Search

This study aimed to understand the exposure levels of trihalomethanes (THMs) in an indoor swimming pool and calculate the risks of exposure to THMs, based on the presence of each THM species, of children swimmers aged 6–17, in Beijing, China. We obtained exposure factors for the children through questionnaires and measured THM concentrations through laboratory tests, and we combined the results with an exposure model to calculate the risks, with consideration of different exposure routes (oral ingestion, inhalation and dermal absorption). In terms of exposure factors for the swimmers aged 6–17, the average body weight, exposure duration, exposure frequency, swimming time, shower time, changing time, warm-up exercise and rest time, skin surface area and ingestion rate of pool water were 40.46 kg, 2.70 years, 96 events/year, 64.03 min/event, 17.04 min/event, 15.31 min/event, 12.71 min/event, 1.37 m2 and 48.93 ml/event, respectively. The THM concentrations in swimming pool water, shower water, swimming pool air and locker room air were 67.17 μg/L, 12.64 μg/L, 358.66 μg/m3 and 40.98 μg/m3, respectively. The average cancer risk of THMs was 5.44 × 10−6, which is an unacceptable risk according to the United State Environmental Protection Agency (USEPA) Guidelines. The average hazard index was 0.007, i.e., less than 1, indicating that the noncancer risk was acceptable. Chloroform (TCM) was the main substance in four species of THMs and inhalation exposure was the main exposure pathway. The risk of cancer and noncancer from inhalation exposure to THMs accounts for 97–99% of the total risk. As a result, the disease control authorities and administrative department should pay attention to the health and safety of swimming facilities and, at the same time, establish standards for THMs in the air through further research.

Glutathione S-transferases (GSTs) are phase II detoxification enzymes, which function via combining with pesticidal molecules and catalyzing the conjugation of molecules by thiol of glutathione, so as to protect tissues from oxidative stress damage. In the tick Haemaphysalis longicornis, glutathione S-transferases (HlGST and HlGST2) have been previously identified. However, the relationship between the transcription of glutathione S-transferases and the essential oil treatment in ticks remains unexplored. Hence, in the present study, the transcription profiles of HlGST and HlGST2 mRNAs were evaluated in H. longicornis after exposure to Cymbopogon citratus essential oil. At 24 h post-exposure of H. longicornis to different sublethal concentrations of C. citratus essential oil, there was significant difference (P = 0.0001) in the transcription of HlGST. Tukey’s test showed that HlGST was significantly induced after treatment with 1% C. citratus essential oil (P = 0.0002); whereas no significant difference (P = 0.3551) was detected after treated by 2% C. citratus essential oil. No significant difference (P = 0.4555) in the transcription of HlGST2 between the treatment and the control group of 50% ethanol. Nevertheless, the down-regulation of HlGST2 in the treatment groups versus the untreated control group was not significant (P = 0.1208). The above results imply that the essential oil can modulate the expression of GST mRNA, therefore, further understanding of the underlying mechanisms of the GST at the molecular level could contribute to the development of effective control measures for ticks and tick-borne diseases.

The ticks feed large amount of blood from their hosts and transmit pathogens to the victims. The salivary gland plays an important role in the blood feeding. When the female ticks are near engorgement, the salivary gland gradually loses its functions and begins to rapidly degenerate. In this study, data-independent acquisition quantitative proteomics was used to study changes in the phosphorylation modification of proteins during salivary gland degeneration in Haemaphysalis longicornis. In this quantitative study, 400 phosphorylated proteins and 850 phosphorylation modification sites were identified. Trough RNA interference experiments, we found that among the proteins with changes in phosphorylation, apoptosis-promoting Hippo protein played a role in salivary gland degeneration.

The paradoxical effect of cobalt on biological processes has aroused controversy regarding the application of cobalt-based biomaterials in bone regeneration. Tuning the dose range of cobalt ions may be a valid strategy to resolve the controversies about cobalt use for orthopedic applications. Recent progress in bone biology has highlighted the effects of multisystem cooperation (especially of osteoimmune, skeletal, and vascular systems) on bone dynamics. Before the application of this dose-tuning strategy, a deeper understanding of its dose-dependent effect on the cooperation of osteoimmune, skeletal, and vascular systems is needed. However, due to the difficulties with investigating the interaction of multiple systems in vitro, the multimodal effects of cobalt on bone homeostasis were investigated here, in an in vivo scenario. Methods: In vitro CCK8 assay and cytoskeletal staining were preformed to detecte the cell cytotoxic reaction in response to 0.1-100 ppm cobalt stimulation. Blood clot containing 0.1 to 5 ppm of cobalt were implanted in the rat calvarium defect. The gene profile of osteoimmune, skeletal, and vascular system as well as the systemic toxicity were evaluated via RT-qPCR, histological analysis and inductively coupled plasma mass spectrometry. The bone regeneration, osteoclastogenesis and vascularization were assessed by micro-ct and histological analysis. Results: Cobalt concentration below 5 ppm did not cause cell toxicity in vitro. No systemic toxicity was observed in vivo at 0.1-5 ppm cobalt concentration. It was found that the early cytokine profiles of the multiple interacting systems were different in response to different cobalt doses. Most of the anti-inflammatory, osteogenic, and proangiogenic factors were upregulated in the 1 ppm cobalt group at the early stage. In the late stage, the 1ppm group was most superior in bone regenerative effect while the 5 ppm group displayed the strongest osteoclastogenesis activity. Conclusions: The 1 ppm concentration of cobalt yielded the most favorable cooperation of the osteoimmune, skeletal, and vascular systems and subsequently optimal bone regeneration outcomes. Tuning the cobalt dose range to manipulate the cooperation of osteoimmune, skeletal, and vascular systems could be a promising and valuable strategy to prevent paradoxical effects of cobalt while preserving its beneficial effects.

Description, AS program is essential for HSC formation., Single-cell transcriptional profiling has rapidly advanced our understanding of the embryonic hematopoiesis; however, whether and what role RNA alternative splicing (AS) plays remains an enigma. This is important for understanding the mechanisms underlying splicing-associated hematopoietic diseases and for the derivation of therapeutic stem cells. Here, we used single-cell full-length transcriptome data to construct an isoform-based transcriptional atlas of the murine endothelial-to-hematopoietic stem cell (HSC) transition, which enables the identification of hemogenic signature isoforms and stage-specific AS events. We showed that the inclusion of these hemogenic-specific AS events was essential for hemogenic function in vitro. Expression data and knockout mouse studies highlighted the critical role of Srsf2: Early Srsf2 deficiency from endothelial cells affected the splicing pattern of several master hematopoietic regulators and significantly impaired HSC generation. These results redefine our understanding of the dynamic HSC developmental transcriptome and demonstrate that elaborately controlled RNA splicing governs cell fate in HSC formation.

Dopamine is the precursor of a variety of natural antioxidant compounds. In the body, dopamine acts as a neurotransmitter that regulates a variety of physiological functions of the central nervous system. Thus, dopamine is used for the clinical treatment of various types of shock. Dopamine could be produced by engineered microbes, but with low efficiency. In this study, DOPA decarboxylase gene from Sus scrofa (Ssddc) was cloned into plasmids with different copy numbers, and transformed into a previously developed L-DOPA producing strain Escherichia coli T004. The resulted strain was capable of producing dopamine from glucose directly. To further improve the production of dopamine, a sequence-based homology alignment mining (SHAM) strategy was applied to screen more efficient DOPA decarboxylases, and five DOPA decarboxylase genes were selected from 100 candidates. In shake-flask fermentation, the DOPA decarboxylase gene from Homo sapiens (Hsddc) showed the highest dopamine production (3.33 g/L), while the DOPA decarboxylase gene from Drosophila Melanogaster (Dmddc) showed the least residual L-DOPA concentration (0.02 g/L). In 5 L fed-batch fermentations, production of dopamine by the two engineered strains reached 13.3 g/L and 16.2 g/L, respectively. The residual concentrations of L-DOPA were 0.45 g/L and 0.23 g/L, respectively. Finally, the Ssddc and Dmddc genes were integrated into the genome of E. coli T004 to obtain genetically stable dopamine-producing strains. In 5 L fed-batch fermentation, 17.7 g/L of dopamine was produced, which records the highest titer reported to date.

Seizure prediction using intracranial electroencephalogram (iEEG) has attracted an increasing attention during recent years. iEEG signals are commonly recorded in the form of multiple channels. Many previous studies generally used the iEEG signals of all channels to predict seizures, ignoring the consideration of channel selection. In this study, a method of one-dimensional convolutional neural networks (1D-CNN) combined with channel selection strategy was proposed for seizure prediction. First, we used 30-s sliding windows to segment the raw iEEG signals. Then, the 30-s iEEG segments, which were in three channel forms (single channel, channels only from seizure onset or free zone and all channels from seizure onset and free zones), were used as the inputs of 1D-CNN for classification, and the patient-specific model was trained. Finally, the channel form with the best classification was selected for each patient. The proposed method was evaluated on the Freiburg Hospital iEEG dataset. In the situation of seizure occurrence period (SOP) of 30[Formula: see text]min and seizure prediction horizon (SPH) of 5[Formula: see text]min, 98.60[Formula: see text] accuracy, 98.85[Formula: see text] sensitivity and 0.01/h false prediction rate (FPR) were achieved. In the situation of SOP of 60[Formula: see text]min and SPH of 5[Formula: see text]min, 98.32[Formula: see text] accuracy, 98.48[Formula: see text] sensitivity and 0.01/h FPR were attained. Compared with the many existing methods using the same iEEG dataset, our method showed a better performance.

Background To assess the root angle characteristics of maxillary incisors, and to analyze the relationship between the root angle and other implant-related anatomical indices to use the sagittal root angle as an index for immediate implant evaluation and design. Methods A random sample consisting of 400 cone-beam computed tomography (CBCT) images and 65 maxillary plaster models were selected for the present study. CBCT and stereolithography (STL) scan images were imported as DICOM files into coDiagnostiX software for matching the hard and soft tissue. The angle between the long axis of the anterior tooth and the corresponding alveolar bone and implant-related hard and soft tissue indices were measured in the sagittal section. Descriptive statistics, frequency analysis, multi-level comparisons, and correlation analyses were performed. Results The average sagittal root angles were 15° at the central incisor and 19° at the lateral incisor. The root angle in males was significantly larger than that in females, and increased with age. The largest angle, 22.35°, was found in the lateral incisors of the oldest (> 50 years old) male group. The root angle was found to correlate with coronal buccal bone thickness, coronal palatal bone thickness, apical buccal bone thickness, palatal bone thickness, and the below apex bone thickness. Conclusions The sagittal root angle could reflect the distribution of other implant-related anatomical indices, which may provide additional reference for the evaluation of immediate implant placement.

Background Interferon-alpha (IFN-α) is a general therapeutic regimen to be utilized in hepatocellular carcinoma (HCC). However, regulatory mechanisms of IFN-α on competing endogenous RNAs (ceRNAs) level in anti-HCC relapse are rarely understood. Methods HCC patients with and without IFN-α treatment were calculated to analyze the expression profile of mRNA, long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA) by RNA sequence, and significant differential expression (DE) of these types of RNAs were selected for further analysis. A ceRNA regulatory network was constructed to explore the potential mechanisms of IFN-α intervention on anti-HCC relapse. Finally, the potential prognostic associated genes among these DE RNAs were identified. Results Totally, 556 mRNAs, 120 circRNAs, 87 lncRNAs, and 96 miRNAs were differentially expressed in patients who received IFN-α treatment. A ceRNA regulatory network including a circRNA-miRNA-mRNA network which composed of 4 up- and 10 down-regulated circRNAs, 8 up- and 5 down-regulated miRNAs, 28 up- and 9 down-regulated mRNAs, and a lncRNA-miRNA-mRNA network which composed of 10 up- and 3 down-regulated lncRNAs, 11 up- and 5 down-regulated miRNAs, 28 up- and 10 down-regulated mRNAs was constructed. Gene enrichment and pathway analysis revealed that the ceRNA network was associated with immune-related pathway and corresponding molecular function in patients who accepted IFN-α treatment. Next, we identified 3 most relevant to IFN-α treatment to HCC among these DE RNAs, namely FAM20A, IGFBP4 and MARCH3, as the prognostic associated genes for HCC. Furthermore, MARCH3 expression correlated with infiltrating levels of tumor infiltrating immune cells (TICCs) in HCC. MARCH3 expression also showed strong correlations with the gene markers of diverse immune cells in HCC. Conclusion Our data discovered a novel ceRNA network in HCC patients receiving IFN-α therapy, which might lay the foundation for better understand the regulatory mechanism of IFN-α treatment.

Objective To improve the understanding and the diagnosis of intracranial ependymal tumors. Methods The clinical, radiological and prognostic features of 48 supratentorial extraventricular ependymomas and 74 intraventricular ependymomas were summarized and compared. Results Supratentorial extraventricular ependymomas, most often located in the frontal lobe (33.3%) and classified as grade III (75.0%), had relatively large eccentric cysts (3.07 ± 2.03 cm), significant enhancement (84.8%), low apparent diffusion coefficient (ADC) values, and associated with higher mortality (41.3%). The majority of intraventricular lesions occurred in the fourth ventricle (86.5%) and classified as grade II (78.4%), had relatively small and multiple cystic changes (1.04 ± 0.87 cm), slight or moderate enhancement (76.9%), high ADC values and associated with lower mortality (20.7%). There were few significant differences between grade II and grade III tumors in these 2 groups, respectively. Young age, high grade and low ADC values are worse prognostic indicators for patients with supratentorial extraventricular ependymomas, but not for those with intraventricular ependymomas. Conclusions Conventional radiological features, combined with clinical manifestations and quantitative information provided by diffusion-weighted imaging, may not only enhance the diagnosis and assist in determining prognosis but also provide a better pathophysiological understanding of intracranial ependymal tumors.

Interleukin-17A (IL-17A)-producing helper T (Th17) cells are a subset of CD4(+) T cells that play important pathological roles in autoimmune diseases. Although the intrinsic pathways of Th17 cell differentiation have been well described, how instructive signals derived from the innate immune system trigger the Th17 response and inflammation remains poorly understood. Here, we report that mice deficient in REGγ, a proteasome activator belonging to the 11S family, exhibit significantly deteriorated autoimmune neuroinflammation in an experimental autoimmune encephalomyelitis (EAE) model with augmented Th17 cell polarization in vivo. The results of the adoptive transfer of CD4(+) T cells or dendritic cells (DCs) suggest that this phenotype is driven by DCs rather than T cells. Furthermore, REGγ deficiency promotes the expression of integrin αvβ8 on DCs, which activates the maturation of TGF-β1 to enhance Th17 cell development. Mechanistically, this process is mediated by the REGγ-proteasome-dependent degradation of IRF8, a transcription factor for αvβ8. Collectively, our findings delineate a previously unknown mechanism by which REGγ-mediated protein degradation in DCs controls the differentiation of Th17 cells and the onset of an experimental autoimmune disease.

NiCr amorphous alloy coatings were deposited by magnetron sputtering at different sputtering current for corrosion resistance. X-ray diffraction performed that the coating was constituted of nearly...

The recently proposed Reusing Inhibition for Negation (RIN) hypothesis posits that the inhibitory control mechanism is reused to understand sentential negation. The RIN hypothesis has only been tes...

Summary Growth hormone (GH) binds to its receptor (growth hormone receptor [GHR]) to exert its pleiotropic effects on growth and metabolism. Disrupted GH/GHR actions not only fail growth but also are involved in many metabolic disorders, as shown in murine models with global or tissue-specific Ghr deficiency and clinical observations. Here we constructed an adipose-specific Ghr knockout mouse model Ad-GHRKO and studied the metabolic adaptability of the mice when stressed by high-fat diet (HFD) or cold. We found that disruption of adipose Ghr accelerated dietary obesity but protected the liver from ectopic adiposity through free fatty acid trapping. The heat-producing brown adipose tissue burning and white adipose tissue browning induced by cold were slowed in the absence of adipose Ghr but were recovered after prolonged cold acclimation. We conclude that at the expense of excessive subcutaneous fat accumulation and lower emergent cold tolerance, down-tuning adipose GHR signaling emulates a healthy obesity situation which has metabolic advantages against HFD., Graphical Abstract, Highlights • Adipose growth hormone receptor defect augments dietary obesity in mice • Lack of adipose growth hormone receptor prevents ectopic adiposity • Adipose growth hormone receptor defect benefits free fatty acid turnover • Adipose growth hormone receptor facilitates thermogenic response to cold, Physiology; Cellular Physiology; Endocrinology; Diabetology

In this work, novel hollow coral-shaped Co3O4 nanostructures are synthesized via a precursor conversion method for the first time, and the detailed process of precursor conversion is revealed. l -ascorbic acid as the structure-directing agent and the origin of oxalate (C2O42−) contributes to the formation of the precursors, providing a low-cost and facile method for preparing Co3O4. Hollow coral-shaped Co3O4 nanostructures are obtained by calcining cobalt oxalate precursors in air. The special Co3O4 nanostructures exhibit noticeable pseudocapacitive properties with a capacitance of 626.5 F g-1 at 5 mV s-1 and show superior stability (capacity retention of 99%) and outstanding Coulombic efficiency (˜100%) within 5000 charge–discharge cycles at 10 A g-1. Furthermore, the asymmetric supercapacitor Co3O4//G fabricated by Co3O4 cathode and graphene hydrogel anode delivers a specific capacitance of 115 F g-1 (47.9 mA h g-1) at 1 A g-1 and attains the maximum energy density of 35.93 Wh kg-1 at the power density of 801.6 W kg-1. The excellent durability of Co3O4//G is demonstrated by the retention of 85.1% of initial capacitance after 5000 cycles at 5 A g-1. The novel and feasible route proposed in the work is expected to be applied prospectively and widely in preparing Co3O4 pseudo-capacitance material, which owns great application value in supercapacitors, as well as in batteries.

Anaplastic thyroid cancer (ATC) is the most aggressive human thyroid malignancy, characterized by dedifferentiation and resistance to radioiodine therapy. The underlying mechanisms regulating ATC dedifferentiation are largely unknown. Here, we show that REGγ, a noncanonical proteasome activator highly expressed in ATC, is an important regulator of differentiation in ATC cells. Ablation of REGγ significantly restored expression of thyroid-specific genes, enhanced iodine uptake, and improved the efficacy of 131I therapy in ATC xenograft models. Mechanistically, REGγ directly binds to the TGF-β signaling antagonist Smad7 and promotes its degradation, leading to the activation of the TGF-β signal pathway. With gain- and loss-of-function studies, we demonstrate that Smad7 is an important mediator for the REGγ function in ATC cell dedifferentiation, which is supported by expression profiles in human ATC tissues. It seems that REGγ impinges on repression of thyroid-specific genes and promotion of tumor malignancy in ATC cells by activating the TGF-β signal pathway via degradation of Smad7. Thus, REGγ may serve as a novel therapeutic target for allowing radioiodine therapy in anaplastic thyroid cancer patients with poor prognosis.

Background Nanoparticles can be used for effective pest management as a combined formulation of metal and some other material that has proven efficacy against a given pest. This study reports the synthesis, characterization and efficacy of Isaria fumosorosea-based zero-valent iron (ZVI) nanoparticles against sweet potato whitefly Bemisia tabaci (Gennadius). Results The I. fumosorosea-ZVI nanoparticles showed a characteristic surface plasmon absorption band at 470 nm during UV-visible spectroscopy. The scanning electron micrographs of nanoparticles showed spherical shaped nanoparticles with sizes ranging between 1.71 and 3.0 µm. The EDX analysis showed the characteristic peak of iron at 0.6 and 6.8 KeV. The XRD analysis showed characteristic peaks at 44.72°, 65.070°, 82.339° and 82.65°. The bioassay results indicated that the percentage of larval mortality of B. tabaci challenged with I. fumosorosea ZVI nanoparticles was both concentration and age dependent. Isaria fumosorosea ZVI nanoparticles showed high pathogenicity against second and third instar nymphs, and pupae with LC50 values of 19.17, 26.10 and 37.71 ppm, respectively. The LT50 was lowest for second instar nymphs (3.15 days) and highest for pupae (4.22 days) when inoculated with a concentration of 50 ppm. Conclusion Isaria fumosorosea ZVI nanoparticles can be an eco-friendly tool for effective B. tabaci management. © 2019 Society of Chemical Industry.

Co2(OH)3Cl was synthesized by a facile solvothermal method with different solvent ratios of water/glycol (Vwater:Vglycol). The Co2(OH)3Cl prepared at the ratio of 1:2 showed uniform cubic nanostructure and provided the highest specific capacitance of 321.79 F g−1 at 0.5 A g−1. The capacitance retention and the Coulombic efficiency were both kept at 100% without obvious decay after continuous 10,000 charge-discharge cycles, demonstrating the durability and eximious stability of the Co2(OH)3Cl when utilized as the supercapacitor electrode material.

The walnut green husk has antibacterial, anti-oxidant, anti-inflammatory and other biological activities, but its lipid-lowering activity has not been reported. This study investigated the effects of walnut green husk extract (WGH) on lipid levels and gut bacteria flora in obese rats induced by high-fat diet. The results showed that WGH significantly reduced body weight gain, reversed liver TC, TG, LDL-C, HDL-C, MDA, ALT, AST and serum TC, TG, LDL-C, MDA, leptin levels, insulin resistance and glucose tolerance in high fat diet-induced obesity rats. Meanwhile, fat accumulation, hepatic steatosis and adipose tissue hypertrophy of HFD were reduced by WGH. 16S rRNA sequencing demonstrated that WGH dramaticlly reversed the disorders of gut bacteria flora HFD-induced, reduced the relative abundance of Fusobacteria, Firmicutes and enhanced the relative abundance of Bacteroidetes at the phylum level, reduced the relative abundance of and Peptostreptococcaceae at the family level, furthermore, reduced the relative abundance of Romboutsia, Lachnoclostridium and increased the relative abundance of Bacteroides at the genus level. In conclusion, these beneficial effects of WGH on reducing obesity and lipid disorders could be associated with the modulation of the gut bacteria.

The ultrasmall sizes of nanoparticles have attracted significant attention for potential applications in the fields of catalysis and nanomedicine. Herein, we reported on the green preparation and X-ray computed tomography (CT) imaging of ultrasmall bimetallic bovine serum albumin-directed gold–silver (Au–Ag@BSA) nanoparticles (2–4 nm) using BSA as a stabilizing and template-directed agent. Further, the effects of synthesis conditions were systematically explored to prepare products by adjusting the different molar ratios of Au/Ag. The resulting Au–Ag@BSA nanoparticles exhibited the spherical shape, well-dispersed ability, as well as long-term room-temperature stability. The cytotoxicity effects of Au–Ag@BSA nanoparticles on A549 and MCF-7 cells were compared with those of individual Ag nanoparticles, and the results indicated a lower cytotoxicity effect by Au–Ag@BSA nanoparticles. Furthermore, the in vivo toxicity of Au–Ag@BSA nanoparticles was investigated in the early stage zebrafish embryos. The result...

Here, norfloxacin (NOR) molecularly imprinted polymers (MIPs) exhibiting improved adsorption and selectivity properties were prepared via simulation and experiment. NOR and methacrylic acid (MAA) were employed as the imprinting molecule and functional monomer, respectively. The imprinting ratio, as well as cross-linking agents of the NOR-MIPs, had been optimised via the LC-ωPBE/6-31G(d,p) method. The nature and mechanism of the interaction between MIPs and MAA, as well as the selectivity of the NOR-MAA stable complex (1:1), were also discussed. Based on the simulation results, the effects of the different imprinting ratios and cross-linking agents on the adsorption of NOR-MIPs were also investigated. Concurrently, the affinity, selectivity and stability of NOR-MIPs were analysed via dynamic, static and selective adsorption, as well as thermogravimetry. The calculated and experimental results demonstrated that the stable complexes comprising NOR and MAA were formed via hydrogen bonding. The complex comprising NOR and MAA in an interaction ratio of 1:6 exhibited the highest number of hydrogen bonds and the lowest binding energy. Trihydroxymethylpropyl trimethylacrylate was more appropriate for the synthesis of NOR-MIPs compared with the two other cross-linking agents. NOR-MIPs achieved the excellent selective adsorption of NOR in single and multiple adsorption systems. This design and synthesis strategy availed a new idea for the efficient preparation of s with specific adsorption performance.

The hydrodynamics in the membrane module of a full-scale sMBR at 500 m3/d was simulated by computational fluid dynamics (CFD) in this study. Several key indexes, including membrane distance (d), aeration design, height of gas-liquid dispersion hm, and freeboard height hf and operational conditions, including SADp and liquid viscosity, were optimized through investigating their impacts on water velocity distribution and membrane shear stress. The CFD model was validated by comparing the simulated trace element RTD curves with experimental results. The optimal design and operational parameters for the full scale sMBR are as following: membrane distance d = 35 mm, air diffusers parallel located 75–100 mm under the bottom of the membrane module, the free board height hf adjusted to 400 mm, and the SADp recommended as 20 in the full-scale MBR studied.

METTL3 encodes the predominant catalytic enzyme to promote m

Background Interferon-alpha (IFN-α) is a general therapeutic regimen to be utilized in HCC. However, regulatory mechanisms of IFN-α on competing endogenous RNAs (ceRNAs) level in HCC are rarely understood. Methods HCC patients with and without IFN-α treatment were calculated to analyze the expression profile of mRNA, lncRNA, miRNA, and circRNA by RNA sequence, and significant differential expression (DE) of these types of RNAs were screened out for the following analysis. A ceRNA regulatory network was constructed to explore effects of IFN-α intervention on HCC. Furthermore, the potential prognostic factors among these DE RNAs were identified. Results In total, 60 (0.37%) mRNAs, 23 (0.08%) circRNAs, 15 (0.11%) lncRNAs, and 23 (0.91%) miRNAs were differentially expressed in patients who received IFN-α treatment. A ceRNA regulatory network including a circRNA-miRNA-mRNA network which composed of 4 up- and 10 down-regulated circRNAs, 8 up- and 5 down-regulated miRNAs, 28 up- and 9 down-regulated mRNAs, and a lncRNA-miRNA-mRNA network which composed of 10 up- and 3 down-regulated lncRNAs, 11 up- and 5 down-regulated miRNAs, 28 up- and 10 down-regulated mRNAs was constructed. Gene enrichment and pathway analysis revealed that the ceRNA network was associated with immune-related pathway and corresponding molecular function in patients who accepted IFN-α treatment. Next, we identified 3 most relevant to IFN-α treatment to HCC among these DE RNAs, namely FAM20A,IGFBP4 and MARCH3, as the prognostic factors of HCC. Furthermore, MARCH3 expression was positively correlated with infiltrating levels of CD4 + T and CD8 + T cells, macrophages, neutrophils, and dendritic cells (DCs) in HCC. MARCH3 expression showed strong correlations with diverse immune marker sets in HCC. Conclusion Our data discovered a novel ceRNA network in HCC patients receiving IFN-α therapy, which might lay the foundation for better understand the regulatory mechanism of IFN-α treatment.

Wang et al provide insight into how epigenetic regulation of the transcriptome can rewire cell fate decisions by mapping the RNA-editing landscape during hematopoiesis. They report that adenosine-to-inosine RNA editing of antizyme inhibitor 1 (Azin1) is a novel regulator of hematopoietic cell fate, capable of influencing self-renewal and differentiation of hematopoietic stem cells. This work sets the scene for developing RNA editing–targeted therapeutics for stem cell expansion and modulating AZIN1-induced cancer stem cell generation., Key Points Deep RNA-sequencing reveals the global landscape of RNA editing in the mouse hematopoietic system.Azin1 is an editable and functional gene in hematopoietic stem cells., Visual Abstract, Adenosine-to-inosine RNA editing and the catalyzing enzyme adenosine deaminase are both essential for hematopoietic development and differentiation. However, the RNA editome during hematopoiesis and the underlying mechanisms are poorly defined. Here, we sorted 12 murine adult hematopoietic cell populations at different stages and identified 30 796 editing sites through RNA sequencing. The dynamic landscape of the RNA editome comprises stage- and group-specific and stable editing patterns, but undergoes significant changes during lineage commitment. Notably, we found that antizyme inhibitor 1 (Azin1) was highly edited in hematopoietic stem and progenitor cells (HSPCs). Azin1 editing results in an amino acid change to induce Azin1 protein (AZI) translocation to the nucleus, enhanced AZI binding affinity for DEAD box polypeptide 1 to alter the chromatin distribution of the latter, and altered expression of multiple hematopoietic regulators that ultimately promote HSPC differentiation. Our findings have delineated an essential role for Azin1 RNA editing in hematopoietic cells, and our data set is a valuable resource for studying RNA editing on a more general basis.

Timely detection of liver fibrosis by X‐ray computed tomography (CT) can prevent its progression to fatal liver diseases. However, it remains quite challenging because conventional CT can only identify the difference in density instead of X‐ray attenuation characteristics. Spectral CT can generate monochromatic imaging to specify X‐ray attenuation characteristics of the scanned matter. Herein, an X‐ray energy‐dependent attenuation strategy originated from bismuth (Bi)‐based nanoprobes (BiF3@PDA@HA) is proposed for the accurate diagnosis of liver fibrosis. Bi element in BiF3@PDA@HA can exhibit characteristic attenuation depending on different levels of X‐ray energy via spectral CT, and that is challenging for conventional CT. In this study, selectively accumulating BiF3@PDA@HA nanoprobes in the hepatic fibrosis areas can significantly elevate CT value for 40 Hounsfield units on 70 keV monochromatic images, successfully differentiating from healthy livers and achieving the diagnosis of liver fibrosis. Furthermore, the enhancement produced by the BiF3@PDA@HA nanoprobes in vivo increases as the monochromatic energy decreases from 70 to 40 keV, optimizing the conspicuity of the diseased areas. As a proof of concept, the strategically designed nanoprobes with energy‐dependent attenuation characteristics not only expand the scope of CT application, but also hold excellent potential for precise imaging‐based disease diagnosis., A strategy of energy‐dependent attenuation based on bismuth (Bi) nanomaterials is proposed. BiF3@PDA@HA nanoprobes accumulated in fibrosis‐afflicted areas can attenuate characteristically depending on monoenergetic X‐ray, further leading to fibrotic livers conspicuous via spectral computed tomography (CT). Yet conventional CT with polyenergetic X‐ray can't distinguish liver fibrosis from healthy liver.

Fluoride has essential effects on bone physiological activity and is widely used in bone biomaterials modification. However, this beneficial effect is highly related to the dose range and improper dosing can lead to pathological conditions such as fluorosis of bone. Therefore, this study first investigated the dose dependent effect of fluoride on bone regeneration. In the range of 0.24–240 μM, in vivo vascularized bone formation can be achieved via fine-tuning the fluoride concentration, and the peak osteogenic effect was found at 2.4–24 μM. The underlying mechanism is related to the modulation of the osteoimmune environment. Fluoride elicited significant osteoimmunomodulatory effect in modulation of the inflammatory cytokines and expression of osteogenic factors (BMP2, OSM, spermine/spermidine) and angiogenic factor (VEGF, IGF-1) during the early response. Fluorine with the doses of 2.4 and 24 μM could increase polyamines and IGF-1 production in macrophages, thus promoting osteogenesis of BMSCs and angiogenesis of HUVECs. These doses could also inhibit the inflammatory response of macrophages. In vitro osteogenesis and angiogenesis were both improved by the fluorine (2.4 and 24 μM)/macrophage conditioned medium, which is consistent with the in vivo results. These results collectively imply that fluoride is an effective osteoimmunomodulatory agent that can regulate both osteogenesis and angiogenesis. “Osteoimmune-smart” bone biomaterials can be developed via incorporating fluorine, and the release concentration should be controlled within the range of 2.4–24 μM for improved bone formation.

Transcoelomic spread of cancer cells across the peritoneal cavity occurs in most initially diagnosed ovarian cancer (OC) patients and accounts for most cancer-related death. However, how OC cells interact with peritoneal stromal cells to evade the immune surveillance remains largely unexplored. Here, through an in vivo genome-wide CRISPR/Cas9 screen, we identified IL20RA, which decreased dramatically in OC patients during peritoneal metastasis, as a key factor preventing the transcoelomic metastasis of OC. Reconstitution of IL20RA in highly metastatic OC cells greatly suppresses the transcoelomic metastasis. OC cells, when disseminate into the peritoneal cavity, greatly induce peritoneum mesothelial cells to express IL-20 and IL-24, which in turn activate the IL20RA downstream signaling in OC cells to produce mature IL-18, eventually resulting in the polarization of macrophages into the M1-like subtype to clear the cancer cells. Thus, we show an IL-20/IL20RA-mediated crosstalk between OC and mesothelial cells that supports a metastasis-repressing immune microenvironment.

Background Babesia is a protozoan parasite that infects red blood cells in some vertebrates. Some species of Babesia can induce zoonoses and cause considerable harm. As the largest immune organ in mammals, the spleen plays an important role in defending against Babesia infection. When infected with Babesia, the spleen is seriously injured but still actively initiates immunomodulatory responses. Methods To explore the molecular mechanisms underlying the immune regulation and self-repair of the spleen in response to infection, this study used data-independent acquisition (DIA) quantitative proteomics to analyse changes in expression levels of global proteins and in phosphorylation modification in spleen tissue after Babesia microti infection in mice. Results After mice were infected with B. microti, their spleens were seriously damaged. Using bioinformatics methods to analyse dynamic changes in a large number of proteins, we found that the spleen still initiated immune responses to combat the infection, with immune-related proteins playing an important role, including cathepsin D (CTSD), interferon-induced protein 44 (IFI44), interleukin-2 enhancer-binding factor 2 (ILF2), interleukin enhancer-binding factor 3 (ILF3) and signal transducer and activator of transcription 5A (STAT5A). In addition, some proteins related to iron metabolism were also involved in the repair of the spleen after B. microti infection, including serotransferrin, lactoferrin, transferrin receptor protein 1 (TfR1) and glutamate-cysteine ligase (GCL). At the same time, the expression and phosphorylation of proteins related to the growth and development of the spleen also changed, including protein kinase C-δ (PKC-δ), mitogen-activated protein kinase (MAPK) 3/1, growth factor receptor-bound protein 2 (Grb2) and P21-activated kinase 2 (PAK2). Conclusions Immune-related proteins, iron metabolism-related proteins and growth and development-related proteins play an important role in the regulation of spleen injury and maintenance of homeostasis. This study provides an important basis for the diagnosis and treatment of babesiosis. Graphical Abstract

To detect the codon usage characteristics of chloroplast genomes in Platycarya genus, the CodonW 、 CUSP and SPSSAU software were employed to analyze the codon usage patterns of the chloroplast genomes protein-coding sequence in Platycarya longipes and Platycarya strobilacea in this research. Results show that the GC content of chloroplast genomes was 37.75% and 37.80%, the average GC content in the 3rd position was 27.16% and 27.25%. the range of effective codon number from 35.19 to 56.98, and there were more than 2/3 genes when ENC value greater than 45, which indicated a weak preference. According to the results of neutrality plot analysis, ENC-plot analysis and PR2-plot analysis, codon bias in most Platycarya chloroplast genes were affected by natural selection, while a few were affected by mutations or other factors. And based on the ENC value, five groups of high-expressed and low-expressed genes were identified, 16 codons were ended with A/U among the 18 optimal codons. The research has implications on codon optimization, enhancing the expression efficiency of exogenous gene and phylogenetic analysis.

To rationally design molecularly imprinted polymers (MIPs) of norfloxacin (NOR), functional monomers, cross-linking agents, and solvents were screened by using the LC-WPBE/6-31G(d,p) method. The nature of the interaction between NOR imprinted molecules and trifluoromethylacrylic acid (TFMAA) functional monomers is discussed. The functional monomers were screened based on the interaction ratio, the number of bonds, and the binding energy of the stable complexes between NOR and 4-vinylpyridine, methacrylic acid, TFMAA, and 2-vinyl-4,6-diamino-1,3,5-triazine. The selection of cross-linking agent was carried out based on the binding energy when the molar ratio of cross-linking agent TFMAA was 1:1. The solvent was optimized by calculating the solvation energy of the NOR–TFMAA stable complex (1:1) using different solvents. The nature of imprinting was obtained by the topological analysis of electron density of stable complexes of NOR and TFMAA based on the atom in molecule theory. On the basis of computational results, TFMAA, trimethylolpropane trimethylacrylate, and toluene were selected as the functional monomer, cross-linking agent, and solvent, respectively. When the molar ratio of NOR:TFMAA was 1:7, the complex that was formed had the lowest binding energy and highest number of hydrogen bonds. In addition, the O and H atoms on the quinoline ring and the N and H atoms on the piperazine ring of NOR interacted with TFMAA and formed ordered complexes matching each other in chemical groups and steric configuration via hydrogen bonding. Therefore, this study can provide a theoretical basis and reference for the design and preparation of NOR–MIPs.

Babesia microti is a protozoan that mainly parasitizes rodent and human erythrocytes. B. microti infection can result in changes in the expression levels of various proteins in the host serum. To explore the mechanism underlying the regulation of serum proteins by the host during B. microti infection, this study used a data-independent acquisition (DIA) quantitative proteomic approach to perform comprehensive quantitative proteomic analysis on the serum of B. microti-infected mice. We identified and analysed 333 serum proteins during the infectious stage and recovery stage within 30 days of infection by B. microti in mice. Through quantitative analysis, we found 57 proteins differentially expressed in the infection stage and 69 proteins differentially expressed in the recovery stage. Bioinformatics analysis revealed that these differentially expressed proteins were mainly concentrated in organelles, cell parts, and extracellular regions that are mainly involved in immune system, metabolic, and cellular processes. Additionally, the differentially expressed proteins mainly had catalytic activity. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis showed that many of the differentially expressed proteins participate in the complement and coagulation cascade reaction, including complement C3, complement FP, and coagulation factor XII. The results of this study can provide more information for the selection of biomarkers for the early clinical monitoring of babesiosis and help in the treatment of babesiosis.

Metabolic reprogramming to fulfill the biosynthetic and bioenergetic demands of cancer cells has aroused great interest in recent years. However, metabolic reprogramming for cancer metastasis has not been well elucidated. Here, we screened a subpopulation of breast cancer cells with highly metastatic capacity to the lung in mice and investigated the metabolic alternations by analyzing the metabolome and the transcriptome, which were confirmed in breast cancer cells, mouse models, and patients’ tissues. The effects and the mechanisms of nucleotide de novo synthesis in cancer metastasis were further evaluated in vitro and in vivo. In our study, we report an increased nucleotide de novo synthesis as a key metabolic hallmark in metastatic breast cancer cells and revealed that enforced nucleotide de novo synthesis was enough to drive the metastasis of breast cancer cells. An increased key metabolite of de novo synthesis, guanosine-5'-triphosphate (GTP), is able to generate more cyclic guanosine monophosphate (cGMP) to activate cGMP-dependent protein kinases PKG and downstream MAPK pathway, resulting in the increased tumor cell stemness and metastasis. Blocking de novo synthesis by silencing phosphoribosylpyrophosphate synthetase 2 (PRPS2) can effectively decrease the stemness of breast cancer cells and reduce the lung metastasis. More interestingly, in breast cancer patients, the level of plasma uric acid (UA), a downstream metabolite of purine, is tightly correlated with patient’s survival. Our study uncovered that increased de novo synthesis is a metabolic hallmark of metastatic breast cancer cells and its metabolites can regulate the signaling pathway to promote the stemness and metastasis of breast cancer., Metabolic reprogramming to fulfil the biosynthetic and bioenergetic demands of cancer cells is well known, but a role in metastasis is less clear. This study shows that nucleotide metabolic reprogramming leads to an enhancement of the cGMP-PKG-MAPK axis, enabling breast cancer cells to effectively colonize and grow in the lung.

Summary Xenopus laevis tolerate dehydration when their environments evaporate during summer months. Protein phosphorylation has previously shown to regulate important adaptations in X. laevis, including the transition to anaerobic metabolism. We therefore performed phosphoproteomic analysis of X. laevis to further elucidate the cellular and metabolic responses to dehydration. Phosphoproteins were enriched in cellular functions and pathways related to glycolysis/gluconeogenesis, the TCA cycle, and protein metabolism, among others. The prominence of phosphoproteins related to glucose metabolism led us to discover that the hypoxia-inducible PFKFB3 enzyme was highly phosphorylated and likely activated during dehydration, a feature of many cancers. Expression of the four transcript variants of the pfkfb3 gene was found all to be upregulated during dehydration, potentially due to the enrichment of hypoxia responsive elements in the pfkfb3 promoter. These results further support the role of anaerobic glycolysis during dehydration in X. laevis and elucidate a potential mechanism for its increased rate., Graphical Abstract, Highlights • Clustering analysis indicated a concerted response in liver but not skeletal muscle • Phosphoproteins were enriched for glycolysis, gluconeogenesis, and the TCA cycle • Phosphopeptides of hypoxia-inducible PFKFB3 were highly abundant during dehydration • Four PFKFB3 variants were upregulated potentially supporting anaerobic glycolysis, Animal Physiology; Cell Biology; Proteomics

BackgroundBabesia is a protozoan parasite in red blood cells of some vertebrates. Some species of Babesia can cause zoonoses and cause great harm. As the largest immune organ in mammals, the spleen plays an important role in defending against Babesia infection. When infected with Babesia, the spleen is seriously injured, but it still actively initiates immunomodulatory responses.MethodsIn order to explore the molecular mechanisms underlying the immune regulation and self-repair of the spleen in response to infection, this study used data-independent acquisition (DIA) quantitative proteomics to analyse changes in expression levels of global proteins and changes in phosphorylation modification in spleen tissue after Babesia microti infection in mice.ResultsAfter the mice were infected with B. microti, their spleen were seriously damaged.Using bioinfor-matics methods to analyze the dynamic changes of a large number of proteins, we found that spleen still initiated immune response to deal with the infection, in which immune-related proteins played an important role, including CTSD, IFI44, ILF2, ILF, and STAT5A. In addition, some proteins related to iron metabolism were also involved in the repair of spleen against B. microti infection, including serotransferrin, lactoferrin, TfR1, and GCL. At the same time, the expression and phosphorylation of proteins related to the growth and development of the spleen also changed, including PKC-δ and MAPK3/1, Grb2, and PAK2. ConclusionsImmune-related proteins, iron metabolism-related proteins and growth and development-related proteins play an important important role in the regulation of spleen injury and maintenance of homeostasis. This study will provide important bases for the diagnosis and treatment of babesiosis.

Purpose To construct and verify a CT-based multidimensional nomogram for the evaluation of lymph node (LN) status in pancreatic ductal adenocarcinoma (PDAC). Materials and Methods We retrospectively assessed data from 172 patients with clinicopathologically confirmed PDAC surgically resected between February 2014 and November 2016. Patients were assigned to either a training cohort (n = 121) or a validation cohort (n = 51). We acquired radiomics features from the preoperative venous phase (VP) CT images. The maximum relevance–minimum redundancy (mRMR) algorithm and the least absolute shrinkage and selection operator (LASSO) methods were used to select the optimal features. We used multivariable logistic regression to construct a combined radiomics model for visualization in the form of a nomogram. Performance of the nomogram was evaluated by the receiver operating characteristic (ROC) curve approach, calibration testing, and analysis of clinical usefulness. Results A Rad score consisting of 10 LN status-related radiomics features was found to be significantly associated with the actual LN status (P < 0.01). A nomogram that consisted of Rad scores, CT-reported parenchymal atrophy, and CT-reported LN status performed well in terms of predictive power in the training cohort (area under the curve, 0.92), and this was confirmed in the validation cohort (area under the curve, 0.95). The nomogram also performed well in the calibration test and decision curve analysis, demonstrating its potential clinical value. Conclusion A multidimensional radiomics nomogram consisting of Rad scores, CT-reported parenchymal atrophy, and CT-reported LN status may contribute to the non-invasive evaluation of LN status in PDAC patients.

Background: The tick Haemaphysalis longicornis is well known as vector of several zoonotic pathogens responsible for various clinical conditions, increasingly threatens the veterinary and public health. It is mainly distributed in East Asia, New Zealand, Australia, and several Pacific islands, and has been expanded rapidly in United States since its first founding on a nonimported domestic sheep in New Jersey. Glutathione S-transferases (GSTs) are phase II detoxification enzymes, which function via combining with pesticidal molecules and catalyzing the conjugation of molecules by thiol of glutathione, so as to protect tissues from oxidative stress damage. In the tick H. longicornis, glutathione S-transferases (HlGST and HlGST2) have been previously identified. However, the relationship between the expression of glutathione S-transferases and the essential oil treatment in ticks remains unexplored. Hence, in the present study, the expression profiles of HlGST and HlGST2 mRNAs were evaluated in H. longicornis after exposure to Cymbopogon citratus essential oil. Results: At 24 h post-exposure of H. longicornis to different sublethal concentrations of C. citratus essential oil, ANOVA results revealed significant difference (F2,6 = 55.94, P = 0.0001) in the expression of HlGST. Tukey’s test showed that HlGST was significantly induced after treatment with 1% C. citratus essential oil (P = 0.0002); whereas no significant difference (P = 0.3551) was detected after treated by 2% C. citratus essential oil. No significant difference (F2,6 = 0.8990, P = 0.4555) in the expression of HlGST2 between the treatment and the control group of 50% ethanol. Nevertheless, the under-expression of HlGST2 in the treatment groups versus the untreated control group was not significant (F3,8 = 2.643, P = 0.1208). Conclusion: The results implied that GST mRNA is a potential molecular target for C. citratus essential oil in H. longicornis. Further understanding of the underlying mechanisms of the GST at the molecular level could contribute to develop effective control measures for ticks and tick-borne diseases.

The regulatory circuitry underlying embryonic stem (ES) cell self-renewal is well defined, but how this circuitry is disintegrated to enable lineage specification is unclear. RNA-binding proteins (RBPs) have essential roles in RNA-mediated gene regulation, and preliminary data suggest that they might regulate ES cell fate. By combining bioinformatic analyses with functional screening, we identified seven RBPs played important roles for the exit from pluripotency of ES cells. We characterized hnRNPLL, which mainly functions as a global regulator of alternative splicing in ES cells. Specifically, hnRNPLL promotes multiple ES cell-preferred exon skipping events during the onset of ES cell differentiation. hnRNPLL depletion thus leads to sustained expression of ES cell-preferred isoforms, resulting in a differentiation deficiency that causes developmental defects and growth impairment in hnRNPLL-KO mice. In particular, hnRNPLL-mediated alternative splicing of two transcription factors, Bptf and Tbx3, is important for pluripotency exit. These data uncover the critical role of RBPs in pluripotency exit and suggest the application of targeting RBPs in controlling ES cell fate.

Ribosomal proteins (RPs) are indispensable in ribosome biogenesis and protein synthesis, and play a crucial role in diverse developmental processes. In the present study, we carried out a comprehensive analysis of RPs in chordates and examined the expression profiles of the complete set of 92 cytoplasmic RP genes in Nile tilapia. The RP genes were randomly distributed throughout the tilapia genome. Phylogenetic and syntenic analyses revealed the existence of duplicated RP genes from 2R (RPL3, RPL7, RPL22 and RPS27) and 3R (RPL5, RPL19, RPL22, RPL41, RPLP2, RPS17, RPS19 and RPS27) in tilapia and even more from 4R in common carp and Atlantic salmon. The RP genes were found to be expressed in all tissues examined, but their expression levels differed among different tissues. Gonadal transcriptome analysis revealed that almost all RP genes were highly expressed, and their expression levels were highly variable between ovaries and testes at different developmental stages in tilapia. No sex- and stage-specific RP genes were found. Eleven RP genes displayed sexually dimorphic expression with nine higher in XY gonad and two higher in XX gonad at all stages examined, which were proved to be phenotypic sex dependent. Quantitative real-time PCR and immunohistochemistry ofRPL5b and RPL24 were performed to validate the transcriptome data. The genomic resources and expression data obtained in this study will contribute to a better understanding of RPs evolution and functions in chordates.

Pressed degreased walnut meal (WM) was prepared from walnut kernel by cold-press deoil. It was rich in polyphenols with high activities of lowering lipids, antioxidation, anti-inflammation, and others, but the hypoglycemic activity has scarcely been reported. The purpose of this research was to investigate the preventive effect of the extracts of WM (WMP) on T2DM rats and the regulation of WMP on intestinal flora. Some results showed that WMP significantly held FBG, FINS and GSP, OGTT, the serum and hepatic TG, TC, HDL-C, LDL-C, AST, ALT, LPS, TNF-α, IL-6, and the hepatic MDA, CAT, SOD, as well as, prevented the pathological damage of the liver and the pancreas. The results of 16SrDNA sequencing demonstrated that WMP impeded the changes of intestinal flora in feces, mainly including Firmicutes, Bacteroidetes, and Proteobacteria. These indicated that WMP had promising effects on T2DM, which could be associated with the modulation of gut bacteria.

SummaryTranscoelomic spread of cancer cells across the peritoneal cavity occurs in most initially diagnosed ovarian cancer (OC) patients and accounts for most cancer-related death. However, how OC cells interact with peritoneal stromal cells to evade the immune surveillance remains largely unexplored. Here, through an in vivo genome-wide CRISPR/Cas9 screen, we identified IL20RA, which decreases dramatically in OC patients during peritoneal metastasis, as a key factor preventing the transcoelomic metastasis of OC. Reconstitution of IL20RA in highly metastatic OC cells greatly suppresses the transcoelomic metastasis. OC cells, when disseminate into the peritoneal cavity, greatly induce peritoneum mesothelial cells to express IL-20 and IL-24, which in turn activate the IL20RA downstream signaling in OC cells to produce mature IL-18, eventually resulting in the polarization of macrophages into M1-like subtype to clear the cancer cells. Thus, we discovered an IL-20/IL20RA-mediated crosstalk between OC and mesothelial cells that supports a metastasis-repressing immune microenvironment.