Golgi Protein 73 Promotes Angiogenesis in Hepatocellular Carcinoma.

Golgi protein 73 (GP73), a resident protein of the Golgi apparatus, is notably elevated in hepatocellular carcinoma (HCC). While its critical role in remodeling the tumor microenvironment (TME) is recognized, the intricate mechanisms are not fully understood. This study reveals that GP73 in HCC cells interacts with prolyl hydroxylase-2 (PHD-2) in a competitive manner, thereby impeding the hydroxylation of hypoxia-induced factor-1α (HIF-1α). The effect above promotes the production and secretion of vascular endothelial growth factor A (VEGFA). Moreover, exosomal GP73 derived from HCC cells can be internalized by human umbilical vein endothelial cells (HUVECs) and competitively interact with HECTD1, an E3 ubiquitin ligase targeting growth factor receptor-bound protein 2 (GRB2). This interaction stabilizes GRB2, thereby activating the Ras-mitogen-activated protein kinase (MAPK) signaling pathway. Consequently, escalated levels of GP73 intensify VEGF production in HCC cells and potentiate mitogenic signaling in vascular endothelial cells, fostering angiogenesis in the TME. Our findings propose that GP73 might serve as a novel target for anti-angiogenic therapy in HCC.

Human Menstrual Blood-Derived Stem Cells Protect against Tacrolimus-Induced Islet Dysfunction via Cystathionine ß-Synthase Mediated IL-6/STAT3 Inactivation.

Diabetes imposes a huge burden worldwide. Islet transplantation is an alternative therapy for diabetes. However, tacrolimus, a kind of immunosuppressant after organ transplantation, is closely related to post-transplant diabetes mellitus. Mesenchymal stem cells (MSCs) have attracted interest for their potential to alleviate diabetes. In vivo experiments revealed that human menstrual blood-derived stem cells (MenSCs) treatment improved tacrolimus-induced blood glucose, body weight, and glucose tolerance disorders in mice. RNA sequencing was used to analyze the potential therapeutic targets of MenSCs. In this study, we illustrated that cystathionine ß-synthase (CBS) contributed to tacrolimus -induced islet dysfunction. Using ß-cell lines (MIN6, ß-TC-6), we demonstrated that MenSCs ameliorated tacrolimus-induced islet dysfunction in vitro. Moreover, MenSC reduced the tacrolimus-induced elevation of CBS levels and significantly enhanced the viability, anti-apoptotic ability, glucose-stimulated insulin secretion (GSIS), and glycolytic flux of ß-cells. We further revealed that MenSCs exerted their therapeutic effects by inhibiting CBS expression to activate the IL6/JAK2/STAT3 pathway. In conclusion, we showed that MenSCs may be a potential strategy to improve tacrolimus-induced islet dysfunction.

A new understanding on the prerequisite of antibiotic biodegradation in wastewater treatment: Adhesive behavior between antibiotic-degrading bacteria and ciprofloxacin.

The extensive exploration of antibiotic biodegradation by antibiotic-degrading bacteria in biological wastewater treatment processes has left a notable gap in understanding the behavior of these bacteria when exposed to antibiotics and the initiation of biodegradation processes. This study, therefore, delves into the adhesive behavior of Paraclostridium bifermentans, isolated from a bioreactor treating ciprofloxacin-laden wastewater, towards ciprofloxacin molecules. For the first time, this behavior is observed and characterized through quartz crystal microbalance with dissipation (QCM-D) and atomic force microscopy. The investigation further extends to identify key regulatory factors and mechanisms governing this adhesive behavior through a comparative proteomics analysis. The results reveal the dominance of extracellular proteins, particularly those involved in nucleotide binding, hydrolase, and transferase, in the adhesion process. These proteins play pivotal roles through direct chemical binding and the regulation of signaling molecule. Furthermore, QCM-D measurements provide evidence that transferase-related signaling molecules, especially tyrosine, augment the binding between ciprofloxacin and transferases, resulting in enhance ciprofloxacin removal by P. bifermentans (increased by ∼1.2-fold). This suggests a role for transferase-related signaling molecules in manipulating the adhesive behavior of P. bifermentans towards ciprofloxacin. These findings contribute to a new understanding of the prerequisites for antibiotic biodegradation and offer potential strategies for improving the application of antibiotic-degrading bacteria in the treatment of antibiotics-laden wastewater.

Enhancing anaerobic digestion performance of oxytetracycline-laden wastewater through micro-nano bubble ozonation pretreatment.

This study investigated the potential of micro-nano bubble (MNB) ozonation pretreatment to eliminate oxytetracycline (OTC) from wastewater and improve subsequent anaerobic digestion (AD) performance. The findings revealed that MNB ozonation achieved efficient OTC oxidation (>99 % in 60 min), and significantly enhanced methane production by 51 % compared to conventional ozonation (under 30 min of pretreatment). Additionally, MNB ozonation resulted in a decrease in the soluble chemical oxygen demand and reduced volatile fatty acid accumulation compared to conventional ozonation. Furthermore, the study sheds light on the profound impact of OTC and its oxidation by-products on the sludge microbiome. Exposure to OTC and its oxidation by-products resulted in alterations in extracellular polymeric substances composition and led to significant shifts in microbial community structure. This study highlights the promise of MNB ozonation as an effective approach for pharmaceutical pollutant removal and the optimization of AD performance in wastewater treatment, with implications for improved environmental sustainability.

Interferon-γ priming enhances the therapeutic effects of menstrual blood-derived stromal cells in a mouse liver ischemia-reperfusion model.

BACKGROUND: Mesenchymal stem cells (MSCs) have been used in liver transplantation and have certain effects in alleviating liver ischemia-reperfusion injury (IRI) and regulating immune rejection. However, some studies have indicated that the effects of MSCs are not very significant. Therefore, approaches that enable MSCs to exert significant and stable therapeutic effects are worth further study. AIM: To enhance the therapeutic potential of human menstrual blood-derived stromal cells (MenSCs) in the mouse liver ischemia-reperfusion (I/R) model via interferon-γ (IFN-γ) priming. METHODS: Apoptosis was analyzed by flow cytometry to evaluate the safety of IFN-γ priming, and indoleamine 2,3-dioxygenase (IDO) levels were measured by quantitative real-time reverse transcription polymerase chain reaction, western blotting, and ELISA to evaluate the efficacy of IFN-γ priming. In vivo, the liver I/R model was established in male C57/BL mice, hematoxylin and eosin and TUNEL staining was performed and serum liver enzyme levels were measured to assess the degree of liver injury, and regulatory T cell (Treg) numbers in spleens were determined by flow cytometry to assess immune tolerance potential. Metabolomics analysis was conducted to elucidate the potential mechanism underlying the regulatory effects of primed MenSCs. In vitro, we established a hypoxia/reoxygenation (H/R) model and analyzed apoptosis by flow cytometry to investigate the mechanism through which primed MenSCs inhibit apoptosis. Transmission electron microscopy, western blotting, and immunofluorescence were used to analyze autophagy levels. RESULTS: IFN-γ-primed MenSCs secreted higher levels of IDO, attenuated liver injury, and increased Treg numbers in the mouse spleens to greater degrees than untreated MenSCs. Metabolomics and autophagy analyses proved that primed MenSCs more strongly induced autophagy in the mouse livers. In the H/R model, autophagy inhibitors increased the level of H/R-induced apoptosis, indicating that autophagy exerted protective effects. In addition, primed MenSCs decreased the level of H/R-induced apoptosis via IDO and autophagy. Further rescue experiments proved that IDO enhanced the protective autophagy by inhibiting the mammalian target of rapamycin (mTOR) pathway and activating the AMPK pathway. CONCLUSION: IFN-γ-primed MenSCs exerted better therapeutic effects in the liver I/R model by secreting higher IDO levels. MenSCs and IDO activated the AMPK-mTOR-autophagy axis to reduce IRI, and IDO increased Treg numbers in the spleen and enhanced the MenSC-mediated induction of immune tolerance. Our study suggests that IFN-γ-primed MenSCs may be a novel and superior MSC product for liver transplantation in the future.

Golgi-protein 73 facilitates vimentin polymerization in hepatocellular carcinoma.

Golgi-protein 73 (GP73) is highly expressed in hepatocellular carcinoma (HCC) and, as a secretory protein, it has been proposed as a serum biomarker indicating progression of HCC. The underlying mechanism by which GP73 may promote HCC metastasis is still poorly understood. In this study, we discovered that GP73 interacted with vimentin to facilitate Serine/Threonine-protein phosphatase PP1-alpha (PP1A)-mediated dephosphorylation of vimentin at S56 and facilitated vimentin polymerization, which blocked vimentin degradation via TRIM56-mediated ubiquitin/proteasome-dependent pathway. Strikingly, Clomipramine, a 5-hydroxytryptamine receptor (5-HTR) agonist approved for the treatment of depression, impaired GP73-mediated vimentin polymerization to effectively inhibit metastasis of HCC with high GP73 expression, which provided a new strategy against HCC metastasis. Lastly, it was found that serum GP73 (sGP73) correlated positively with vimentin in primary tissues of HCC, suggesting that sGP73 might serve as a potential serum biomarker for companion diagnosis of HCC with highly expressed vimentin. In summary, this study reveals the process of GP73-mediated vimentin polymerization and proves that Clomipramine serves as a potential drug targeting vimentin for metastatic HCC patients with high sGP73 level.

Strong succession in prokaryotic association networks and community assembly mechanisms in an acid mine drainage-impacted riverine ecosystem.

Acid mine drainage (AMD) serves as an ideal model system for investigating microbial ecology, interaction, and assembly mechanism in natural environments. While previous studies have explored the structure and function of microbial communities in AMD, the succession patterns of microbial association networks and underlying assembly mechanisms during natural attenuation processes remain elusive. Here, we investigated prokaryotic microbial diversity and community assembly along an AMD-impacted river, from the extremely acidic, heavily polluted headwaters to the nearly neutral downstream sites. Microbial diversity was increased along the river, and microbial community composition shifted from acidophile-dominated to freshwater taxa-dominated communities. The complexity and relative modularity of the microbial networks were also increased, indicating greater network stability during succession. Deterministic processes, including abiotic selection of pH and high contents of sulfur and iron, governed community assembly in the headwaters. Although the stochasticity ratio was increased downstream, manganese content, microbial negative cohesion, and relative modularity played important roles in shaping microbial community structure. Overall, this study provides valuable insights into the ecological processes that govern microbial community succession in AMD-impacted riverine ecosystems. These findings have important implications for in-situ remediation of AMD contamination.

Human menstrual blood-derived stem cells reverse sorafenib resistance in hepatocellular carcinoma cells through the hyperactivation of mitophagy.

BACKGROUND: Sorafenib is a first-line drug targeting the RTK-MAPK signalling pathway used to treat advanced hepatocellular carcinoma (HCC). However, tumour cells readily develop sorafenib resistance, limiting long-term therapy with this drug. In our previous study, we found that human menstrual blood-derived stem cells (MenSCs) altered the expression of some sorafenib resistance-associated genes in HCC cells. Therefore, we wanted to further explore the feasibility of MenSC-based combination therapy in treating sorafenib-resistant HCC (HCC-SR) cells. METHODS: The therapeutic efficiency of sorafenib was determined using CCK-8 (Cell Counting Kit-8), Annexin V/PI and clone formation assays in vitro and a xenograft mouse model in vivo. DNA methylation was determined using RT‒PCR and methylated DNA immunoprecipitation (MeDIP). Autophagy was detected by measuring LC3-II degradation and autophagosome maturation. Transmission electron microscopy identified autophagosomes and mitochondria. Physiological functions of mitochondria were assessed by measuring the ATP content, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP). RESULTS: The tumour suppressor genes BCL2 interacting protein 3 (BNIP3) and BCL2 interacting protein 3 like (BNIP3L) were silenced by promoter methylation and that BNIP3 and BNIP3L levels correlated negatively with sorafenib resistance in HCC-SR cells. Strikingly, MenSCs reversed sorafenib resistance. MenSCs upregulated BNIP3 and BNIP3L expression in HCC-SR cells via tet methylcytosine dioxygenase 2 (TET2)-mediated active demethylation. In HCC-SR cells receiving sorafenib and MenSC combination therapy, pressure from sorafenib and elevated BNIP3 and BNIP3L levels disrupted balanced autophagy. Hyperactivation of mitophagy significantly caused severe mitochondrial dysfunction and eventually led to the autophagic death of HCC-SR cells. CONCLUSIONS: Our research suggests that combining sorafenib and MenSCs may be a potentially new strategy to reverse sorafenib resistance in HCC-SR cells.

TNF-α Enhances the Therapeutic Effects of MenSC-Derived Small Extracellular Vesicles on Inflammatory Bowel Disease through Macrophage Polarization by miR-24-3p.

Human menstrual blood-derived mesenchymal stem cells (MenSCs) and their secreted small extracellular vesicles (EVs) had been proven to relieve inflammation, tissue damage, and fibrosis in various organs. The microenvironment induced by inflammatory cytokines can promote mesenchymal stem cells (MSCs) to secrete more substances (including EVs) that could regulate inflammation. Inflammatory bowel disease (IBD) is a chronic idiopathic intestinal inflammation, the etiology and mechanism of which are unclear. At present, the existing therapeutic methods are ineffective for many patients and have obvious side effects. Hence, we explored the role of tumor necrosis factor α- (TNF-α-) pretreated MenSC-derived small EV (MenSCs-sEVTNF-α ) in a mouse model of dextran sulfate sodium- (DSS-) induced colitis, expecting to find better therapeutic alterations. In this research, the small EVs of MenSCs were obtained by ultracentrifugation. MicroRNAs of small EVs derived from MenSCs before and after TNF-α treatment were sequenced, and the differential microRNAs were analyzed by bioinformatics. The small EVs secreted by TNF-α-stimulating MenSCs were more effective in colonic mice than those secreted directly by MenSCs, as evidenced by the results of histopathology analysis of colonic tissue, immunohistochemistry for tight junction proteins, and enzyme-linked immunosorbent assay (ELISA) for cytokine expression profiles in vivo. The process of MenSCs-sEVTNF-α relieving colonic inflammation was accompanied by the polarization of M2 macrophages in the colon and miR-24-3p upregulation in small EVs. In vitro, both MenSC-derived sEV (MenSCs-sEV) and MenSCs-sEVTNF-α reduced the expression of proinflammatory cytokines, and MenSCs-sEVTNF-α can increase the portion of M2 macrophages. In conclusion, after TNF-α stimulation, the expression of miR-24-3p in small EVs derived from MenSCs was upregulated. MiR-24-3p was proved to target and downregulate interferon regulatory factor 1 (IRF1) expression in the murine colon and then promoted the polarization of M2 macrophages. The polarization of M2 macrophages in colonic tissues then reduced the damage caused by hyperinflammation.

Ozone Micronano-bubble-Enhanced Selective Degradation of Oxytetracycline from Production Wastewater: The Overlooked Singlet Oxygen Oxidation.

The efficient and selective removal of refractory antibiotics from high-strength antibiotic production wastewater is crucial but remains a substantial challenge. In this study, a novel ozone micronano-bubble (MNB)-enhanced treatment system was constructed for antibiotic production wastewater treatment. Compared with conventional ozone, ozone MNBs exhibit excellent treatment efficiency for oxytetracycline (OTC) degradation and toxicity decrease. Notably, this study identifies the overlooked singlet oxygen (1O2) for the first time as a crucial active species in the ozone MNB system through probe and electron paramagnetic resonance methods. Subsequently, the oxidation mechanisms of OTC by ozone MNBs are systematically investigated. Owing to the high reactivity of OTC toward 1O2, ozone MNBs enhance the selective and anti-interference performance of OTC degradation in raw OTC production wastewater with complex matrixes. This study provides insights into the mechanism of ozone MNB-enhanced pollutant degradation and a new perspective for the efficient treatment of high-concentration industrial wastewater using ozone MNBs. In addition, this study presents a promising technology with scientific guidance for the treatment of antibiotic production wastewater.

Enhanced performance and electron transfer of sulfur-mediated biological process under polyethylene terephthalate microplastics exposure.

Microplastics are ubiquitous in estuaries, coasts, sewage and wastewater treatment plants (WWTPs), which could arouse unexpected effects on critical microbial processes in wastewater treatment. In this study, polyethylene terephthalate microplastics (PET-MPs) were selected to investigate the mechanism of its influence on the performance of sulfur-mediated biological process from the perspective of microbial metabolic activity, electron transfer capacity and microbial community. The results indicated that the exposure of 50 particles/L PET-MPs improved the chemical oxygen demand (COD) and sulfate removal efficiencies by 6.6 ± 0.5% and 4.5 ± 0.3%, respectively, due to the stimulation of microbial metabolic activity and the enrichment of sulfate-reducing bacteria (SRB) species, such as Desulfobacter. In addition, we found that the PET-MPs promoted Cytochrome C (Cyt C) production and improved the direct electron transfer (DET) capacity mediated by Cyt C. The long-term presence of PET-MPs stimulated the secretion of extracellular polymeric substance (EPS), especially the proteins and humic substances, which have been verified to be electroactive polymers to act as electron shuttles to promote the interspecies electron transfer pathway in sulfur-mediated biological process. Meanwhile, the transformation products (bis-(2-hydroxyethyl) terephthalate (BHET) and Mono (2-hydroxyethyl) terephthalic acid (MHET) of PET-MPs were detected in sulfur-mediated biological process. These findings indicate that the sulfur-mediated biological process has good adaptability to the toxicity of PET-MPs, which strengthens a deeper understanding of the dual function of microplastics in WWTPs.

Microbubble- and nanobubble-aeration for upgrading conventional activated sludge process: A review.

The activated sludge process (ASP) is widely used for wastewater treatment, and the aeration efficiency is crucial to the operation of wastewater treatment plants. Recently, microbubble (MB)- and nanobubble (NB)-aeration has attracted much attention as there is growing evidence that it holds a great promise for upgrading the process efficiency of current ASP under conventional macro-bubble-aeration. However, a comprehensive review to elucidate the potential application of MB- and NB-aeration in ASP is still lacking. Therefore, this review will provide a systematic introduction to MB- and NB-aeration (including the unique properties and generation methods of MBs and NBs), and gain mechanistic insights on how MB- and NB-aeration improve gas-liquid mass transfer. The recent advances in MB- and NB-aeration applications to ASP and the resultant effects are also highlighted and discussed in-depth. The review concludes with a brief consideration of future research interests.

Insights into the microbial response mechanisms to ciprofloxacin during sulfur-mediated biological wastewater treatment using a metagenomics approach.

The fate and removal of ciprofloxacin, a class of fluoroquinolone antibiotic, during sulfur-mediated biological wastewater treatment has been recently well documented. However, little is known regarding the genetic response of microorganisms to ciprofloxacin. Here, a lab-scale anaerobic sulfate-reducing bioreactor was continuously operated over a long term for ciprofloxacin-contaminated wastewater treatment to investigate the response of the microorganisms to ciprofloxacin by adopting a metagenomics approach. It was found that total organic carbon (TOC) removal and sulfate reduction were promoted by approximately 10% under ciprofloxacin stress, along with the enrichment of functional genera (e.g., Desulfobacter, Geobacter) involved in carbon and sulfur metabolism. The metagenomic analytical results demonstrated that ciprofloxacin triggered the microbial SOS response, as demonstrated by the up-regulation of the multidrug efflux pump genes (8-125-fold higher than that of the control) and ciprofloxacin-degrading genes (4-33-fold higher than that of the control). Moreover, the contents of ATP, NADH, and cytochrome C, as well as related functional genes (including genes involved in energy generation, electron transport, carbon metabolism, and sulfur metabolism) were markedly increased under ciprofloxacin stress. This demonstrated that the carbon and sulfur metabolisms were enhanced for energy (ATP) generation and electron transport in response to ciprofloxacin-induced stress. Interestingly, the microbes tended to cooperate while being subjected exposure to exogenous ciprofloxacin according to the reconstructed metabolic network using the NetSeed model. Particularly, the species with higher complementarity indices played more pivotal roles in strengthening microbial metabolism and the SOS response under long-term ciprofloxacin stress. This study characterized the response mechanisms of microorganisms to ciprofloxacin at the genetic level in sulfur-mediated biological wastewater treatment. These new understandings will contribute the scientific basis for improving and optimizing the sulfur-mediated bioprocess for antibiotics-laden wastewater treatment.

Partial nitrification in free nitrous acid-treated sediment planting Myriophyllum aquaticum constructed wetland strengthens the treatment of black-odor water.

Black-odor water pollution in rural areas, especially swine wastewater, can lead to the deterioration of water quality and thus seriously affect the daily life of people in the area. However, there is a lack of effective treatment measures with simultaneous attention to carbon, nitrogen and sulfur pollution in rural black-odor water bodies. This study evaluated the feasibility of an in-situ pilot-scale constructed wetland (CW) for the synchronous removal of COD, ammonium, and sulfur compounds in the swine wastewater. In this study, the operation strategy of CW sediment pretreated with free nitrous acid (FNA) and Myriophyllum aquaticum plantation was established. Throughout the 114-day operation, the total removal efficiencies of COD and ammonium nitrogen in experimental groups were 81.2 ± 4.2 % and 72.8 ± 1.8 %, respectively, which were significantly higher than CW without any treatment. Removal efficiencies of Sulfur compounds, i.e. sulfide, sulfate, thiosulfate, and sulfite, were 92.3 ± 1.9 % (61.2 % higher than the no-treatment group), 42.1 ± 3.8 %, 97.9 ± 1.7 %, and 42.7 ± 4.5 % respectively. High-throughput sequencing and qPCR revealed that experimental group significantly increased denitrification genes (nirK, nosZ) and sulfur oxidation genes (soxB, fccAB) and enriched the corresponding microbial taxa (Bacillus, Conexibacter and Clostridium sensu stricto). Moreover, metabolic pathways related to nitrogen and sulfur and the degradation of organic matter were up-regulated. These results indicated that partial nitrification in CW planted with M. aquaticum promoted sulfur oxidation denitrification and heterotrophic denitrification. Overall, the in-situ pilot-scale study revealed that the cultivation of M. aquaticum in FNA-treated CW can be a sustainable approach to treat black-odor water bodies.

Stress responses of sulfate-reducing bacteria sludge upon exposure to polyethylene microplastics.

The stress responses of sulfate-reducing bacteria (SRB) sludge to polyethylene (PE) microplastic exposure were revealed for the first time. In this study, a lab-scale sulfate-reducing up-flow sludge bed reactor was continuously operated with different concentrations of PE microplastics in the feed (20, 100, and 500 microplastic particles (MPs)/L). Exposure to low levels of PE microplastics (i.e., 20 MPs/L) had a limited effect on SRB consortia, whereas higher levels of PE microplastics imposed apparent physiological stresses on SRB consortia. Despite this, the overall reactor performance, i.e., chemical oxygen demand removal and sulfate conversion, was less affected by prolonged exposure to PE microplastics. Moreover, as the concentration of PE microplastics increased, the SRB consortia promoted the production of extracellular polymeric substances to a greater extent, especially the secretion of proteins. As a result, protective effects against the cytotoxicity of PE microplastics were provided. Batch experiments further demonstrated that leaching additives from PE microplastics (including acetyl tri-n­butyl citrate and bisphenol A, concentrations up to 5 µg/g sludge) exerted only a minor effect on the activity of SRB consortia. Additionally, microbial community analysis revealed active and potentially efficient sulfate reducers at different operational stages. Our results provide insight into the stress responses of SRB sludge under PE microplastic exposure and suggested that SRB consortia can gradually adapt to and resist high levels of PE microplastics. These findings may promote a better understanding of the stable operation of SRB sludge systems under specific environmental stimuli for practical applications.

Micro and nano bubbles promoted biofilm formation with strengthen of COD and TN removal synchronously in a blackened and odorous water.

Blackening and odorization of rivers (BOR) distributed widely in urban cities with high density of human beings. Amounts of pollution control methods have been developed for treatment of these contaminated rivers. Among them, artificial aeration is an effective method for BOR treatment. As a novel developed aeration approach, Micro and nano bubbles (MNBs) takes advances of high specific surface area, high oxygen transfer, long retain time and interface effect. Thus, MNBs aeration was used in an anoxic-oxic (AO) process with traditional activated sludge methods to treat water of BOR in this study. A special designed reactor was made to allow both MNBs and macro bubbles aeration of which mode could be altered easily. The results revealed that MNBs improved removal of COD, NH4+-N and TN distinctly in water of BOR. MNBs provided high dissolved oxygen and promoted the transformation from floc sludge to biofilm. Significant difference between the microbial community of MNBs and macro bubbles sludges was revealed by 16S rRNA amplicon sequencing. Function predictions of MNBs and macro bubbles sludges indicated MNBs enhanced nitrification and aerobic ammonia oxidation without negative impact on denitrification. Moreover, biofilm formed bacteria were enriched by MNBs aeration. This study demonstrated MNBs would be a great potential for the combination of activated sludge and biofilm to treat BOR.

Golgi Phosphoprotein 73: The Driver of Epithelial-Mesenchymal Transition in Cancer.

Golgi phosphoprotein 73 (GP73, also termed as GOLM1 or GOLPH2) is a glycosylated protein residing on cis-Golgi cisternae and highly expressed in various types of cancer tissues. Since GP73 is a secretory protein and detectable in serum derived from cancer patients, it has been regarded as a novel serum biomarker for the diagnosis of different cancers, especially hepatocellular carcinoma (HCC). However, the functional roles of GP73 in cancer development are still poorly understood. In recent years, it has been discovered that GP73 acts as a multifunctional protein-facilitating cancer progression, and strikingly, it has been identified as a leading factor promoting epithelial-mesenchymal transition (EMT) of cancer cells and causing cancer metastasis. In this review, we have overviewed the latest findings of the functional roles of GP73 in elevating cancer progression, especially in facilitating EMT and cancer metastasis through modulating expression, transactivation, and trafficking of EMT-related proteins. In addition, unsolved research fields of GP73 have been lightened, which might be helpful to elucidate the regulatory mechanisms of GP73 on EMT and provide potential approaches in therapeutics against cancer metastasis.

Enhancing nitrogen removal from anaerobically-digested swine wastewater through integration of Myriophyllum aquaticum and free nitrous acid-based technology in a constructed wetland.

Despite of low operation costs and convenient maintenance, the application of natural systems for swine wastewater treatment has been limited by large construction area and unsatisfactory effluent quality. Introducing ammonium high uptake aquatic plants and shifting nitrogen removal pathway from nitrate to nitrite in constructed wetlands (CWs) has been regarded as promising approach to promote their performances. This study aimed to establish nitrite pathway and enhance N removal via free nitrous acid (FNA)-sediment treatment and Myriophyllum aquaticum vegetation in the CWs treating anaerobically digested swine wastewater. Nitrite pathway was successfully and stably achieved in the M. aquaticum CW with FNA-treated sediment. The overall removal efficiencies of ammonium nitrogen and total nitrogen were 42.3 ± 10.2% and 37.7 ± 9.3% in the planted CWs with FNA-treated sediment, which were 76.3% and 65.4% higher than those in the conventional oxidation pond system, respectively. Microbial community analysis (qPCR and metagenomics) suggested that the nitrite pathway established through FNA-sediment treatment was based on the inactivation of nitrite oxidizing bacteria (lower nxrA gene abundance) and the reduction of relative abundances of NOB (especially Nitrobacter and Nitrospira). During the denitrification processes, the integration of M. aquaticum vegetation with FNA-sediment treatment can lower the nitrate reduction by decreasing narG gene abundances and decreasing the relative abundances of napA affiliated bacteria (especially Bradyrhizobium), while strengthening reduction of nitrite and nitrous oxide by increasing nirK and nosZ gene abundances and enriching the corresponding affiliated microbial taxa, Mycobacterium and Bacillus, respectively. Our findings suggest that applying FNA-based technology in CW systems is technically and economically feasible, which holds promise for upgrading current CW systems treating swine wastewater to meet future water quality requirements.

Multifunctional role of microRNAs in mesenchymal stem cell-derived exosomes in treatment of diseases.

Mesenchymal stem cells can be replaced by exosomes for the treatment of inflammatory diseases, injury repair, degenerative diseases, and tumors. Exosomes are small vesicles rich in a variety of nucleic acids [including messenger RNA, Long non-coding RNA, microRNA (miRNA), and circular RNA], proteins, and lipids. Exosomes can be secreted by most cells in the human body and are known to play a key role in the communication of information and material transport between cells. Like exosomes, miRNAs were neglected before their role in various activities of organisms was discovered. Several studies have confirmed that miRNAs play a vital role within exosomes. This review focuses on the specific role of miRNAs in MSC-derived exosomes (MSC-exosomes) and the methods commonly used by researchers to study miRNAs in exosomes. Taken together, miRNAs from MSC-exosomes display immense potential and practical value, both in basic medicine and future clinical applications, in treating several diseases.

Human menstrual blood-derived stem cells mitigate bleomycin-induced pulmonary fibrosis through anti-apoptosis and anti-inflammatory effects.

BACKGROUND: Idiopathic pulmonary fibrosis is a kind of diffuse interstitial lung disease, the pathogenesis of which is unclear, and there is currently a lack of good treatment to improve the survival rate. Human menstrual blood-derived mesenchymal stem cells (MenSCs) have shown great potential in regenerative medicine. This study aimed to explore the therapeutic potential of MenSCs for bleomycin-induced pulmonary fibrosis. METHODS: We investigated the transplantation of MenSCs in a pulmonary fibrosis mouse model induced by BLM. Mouse was divided into three groups: control group, BLM group, MenSC group. Twenty-one days after MenSC transplantation, we examined collagen content, pathological, fibrosis area in the lung tissue, and the level of inflammatory factors of serum. RNA sequence was used to examine the differential expressed gene between three groups. Transwell coculture experiments were further used to examine the function of MenSCs to MLE-12 cells and mouse lung fibroblasts (MLFs) in vitro. RESULTS: We observed that transplantation of MenSCs significantly improves pulmonary fibrosis mouse through evaluations of pathological lesions, collagen deposition, and inflammation. Transwell coculturing experiments showed that MenSCs suppress the proliferation and the differentiation of MLFs and inhibit the apoptosis of MLE-12 cells. Furthermore, antibody array results demonstrated that MenSCs inhibit the apoptosis of MLE-12 cells by suppressing the expression of inflammatory-related cytokines, including RANTES, Eotaxin, GM-CSF, MIP-1γ, MCP-5, CCL1, and GITR. CONCLUSIONS: Collectively, our results suggested MenSCs have a great potential in the treatment of pulmonary fibrosis, and cytokines revealed in antibody array are expected to become the target of future therapy of MenSCs in clinical treatment of pulmonary fibrosis.