Early histological transformation of follicular lymphoma to diffuse large B-cell lymphoma indicating adverse survival: A population-based analysis and validation.

INTRODUCTION: The histological transformation (HT) of follicular lymphoma (FL) is a crucial biological event. The study aimed to evaluate the incidence, clinicial characteristics, prognosis and impact of HT time on survival of FL transforming to diffuse large B-cell lymphoma in population-based large-scale cohorts. METHODS: A retrospective cohort study of FL with HT was performed in the Surveillance, Epidemiology, and End Results database. The Hematological Malignancy Research Network FL cohort and Aristotle study FL cohort were used to assess the external validity. RESULTS: Among 44,127 FL cases from the Surveillance, Epidemiology, and End Results database, 1311 cases were pathology-proven recorded to transform to diffuse large B-cell lymphoma. The cumulative rates of HT at 5, 10, and 15 years after FL diagnosis were estimated to be 1.19%, 2.93%, and 5.01%, respectively. Significantly worse overall survival and cancer-specific survival were exhibited in patients with HT than those without HT. Early HT (transformation of FL within 48 months after FL diagnosis [TOD48]) was an independent predictor for adverse overall survival of HT patients, regardless of treatment modalities before transformation. The adverse prognostic effect of TOD48 was validated in the Hematological Malignancy Research Network cohort and Aristotle study cohort. Older age (>75 years) and B symptoms within FL at diagnosis were the independent risk factors of TOD48. Furthermore, a novel prognostic model combining TOD48 with Follicular Lymphoma International Prognostic Index (TOD48-FLIPI) was constructed and validated for risk stratification. CONCLUSION: TOD48 was a risk indicator of HT, and the novel prognostic model "TOD48-FLIPI" for HT patients was proposed.

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.

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.

Insights into the evolution of the ISG15 and UBA7 system.

The genetic origins of novelty are of central interest in evolutionary biology. ISG15 and UBA7 are present only in vertebrates. The emergence and evolution of them are not clear. Phylogenetic comparisons revealed that UBA7 descends from gene duplication, and ISG15 and UBA7 arose from UBB/UBC and UBA1, respectively. Uba7 exhibits ubiquitin-activation activity in fish but not tetrapods, suggesting that the relationship of ISG15/Uba7 was promiscuous in origin but was later coopted toward higher specificity. Zebrafish Uba7 is capable of activating the ubiquitin cascade in vitro and in vivo, and it displays distinct specificity preference toward substrates and E2 enzymes compared to zebrafish Uba1. These results together provide a framework for understanding the origin and diversification of ISG15/Uba7 and may serve as a paradigmatic example in which an originally minor functionality in an old gene is made into a new high-specificity protein through random mutations and natural selection.

Systematic genome editing of the genes on zebrafish Chromosome 1 by CRISPR/Cas9.

Genome editing by the well-established CRISPR/Cas9 technology has greatly facilitated our understanding of many biological processes. However, a complete whole-genome knockout for any species or model organism has rarely been achieved. Here, we performed a systematic knockout of all the genes (1333) on Chromosome 1 in zebrafish, successfully mutated 1029 genes, and generated 1039 germline-transmissible alleles corresponding to 636 genes. Meanwhile, by high-throughput bioinformatics analysis, we found that sequence features play pivotal roles in effective gRNA targeting at specific genes of interest, while the success rate of gene targeting positively correlates with GC content of the target sites. Moreover, we found that nearly one-fourth of all mutants are related to human diseases, and several representative CRISPR/Cas9-generated mutants are described here. Furthermore, we tried to identify the underlying mechanisms leading to distinct phenotypes between genetic mutants and antisense morpholino-mediated knockdown embryos. Altogether, this work has generated the first chromosome-wide collection of zebrafish genetic mutants by the CRISPR/Cas9 technology, which will serve as a valuable resource for the community, and our bioinformatics analysis also provides some useful guidance to design gene-specific gRNAs for successful gene editing.

Pharmacodynamic, pharmacokinetic, and phase 1a study of bisthianostat, a novel histone deacetylase inhibitor, for the treatment of relapsed or refractory multiple myeloma.

HDAC inhibitors (HDACis) have been intensively studied for their roles and potential as drug targets in T-cell lymphomas and other hematologic malignancies. Bisthianostat is a novel bisthiazole-based pan-HDACi evolved from natural HDACi largazole. Here, we report the preclinical study of bisthianostat alone and in combination with bortezomib in the treatment of multiple myeloma (MM), as well as preliminary first-in-human findings from an ongoing phase 1a study. Bisthianostat dose dependently induced acetylation of tubulin and H3 and increased PARP cleavage and apoptosis in RPMI-8226 cells. In RPMI-8226 and MM.1S cell xenograft mouse models, oral administration of bisthianostat (50, 75, 100 mg·kg-1·d-1, bid) for 18 days dose dependently inhibited tumor growth. Furthermore, bisthianostat in combination with bortezomib displayed synergistic antitumor effect against RPMI-8226 and MM.1S cell in vitro and in vivo. Preclinical pharmacokinetic study showed bisthianostat was quickly absorbed with moderate oral bioavailability (F% = 16.9%-35.5%). Bisthianostat tended to distribute in blood with Vss value of 0.31 L/kg. This distribution parameter might be beneficial to treat hematologic neoplasms such as MM with few side effects. In an ongoing phase 1a study, bisthianostat treatment was well tolerated and no grade 3/4 nonhematological adverse events (AEs) had occurred together with good pharmacokinetics profiles in eight patients with relapsed or refractory MM (R/R MM). The overall single-agent efficacy was modest, stable disease (SD) was identified in four (50%) patients at the end of first dosing cycle (day 28). These preliminary in-patient results suggest that bisthianostat is a promising HDACi drug with a comparable safety window in R/R MM, supporting for its further phase 1b clinical trial in combination with traditional MM therapies.

Heavy metal(loid)s in multiple media within a mussel mariculture area of Shangchuan Island, China: Partition, transfer and health risks.

Limited research has been conducted on the heavy metal (loid) (HM) exchanges among seawater, sediments and cultured mussels in mariculture areas. To determine the impacts of mussel mariculture on the transfer and risks of HMs in coastal environments, samples of seawater, sediments and cultured mussels from a typical mariculture area in the South China Sea were analysed. The logarithmic partition coefficients of sediment/water indicated that HMs were preferentially retained by sediments. There were relatively low ecological risks in mussel raft mariculture areas. Principal component analysis and correlation analysis revealed the influences of terrestrial input and ocean circulation on the HMs in seawater, and the bioaccumulation factors reflected the possible accumulation of HMs in seawater by cultured mussels. Mussel farming was the indirect source of HMs in sediments, and the biochemical processes of cultured mussels promoted the transfer and accumulation of HMs into sediments. Health risk assessment revealed that children were more susceptible than adults, and Cd, As and Cr were among the threatening elements. Nonetheless, the health risks that were possibly caused by the daily consumption of farmed mussels were still within safe limits. Thus, the potential pollution remediation and biomonitoring functions of mussel aquaculture in coastal water environments will be further studied in the future.

The effector of Hippo signaling, Taz, is required for formation of the micropyle and fertilization in zebrafish.

The mechanisms that ensure fertilization of egg by a sperm are not fully understood. In all teleosts, a channel called the 'micropyle' is the only route of entry for sperm to enter and fertilize the egg. The micropyle forms by penetration of the vitelline envelope by a single specialized follicle cell, the micropylar cell. The mechanisms underlying micropylar cell specification and micropyle formation are poorly understood. Here, we show that an effector of the Hippo signaling pathway, the Transcriptional co-activator with a PDZ-binding domain (Taz), plays crucial roles in micropyle formation and fertilization in zebrafish (Danio rerio). Genome editing mutants affecting taz can grow to adults. However, eggs from homozygous taz females are not fertilized even though oocytes in mutant females are histologically normal with intact animal-vegetal polarity, complete meiosis and proper ovulation. We find that taz mutant eggs have no micropyle. Taz protein is specifically enriched in mid-oogenesis in the micropylar cell located at the animal pole of wild type oocyte, where it might regulate the cytoskeleton. Taz protein and micropylar cells are not detected in taz mutant ovaries. Our work identifies a novel role for the Hippo/Taz pathway in micropylar cell specification in zebrafish, and uncovers the molecular basis of micropyle formation in teleosts.

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

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

Quantitative Proteomic Analysis Reveals the Key Molecular Events Driving Phaeocystis globosa Bloom and Dissipation.

Phaeocystis globosa is a marine-bloom-forming haptophyte with a polymorphic life cycle alternating between free-living cells and a colonial morphotype, that produces high biomass and impacts ecological structure and function. The mechanisms of P. globosa bloom formation have been extensively studied, and various environmental factors are believed to trigger these events. However, little is known about the intrinsic biological processes that drive the bloom process, and the mechanisms underlying P. globosa bloom formation remain enigmatic. Here, we investigated a P. globosa bloom occurring along the Chinese coast and compared the proteomes of in situ P. globosa colonies from bloom and dissipation phases using a tandem mass tag (TMT)-based quantitative proteomic approach. Among the 5540 proteins identified, 191 and 109 proteins displayed higher abundances in the bloom and dissipation phases, respectively. The levels of proteins involved in photosynthesis, pigment metabolism, nitrogen metabolism, and matrix substrate biosynthesis were distinctly different between these two phases. Ambient nitrate is a key trigger of P. globosa bloom formation, while the enhanced light harvest and multiple inorganic carbon-concentrating mechanisms support the prosperousness of colonies in the bloom phase. Additionally, colonies in the bloom phase have greater carbon fixation potential, with more carbon and energy being fixed and flowing toward the colonial matrix biosynthesis. Our study revealed the key biological processes underlying P. globosa blooms and provides new insights into the mechanisms behind bloom formation.

Distinct clinical features and prognostic factors of hepatitis C virus-associated non-Hodgkin's lymphoma: a systematic review and meta-analysis.

BACKGROUND: Increasing evidence suggests that hepatitis C virus (HCV) infection is associated with non-Hodgkin's lymphoma (NHL). However, no clear consensus has been reached about the clinical features and effective treatment of HCV-associated NHL patients. We therefore performed a systematic review and meta-analysis to explore the clinical characteristics and effectiveness of antiviral treatment or rituximab administration among NHL patients with HCV infection. METHODS: Eight electronic databases, including PubMed, OVID, EMBASE, Cochrane Library, ClinicalTrials, WANFANG, CNKI, and VIP, were searched for eligible studies up to July 31, 2021. The hazard ratio (HR) or odds ratio (OR) corresponding to the 95% confidence interval (CI) was calculated to estimate the outcomes. Publication bias was assessed by Egger's and Begg's tests. Statistical analysis was performed with RevMan 5.4 software and Stata version 15. RESULTS: There were 27 shortlisted articles out of a total of 13,368 NHL patients included in the current meta-analysis. Our results demonstrated that NHL patients with HCV infection had a significantly shorter overall survival (OS: HR 1.89; 95% CI 1.42-2.51, P < 0.0001) and progression-free survival (PFS: HR 1.58; 95% CI 1.26-1.98, P < 0.0001), a lower overall response rate (ORR: OR 0.58, 95% CI 0.46-0.73, P < 0.00001) and a higher incidence of hepatic dysfunction during chemotherapy (OR 5.96; 95% CI 2.61-13.62, P < 0.0001) than NHL patients without HCV infection. HCV-positive NHL patients exhibited an advanced disease stage, an elevated level of LDH, a high-intermediate and high IPI/FLIPI risk as well as a higher incidence of spleen and liver involvement. Moreover, antiviral treatment prolonged survival (OS: HR 0.38; 95% CI 0.24-0.60, P < 0.0001), reduced disease progression [PFS/DFS (disease-free survival): HR 0.63; 95% CI 0.46-0.86, P = 0.003] and reinforced the treatment response (ORR: OR 2.62; 95% CI 1.34-5.11, P = 0.005) among the HCV-infected NHL patients. Finally, rituximab administration was associated with a favourable OS, while liver cirrhosis and low levels of albumin predicted a poor OS for HCV-positive NHL patients. CONCLUSIONS: The current study provided compelling evidence about an inferior prognosis and distinct clinical characteristics among HCV-associated NHL patients. Antiviral treatment and rituximab-containing regimens were shown to be efficacious in improving the clinical outcomes of NHL patients with HCV infection.

Microzooplankton grazing and its key group composition in subtropical eutrophic coast of Southern China: in relation to environmental changes.

Microzooplanton play a crucial role in marine ecosystems, as they transfer matter and energy from pico- and nano-phytoplankton to mesozooplankton. In this study, we explored the seasonal variations of microzooplankton grazing derived from dilution experiments in a typical eutrophic coast of Southern China, as well as the abundance and biodiversity of its key group (ciliate), to further understand its function in the subtropical coastal food web associated with potential regulation factors. A total of 29 ciliate species belonging to 18 genera were identified, with the dominating species of Mesodinium rubrum, Strombidium globosaneum and Strombidium conicum. The spatial difference of ciliates abundance was attributed by the changes of temperature and salinity. Phytoplankton growth rate (µ) and microzooplankton grazing rate (m) ranged from 0.03 to 1.36 d-1 and 0.10 to 1.57 d-1, respectively, and both µ and m showed the highest values in summer and the lowest in winter. Moreover, microzooplankton grazing pressure on the phytoplankton standing stocks and potential primary production ranged from 10% to 79% and 58% to 471%, respectively. Our results indicated that temperature is the main environmental driving force for the seasonal changes of µ and m, and that the impacts of run-offs from the Pearl River and offshore seawater intrusion from the South China Sea are responsible for the spatial-temporal variations of phytoplankton growth and microzooplankton grazing.

Mypt1 regulates Bmp signaling to promote embryonic exocrine pancreas growth in zebrafish.

Myosin phosphatase targeting subunit 1 (Mypt1) is the regulatory subunit of myosin phosphatase which dephosphorylates the light chain of myosin II to inhibit its contraction. Although biochemical properties of Mypt1 have been characterized in detail, its biological functions in organisms are not well understood. The zebrafish mypt1 sq181 allele was found defective in the ventral pancreatic bud and extrapancreatic duct development, resulting in dysplasia of exocrine pancreas. In mypt1 sq181 mutant, the early growth of the ventral pancreatic bud was initiated but failed to expand due to impaired cell proliferation and increased cell apoptosis. As Mypt1 is essential for cell migration, the loss-of-function of Mypt1 in the mutant disrupted the lateral plate mesoderm migration during gut looping, therefore, altering the Bmp2a expression pattern within it, and eventually leading to impaired Bmp signaling in the adjacent exocrine pancreas. Overexpression of bmp2a could rescue the development of exocrine pancreas, suggesting that the impaired Bmp2a signaling is responsible for the pancreatic development defects. Bmp2a has been reported to promote the early specification of the ventral pancreatic bud, and our study reveals that it continues to serve as a cell proliferation/survival signal to ensure pancreatic bud growth properly in zebrafish.

Ikzf1 regulates embryonic T lymphopoiesis via Ccr9 and Irf4 in zebrafish.

Ikzf1 is a Krüppel-like zinc-finger transcription factor that plays indispensable roles in T and B cell development. Although the function of Ikzf1 has been studied extensively, the molecular mechanism underlying T lymphopoiesis remains incompletely defined during the embryonic stage. Here we report that the genetic ablation of ikzf1 in mutant zebrafish resulted in abrogated embryonic T lymphopoiesis. This was ascribed to impaired thymic migration, proliferation, and differentiation of hematopoietic stem/progenitor cells (HSPCs). Ccr9a and Irf4a, two indispensable factors in T lymphopoiesis, were the direct targets of Ikzf1 and were absent in the ikzf1 mutants. Genetic deletion of either ccr9a or irf4a in the corresponding mutant embryos led to obvious T cell development deficiency, which was mainly caused by disrupted thymic migration of HSPCs. Restoration of ccr9a in ikzf1 mutants obviously promoted HSPC thymus homing. However, the HSPCs then failed to differentiate into T cells. Additional replenishment of irf4a efficiently induced HSPC proliferation and T cell differentiation. Our findings further demonstrate that Ikzf1 regulates embryonic T lymphopoiesis via Ccr9 and Irf4 and provide new insight into the genetic network of T lymphocyte development.

Yap1/Taz are essential for the liver development in zebrafish.

Hippo pathway regulates cell proliferation and differentiation. Yes-associated protein (Yap) and transcriptional coactivator with PDZ-binding motif (Taz) are effectors of Hippo pathway. The function of Yap/Taz in embryonic liver development has yet to be reported. Here yap1 and taz were found expressed in liver and other digestive organs in zebrafish embryos, and knockout of yap1 or taz did not lead to visible defects during embryogenesis. Interestingly, Taz was significantly increased in yap1 mutants, which may account for their normal development, albeit losing Yap1. However, yap1-/-; taz+/- embryos exhibited smaller digestive organs, and more than half of them showed bilateral livers and pancreas and non-looped intestines. Further analysis revealed that the disrupted gene function in yap1-/-; taz+/- embryos did not disturb liver bud formation, but instead impaired cell proliferation in liver and movement of the neighboring lateral plate mesoderm (LPM). Overexpression of wild type yap1 or taz could rescue the defective liver phenotypes in yap1-/-; taz+/- embryos, indicating that Yap1 cooperate with Taz to regulate the liver development. In addition, Yap1 was found to function in a Tead-dependent manner in the liver development. Our results suggest that Yap1/Taz regulate LPM movement and promote cell proliferation to ensure proper liver development in zebrafish.

A case of ureteral myeloid sarcoma post-renal transplantation.

BACKGROUND: Significant attention has been directed toward the high incidence of malignant tumours that occur post-transplantation. However, there are few reports of myeloid sarcomas (MSs) following renal transplantation. CASE PRESENTATION: This case report describes a 26-year-old male patient who presented with repeatedly high creatinine levels and hydronephrosis six months post-renal transplantation. Surgical pathology revealed ureteral MS; however, the tumour recurred following resection. Bone marrow biopsy indicated that the patient also had acute promyelocytic leukaemia. The tumour was treated with local radiotherapy, and the leukaemia was treated with systemic chemotherapy. The patient's conditions were satisfactory at the one-year follow-up. CONCLUSIONS: This report is the first to describe a ureteral MS post-renal transplantation. Our findings suggest that surgical resection combined with radiotherapy and chemotherapy can help control the status of patients with this condition.

Bioaccessibility and human health implications of heavy metals in different trophic level marine organisms: A case study of the South China Sea.

This study investigated the total concentrations and bioaccessibility of heavy metals in edible tissues and trophic levels of 12 marine organism species in the South China Sea. The results were used to estimate health risks to humans. Of the heavy metals detected, nickel (Ni) was present at the highest concentrations, followed in descending, order by iron (Fe), zinc (Zn), manganese (Mn), chromium (Cr), copper (Cu), cadmium (Cd) and lead (Pb). Cd had the highest percentage bioaccessibility (61.91%). There were no correlations between log-transformed total metal concentrations and trophic level values, nor between log-transformed bioaccessibility metal concentrations and trophic level values. This indicates there is no biomagnification among these trace metals. The carcinogenic risk probabilities for Pb and Cr to urban and rural residents were below the acceptable level (< 1â€¯× 10-4). The target hazard quotient (THQ) value for each metal and the total THQ values for all metals studied indicated no significant risk of non-carcinogenic effects to urban and rural residents from consuming marine organisms from the South China Sea.

Analysis of mutants from a genetic screening reveals the control of intestine and liver development by many common genes in zebrafish.

Both the intestine and liver develop from the endoderm, yet little is known how these two digestive organs share and differ in their developmental programs, at the molecular level. A classical forward genetic screen, with no gene bias, is an effective way to address this question by examining the defects of the intestine and liver in obtained mutants to assess mutated genes responsible for the development of either organ or both. We report here such a screen in zebrafish. ENU was used as the mutagen because of its high mutagenic efficiency and no site preference. Embryos were collected at 3.5 dpf for RNA whole mount in situ hybridization with a cocktail probe of the intestine marker ifabp and the liver marker lfabp to check phenotypes and determine their parental heterozygosis. A total of 52 F2 putative mutants were identified, and those with general developmental defects were aborted. To rule out non-inheritable phenotypes caused by high mutation background, F2 putative mutants were outcrossed with wild type fish and a re-screen in F3 generations was performed. After complementation tests between F3 mutants with similar phenotypes originating from the same F2 families, a total of 37 F3 mutant lines originated from 22 F2 families were identified after screening 78 mutagenized genomes. Classification of mutant phenotypes indicated that 31 out of the 37 mutants showed defects in both the intestine and liver. In addition, four "intestine specific mutants" and two "liver specific mutants" showed selectively more severe phenotype in the intestine and liver respectively. These results suggested that the intestine and liver share a substantial number of essential genes during both organs development in zebrafish. Further studies of the mutants are likely to shed more insights into the molecular basis of the digestive system development in the zebrafish and vertebrate.