-ICC: an ensemble machine learning-based integration algorithm for metastasis prediction and risk stratification in intrahepatic cholangiocarcinoma.

Robust strategies to identify patients at high risk for tumor metastasis, such as those frequently observed in intrahepatic cholangiocarcinoma (ICC), remain limited. While gene/protein expression profiling holds great potential as an approach to cancer diagnosis and prognosis, previously developed protocols using multiple diagnostic signatures for expression-based metastasis prediction have not been widely applied successfully because batch effects and different data types greatly decreased the predictive performance of gene/protein expression profile-based signatures in interlaboratory and data type dependent validation. To address this problem and assist in more precise diagnosis, we performed a genome-wide integrative proteome and transcriptome analysis and developed an ensemble machine learning-based integration algorithm for metastasis prediction (EMLI-Metastasis) and risk stratification (EMLI-Prognosis) in ICC. Based on massive proteome (216) and transcriptome (244) data sets, 132 feature (biomarker) genes were selected and used to train the EMLI-Metastasis algorithm. To accurately detect the metastasis of ICC patients, we developed a weighted ensemble machine learning method based on k-Top Scoring Pairs (k-TSP) method. This approach generates a metastasis classifier for each bootstrap aggregating training data set. Ten binary expression rank-based classifiers were generated for detection of metastasis separately. To further improve the accuracy of the method, the 10 binary metastasis classifiers were combined by weighted voting based on the score from the prediction results of each classifier. The prediction accuracy of the EMLI-Metastasis algorithm achieved 97.1% and 85.0% in proteome and transcriptome datasets, respectively. Among the 132 feature genes, 21 gene-pair signatures were developed to establish a metastasis-related prognosis risk-stratification model in ICC (EMLI-Prognosis). Based on EMLI-Prognosis algorithm, patients in the high-risk group had significantly dismal overall survival relative to the low-risk group in the clinical cohort (P-value < 0.05). Taken together, the EMLI-ICC algorithm provides a powerful and robust means for accurate metastasis prediction and risk stratification across proteome and transcriptome data types that is superior to currently used clinicopathological features in patients with ICC. Our developed algorithm could have profound implications not just in improved clinical care in cancer metastasis risk prediction, but also more broadly in machine-learning-based multi-cohort diagnosis method development. To make the EMLI-ICC algorithm easily accessible for clinical application, we established a web-based server for metastasis risk prediction (http://ibi.zju.edu.cn/EMLI/).

Cancer cell membrane-wrapped nanoparticles for cancer immunotherapy: A review of current developments.

Background: As the forefront of nanomedicine, bionic nanotechnology has been widely used for drug delivery in order to obtain better efficacy but less toxicity for cancer treatments. With the rise of immunotherapy, the combination of nanotechnology and immunotherapy will play a greater potential of anti-tumor therapy. Due to its advantage of homologous targeting and antigen library from source cells, cancer cell membrane (CCM)-wrapped nanoparticles (CCNPs) has become an emerging topic in the field of immunotherapy. Key scientific concepts of review: CCNP strategies include targeting or modulating the tumor immune microenvironment and combination therapy with immune checkpoint inhibitors and cancer vaccines. This review summarizes the current developments in CCNPs for cancer immunotherapy and provides insight into the challenges of transferring this technology from the laboratory to the clinic as well as the potential future of this technology. Conclusion: This review described CCNPs have enormous potential in cancer immunotherapy, but there are still challenges in terms of translating their effects in vitro to the clinical setting. We believe that these challenges can be addressed in the future with a focus on individualized treatment with CCNPs as well as CCNPs combined with other effective treatments.

Effects of Temperature on Transparent Exopolymer Particle Production and Organic Carbon Allocation of Four Marine Phytoplankton Species.

Transparent exopolymer particles (TEP) are sticky polymeric substances that are commonly found in the periphery of microbial cells or colonies. They can naturally flocculate smaller suspended particles into larger aggregates and thus play a crucial role in the biological pump and the global carbon cycle. Phytoplankton are the major contributors to marine TEP production, whereas the way TEP production interacts with abiotic factors at the species level is generally unknown but critical for estimating carbon fluxes. In this study, the effects of temperature on TEP production and carbon allocation were studied in two representative diatom species (Nitzschia closterium and Chaetoceros affinis) and two model dinoflagellate species (Prorocentrum micans and Scrippisella trichoidea). The results showed that temperature had a significant impact on TEP production in all species. First, increased temperature promoted the TEP production of all four species. Second, elevated temperature affected the carbon pool allocation, with enhanced dissolved organic carbon (DOC) exudation in the form of TEP in all species. The TEP-C/DOC percentages of N. closterium and P. micans were 93.42 ± 5.88% and 82.03 ± 21.36% at the highest temperature (24 °C), respectively, which was approximately two to five times higher than those percentages at 16 °C. In contrast, TEP's contribution to the POC pool is lower than that to the DOC pool, ranging from 6.74 ± 0.79% to 28.31 ± 1.79% for all species. Moreover, phytoplankton TEP production may be related to cellular size and physiology. The TEP content produced by the smallest N. closterium (218.96 ± 15.04 fg Xeq./µm3) was ~5 times higher compared to P. micans, S. trichoidea, or C. affinis. In conclusion, TEP production is temperature sensitive and species specific, which should be taken into consideration the regarding TEP-mediated oceanic carbon cycle, particularly in the context of global warming.

Immunotherapy of cholangiocarcinoma: Therapeutic strategies and predictive biomarkers.

Cholangiocarcinoma (CCA) is a group of malignant heterogeneous cancer arising from the biliary tree. CCA has become a global health problem with rising incidence and mortality that threatens the health of human beings. The immune microenvironment of CCA is characterized by abundant cancer-associated fibroblast and suppressive immune components. The increasing body of knowledge and recent developments in transcriptomic studies have given insight into the immune landscape of CCA, paving the way for better application of immunotherapy. Immunotherapy mainly applies in a limited subset of CCA with deficient mismatch and high microsatellite instability. With limited response rates and treatment efficacy, researchers are looking into novel strategies on combination strategies and alternatives, such as immune vaccines and adoptive cell therapy. Biomarker identification is also critical for patient selection. We present an up-to-date summary of the current research on immunotherapy for CCA patients, covering pre-clinical and clinical exploration beyond immune checkpoint inhibitors, immune vaccines, and adoptive cell therapy. In addition, we review the promising biomarkers for CCA immunotherapy and discuss recent development.

The Landscape and Clinical Application of the Tumor Microenvironment in Gastroenteropancreatic Neuroendocrine Neoplasms.

Gastroenteropancreatic neuroendocrine neoplasms feature high heterogeneity. Neuroendocrine tumor cells are closely associated with the tumor microenvironment. Tumor-infiltrating immune cells are mutually educated by each other and by tumor cells. Immune cells have dual protumorigenic and antitumorigenic effects. The immune environment is conducive to the invasion and metastasis of the tumor; in turn, tumor cells can change the immune environment. These cells also form cytokines, immune checkpoint systems, and tertiary lymphoid structures to participate in the process of mutual adaptation. Additionally, the fibroblasts, vascular structure, and microbiota exhibit interactions with tumor cells. From bench to bedside, clinical practice related to the tumor microenvironment is also regarded as promising. Targeting immune components and angiogenic regulatory molecules has been shown to be effective. The clinical efficacy of immune checkpoint inhibitors, adoptive cell therapy, and oncolytic viruses remains to be further discussed in clinical trials. Moreover, combination therapy is feasible for advanced high-grade tumors. The regulation of the tumor microenvironment based on multiple omics results can suggest innovative therapeutic strategies to prevent tumors from succeeding in immune escape and to support antitumoral effects.