Transplantation of microencapsulated neural stem cells inhibits neuropathic pain mediated by P2X7 receptor overexpression.

BACKGROUND: Neuropathic pain (NPP) is a common clinical symptom, its pathological mechanism is complex, and there is currently no good treatment method. Therefore, exploring the treatment method of NPP is a critical issue that needs to be urgently solved. METHODS: Neural stem cells (NSC) and microencapsulated neural stem cells (MC-NSC) were transplanted into the site of sciatic nerve injury, and behavioral methods were used to detect changes in pain. Expression levels of P2X7R were detected in the dorsal root ganglion (DRG) by molecular biological methods. RESULTS: After sciatic nerve injury, mechanical withdrawal thresholds (MWT) and thermal withdrawal latency (TWL) of rats were significantly reduced, the expression levels of P2X7R in the DRG were significantly increased. After transplantation of NSC and MC-NSC, it was found that expression levels of P2X7R were significantly reduced and pain was significantly suppressed. Importantly, compared with NSC transplantation, MC-NSC could better reduce the expression levels of P2X7R and inhibit pain. CONCLUSION: MC-NSC can better decrease the expression levels of P2X7R and relieve NPP. Our results provide a novel method and data support for the treatment of NPP.

MicroRNA-133b/EGFR axis regulates esophageal squamous cell carcinoma metastases by suppressing anoikis resistance and anchorage-independent growth.

BACKGROUND: Anoikis resistance has been demonstrated to facilitate distant metastases of cancers. MicroRNA-133b (miR-133b) is found to be down-regulated in various tumors, including esophageal squamous cell carcinoma (ESCC), and closely correlates with the malignant phenotype of ESCC. This study aimed to evaluate the roles of miR-133b in metastases of ESCC via regulating anoikis. METHODS: The expression of miR-133b and related molecules were detected in ESCC tissues and cells. The target relationship between miR-133b and epidermal growth factor receptor (EGFR) was verified by dual luciferase reporter assay. Cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Anoikis and anchorage-independent growth were assessed by anoikis assay and soft agar assay. Migration and invasion were evaluated by scratch and transwell assays. The expressions of related molecules were detected by reverse transcription-quantitative polymerase chain reaction and western blotting. The in vivo results were determined by tumor xenografts in nude mice. RESULTS: MiR-133b level was decreased in ESCC tissues and cells, which negatively correlated with EGFR, integrin ß4 (ITGB4), and phosphorylated focal adhesion kinase levels. Moreover, miR-133b down-regulated EGFR expression in ESCC cells. Overexpression of miR-133b inhibited the anoikis resistance, migration, invasion and epithelial-mesenchymal transition of ESCC cells via targeting EGFR. Finally, miR-133b overexpression suppressed tumor growth and lung metastases of ESCC in vivo. ITGB4/FAK/growth factor receptor-bound protein 2 (Grb2), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK) pathways were involved in the regulatory mechanisms of miR-133b/EGFR axis in ESCC metastases in vitro and in vivo. CONCLUSIONS: The results suggested that miR-133b/EGFR axis regulated metastases of ESCC by affecting anoikis resistance via ITGB4/FAK/Grb2, AKT, and ERK pathways.

A five-variable signature predicts radioresistance and prognosis in nasopharyngeal carcinoma patients receiving radical radiotherapy.

Radioresistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment. Clinical tumor-node-metastasis (TNM) staging has limited accuracy in predicting NPC radioresponse and determining its therapeutic regimens. To construct a risk score model for predicting NPC radioresistance, immunohistochemistry was used to assess the expression of four proteins (14-3-3σ, Maspin, RKIP, and GRP78) in 149 NPC samples with different radiosensitivity. Sequentially, a logistic regression analysis was performed to identify independent predictors of NPC radioresistance and establish a risk score model. As a result, a risk score model, Z = -3.189 - 1.478 (14-3-3σ) - 1.082 (Maspin) - 1.666 (RKIP) + 2.499 (GRP78) + 2.597 (TNM stage), was constructed, and a patient's risk score was estimated by the formula: e (Z)/(e (Z) + 1) × 100, where "e" is the base of natural logarithm. High-risk score was closely associated with NPC radioresistance, and was observed more frequently in the radioresistant patients than that in the radiosensitive patients. The sensitivity, specificity, and accuracy of the risk score model for predicting NPC radioresistance was 88.00, 86.48, and 87.25 %, respectively, which was clearly superior to each individual protein and TNM stage. Furthermore, Kaplan-Meier survival analysis showed that high-risk score correlated with the markedly reduced overall survival (OS) and disease-free survival (DFS) of the patients, and Cox regression analysis showed that the risk score model was an independent predictor for OS and DFS. This study constructs a risk score model for predicting NPC radioresistance and patient survival, and it may serve as a complement to current radioresistance risk stratification approaches.

Ibrutinib facilitates the sensitivity of colorectal cancer cells to ferroptosis through BTK/NRF2 pathway.

Ibrutinib is a drug that inhibits the protein Burton's tyrosine kinase and thereby the nuclear translocation of Nrf2, which played a key role in mediating the activation of antioxidants during stress conditions and ferroptosis resistance. This study aimed to identify the effect of Ibrutinib and ferroptosis inducer on colorectal cancer (CRC) treatment and its underlying mechanism. In our study, we found the upregulation of Nrf2 was correlated with CRC progression and antioxidant proteins. Ibrutinib sensitized CRC to ferroptosis inducers, suggested by further reduced CRC cell viability, proliferation and decreased antioxidant protein levels in CRC cells after combination treatment of Ibrutinib and RSL3 or Ibrutinib and Erastin both in vivo and in vitro. Knockout of Nrf2 diminished the regulatory effect of Ibrutinib on CRC sensitivity to ferroptosis inducers. Altogether, this study demonstrated that Ibrutinib increases the sensitivity of CRC cell to ferroptosis inducers by inhibiting Nrf2.

Prognostic significance of the preoperative hemoglobin to albumin ratio for the short-term survival of gastric cancer patients.

BACKGROUND: Hemoglobin and albumin are associated with the prognosis of gastric cancer (GC) patients. However, the prognostic value of the hemoglobin to albumin ratio (HAR) for the short-term survival of GC patients with D2 radical resection has not been studied. AIM: To investigate the significance of the HAR in evaluating the short-term survival of GC patients after D2 radical resection and to construct a nomogram to predict the prognosis in GC patients after surgery, thus providing a reference for the development of postoperative individualized treatment and follow-up plans. METHODS: Cox regression and Kaplan-Meier analysis was used for prognostic analysis. Logistic regression was used to analyze the relationships between HAR and the clinicopathological characteristics of the GC patients. A prognostic nomogram model for the short-term survival of GC patients was constructed by R software. RESULTS: HAR was an independent risk factor for the short-term survival of GC patients. GC patients with a low HAR had a poor prognosis (P < 0.001). Low HAR was markedly related to high stage [odds ratio (OR) = 0.45 for II vs I; OR = 0.48 for III vs I], T classification (OR = 0.52 for T4 vs T1) and large tumor size (OR = 0.51 for ≥ 4 cm vs < 4 cm) (all P < 0.05). The nomogram model was based on HAR, age, CA19-9, CA125 and stage, and the C-index was 0.820. CONCLUSION: Preoperative low HAR was associated with short-term survival in GC patients. The prognostic nomogram model can accurately predict the short-term survival of GC patients with D2 radical resection.

Nano-drug delivery system for pancreatic cancer: A visualization and bibliometric analysis.

Background: Nano drug delivery system (NDDS) can significantly improve the delivery and efficacy of drugs against pancreatic cancer (PC) in many ways. The purpose of this study is to explore the related research fields of NDDS for PC from the perspective of bibliometrics. Methods: Articles and reviews on NDDS for PC published between 2003 and 2022 were obtained from the Web of Science Core Collection. CiteSpace, VOSviewer, R-bibliometrix, and Microsoft Excel were comprehensively used for bibliometric and visual analysis. Results: A total of 1329 papers on NDDS for PC were included. The number of papers showed an upward trend over the past 20 years. The United States contributed the most papers, followed by China, and India. Also, the United States had the highest number of total citations and H-index. The institution with the most papers was Chinese Acad Sci, which was also the most important in international institutional cooperation. Professors Couvreur P and Kazuoka K made great achievements in this field. JOURNAL OF CONTROLLED RELEASE published the most papers and was cited the most. The topics related to the tumor microenvironment such as "tumor microenvironment", "tumor penetration", "hypoxia", "exosome", and "autophagy", PC treatment-related topics such as "immunotherapy", "combination therapy", "alternating magnetic field/magnetic hyperthermia", and "ultrasound", and gene therapy dominated by "siRNA" and "miRNA" were the research hotspots in the field of NDDS for PC. Conclusion: This study systematically uncovered a holistic picture of the performance of NDDS for PC-related literature over the past 20 years. We provided scholars to understand key information in this field with the perspective of bibliometrics, which we believe may greatly facilitate future research in this field.

Retraction Notice to: lncRNA GAS5 Inhibits Cell Migration and Invasion and Promotes Autophagy by Targeting miR-222-3p via the GAS5/PTEN-Signaling Pathway in CRC.

[This retracts the article DOI: 10.1016/j.omtn.2019.06.009.].

m6A-modified circFNDC3B inhibits colorectal cancer stemness and metastasis via RNF41-dependent ASB6 degradation.

Colorectal cancer (CRC) is the third most frequently diagnosed cancer with unfavorable clinical outcomes worldwide. circFNDC3B plays as a tumor suppressor in CRC, however, the mechanism of circFNDC3B in CRC remains ambiguous. The stem-like properties of CRC cells were detected by the evaluation of stemness markers, sphere formation assay and flow cytometry. qRT-PCR, FISH, IHC, and western blotting assessed the expression and localization of circFNDC3B, RNF41, ASB6, and stemness markers in CRC. The metastatic capabilities of CRC cells were examined by wound healing and Transwell assays, as well as in vivo liver metastasis model. Bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down assay and co-IP were used to detect the associations among circFNDC3B, FXR2, RNF41, and ASB6. Downregulated circFNDC3B was associated with unfavorite survival in CRC patients, and circFNDC3B overexpression suppressed CRC stemness and metastasis. Mechanistically, studies revealed that YTHDC1 facilitated cytoplasmic translocation of m6A-modified circFNDC3B, and circFNDC3B enhanced RNF41 mRNA stability and expression via binding to FXR2. circFNDC3B promoted ASB6 degradation through RNF41-mediated ubiquitination. Functional studies showed that silencing of RNF41 counteracted circFNDC3B-suppressed CRC stemness and metastasis, and ASB6 overexpression reversed circFNDC3B- or RNF41-mediated regulation of CRC stemness and metastasis. Elevated ASB6 was positively correlated with unfavorite survival in CRC patients. In vivo experiments further showed that circFNDC3B or RNF41 overexpression repressed tumor growth, stemness and liver metastasis via modulating ASB6. Taken together, m6A-modified circFNDC3B inhibited CRC stemness and metastasis via RNF41-dependent ASB6 degradation. These findings provide novel insights and important clues for targeted therapeutic strategies of CRC.

PI3K/Akt/GSK-3ß signal pathway is involved in P2X7 receptor-induced proliferation and EMT of colorectal cancer cells.

P2X7 receptor (P2X7R) plays an important role in regulating the growth of tumor cells. However, the role of P2X7R in colorectal cancer (CRC) has remained poorly understood. Therefore, in this study, in vivo and in vitro experiments were performed to investigate the effect of P2X7R on the proliferation of CRC. The results showed that P2X7R was expressed in CRC cell lines (SW620 and HCT116). ATP and BzATP increased the expression of P2X7R in CRC cells, while the application of P2X7R antagonist A438079 and AZD9056 decreased the P2X7R expression induced by BzATP. Moreover, ATP and BzATP induced the activation of P2X7R to promote the proliferation, migration and invasion of CRC cells. Conversely, A438079, AZD9056 or siRNA transfection targeting P2X7R (siP2X7R) knockdown P2X7R expression inhibited the proliferation and migration of CRC cells. TGF-ß1 promoted the migration and invasion of CRC cells, while the application of P2X7R antagonist could inhibit TGF-ß1 induced migration of CRC cells. Furthermore, activation of P2X7R increased the expression of Vimentin, Snail, Fibronectin and decreased the expression of E-cadherin. While reducing the expression of P2X7R could inhibit these genes expression. In addition, ATP and BzATP increased the expression of p-Akt, p-GSK-3beta and ß-catenin via P2X7R. P13/Akt pathway inhibitor LY294002 inhibited the proliferation of CRC cells, and the P13/Akt signaling was required for BzATP induced the proliferation of CRC cells. Our conclusion is that P2X7R mediated the PI3K/Akt/GSK-3beta signaling to promote the proliferation and EMT of CRC, indicating that P2X7R may be used as a potential therapeutic target for CRC.

CircFNDC3B sequestrates miR-937-5p to derepress TIMP3 and inhibit colorectal cancer progression.

Circular RNA (circRNA) are single-stranded RNA with covalently closed 3' and 5' ends, with many recognized to be involved in human diseases as gene regulators, typically by interacting with other RNA. CircFNDC3B is a circRNA formed by back-splicing of exons 5 and 6 of the FNDC3B gene. CircFNDC3B was recently implicated in renal carcinoma, gastric and bladder cancer. However, the expression levels of circFNDC3B and its role in colorectal cancer (CRC) remain unclear. Expression of circFNDC3B and TIMP3 levels in CRC tissues and cell lines were found to be low, whereas microRNA (miR)-937-5p expression was high in CRC. MicroRNA-937-5p downregulated TIMP3, thereby promoting tumor cell proliferation, invasion, migration and angiogenesis. Moreover, CircFNDC3B was shown to bind to miR-937-5p. CircFNDC3B and circFNDC3B-enriched exosomes inhibited tumorigenic, metastatic and angiogenic properties of CRC, and miR-937-5p overexpression or TIMP3 knockdown could reverse these effects. In vivo CRC tumor growth, angiogenesis and liver metastasis were suppressed by circFNDC3B overexpression, circFNDC3B-enriched exosomes or miR-937-5p knockdown. In conclusion, our work reports a tumor-suppressing role for the circFNDC3B-miR-97-5p-TIMP3 pathway and suggests that circFNDC3B-enriched exosomes can inhibit angiogenesis and CRC progression.

Does brain radiotherapy improve survival in patients with esophageal squamous cell carcinoma with brain metastasis?

BACKGROUND: To investigate the clinical characteristics, influencing factors, and their impact on survival in patients with brain metastases from esophageal squamous cell carcinoma (BM-ESCC). METHODS: A total of 67 patients with patients with newly diagnosed BM-ESCC were retrospectively analyzed from December 2000 to December 2016, in order to examine the correlation between clinicopathological characteristics and brain metastases, and between brain metastases and survival. RESULTS: The number of BM-ESCC was positively correlated with T and N stages (P<0.05). The higher the T and N stages, the higher the incidence. The median survival time was 9.65 months. N stage was an independent risk factor for BM-ESCC. N0 + N1 was associated with a lower risk of brain metastases (P<0.05). Patients with 1 brain metastasis had a significantly longer survival than those with 2 and 3 brain metastases. N stage-stratified analysis revealed that N0 + N1 patients had a longer survival than N2 and N3 patients (P<0.05). Cox regression analysis revealed that mortality in T3 + T4 patients was 2.337 times that of Tis + T1 patients; mortality in N3 patients was 3.486 times that of N0 + N1 patients; and mortality in untreated patients was 2.772 times that of those treated with whole brain radiotherapy. CONCLUSIONS: The number of BM-ESCC is correlated to T and N stages. The higher the N stage, the higher risk of brain metastases. The higher of T and N stages in ESCC, the worse in prognosis. Whole brain radiotherapy could offer greater survival benefits.

Transplantation of olfactory ensheathing cells combined with chitosan down-regulates the expression of P2X7 receptor in the spinal cord and inhibits neuropathic pain.

BACKGROUND: Neuropathic pain (NPP) is the common symptom of most clinical diseases, and its treatment has always been a difficult problem at present. Therefore, the purpose of this study is to explore a new method for the treatment of NPP by transplanting olfactory ensheathing cells combined with chitosan (OECs-CS). METHODS: Animal model of chronic compression sciatic nerve injury (CCI) was made, olfactory ensheathing cells (OECs) were cultured, chitosan (CS) biomaterials were prepared, and biocompatibility of OECs and CS were detected by MTT method, OECs and OECs-CS were transplanted into the site of the injured sciatic nerve respectively, behavioral method was used to measured the mechanical withdrawal thresholds (MWT) and thermal withdrawal latency (TWL) of rats. On days 7 and 14 after surgery, the expression level of P2X7 receptor (P2X7R) in the L4-5 spinal cord was measured by using in situ hybridization, western-blotting and qRT-PCR. To explore the therapeutic effect of OECs-CS transplantation on pain suppression. RESULTS: After chronic compression sciatic nerve injury, the MWT and TWL of rats were significantly reduced, and the expression levels of P2X7R protein and mRNA in the L4-5 spinal cord was significantly increased. After the transplantation of OECs and OECs-CS, the expression levels of P2X7R was significantly reduced, and the MWT and TWL of rats were significantly increased. Importantly, compared with the transplantation of OECs, OECs-CS transplantation could better reduce the expression levels of P2X7R, and relieve hyperalgesia in rats. Moreover, compared with the CCI + OECs-CS group on days 7 after surgery, the expression levels of P2X7R in the CCI + OECs-CS group was reduced on days 14 after surgery, and the pain in rats was relieved. CONCLUSION: OECs and OECs-CS transplantation can inhibit P2X7R overexpression mediated NPP, while OECs-CS transplantation has better therapeutic effect than OECs transplantation alone. Our results provide a novel method and theoretical basis for the treatment of NPP.

Probing nanoscale spatial distribution of plasmonically excited hot carriers.

Surface plasmons (SPs) of metals enable the tight focusing and strong absorption of light to realize an efficient utilization of photons at nanoscale. In particular, the SP-generated hot carriers have emerged as a promising way to efficiently drive photochemical and photoelectric processes under moderate conditions. In situ measuring of the transport process and spatial distribution of hot carriers in real space is crucial to efficiently capture the hot carriers. Here, we use electrochemical tip-enhanced Raman spectroscopy (EC-TERS) to in situ monitor an SP-driven decarboxylation and resolve the spatial distribution of hot carriers with a nanometer spatial resolution. The transport distance of about 20 nm for the reactive hot carriers is obtained from the TERS imaging result. The hot carriers with a higher energy have a shorter transport distance. These conclusions can be guides for the design and arrangement of reactants and devices to efficiently make use of plasmonic hot carriers.

lncRNA GAS5 Inhibits Cell Migration and Invasion and Promotes Autophagy by Targeting miR-222-3p via the GAS5/PTEN-Signaling Pathway in CRC.

Colorectal cancer (CRC) is a frequently occurring lethal disorder with heterogeneous outcomes and drug responses. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) play a critical role in carcinogenesis. Hence, the aim of this study was to investigate the role of lncRNA growth arrest-specific 5 (GAS5) in CRC cells via mediation of the microRNA-222-3p (miR-222-3p)/GAS5/phosphatase and tensin homolog (PTEN)-signaling pathway. HCT116 and SW480 cells were collected and treated with small interfering (si)-lncRNA GAS5, overexpressing (oe)-lncRNA GAS5, miR-222-3p mimic, miR-222-3p inhibitor, or si-lncRNA GAS5 + miR-222-3p mimic. The miR-222-3p level and mRNA and protein levels of GAS5, Beclin1, light-chain 3B (LC3B), PTEN, and Akt were detected. Besides, cell migration, invasion, and apoptosis as well as acidic vesicular organelles (AVOs) were examined respectively. Xenografts in nude mice were also performed to detect tumorigenesis in vivo. Results suggested that the downregulation of lncRNA GAS5 decreased the expressions of Beclin1, LC3B, and PTEN. When treated with oe-lncRNA GAS5 or miR-222-3p inhibitor, HCT116 and SW480 cells exhibited suppressed invasion and migration abilities and increased apoptotic cells and autophagosome and AVO activities. Moreover, overexpression of GAS5 inhibited the tumorigenesis of CRC cells in vivo. Taken together, lncRNA GAS5 upregulated the expression of PTEN by functioning as a competing endogenous RNA (ceRNA) of miR-222-3p, thus inhibiting CRC cell migration and invasion and promoting cell autophagy.

miR-133b inhibits cell proliferation, migration and invasion of esophageal squamous cell carcinoma by targeting EGFR.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor entity characterized by early metastasis and late diagnosis. MicroRNA-133b (miR-133b) has been considered as a tumor suppressor in many human cancers by regulating epidermal growth factor receptor (EGFR). However, the specific effects of miR-133b and EGFR on ESCC remain unclear. METHODS: qRT-PCR and western blotting were applied for measuring expression of mRNA and protein. Flow cytometry was used for detecting cell cycle and apoptosis. Cell proliferation, migration and invasion were detected by colony formation and transwell assays. Luciferase reporter assay was used to confirm the interaction between miR-133b and EGFR. RESULTS: Low expression of miR-133b and high expression of EGFR were identified in ESCC cells and tissues. Overexpression of miR-133b or knockdown of EGFR suppressed the cell proliferation, migration, and invasion of ESCC cells, and raised the percentage of G1 phase cells. The apoptosis of ESCC cells were promoted by increasing miR-133b and decreasing EGFR expression. Luciferase reporter assay confirmed EGFR as the target of miR-133b in ESCC cells. Overexpression of miR-133b significantly decreased the phosphorylation of PI3K, ERK and AKT by directly down-regulating EGFR. Higher expression of E-cadherin and CK-18 and lower expression of Vimentin and N-cadherin were observed after the transfection of miR-133b mimics or shEGFR. CONCLUSION: Overexpression of miR-133b could suppress proliferation, migration and invasion of ESCC cells by inhibiting MAPK/ERK and PI3K/AKT signaling pathways through targeting EGFR, indicating that miR-133b might be a potential therapeutic target for the treatment of ESCC.

S897 phosphorylation of EphA2 is indispensable for EphA2-dependent nasopharyngeal carcinoma cell invasion, metastasis and stem properties.

Our phosphoproteomics identified that phosphorylation of EphA2 at serine 897 (pS897-EphA2) was significantly upregulated in the high metastatic nasopharyngeal carcinoma (NPC) cells relative to non-metastatic NPC cells. However, the role and underlying mechanism of pS897-EphA2 in cancer metastasis and stem properties maintenance remain poorly understood. In this study, we established NPC cell lines with stable expression of exogenous EphA2 and EphA2-S897A using endogenous EphA2 knockdown cells, and observed that pS897-EphA2 maintained EphA2-dependent NPC cell in vitro migration and invasion, in vivo metastasis and cancer stem properties. Using phospho-kinase antibody array to identify signaling downstream of pS897-EphA2, we found that AKT/Stat3 signaling mediated pS897-EphA2-promoting NPC cell invasion, metastasis and stem properties, and Sox-2 and c-Myc were the effectors of pS897-EphA2. Immunohistochemistry showed that pS897-EphA2 was positively correlated with NPC metastasis and negatively correlated with patient overall survival. Moreover, ERK/RSK signaling controlled serum-induced pS897-EphA2 in NPC cells. Collectively, our results demonstrate that pS897-EphA2 is indispensable for EphA2-dependent NPC cell invasion, metastasis and stem properties by activating AKT/Stat3/Sox-2 and c-Myc signaling pathway, suggesting that pS897-EphA2 can serve as a therapeutic target in NPC and perhaps in other cancers.

[Lab-scale ANAMMOX Process in a Wastewater Treatment Plant].

A lab-scale, completely anaerobic ammonium oxidation (ANAMMOX) process was operated in a municipal wastewater treatment plant (WWTP). Sewage effluent treated by an A/O process and nitrification process was input as the substance to start up the up-flow ANAMMOX filter reactor. After the 109th day, the ammonia removal rate and nitrite removal rate were greater than 90% for 15 successive days and the nitrogen removal rate was higher than 70%. The ANAMMOX filter reactor successfully started up. From days 245 to 333, the reactor was running during the winter. The weight of biomass reached 12.24 mg·g-1, and the average nitrogen removal rate was 54.3%. Backwash was adopted at day 461, and the weight of biomass decreased to 8.01 mg·g-1. From days 605 to 693, the reactor was running in the winter again. The weight of biomass was 10.41 mg·g-1, and the average nitrogen removal rate was sustained at 69.7%. Compared with the previous winter, the weight of biomass was lighter but the total nitrogen removal loading was 23% greater. For the entire operation, the ANAMMOX rate at high temperature was stable but that at low temperature increased from 1.5 kg·(kg·d)-1 to 3.6 kg·(kg·d)-1. The results show:Long-term domestication at low temperature was in favor of improving treatment efficiency of ANAMMOX process in cold environment and realized ANAMMOX process operated efficiently in winter.

[Effect of Carbon Source on Lab-scale SAD Process in a Wastewater Treatment Plant].

Lab-scale anaerobic ammonia oxidation and denitrification (SAD) processes were operated simultaneously in a municipal waste water treatment plant (WWTP). Sewage treated by the A/O and nitrification process was used as the substance to start up an anaerobic ammonia oxidation filter reactor. Adding glucose and sodium propionate to influent was used as the substance to start up the SAD filter reactor after the successful start-up of the ANAMMOX reactor. The SAD process performed well with an average total nitrogen concentration in the effluent of 6.41 mg·L-1 when 30 mg·L-1 glucose was added to the effluent sewage at ambient temperature. Compared with the ANAMMOX process, the total nitrogen concentration in the effluent from the SAD process decreased 42%. The stability of the SAD process was destroyed and the SAD process turned into a denitrification process when 30 mg·L-1 glucose was added in the influent sewage in a low temperature environment. In normal and low temperature environments, the SAD process functioned well, and the average total nitrogen concentration of the effluent was 6.54 mg·L-1 when 30 mg·L-1 sodium propionate was added in the influent sewage. Compared with glucose, sodium propionate had little influence on the SAD process.

Annexin A1-suppressed autophagy promotes nasopharyngeal carcinoma cell invasion and metastasis by PI3K/AKT signaling activation.

Annexin A1 (ANXA1) is dysregulated in the various tumors. However, the role and mechanism of ANXA1 in the cancers are poorly understood. In this study, we first showed a clinically positive correlation between ANXA1 and autophagy-associated protein SQSTM1 expression in nasopharyngeal carcinoma (NPC) and ANXA1-regulating SQSTM1 expression through autophagy, and further demonstrated that ANXA1 inhibited BECN1 and ATG5-dependent autophagy in the NPC cells. Using phospho-kinase antibody array to identify signaling through which ANXA1 regulated NPC cell autophagy, we found that ANXA1-suppressed autophagy was associated with PI3K/AKT signaling activation. We also showed that ANXA1 expression was significantly increased in the NPCs with metastasis relative to NPCs without metastasis and positively correlated with lymphonode and distant metastasis; high ANXA1 expression in the NPC cells promoted in vitro tumor cell migration and invasion and in vivo metastasis. Lastly, we showed that inhibition of autophagy restored the ability of tumor cell migration and invasion, epithelial-mesenchymal transition (EMT)-like alterations and in vivo metastasis in the ANXA1 knockdown NPC cells with autophagy activation; ANXA1-suppresed autophagy induced EMT-like alterations possibly by inhibiting autophagy-mediated degradation of Snail. Our data suggest that ANXA1-suppressed autophagy promotes NPC cell migration, invasion and metastasis by activating PI3K/AKT signaling pathway, highlighting that the activation of autophagy may inhibit metastasis of NPC with high ANXA1 expression.