Targeted nanoparticles for imaging and therapy of endometriosis.

In this brief review, we discuss our efforts to validate nanoplatforms for imaging and treatment of endometriosis. We specifically highlight our use of nonhuman primates and primate tissues in this effort. Endometriosis is a painful disorder of women and nonhuman primates (NHPs) where endometrium-like tissue exists outside of the uterus. There are no reliable, specific, and noninvasive diagnostic tests for endometriosis. Laparoscopic imaging remains the gold standard for identifying small endometriotic lesions in both women and monkeys. Visualizing and surgically removing microscopic lesions remains a clinical challenge. To address this challenge, we have created nanoparticle reagents that, when administered intravenously, enter endometriotic lesions both passively and by targeting endometriotic cells. The particles can carry payloads, including near-infrared fluorescent dyes and magnetic nanoparticles. These agents can be used for imaging and thermal ablation of diseased tissues. We evaluated this approach on macaque endometriotic cells, human and macaque endometrium engrafted into immunodeficient mice, in endometrium subcutaneously autografted in macaques, and in rhesus monkeys with spontaneous endometriosis. Employing these models, we report that nanoplatform-based reagents can improve imaging and provide thermal ablation of endometriotic tissues.

Exploratory study on the metabolic similarity of denitrifying carbon sources.

Mixed carbon sources have been developed for denitrification to eliminate the "carbon dependency" problem of single carbon. The metabolic correlation between different carbon sources is significant as guidance for the development of novel mixed carbon sources. In this study, to explore the metabolic similarity of denitrifying carbon sources, we selected alcohols (methanol, ethanol, and glycerol) and saccharide carbon sources (glucose, sucrose, and starch). Batch denitrification experiments revealed that methanol-acclimated sludge improved the denitrification rate of both methanol (14.42 mg-N/gMLVSS*h) and ethanol (9.65 mg-N/gMLVSS*h), whereas ethanol-acclimated sludge improved the denitrification rate of both methanol (7.80 mg-N/gMLVSS*h) and ethanol (22.23 mg-N/gMLVSS*h). In addition, the glucose-acclimated sludge and sucrose-acclimated sludge possibly improved the denitrification rate of glucose and sucrose, and the glycerol-acclimated sludge improved the denitrification rate of volatile fatty acids (VFAs), alcohols, and saccharide carbon sources. Functional gene analysis revealed that methanol, ethanol, and glycerol exhibited active alcohol oxidation and glyoxylate metabolism, and glycerol, glucose, and sucrose exhibited active glycolysis metabolism. This indicated that the similarity in the denitrification metabolism of these carbon sources was based on functional gene similarity, and glycerol-acclimated sludge exhibited the most diverse metabolism, which ensured its good denitrification effect with other carbon sources.

A protocol for creating endometriosis in rhesus macaques (Macaca mulatta).

BACKGROUND: Endometriosis is the presence of endometrium-like tissue outside the uterine cavity. An experimental model of endometriosis has been created in the baboon by the transcervical collection and laparoscopic inoculation of menstrual endometrium. Macaques are the preferred model for pharmaceutical development, but the complex anatomy of the macaque cervix makes the baboon method impractical. In this work, we sought to validate a surgical approach for creating endometriosis in macaques. METHODS: Menstrual endometrium was collected via laparoscopic intrauterine puncture and transferred to the peritoneal cavity. We repeated this procedure during three menstruations. Endometriotic tissue was identified during laparoscopy, collected, and characterized by immunohistochemistry. RESULTS: Sham surgery-treated animals (n = 3) failed to develop endometriosis. We identified red, powder burnt, and white lesions in 13/14 of the treated animals; the stroma of the red lesions stained positive for ovarian steroid receptors. CONCLUSION: This surgical technique can reliably create hormone-responsive endometriosis in macaques for therapeutic studies.

The ecological response and distribution characteristics of microorganisms and polycyclic aromatic hydrocarbons in a retired coal gas plant post-thermal remediation site.

Thermal remediation is one of the most common approaches of removing organic pollutants in the retired contamination sites. However, little is known about the performance of bacterial community characteristics after in situ thermal remediation. In this study, the ecological response and spatial distributional characteristics of microorganisms and polycyclic aromatic hydrocarbons (PAHs) were investigated using a high throughput sequencing method in a retired coal gas plant site after in situ thermal remediation in Nanjing, China. Combination of Venn, clustering-correlation heatmap and two - factor correlation network analysis revealed that, microbial communities were obviously affected and classified by soil depths, temperature, and contamination level, respectively. The common and endemic microorganisms of each group were identified. The relative abundances of Thermaerobacter, Calditerricola, Brevibacillus, Ralstonia and Rhodococcus (aerobic bacteria) gradually declined with the increase of soil depth, while those of Bacillus, Fictibacillus, Paenibacillus, Rheinheimera presented opposite tendency. Some thermophilic degradation bacteria of PAHs, including Thermaerobacter, Calditerricola, Bacillus, Rhodococcus, unclassified_p__Firmicutes, Arthrobacter and Deinococcus, were identified and increased in the abundance at heavily polluted sites. Additionally, Proteobacteria, Bacteroidota, Deinococcota, Chloroflexi, Acidobacteriota, and Actinobacteriota showed negative response to the increase of soil depth, temperature and pollution level, while Firmicutes presented a positive response. This implied that Firmicutes has better stress resistance and adaptability to thermal remediation condition. The key environmental factors affecting microorganism composition and distribution were Temperature, Total nitrogen, Oxidation-Reduction Potential, Organic matters, and PAHs concentrations, which explains the dominant driving mechanism of soil depth, temperature, and contamination level on microbial characteristics in thermal remediation site. Our study could contribute to a better understanding of the resilience and adaptation mechanisms of microbial community at the contaminated site after the in situ thermal remediation.

The combined impact of testosterone and Western-style diet on endometriosis severity and progression in rhesus macaques†.

Polycystic ovary syndrome (PCOS) is associated with irregular menstrual cycles, hyperandrogenemia, and obesity. It is currently accepted that women with PCOS are also at risk for endometriosis, but the effect of androgen and obesity on endometriosis has been underexplored. The goal of this study was to determine how testosterone (T) and an obesogenic diet impact the progression of endometriosis in a nonhuman primate (NHP) model. Female rhesus macaques were treated with T (serum levels approximately 1.35 ng/ml), Western-style diet (WSD; 36% of calories from fat compared to 16% in standard monkey chow) or the combination (T + WSD) at the time of menarche as part of a longitudinal study for ~7 years. Severity of endometriosis was determined based on American Society for Reproductive Medicine (ASRM) revised criteria, and staged 1-4. Stages 1 and 2 were associated with extent of abdominal adhesions, while stages 3 and 4 were associated with presence of chocolate cysts. The combined treatment of T + WSD resulted in earlier onset of endometriosis and more severe types associated with large chocolate cysts compared to all other treatments. There was a strong correlation between glucose clearance, homeostatic model assessment for insulin resistance (HOMA-IR), and total percentage of body fat with presence of cysts, indicating possible indirect contribution of hyperandrogenemia via metabolic dysfunction. An RNA-seq analysis of omental adipose tissue revealed significant impacts on a number of inflammatory signaling pathways. The interactions between obesity, hyperandrogenemia, and abdominal inflammation deserve additional investigation in NHP model species.

Molecular mechanisms through which different carbon sources affect denitrification by Thauera linaloolentis: Electron generation, transfer, and competition.

Characterizing the molecular mechanism through which different carbon sources affect the denitrification process would provide a basis for the proper selection of carbon sources, thus avoiding excessive carbon source dosing and secondary pollution while also improving denitrification efficiency. Here, we selected Thauera linaloolentis as a model organism of denitrification, whose genomic information was elucidated by draft genome sequencing and KEGG annotations, to investigate the growth kinetics, denitrification performances and characteristics of metabolic pathways under diverse carbon source conditions. We reconstructed a metabolic network of Thauera linaloolentis based on genomic analysis to help develop a systematic method of researching electron pathways. Our findings indicated that carbon sources with simple metabolic pathways (e.g., ethanol and sodium acetate) promoted the reproduction of Thauera linaloolentis, and its maximum growth density reached OD600 = 0.36 and maximum specific growth rate reached 0.145 h-1. These carbon sources also accelerated the denitrification process without the accumulation of intermediates. Nitrate could be reduced completely under any carbon source condition; but in the "glucose group", the maximum accumulation of nitrite was 117.00 mg/L (1.51 times more than that in the "ethanol group", which was 77.41 mg/L), the maximum accumulation of nitric oxide was 363.02 µg/L (7.35 times more than that in the "ethanol group", which was 49.40 µg/L), and the maximum accumulation of nitrous oxide was 22.58 mg/L (26.56 times more than that in the "ethanol group", which was 0.85 mg/L). Molecular biological analyses demonstrated that diverse types of carbon sources directly induced different carbon metabolic activities, resulting in variations in electron generation efficiency. Furthermore, the activities of the electron transport system were positively correlated with different carbon metabolic activities. Finally, these differences were reflected in the phenomenon of electronic competition between denitrifying reductases. Thus we concluded that this was the main molecular mechanism through which the carbon source type affected the denitrification process. In brief, carbon sources with simple metabolic pathways induced higher efficiency of electron generation, transfer, and competition, which promoted rapid proliferation and complete denitrification; otherwise Thauera linaloolentis would grow slowly and intermediate products would accumulate seriously. Our study established a method to evaluate and optimize carbon source utilization efficiency based on confirmed molecular mechanisms.

Insights into the relationship between denitrification and organic carbon release of solid-phase denitrification systems: Mechanism and microbial characteristics.

Solid-phase denitrification is a promising alternative denitrification technology when facing a shortage of carbon sources. Nevertheless, it is still unclear whether there is a certain interaction between the denitrification process and the carbon release process in a solid-phase denitrification system. In this study, the concept of "Self-adaptation" was proposed for the relationship between denitrification and carbon release. At various influent nitrate loads, the PCL-supported denitrification system achieved an average nitrate removal rate of over 90.59 ± 7.01 % and a maximum denitrification rate of 0.67 ± 0.06 gN/(L·d). Microorganisms can spontaneously regulate the carbon release rate of PCL in response to changes in influent nitrate load, demonstrating "self-adaptation" of the PCL-supported solid-phase denitrification system. Regulation of carbon release rate via the "Self-adaptation" was achieved by changes in extracellular depolymerase activity. Acidovorax_sp. played a key role in "Self-adaptation", for its function of both denitrification and PCL degradation.

Photothermal Localization in an Optofluidic Microreactor for Rapid Pretreatment toward Online Pollutant Analysis.

The realization of high-efficient digestion in a microfluidic reactor is considered to be advantageous for pretreatment toward online pollutant detection. However, it is difficult to achieve satisfactory device performance due to the gap between the low digestion reaction efficiency and the demand for rapid pretreatment for online detection. Herein, we design and manufacture an optofluidic microreactor combined with a MnO2 nanofilm localizing the heat inside the reaction chamber under solar irradiation, which contributes a lot to the on-chip nutrient digestion efficiency enhancement. The overall temperature of the water sample in the reactor chamber can be dramatically increased in a fleeting time of less than 1 s and maintained at 78 °C. The digestion rate constant of the microreactor is improved by about 100 times compared with that obtained by the traditional method in the national standard, which is attributed to temperature enhancement and various oxidation reactions in the heated reaction chamber. Notably, when pretreating the actual total phosphorus water samples, the digestion efficiency is demonstrated to be higher than 95% within 12 s under solar light irradiation. The optofluidic platform brings many benefits to accelerate the various photochemically enhanced reactions using solar light and is extremely adapted for rapid pretreatment of biochemical samples to further develop their online analysis.

Drosophila Innate Immunity Involves Multiple Signaling Pathways and Coordinated Communication Between Different Tissues.

The innate immune response provides the first line of defense against invading pathogens, and immune disorders cause a variety of diseases. The fruit fly Drosophila melanogaster employs multiple innate immune reactions to resist infection. First, epithelial tissues function as physical barriers to prevent pathogen invasion. In addition, macrophage-like plasmatocytes eliminate intruders through phagocytosis, and lamellocytes encapsulate large particles, such as wasp eggs, that cannot be phagocytosed. Regarding humoral immune responses, the fat body, equivalent to the mammalian liver, secretes antimicrobial peptides into hemolymph, killing bacteria and fungi. Drosophila has been shown to be a powerful in vivo model for studying the mechanism of innate immunity and host-pathogen interactions because Drosophila and higher organisms share conserved signaling pathways and factors. Moreover, the ease with which Drosophila genetic and physiological characteristics can be manipulated prevents interference by adaptive immunity. In this review, we discuss the signaling pathways activated in Drosophila innate immunity, namely, the Toll, Imd, JNK, JAK/STAT pathways, and other factors, as well as relevant regulatory networks. We also review the mechanisms by which different tissues, including hemocytes, the fat body, the lymph gland, muscles, the gut and the brain coordinate innate immune responses. Furthermore, the latest studies in this field are outlined in this review. In summary, understanding the mechanism underlying innate immunity orchestration in Drosophila will help us better study human innate immunity-related diseases.

High nuclear ABCG1 expression is a poor predictor for hepatocellular carcinoma patient survival.

BACKGROUND: ATP-binding cassette transporter G1 (ABCG1) regulates cellular cholesterol homeostasis and plays a significant role in tumor immunity. But, for hepatocellular carcinoma (HCC), the role of ABCG1 has not been investigated. Thus, the aim of this study was to evaluate the prognostic value and clinicopathological significance of ABCG1 in HCC. METHODS: One hundred and four adult patients with HCC were enrolled, and ABCG1 expression in paired HCC specimens was determined by immunohistochemistry. All these patients were stratified by ABCG1 expression, Kaplan-Meier analysis was used to compare the overall survival (OS) and recurrence-free survival (RFS), and Cox regression analysis was used to determine independent predictors of tumor recurrence. RESULTS: Upregulation of ABCG1 was observed in HCC samples compared to matched tumor-adjacent tissues. Patients with high nuclear ABCG1 expression had lower OS and RFS (P = 0.012 and P = 0.020, respectively). High nuclear ABCG1 expression was related to larger tumor size (P = 0.004) and tumor recurrence (P = 0.027). Although ABCG1 was expressed in the cytoplasm, cytosolic expression could not predict the outcome in patients with HCC. A new stratification pattern was established based on the heterogenous ABCG1 expression pattern: high risk (Highnucleus/Lowcytosol), moderate risk (Highnucleus/Highcytosol or Lownucleus/Lowcytosol), and low risk (Lownucleus/Highcytosol). This ABCG1-based risk stratification could distinguish the different OS and RFS in patients with HCC. Multivariate Cox regression analysis indicated that ABCG1 high risk was an independent predictor of poor RFS (P = 0.015). CONCLUSIONS: High nuclear ABCG1 expression indicates poor prognosis in patients with HCC. Asymmetric distribution of ABCG1 in the nucleus and cytoplasm may have an important role in tumor recurrence.

Physiological Action of Progesterone in the Nonhuman Primate Oviduct.

Therapies that target progesterone action hold potential as contraceptives and in managing gynecological disorders. Recent literature reviews describe the role of steroid hormones in regulating the mammalian oviduct and document that estrogen is required to stimulate epithelial differentiation into a fully functional ciliated and secretory state. However, these reviews do not specifically address progesterone action in nonhuman primates (NHPs). Primates differ from most other mammals in that estrogen levels are >50 pg/mL during the entire menstrual cycle, except for a brief decline immediately preceding menstruation. Progesterone secreted in the luteal phase suppresses oviductal ciliation and secretion; at the end of the menstrual cycle, the drop in progesterone triggers renewed estrogen-driven tubal cell proliferation ciliation secretory activity. Thus, progesterone, not estrogen, drives fallopian tube cycles. Specific receptors mediate these actions of progesterone, and synthetic progesterone receptor modulators (PRMs) disrupt the normal cyclic regulation of the tube, significantly altering steroid receptor expression, cilia abundance, cilia beat frequency, and the tubal secretory milieu. Addressing the role of progesterone in the NHP oviduct is a critical step in advancing PRMs as pharmaceutical therapies.

Long-term Hyperandrogenemia and/or Western-style Diet in Rhesus Macaque Females Impairs Preimplantation Embryogenesis.

Hyperandrogenemia and obesity are common in women with polycystic ovary syndrome, but it is currently unclear how each alone or in combination contribute to reproductive dysfunction and female infertility. To distinguish the individual and combined effects of hyperandrogenemia and an obesogenic diet on ovarian function, prepubertal female rhesus macaques received a standard control (C) diet, testosterone (T) implants, an obesogenic Western-style diet (WSD), or both (T + WSD). After 5 to 6 years of treatment, the females underwent metabolic assessments and controlled ovarian stimulations. Follicular fluid (FF) was collected for steroid and cytokine analysis and the oocytes fertilized in vitro. Although the T + WSD females exhibited higher insulin resistance compared to the controls, there were no significant differences in metabolic parameters between treatments. Significantly higher concentrations of CXCL-10 were detected in the FF from the T group, but no significant differences in intrafollicular steroid levels were observed. Immunostaining of cleavage-stage embryos revealed multiple nuclear abnormalities in the T, WSD, and T + WSD groups. Single-cell DNA sequencing showed that while C embryos contained primarily euploid blastomeres, most cells in the other treatment groups were aneuploid. Despite yielding a higher number of mature oocytes, T + WSD treatment resulted in significantly reduced blastocyst formation rates compared to the T group. RNA sequencing analysis of individual blastocysts showed differential expression of genes involved in critical implantation processes between the C group and other treatments. Collectively, we show that long-term WSD consumption reduces the capacity of fertilized oocytes to develop into blastocysts and that the addition of T further impacts gene expression and embryogenesis.

Optofluidic Platform for Rapid On-Chip Analysis of Total Phosphorus in Surface Water Using Absorption Spectrometry.

Optofluidic devices are of high interest for online monitoring and analyzing biochemical targets in water by integrating the complex on-chip pretreatment of target analytes and spectral analysis. Compared with the traditional bulk equipment, versatile optical detection and biochemical analysis are more easily integrated on an optofluidic chip, which promotes the development of on-chip real-time rapid detection and monitoring. Here, we report an optofluidic platform for online monitoring total phosphorous in water by absorption spectrometry, which naturally combines the merits of both the photo-Fenton effect and microfluidics to realize the rapid on-chip digestion of phosphate at room temperature and normal pressure. The functional cells for chromogenic reaction and optical absorption detection are, respectively, fabricated on the platform to analyze the content of total phosphorus in surface water. In the experiment, the on-chip digestion time of phosphate is dramatically declined to 8.6 sec, and thus, the detection time is greatly shortened to a few minutes. The detection range of total phosphorus is demonstrated as 0.005-1.00 mg L-1, which satisfies the detection requirements of most environmental water samples. Its availability for measuring the total phosphorous in real water samples is also verified. Predictably, this platform is adapted to on-chip analysis of many other biochemical targets in water.

The Progress in the Treatment of Hepatocellular Carcinoma With Portal Vein Tumor Thrombus.

Hepatocellular carcinoma (HCC) is one of most prevalent cancer and is a serious healthcare issue worldwide. Portal vein tumor thrombus (PVTT) is a frequent complication and remains as the blockage in the treatment of HCC with high recurrence rate and poor prognosis. There is still no global consensus or standard guideline on the management of HCC with PVTT. In western countries, Sorafenib and Lenvatinib are recommended as the first-line treatment options for HCC patients with PVTT where this condition is now regarded as BCLC Stage C regardless of PVTT types. However, there is growing evidence that supports the close relationship of the extent of PVTT to the prognosis of HCC. Besides the targeted therapy, more aggressive treatment modalities have been proposed and practiced in the clinic which may improve the prognosis of HCC patients with PVTT and prolong the patients' survival time, such as transarterial chemoembolization, radiotherapy, hepatic resection, liver transplantation, and various combination therapies. Herein, we aim to review and summarize the advances in the treatment of HCC with PVTT.

Regulation of anaerobic fermentation for producing short-chain fatty acids from primary sludge in WWTPs by different alkalis.

Carbon source production from primary sludge in wastewater treatment plants (WWTPs) via anaerobic fermentation process has been paid more attention. However, slow hydrolysis rate and low yield of short-chain fatty acids (SCFAs) limited its application. This study aimed at improving the anaerobic fermentation efficiency of primary sludge by alkali regulation (NaOH, Na2CO3 and Ca(OH)2), and revealing the mechanism. Results showed that three kinds of alkalis allowed enhancing hydrolysis and acidification, and reducing methane production in the anaerobic fermentation process of primary sludge. The Na2CO3 regulation contributed to highest yield and productivity of SCFAs, reaching 1626 mg COD/L and 0.189 g COD/g VSS at 4th day, respectively. Microbial community structure analysis indicated that the relative abundance of fermentative microbial community was improved in the alkali regulation system, where methanogenic archaea was effectively inhibited. The continuous flow experiment further verified that the Na2CO3 regulation could steadily increase yield of SCFAs in the anaerobic fermentation process of primary sludge, and the yield was also the highest among three kinds of alkali regulation.

Optimization nutrient removal at different volume ratio of anoxic-to-aerobic zone in integrated fixed-film activated sludge (IFAS) system.

This study evaluated the influence of different volume ratios of the anoxic-to-aerobic zone (Vano/Vaer) on the enhancement of nitrogen and phosphorus removal in an integrated fixed-film activated sludge (IFAS) system. As the Vano/Vaer increased from 1:2 to 2:1, the removal of organic carbon, nitrogen and phosphorus nutrients of the IFAS system was improved. At Vano/Vaer = 1:1, the removal effect of nitrogen and phosphorus nutrients was optimal, and the average removal rates of COD, NH4+-N, TN, and TP of the system reached 90 ± 3.2%, 98.2 ± 1.4%, 88.9 ± 2.2%, and 89.1 ± 2.7%, respectively. As the volume of the anoxic zone continued to increase, the denitrifying phosphate-accumulating capacity of the system was enhanced, and the highest ratio of specific anoxic and aerobic phosphorus uptake rate could reach 65.3%. Analysis of the molecular evaluation showed that, the proportion of nitrifying bacteria in the biofilm gradually increased as Vano increased. Moreover, denitrifying phosphate-accumulating organisms (DNPAOs), ammonia-oxidizing archaea (AOA), and anaerobic ammonium oxidizing (Anammox) bacteria were all enriched all showed enrichment in the biofilm of fiber carriers, which further strengthened the system's synergistic removal of nitrogen and phosphorus.

Modeling sulfide production in full flow concrete sewers based on the HRT variation of sewerage.

The corrosion and odor in concrete sewers are mainly related to the sulfide production, which is, under certain circumstances, directly proportional to the hydraulic retention time (HRT) of the sewer. To reduce the corrosion and control the odor in concrete sewers, it is necessary to model the production of sulfide in the concrete sewers with different HRTs. However, previous researches were mostly carried out in simulated Perspex-made sewers, and the obtained theoretical formulas based on the Monod equation were impractical because of the complexity. An actual concrete pipe with domestic sewage was employed in this study to obtain a simple but practical model, which can be applied to quantitively describe the sulfide production according to the HRT of the sewer and the chemical oxygen demand (COD) of the sewage. The empirical equation obtained was rs = (0.045 × lnHRT + 0.071) × ([COD] - b)0.6, the coefficient is a logarithmic function of the HRT, and the sulfide production rate and COD have a power relationship. Based on the data of COD and HRT obtained in the realistic sewer, the production of sulfide in the sewer can be predicted for better maintaining sewers through sulfide control.

Childhood emotional neglect and problematic mobile phone use among Chinese adolescents: A longitudinal moderated mediation model involving school engagement and sensation seeking.

BACKGROUND: Childhood emotional neglect has been shown to be associated with a range of emotional, behavioral and social problems. We hypothesized that childhood emotional neglect might predispose adolescents to engage in Problematic Mobile Phone Use (PMPU) as a way to meet their needs for relatedness. OBJECTIVE: Using a longitudinal design, we aimed to reveal the explanatory mechanism in the association between childhood emotional neglect and PMPU among Chinese adolescents, by testing the mediating effect of school engagement and the moderating effect of sensation seeking. METHODS: Participants were 1987 Chinese adolescents (56.13 % male; Mage at Wave 1 = 12.32) who completed self-report questionnaires regarding childhood emotional neglect, school engagement, PMPU and sensation seeking at three time points in the course of a year. RESULTS: The results of structural equation modeling (SEM) showed that retrospective reports of childhood emotional neglect at Wave 1 were positively associated with adolescent PMPU at Wave 3, and school engagement at Wave 2 fully mediated the association. Meanwhile, sensation seeking at Wave 3 moderated the pathway from school engagement to later adolescent PMPU in the mediated model. Specifically, the effect of low school engagement on PMPU was stronger for adolescents who reported high sensation seeking. CONCLUSION: Identifying the processes by which childhood emotional neglect is associated with adolescent PMPU over time has potential applied value for prevention and intervention.

Rab5 and Rab11 maintain hematopoietic homeostasis by restricting multiple signaling pathways in Drosophila.

The hematopoietic system of Drosophila is a powerful genetic model for studying hematopoiesis, and vesicle trafficking is important for signal transduction during various developmental processes; however, its interaction with hematopoiesis is currently largely unknown. In this article, we selected three endosome markers, Rab5, Rab7, and Rab11, that play a key role in membrane trafficking and determined whether they participate in hematopoiesis. Inhibiting Rab5 or Rab11 in hemocytes or the cortical zone (CZ) significantly induced cell overproliferation and lamellocyte formation in circulating hemocytes and lymph glands and disrupted blood cell progenitor maintenance. Lamellocyte formation involves the JNK, Toll, and Ras/EGFR signaling pathways. Notably, lamellocyte formation was also associated with JNK-dependent autophagy. In conclusion, we identified Rab5 and Rab11 as novel regulators of hematopoiesis, and our results advance the understanding of the mechanisms underlying the maintenance of hematopoietic homeostasis as well as the pathology of blood disorders such as leukemia.