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Background: Previous researches mainly focused on whether cancer stem cells exist in diffuse large B-cell lymphoma (DLBCL). However, subgroups with dismal prognosis and stem cell-like characteristics have been overlooked. Methods: Using large scale data (n = 2133), we conducted machine learning algorithms to identify a high risk DLBCL subgroup with stem cell-like features, and then investigated the potential mechanisms in shaping this subgroup using transcriptome, genome and single-cell RNA-seq data, and in vitro experiments. Results: We identified a high-risk subgroup (25.6 % of DLBCL) with stem cell-like characteristics and dismal prognosis. This high-risk group (HRG) was featured by upregulation of key enzyme (ODC1) in polyamine metabolism and cold tumor microenvironment (TME), and had a poor prognosis with lower 3-year overall survival (OS) (54.3 % vs. 83.6 %, P < 0.0001) and progression-free survival (PFS) (42.8 % vs. 74.7 %, P < 0.0001) rates compared to the low-risk group. HRG also exhibited malignant proliferative phenotypes similar to Burkitt lymphoma. Patients with MYC rearrangement, double-hit, double-expressors, or complete remission might have either favorable or poor prognosis, which could be further distinguished by our risk stratification model. Genomic analysis revealed widespread copy number losses in the chemokine and interferon coding regions 8p23.1 and 9p21.3 in HRG. We identified ODC1 as a therapeutic vulnerability for HRG-DLBCL. Single-cell analysis and in vitro experiments demonstrated that ODC1 overexpression enhanced DLBCL cell proliferation and drove macrophage polarization towards the M2 phenotype. Conversely, ODC1 inhibition reduced DLBCL cell proliferation, induced cell cycle arrest and apoptosis, and promoted macrophage polarization towards the M1 phenotype. Finally, we developed a comprehensive database of DLBCL for clinical application. Conclusions: Our study effectively advances the precise risk stratification of DLBCL and reveals that ODC1 and immune-deserted microenvironment jointly shape a group of DLBCL patients with stem cell-like features. Targeting ODC1 regulates immunotherapies in DLBCL, offering new insights for DLBCL treatment.

Background: The stage at diagnosis is a major factor in making treatment strategies and cancer control policies. However, the stage distribution for liver cancer in China was not well studied. In this multi-center hospital-based study, we aimed to identify the distribution and factors associated with stage at diagnosis for liver cancer in China. Methods: We included patients diagnosed with primary liver cancer in 13 hospitals of 10 provinces covering various geographic and socioeconomic populations during 2016–2017 in China. The stage distribution overall, and by sex and age at diagnosis were analyzed. We used logistic regression to identify the factors associated with stage III-IV disease. We further compared these estimates with data from the USA. Results: We included 2,991 patients with known stage at diagnosis in China. The proportion of patients diagnosed with stage I, II, III, and IV was 17.5%, 25.6%, 29.3%, and 27.6%, respectively. The proportion of stage III-IV cases was higher in women [65.1% vs 54.9%, adjusted odds ratio (OR) = 1.5, 95% CI: 1.2, 1.8] and those ≥ 60 years (61.6% vs 52.8%, OR = 1.4, 95% CI: 1.2, 1.6). We found an increased risk of stage III-IV among drinkers and those without a family history of cancer. Compared to the USA, our study population had a substantially higher proportion of stage III-IV cases (56.9% vs 45.6%). Conclusion: The disparities in liver cancer stage at diagnosis among different populations within China, and between China and the USA, imply the necessity for improving cancer awareness and early detection for liver cancer in China.

Abstract Background Multiple myeloma (MM) is a heterogeneous disease with different patterns of clonal evolution and a complex tumor microenvironment, representing a challenge for clinicians and pathologists to understand and dissect the contribution and impact of polyclonality on tumor progression. Methods In this study, we established a global cell ecological landscape of the bone marrow (BM) from MM patients, combining single-cell RNA sequencing and single-molecule long-read genome sequencing data. Results The malignant mutation event was localized to the tumor cell clusters with shared mutation of ANK1 and IFITM2 in all malignant subpopulations of all MM patients. Therefore, these two variants occur in the early stage of malignant clonal origin to mediate the malignant transformation of proplasmacytes or plasmacytes to MM cells. Tumor cell stemness index score and pseudo-sequential clonal evolution analysis can be used to divide the evolution model of MM into two clonal origins: types I and IX. Notably, clonal evolution and the tumor microenvironment showed an interactive relationship, in which the evolution process is not only selected by but also reacts to the microenvironment; thus, vesicle secretion enriches immune cells with malignant-labeled mRNA for depletion. Interestingly, microenvironmental modification exhibited significant heterogeneity among patients. Conclusions This characterization of the malignant clonal evolution pattern of MM at the single-cell level provides a theoretical basis and scientific evidence for a personalized precision therapy strategy and further development of a potential new adjuvant strategy combining epigenetic agent and immune checkpoint blockade.

The spatial distribution and heterogeneity of soil and vegetation, as the root of the maintenance of ecosystem services in the riparian zone, play a decisive role in the ecological functions of the riverscape. In this study, a field survey of wetland plant communities and soil sampling were conducted in both longitudinal and lateral dimensions from the perspective of the riverscape of the Ulgai River, a typical inland river on the Mongolian Plateau. The diversity of wetland plant communities, soil physicochemical properties, and the correlations between them were systematically analyzed. The results showed that a total of 87 species belonging to 65 genera and 24 families of plants were present, with Asteraceae, Poaceae, and Cyperaceae as the main families. The plant composition and species diversity in the riparian zone at different dimensions showed obvious spatial patterns of succession. Although the correlation coefficient and significance of the physicochemical properties of river length and river width in the study area were different, most correlations remained consistent, among which soil moisture, soil pH, and total carbon were correlated with many physicochemical factors. The soil ammonium and nitrate nitrogen along the river length direction and electrical conductivity and organic carbon content along the river width direction were the main limiting factors affecting the diversity and distribution of plant species in the riparian zone based on the redundancy analysis. This study provides a theoretical basis for the continuous improvement of the current soil quality and the restoration of the degraded wetland ecosystems of inland rivers in arid and semi-arid regions, as well as a new perspective for the study of riverscape ecology.

Summary: Background: Limited data indicate that patients with colorectal cancer (CRC) are at higher risk of developing type 2 diabetes (T2D). We prospectively examined the risk of T2D between individuals with and without CRC in three large cohorts and conducted a meta-analysis. Methods: We assessed the diagnosis of CRC and T2D among 111,485 women from the Nurses' Health Study, 112,958 women from the Nurses' Health Study II, and 46,581 men from the Health Professionals Follow-up Study. We used multivariable Cox regression with time-varying covariates to calculate the hazard ratio (HR) of T2D in relation to CRC diagnosis. We further performed a systematic review and meta-analysis of cohort studies. Findings: Up to 36 years of follow-up (6.9 million person-years), we documented 3402 incident CRC cases and 26,469 T2D cases. Compared to non-CRC individuals, those with CRC were more likely to develop T2D (multivariable-adjusted HR 1.20, 95% CI 1.05–1.38). The association was most evident for individuals with fewer risk factors for T2D. In the meta-analysis of seven cohort studies (1,061,744 participants), CRC was associated with higher T2D risk (meta-analysis HR 1.21, 95% CI 1.11–1.31, I2 = 57.9%). By CRC duration, a statistically significant association was observed in the first 10 years but not after 10 years of CRC diagnosis (≤5 years, meta-analysis HR 1.32, 95% CI 1.27–1.36; 5.1–10 years, 1.14 [1.04–1.25]; >10 years, 1.14 [0.91–1.37]). Interpretation: CRC was associated with increased T2D risk, especially in the first ten years after CRC diagnosis. Our findings highlight the importance of T2D prevention for CRC survivorship care. Funding: NHS cohort infrastructure grant (UM1 CA186107), NHS program project grant that funds cancer research (P01 CA87969), NHS II cohort infrastructure grant (U01 CA176726), HPFS cohort infrastructure grant (U01 CA167552) and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2021-I2M-1-010).

Deoxyribonucleic acid methylation and gene transcription have been proved as two underlying mechanisms involved in rapid plastic response to environmental stresses. However, it remains elusive on how DNA methylation regulates gene transcription under acute and recurring environmental challenges to form the stress memory, further contributing to invasion success during range expansions. Using a model invasive species Ciona robusta, we investigated the regulatory roles of DNA methylation on gene transcription and their contribution to the formation of stress memory at 30 genes under acute and recurring osmotic challenges simulated during the invasion process. We found the bimodal distribution of methylation level for the 68 mCpGs identified across all the genes after challenges, but only five sites were significantly correlated with the expression of their corresponding genes. These genes participated in the biological processes of Ca2+ transport and metabolism of lipid and proline. At the DNA methylation level, we found two early-responding and four tardy-responding sites of stress memory and these sites were functionally related to genes involved in the biosynthesis of proline, metabolism of lipid, and transport of taurine and Ca2+. At the transcriptional level, three tardy-responding and five early-responding memory genes were involved in the transport of ions, regulation of water channels, biosynthesis of taurine, and metabolism of lipid. Altogether, the findings here suggest that DNA methylation and gene transcription should work in concert to facilitate the formation of stress memory, thus further improving the performance of invaders under recurring environmental challenges during biological invasions.

Ascidians, particularly those highly invasive ones, are typical fouling organisms to cause significantly negative ecological and economic influence in coastal ecosystems. Stolon, which is the unique structure of some solitary ascidians to complete the essential process of adhesion, possesses extremely high tolerance to environmental stresses during biofouling and invasions. However, the mechanisms underlying environmental tolerance remain largely unknown. Here, we used the quantitative proteomics technology, isobaric tags for relative and absolute quantitation (iTRAQ), to investigate the molecular response to environmental challenges (temperature and salinity) in the stolon of a highly invasive fouling ascidian, Ciona robusta. When compared with the control, a total of 75, 86, 123, and 83 differential abundance proteins were identified under low salinity, high salinity, low temperature, and high temperature stress, respectively. Bioinformatic analyses uncovered the key pathways under both temperature and salinity stresses, including “cytoskeleton,” “signal transduction,” and “posttranslational modification,” which were involved in stolon structure stability, protein synthesis, and stress response activation. Under the low salinity stress, the “extracellular matrix” pathway was identified to play a crucial role by regulating cell signal transduction and protein synthesis. To deal with the high salinity stress, stolon could store more energy by activating “carbohydrate/lipid transport” and “catabolism” pathways. The energy generated by “lipid metabolism” pathway might be beneficial to resist the low temperature stress. The upregulation of “cell cycle” pathway could inhibit cell growth, thus helping stolon conserve more energy against the high temperature stress. Our results here provide valuable references of candidate pathways and associated genes for studying mechanisms of harsh environmental adaptation and developing antifouling strategies in marine and coastal ecosystems.

Freshwater ecosystems harbor a vast diversity of micro-eukaryotes (rotifers, crustaceans and protists), and such diverse taxonomic groups play important roles in ecosystem functioning and services. Unfortunately, freshwater ecosystems and biodiversity therein are threatened by many environmental stressors, particularly those derived from intensive human activities such as chemical pollution. In the past several decades, significant efforts have been devoted to halting biodiversity loss to recover services and functioning of freshwater ecosystems. Biodiversity monitoring is the first and a crucial step towards diagnosing pollution impacts on ecosystems and making conservation plans. Yet, bio-monitoring of ubiquitous micro-eukaryotes is extremely challenging, owing to many technical issues associated with micro-zooplankton such as microscopic size, fuzzy morphological features, and extremely high biodiversity. Here, we review current methods used for monitoring zooplankton biodiversity to advance management of impaired freshwater ecosystems. We discuss the development of traditional morphology-based identification methods such as scanning electron microscope (SEM) and ZOOSCAN and FlowCAM automatic systems, and DNA-based strategies such as metabarcoding and real-time quantitative PCR. In addition, we summarize advantages and disadvantages of these methods when applied for monitoring impacted ecosystems, and we propose practical DNA-based monitoring workflows for studying biological consequences of environmental pollution in freshwater ecosystems. Finally, we propose possible solutions for existing technical issues to improve accuracy and efficiency of DNA-based biodiversity monitoring.