Meteorin regulates mesendoderm development by enhancing nodal expression

During gastrulation, distinct lineage specification into three germ layers, the mesoderm, endoderm and ectoderm, occurs through an elaborate harmony between signaling molecules along the embryonic proximo-distal and anterior-posterior axes, and Nodal signaling plays a key role in the early embryonic development governing embryonic axis formation, mesoderm and endoderm specification, and left-right asymmetry determination. However, the mechanism by which Nodal expression is regulated is largely unknown. Here, we show that Meteorin regulates Nodal expression and is required for mesendoderm development. It is highly expressed in the inner cell mass of blastocysts and further in the epiblast and extra-embryonic ectoderm during gastrulation. Genetic ablation of the Meteorin gene resulted in early embryonic lethality, presumably due to impaired lineage allocation and subsequent cell accumulation. Embryoid body culture using Meteorin-null embryonic stem (ES) cells showed reduced Nodal expression and concomitant impairment of mesendoderm specification. Meteorin-null embryos displayed reduced levels of Nodal transcripts before the gastrulation stage, and impaired expression of Goosecoid, a definitive endoderm marker, during gastrulation, while the proximo-distal and anterior-posterior axes and primitive streak formation were preserved. Our results show that Meteorin is a novel regulator of Nodal transcription and is required to maintain sufficient Nodal levels for endoderm formation, thereby providing new insights in the regulation of mesendoderm allocation.open1113sciescopu

Racial differences in long-term social, physical, and psychological health among adolescent and young adult cancer survivors

Background The current guidelines for survivorship in adolescents and young adults (AYA) cancer are based on studies conducted in the United States and European AYA survivors. However, previous studies have shown that the health-related quality of life in cancer survivors can vary depending on race, yet the long-term health differences among AYA survivors by race/ethnicity have not been fully explored. Therefore, our aim is to compare the psychosocial and physical health of AYA survivors and their matched controls across different racial and ethnic groups. Methods We conducted a cross-sectional study using US National Health and Nutrition Examination Survey (NHANES) and the Korea NHANES from 2007 to 2018. We included AYA cancer survivors who were diagnosed with any type of cancer aged between 15 and 39 years, and who were adult with aged over 18 years old at survey year. We then stratified the study population by race/ethnicity with Non-Hispanic White (NHW, n = 310), African American (AA, n = 42), Hispanic (n = 81) from NHANES, and Asian (n = 389) from the Korea NHANES. We also selected 5 times age-, sex-, race-, and survey year-matched general population among participants who had never been diagnosed with cancer (N = 4110). Variables were defined using questionnaire data, physical exams, and laboratory tests. Results Compared to NHW, Hispanics (aOR 1.15, 95% CI 1.00–1.32) had poor or fair general health, lower education (aOR 1.23, 95% CI 1.07–1.40), and lower household income (aOR 1.16, 95% CI 1.01–1.33). AA survivors were more likely to be non-coupled (aOR 1.35, 95% 1.15–1.60) and have hypertension (aOR 1.18, 95% CI 1.03–1.36). Asians were more former/current drinkers (aOR 1.21, 95% CI 1.05–1.40). NHW are more likely to experience psychological limitation. Compared to matched general, NHW and Asian survivors had poor general health and psychological health. Conclusions This study provides evidence for future studies concerning long-term health after AYA cancer survivorship that may vary according to race.This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (NRF-2022R1A2C1013119

Improvement of Anaerobic Digestion by Addition of Halloysite and Magnetite Powders

Objectives This study aimed to explore the potential of halloysite and magnetite powders to enhance anaerobic digestion efficiency and to compare their effects. Methods Anaerobic digestion experiments were conducted in a total of four consecutive batch processes using reactors with halloysite and magnetite powders added at concentrations of 1 g/L, 10 g/L, and 50 g/L, as well as a control reactor without any powder addition. Cumulative methane production was measured in each batch, and the Gompertz model was applied to calculate kinetic parameters, which were then compared with the control. Additionally, microbial community analysis was performed using 16S rRNA amplicon sequencing, and correlations between the powder concentrations, Gompertz kinetic parameters, and microbial groups were evaluated. Results and Discussion Both powders demonstrated an effect on improving methane production rates. When halloysite was added at a concentration of 50 g/L, an increase in methane production rate was observed in all batches. Compared to the control, the lag phase (λ) was reduced by up to 31.4%, and the maximum methane production rate (Rm) increased by 17.6%. While the effects of halloysite at concentrations of 1 g/L and 10 g/L were less significant compared to 50 g/L, trends of reduced lag phase and increased Rm were noted in at least two batches. For magnetite powder, the most effective concentration in the first and second batches was 1 g/L, but in the third and fourth batches, lag phase (λ) was reduced by up to 39.3%, and the maximum methane production rate (Rm) increased by 13.2% at concentrations of 10 g/L and 50 g/L. Microbial community analysis revealed an increased dominance of Geobacter and Methanosarcina associated with the DIET mechanism as the amount of magnetite increased. Conclusion This study confirms the potential of halloysite and magnetite powders to enhance methane production rates in anaerobic digestion processes. These findings suggest the feasibility of using powdered additives to improve the efficiency of anaerobic digestion, providing foundational data for future related research

Graphene quantum dots as anti-inflammatory therapy for colitis

While graphene and its derivatives have been suggested as a potential nanomedicine in several biomimetic models, their specific roles in immunological disorders still remain elusive. Graphene quantum dots (GQDs) may be suitable for treating intestinal bowel diseases (IBDs) because of their low toxicity in vivo and ease of clearance. Here, GQDs are intraperitoneally injected to dextran sulfate sodium (DSS)-induced chronic and acute colitis model, and its efficacy has been confirmed. In particular, GQDs effectively prevent tissue degeneration and ameliorate intestinal inflammation by inhibiting T(H)1/T(H)17 polarization. Moreover, GQDs switch the polarization of macrophages from classically activated M1 to M2 and enhance intestinal infiltration of regulatory T cells (T-regs). Therefore, GQDs effectively attenuate excessive inflammation by regulating immune cells, indicating that they can be used as promising alternative therapeutic agents for the treatment of autoimmune disorders, including IBDs.

Mind bomb 1 in the lymphopoietic niches is essential for T and marginal zone B cell development

Notch signaling regulates lineage decisions at multiple stages of lymphocyte development, and Notch activation requires the endocytosis of Notch ligands in the signal-sending cells. Four E3 ubiquitin ligases, Mind bomb (Mib) 1, Mib2, Neuralized (Neur) 1, and Neur2, regulate the Notch ligands to activate Notch signaling, but their roles in lymphocyte development have not been defined. We show that Mib1 regulates T and marginal zone B (MZB) cell development in the lymphopoietic niches. Inactivation of the Mib1 gene, but not the other E3 ligases, Mib2, Neur1, and Neur2, abrogated T and MZB cell development. Reciprocal bone marrow (BM) transplantation experiments revealed that Mib1 in the thymic and splenic niches is essential for T and MZB cell development. Interestingly, when BM cells from transgenic Notch reporter mice were transplanted into Mib1-null mice, the Notch signaling was abolished in the double-negative thymocytes. In addition, the endocytosis of Dll1 was impaired in the Mib1-null microenvironment. Moreover, the block in T cell development and the failure of Dll1 endocytosis were also observed in coculture system by Mib1 knockdown. Our study reveals that Mib1 is the essential E3 ligase in T and MZB cell development, through the regulation of Notch ligands in the thymic and splenic microenvironments

Disruption of Microtubules Sensitizes the DNA Damage-induced Apoptosis Through Inhibiting Nuclear Factor κB (NF-κB) DNA-binding Activity

The massive reorganization of microtubule network involves in transcriptional regulation of several genes by controlling transcriptional factor, nuclear factor-kappa B (NF-κB) activity. The exact molecular mechanism by which microtubule rearrangement leads to NF-κB activation largely remains to be identified. However microtubule disrupting agents may possibly act in synergy or antagonism against apoptotic cell death in response to conventional chemotherapy targeting DNA damage such as adriamycin or comptothecin in cancer cells. Interestingly pretreatment of microtubule disrupting agents (colchicine, vinblastine and nocodazole) was observed to lead to paradoxical suppression of DNA damage-induced NF-κB binding activity, even though these could enhance NF-κB signaling in the absence of other stimuli. Moreover this suppressed NF-κB binding activity subsequently resulted in synergic apoptotic response, as evident by the combination with Adr and low doses of microtubule disrupting agents was able to potentiate the cytotoxic action through caspase-dependent pathway. Taken together, these results suggested that inhibition of microtubule network chemosensitizes the cancer cells to die by apoptosis through suppressing NF-κB DNA binding activity. Therefore, our study provided a possible anti-cancer mechanism of microtubule disrupting agent to overcome resistance against to chemotherapy such as DNA damaging agent

Efficacy of an Educational Material on Second Primary Cancer Screening Practice for Cancer Survivors: A Randomized Controlled Trial

<div><h3>Background</h3><p>Cancer surivors have limited knowledge about second primary cancer (SPC) screening and suboptimal rates of completion of screening practices for SPC. Our objective was to test the efficacy of an educational material on the knowledge, attitudes, and screening practices for SPC among cancer survivors.</p> <h3>Methods</h3><p>Randomized, controlled trial among 326 cancer survivors from 6 oncology care outpatient clinics in Korea. Patients were randomized to an intervention or an attention control group. The intervention was a photo-novel, culturally tailored to increase knowledge about SPC screening. Knowledge and attitudes regarding SPC screening were assessed two weeks after the intervention, and screening practices were assessed after one year.</p> <h3>Results</h3><p>At two weeks post-intervention, the average knowledge score was significantly higher in the intervention compared to the control group (0.81 vs. 0.75, P<0.01), with no significant difference in their attitude scores (2.64 vs. 2.57, P = 0.18). After 1 year of follow-up, the completion rate of all appropriate cancer screening was 47.2% in both intervention and control groups.</p> <h3>Conclusion</h3><p>While the educatinal material was effective for increasing knowledge of SPC screening, it did not promote cancer screening practice among cancer survivors. More effective interventions are needed to increase SPC screening rates in this population.</p> <h3>Trial Registration</h3><p>ClinicalTrial.gov <a href="http://clinicaltrials.gov/ct2/show/NCT00948337">NCT00948337</a></p> </div

Sex differences in oncogenic mutational processes.

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Inferring structural variant cancer cell fraction

Abstract: We present SVclone, a computational method for inferring the cancer cell fraction of structural variant (SV) breakpoints from whole-genome sequencing data. SVclone accurately determines the variant allele frequencies of both SV breakends, then simultaneously estimates the cancer cell fraction and SV copy number. We assess performance using in silico mixtures of real samples, at known proportions, created from two clonal metastases from the same patient. We find that SVclone’s performance is comparable to single-nucleotide variant-based methods, despite having an order of magnitude fewer data points. As part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) consortium, which aggregated whole-genome sequencing data from 2658 cancers across 38 tumour types, we use SVclone to reveal a subset of liver, ovarian and pancreatic cancers with subclonally enriched copy-number neutral rearrangements that show decreased overall survival. SVclone enables improved characterisation of SV intra-tumour heterogeneity