KIAA1199 drives immune suppression to promote colorectal cancer liver metastasis by modulating neutrophil infiltration.

BACKGROUND AND AIMS: Metastasis is the primary cause of cancer mortality, and colorectal cancer (CRC) frequently metastasizes to the liver. Our previous studies demonstrated the critical role of KIAA1199 in tumor invasion and metastasis in CRC. In the present study, we described an immune regulatory effect of KIAA1199 that creates a permissive environment for metastasis. APPROACH AND RESULTS: Flow cytometry was used to examine the effects of KIAA1199 on the infiltration of tumor immune cells. Neutrophils and T cells were isolated, stimulated, and/or cultured for in vitro function assays. In the patients with CRC, high expression levels of KIAA1199 were associated with an increased neutrophil infiltration into the liver. This result was further validated in mouse metastasis models. The increased influx of neutrophils contributed to the KIAA1199-driven CRC liver metastasis. Mechanistically, KIAA1199 activated the TGFß signaling pathway by interacting with the TGFBR1/2 to stimulate CXCL1 and CXCL3 production, thereby driving the aggregation of immunosuppressive neutrophils. Genetic blockade or pharmacologic inhibition of KIAA1199 restored tumor immune infiltration, impeded tumor progression, and potentiated response to immune checkpoint blockade (ICB). CONCLUSIONS: These findings indicated that KIAA1199 could facilitate the liver infiltration of immunosuppressive neutrophils via the TGFß-chemokine (C-X-C motif) ligand (CXCL)3/1-CXCR2 axis, which might be clinically targeted for the treatment of hepatic metastasis.

Efficacy and safety of ciprofol vs. propofol for the induction and maintenance of general anaesthesia: A multicentre, single-blind, randomised, parallel-group, phase 3 clinical trial.

BACKGROUND: HSK3486 (ciprofol) is a 2,6-disubstituted phenol derivative that acts like propofol as an agonist at the gamma-aminobutyric acid-A (GABA A ) receptor. OBJECTIVE: To investigate the efficacy and safety of HSK3486 for general anaesthesia induction and maintenance. DESIGN: A single-blinded, randomised, parallel-group, phase 3 trial. SETTING: Involving 10 study centres, from November 24, 2020 to January 25, 2021. PATIENTS: A total of 129 patients undergoing nonemergency, noncardiothoracic, and nonneurosurgical elective surgery. INTERVENTION: Patients were randomly assigned at a 2:1 ratio into HSK3486 or propofol groups, to receive HSK3486 (0.4 mg kg -1 ) or propofol (2.0 mg kg -1 ) for induction before a maintenance infusion at initial rates of 0.8 and 5.0 mg kg -1 h -1 , and were adjusted to maintain a bispectral index (BIS) of 40-60 until the end of surgery. MAIN OUTCOME MEASURES: Noninferiority between the drugs was evaluated as the lower limit of the 95% confidence interval (CI) for the between-group difference in the success rate of anesthetic maintenance (primary outcome) >-8%. Secondary outcomes included successful anaesthetic induction, full alertness and spontaneous breathing recovery, time until leaving the postanaesthesia care unit and changes in BIS. Safety profiles were also measured. RESULTS: Of 129 enrolled patients, 128 completed the trial, with 86 in the HSK3486 group and 42 in the propofol group. The success rate for the maintenance of general anaesthesia was 100% for both groups, and noninferiority of HSK3486 was confirmed (95% CI -4.28% to 8.38%). No significant differences were found between the two groups of patients with regard to secondary outcomes (all P  > 0.05). There appeared to be a comparable incidence of treatment for emergency adverse events (TEAEs) (80.2% vs. 81.0%, P  = 1.000) and drug-related TEAEs (57.0% vs. 64.3%, P  = 0.451) in the HSK3486 and propofol groups. CONCLUSION: HSK3486 had a noninferior efficacy profile compared to propofol, exhibiting excellent tolerance. TRIAL REGISTRATION: Clinicaltrials.gov, identifier: NCT04511728.

Occurrence, source apportionment and ecological risk assessment of thirty antibiotics in farmland system.

Antibiotics are widely used in medical care, livestock production, and aquaculture. However, antibiotic pollution has attracted increasing global concerns due to their ecological risks after entering into environmental ecosystem via animal excretion, effulent from industrial and domestic sewage treatment facilities. In this study, 30 antibiotics were investigated in soils and irrigation rivers using ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometer. This study evaluated the occurrence, source apportionment, and ecological risks of these target compounds in soils and irrigation rivers (i.e., sediments and water) of farmland system by using principal component analysis-multivariate linear regression (PCA-MLR) and risk quotients (RQ). The concentration range of antibiotics in soils, sediments, and water was 0.38-689.58 ng/g, 81.99-658.00 ng/g, and 134.45-1547.06 ng/L, respectively. In soils, the most abundant antibiotics were quinolones and antifungals with an average concentration of 30.00 ng/g and 7.69 ng/g, respectively, contributing to 40% of total antibiotics. Macrolides were the most frequently detected antibiotics in soils with an average concentration of 4.94 ng/g. In irrigation rivers, quinolones and tetracyclines, the most abundant antibiotics, accounted for 78% and 65% of antibiotics in water and sediments, respectively. Higher antibiotic contamination of irrigation water was primarily distributed in highly populated urban areas, while increasing antibiotic contamination of sediments and soils was particularly observed in rural areas. PCA-MLR analysis indicated that antibiotic contamination in soils was mainly ascribed to the irrigation of sewage-receiving water body and manure application of livestock and poultry farming, which cumulatively contributed to 76% of antibiotics. According to RQ assessment, quinolones in irrigation rivers posed high risk to algae and daphnia, contributing 85% and 72% to the mixture risk, respectively. In soils, macrolides, quinolones and sulfonamides were responsible for more than 90% to the mixture risk of antibiotics. Ultimately, these findings can improve our fundamental knowledge on contamination characteristics and source pathways towards risk management of antibiotics in farmland system.

The role of sema4D in vasculogenic mimicry formation in non-small cell lung cancer and the underlying mechanisms.

Vasculogenic mimicry (VM) is a special vascular pattern in malignant tumors, which is composed of highly aggressive tumor cells. This tumor cell-mediated blood supply pattern is closely associated with a poor prognosis in cancer patients. The interaction of axon guidance factor Sema4D and its high affinity receptor plexinB1 could activate small GTPase RhoA and its downstream ROCKs; this process has an active role in the migration of endothelial cells and tumor angiogenesis. Here, we have begun to uncover the role of this pathway in VM formation in non-small cell lung cancer (NSCLC). First, we confirmed this special form of vasculature in NSCLC tissues and found the existence of VM channels in tumor tissues was correlated with Sema4D expression. Further, we found that inhibition of Sema4D in the human NSCLC cells H1299 and HCC827 reduces VM formation both in vitro and in vivo. Moreover, we demonstrated that downregulating the expression of plexinB1 by siRNA expressing vectors and inhibiting the RhoA/ROCK signaling pathway using fasudil can reduce VM formation of H1299 and HCC827 cells. Finally, we found that suppression of Sema4D leads to less stress fibers and depleted the motility of H1299 and HCC827 cells. Collectively, our study implicates Sema4D plays an important role in the process of VM formation in NSCLC through activating the RhoA/ROCK pathway and regulating tumor cell plasticity and migration. Modulation of the Sema4D/plexinB1 and downstream RhoA/ROCK pathway may prevent the tumor blood supply through the VM pattern, which may eventually halt growth and metastasis of NSCLC.

Block Copolymer Nanoparticles Remove Biofilms of Drug-Resistant Gram-Positive Bacteria by Nanoscale Bacterial Debridement.

Biofilms and the rapid evolution of multidrug resistance complicate the treatment of bacterial infections. Antibiofilm agents such as metallic-inorganic nanoparticles or peptides act by exerting antibacterial effects and, hence, do not combat biofilms of antibiotics-resistant strains. In this Letter, we show that the block copolymer DA95B5, dextran- block-poly((3-acrylamidopropyl) trimethylammonium chloride (AMPTMA)- co-butyl methacrylate (BMA)), effectively removes preformed biofilms of various clinically relevant multidrug-resistant Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE V583), and Enteroccocus faecalis (OG1RF). DA95B5 self-assembles into core-shell nanoparticles with a nonfouling dextran shell and a cationic core. These nanoparticles diffuse into biofilms and attach to bacteria but do not kill them; instead, they promote the gradual dispersal of biofilm bacteria, probably because the solubility of the bacteria-nanoparticle complex is enhanced by the nanoparticle dextran shell. DA95B5, when applied as a solution to a hydrogel pad dressing, shows excellent in vivo MRSA biofilm removal efficacy of 3.6 log reduction in a murine excisional wound model, which is significantly superior to that for vancomycin. Furthermore, DA95B5 has very low in vitro hemolysis and negligible in vivo acute toxicity. This new strategy for biofilm removal (nanoscale bacterial debridement) is orthogonal to conventional rapidly developing resistance traits in bacteria so that it is as effective toward resistant strains as it is toward sensitive strains and may have widespread applications.

Enhanced Phytoextraction for Co-contaminated Soil with Cd and Pb by Ryegrass (Lolium perenne L.).

A pot experiment was conducted to investigate the effect of three additives - citric acid (CA), polyaspartic acid (PASP), and FeCl3 - on the phytoextraction efficiency of cadmium (Cd) and lead (Pb) by ryegrass (Lolium perenneL.) from artificially contaminated soils with different heavy metal concentrations. The results showed that as the concentration of pollutants increased, the TI (tolerance index) and BCF (bio-concentration factor) of ryegrass gradually increased only when FeCl3 was applied. FeCl3 also exhibited the most significant biomass enhancement and heavy metal accumulation of ryegrass, as well as the highest phytoextraction efficiency in heavily-polluted soils. The overall orders of the optimal phytoextraction efficiency for the three additives in terms of their MER (metal extraction ratio) were: FeCl3 > PASP > CA. Therefore, FeCl3 can be used to improve the Cd and Pb phytoextraction efficiency of ryegrass in heavily-polluted soils.

Correlation between circulating endothelial progenitor cells and serum carcinoembryonic antigen level in colorectal cancer.

Circulating endothelial progenitor cells (cEPCs) play an important role in cancer development. Previous studies showed that serum carcinoembryonic antigen (CEA) levels and the number of circulating endothelial progenitor cells (cEPCs) in the peripheral blood are both involved in tumor neoangiogenesis, and can be used for monitoring tumor progression, recurrence, metastasis, and therapeutic responses. However, the clinical relevance of these biomarkers remains unknown. In this study, 40 colorectal cancer (CRC) patients and 17 healthy volunteers were recruited and the amount of cEPCs in the peripheral blood was measured by flow cytometry. The serum CEA level was determined by CEA-RIACT assay. Results showed that cEPC level positively correlated with the stage of the disease, but not with the age and gender of the patients. Moreover, patients with higher serum CEA levels had higher cEPC levels. These results provide clinical evidence for a correlation between two commonly used biomarkers. Further understanding the role of serum CEA in cEPC-mediated tumor vascularization may improve clinical CRC diagnosis and provide useful insights into the design of therapeutic interventions that target tumor vasculature.

RhoA/ROCK pathway inhibition by fasudil suppresses the vasculogenic mimicry of U2OS osteosarcoma cells in vitro.

GTPase RhoA and its downstream Rho-associated coiled-coil-containing protein kinases (ROCKs) are frequently overexpressed in human cancers. Inhibition of the RhoA/ROCK pathway blocks angiogenesis mediated by the vascular endothelial growth factor, which led us to investigate the role of this pathway in vasculogenic mimicry (VM) - a process by which aggressive cancer cells form vessel-like structures that provide adequate blood supply for tumor growth. We showed that the expression of RhoA and its effector kinases ROCK1/2 was much higher in human osteosarcoma (OS) tissues and the human OS cell line U2OS than in nontumorous tissues and cell line hFOB 1.19 using western blot analysis and real-time PCR. Inhibition of the RhoA/ROCK signaling pathway by the pharmacological inhibitor fasudil reduced vascular-like channels of U2OS cells in Matrigel. Furthermore, we used rhodamine-phalloidin immunofluorescence, wound healing assay, and transwell migration assay to examine the effect of fasudil on tumor cell plasticity and motility, both of which play key roles in VM formation. Finally, we explored the underlying mechanisms of fasudil-induced VM destruction. In this context, we showed that the RhoA/ROCK signaling pathway is a novel regulator in VM of U2OS OS cells and suggest that fasudil in conjunction with established treatments may present a novel therapeutic strategy for OS.

VEGF-PKD1-HDAC7 signaling promotes endothelial progenitor cell migration and tube formation.

Histone acetylation/deacetylation is a key mechanism for regulating transcription, which plays an important role in the control of gene expression, tissue growth, and development. In particular, histone deacetylase 7 (HDAC7), a member of class IIa HDACs, is crucial in maintaining vascular integrity. Endothelial progenitor cells (EPCs) play an important role in angiogenesis. However, whether HDAC7 plays a role in the processes of EPCs angiogenesis remains unclear. Migration and tube formation were the two major components of EPC angiogenesis. In this study, we show for the first time that HDAC7 silencing weakened the migration and tube formation abilities of EPCs. VEGF-A induced an increase of phospho-HDAC7 and its nuclear export in a time-dependent manner, which could be partly inhibited by protein kinase D1 (PKD1) inhibitor, but not by the PI3K inhibitor or the MEK inhibitor. Our results showed that EPCs involved in the angiogenesis might be controlled by VEGF-PKD1-HDAC7 axis, which regulates the EPCs angiogenesis by PKD1, but not the ERK and PI3K pathway.

Mechanistic insights from DGT and soil solution measurements on the uptake of Ni and Cd by radish.

This work tests the previously proposed hypothesis that plant uptake of metals is determined dominantly by diffusional controlled or plant limiting uptake mechanisms at, respectively, low and high metal concentrations. Radish (Raphanus sativus) was grown in 13 soils spiked with Ni (10 and 100 mg kg(-1)) and Cd (0.5 and 4 mg kg(-1)) for 4 weeks to investigate the mechanisms affecting plant uptake. Soil solution concentrations, Css, of Ni and Cd were measured, along with the DGT interfacial concentration, CDGT, and the derived effective concentration in soil solution, CE. Free ion activities, aNi(2+) and aCd(2+), were obtained using WHAM 6. Although there was a poor relationship between Ni in radish roots and either Css or aNi(2+) in unamended soils, the distribution of data could be rationalized in terms of the extent of release of Ni from the soil solid phase, as identified by DGT and soil solution measurements. By contrast Ni in radish was linearly related to CE, demonstrating diffusion limited uptake. For soils amended with high concentrations of Ni, linear relationships were obtained for Ni in radish plotted against, Css, aNi(2+), and CE, consistent with the plant controlling uptake. For Ni the hypothesis concerning dominant diffusional and plant limiting uptake mechanisms was demonstrated. Poor relationships between Cd in radish and Css, aCd(2+), and CE, irrespective of amendment by Cd, showed the importance of factors other than diffusional supply, such as rhizosphere and inhibitory processes, and that fulfilment of this hypothesis is plant and metal specific.

Synthesis and characterization of surface-modified Fe3O4 super-paramagnetic nanoparticles.

Aqueous dispersion and stability of Fe3O4 nanoparticles remain an issue unresolved since aggregation of naked iron nanoparticles in water. In this study, we successfully synthesized different Fe3O4 super-paramagnetic nanoparticles which were modified by three kinds of materials [DSPE-MPEG2000, TiO2 and poly acrylic acid (PAA)] and further detected their characteristics. Transmission electron microscopy (TEM) clearly showed sizes and morphology of the four kinds of nanoparticles. X-ray diffraction (XRD) proved successfully coating of the three kinds of nanoparticles and their structures were maintained. Vibrating sample magnetometer (VSM) verified that their magnetic properties fitted for the super-paramagnetic function. More importantly, the particle size analysis indicated that Fe3O4@PAA had a better size distribution, biocompatibility, stability and dispersion than the other two kinds of nanoparticles. In addition, using CNE2 cells as a model, we found that all nanoparticles were nontoxic. Taken together, our data suggest that Fe3O4@PAA nanoaparticles are superior in the application of biomedical field among the four kinds of Fe3O4 nanoparticles in the future.

Neutrophil extracellular traps in cancer.

Neutrophil extracellular traps (NETs), which consist of chromatin DNA studded with granule proteins, are released by neutrophils in response to both infectious and sterile inflammation. Beyond the canonical role in defense against pathogens, the extrusion of NETs also contributes to the initiation, metastasis, and therapeutic response of malignant diseases. Recently, NETs have been implicated in the development and therapeutic responses of various types of tumors. Although extensive work regarding inflammation in tumors has been reported, a comprehensive summary of how these web-like extracellular structures initiate and propagate tumor progression under the specific microenvironment is lacking. In this review, we demonstrate the initiators and related signaling pathways that trigger NETs formation in cancers. Additionally, this review will outline the current molecular mechanisms and regulatory networks of NETs during dormant cancer cells awakening, circulating tumor cells (CTCs) extravasation, and metastatic recurrence of cancer. This is followed by a perspective on the current and potential clinical potential of NETs as therapeutic targets in the treatment of both local and metastatic disease, including the improvement of the efficacy of existing therapies.

Intratumoral Delivery of Interleukin 9 via Oncolytic Vaccinia Virus Elicits Potent Antitumor Effects in Tumor Models.

The success of cancer immunotherapy is largely associated with immunologically hot tumors. Approaches that promote the infiltration of immune cells into tumor beds are urgently needed to transform cold tumors into hot tumors. Oncolytic viruses can transform the tumor microenvironment (TME), resulting in immunologically hot tumors. Cytokines are good candidates for arming oncolytic viruses to enhance their function in this transformation. Here, we used the oncolytic vaccinia virus (oVV) to deliver interleukin-9 (IL-9) into the tumor bed and explored its antitumor effects in colon and lung tumor models. Our data show that IL-9 prolongs viral persistence, which is probably mediated by the up-regulation of IL-10. The vvDD-IL-9 treatment elevated the expression of Th1 chemokines and antitumor factors such as IFN-γ, granzyme B, and perforin. IL-9 expression increased the percentages of CD4+ and CD8+ T cells in the TME and decreased the percentage of oVV-induced immune suppressive myeloid-derived suppressor cells (MDSC), leading to potent antitumor effects compared with parental virus treatment. The vvDD-IL-9 treatment also increased the percentage of regulatory T cells (Tregs) in the TME and elevated the expression of immune checkpoint molecules such as PD-1, PD-L1, and CTLA-4, but not GITR. The combination therapy of vvDD-IL-9 and the anti-CTLA-4 antibody, but not the anti-GITR antibody, induced systemic tumor-specific antitumor immunity and significantly extended the overall survival of mice, indicating a potential translation of the IL-9-expressing oncolytic virus into a clinical trial to enhance the antitumor effects elicited by an immune checkpoint blockade for cancer immunotherapy.

Efficacy and safety of radiotherapy combined with anti-angiogenic therapy and immune checkpoint inhibitors in MSS/pMMR metastatic colorectal cancer.

PURPOSE: Several studies have demonstrated the effectiveness of anti-angiogenic drugs in combination with immune checkpoint inhibitors (ICIs) in patients with microsatellite stable (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC). However, whether combination radiotherapy (RT) can further improve the prognosis of mCRC patients after second-line treatment remains to be explored. METHODS: Retrospective analysis of data from mCRC patients who received anti-angiogenic targeted therapy (TT) and immunotherapy (IT) with or without RT after the failure of standard therapy. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety were evaluated. RESULTS: A total of 82 patients who received TT + IT were analyzed. For RT group (n = 42) versus NRT group (n = 40), ORR was 21.4% (9/42) versus 5.0% (2/40); DCR was 83.8% (35/42) versus 65.0% (26/40). Compared with NRT group, RT improved PFS (median: 5.0 vs. 3.6 months; p = 0.04) and OS (median: 15.2 vs. 7.2 months; p = 0.01). In addition, in the population receiving RT, the PFS of RT sequential/simultaneous TT + IT was superior to TT + IT sequential RT (median: 7.1 vs. 6.2 vs. 3.5 months, p = 0.004). Multivariate analysis suggested RT was an independent prognostic factor for PFS and OS. No treatment-related deaths were reported. CONCLUSIONS: Compared with TT + IT, RT combined with TT + IT improved survival outcomes in MSS/pMMR mCRC patients, with manageable toxicity. RT sequential/simultaneous TT + IT treatment is expected to be the optimal strategy for MSS/PMMR mCRC.

Efficacy and safety of ciprofol for sedation in outpatient gynecological procedures: a phase III multicenter randomized trial.

Objective: Ciprofol (also known as cipepofol and HSK3486), is a compound similar to propofol in chemical structure and hypnotic effect. Herein we evaluated the efficacy and safety of ciprofol for sedation in outpatient gynecological procedures. Methods: This phase III multicenter randomized trial with a non-inferiority design was conducted in nine tertiary hospitals. We enrolled 135 women aged 18-65 years who were scheduled for ambulatory gynecological procedures. Patients were randomly assigned to receive either ciprofol (0.4 mg/kg for induction and 0.2 mg/kg for maintenance) or propofol (2.0 mg/kg for induction and 1.0 mg/kg for maintenance) sedation in a 2:1 ratio. Patients and investigators for data collection and outcome assessment were blinded to study group assignments. The primary outcome was the success rate of sedation, defined as completion of procedure without remedial anesthetics. The non-inferiority margin was set at -8%. Secondary outcomes included time to successful induction, time to full awake, time to meet discharge criteria, and satisfaction with sedation assessed by patients and doctors. We also monitored occurrence of adverse events and injection pain. Results: A total of 135 patients were enrolled; 134 patients (90 patients received ciprofol sedation and 44 patients propofol sedation) were included in final intention-to-treat analysis. The success rates were both 100% in the two groups (rate difference, 0.0%; 95% CI, -4.1 to 8.0%), i.e., ciprofol was non-inferior to propofol. When compared with propofol sedation, patients given ciprofol required more time to reach successful induction (median difference [MD], 2 s; 95% CI, 1 to 7; p < 0.001), and required more time to reach full awake (MD, 2.3 min; 95% CI, 1.4 to 3.1; p < 0.001) and discharge criteria (MD, 2.3 min; 95% CI, 1.5 to 3.2; p < 0.001). Fewer patients in the ciprofol group were dissatisfied with sedation (relative risk, 0.21; 95% CI, 0.06 to 0.77; p = 0.024). Patients given ciprofol sedation had lower incidences of treat-emergent adverse events (34.4% [31/90] vs. 79.5% [35/44]; p < 0.001) and injection pain (6.7% [6/90] vs. 61.4% [27/44]; p < 0.001). Conclusion: Ciprofol for sedation in ambulatory gynecological procedures was non-inferior to propofol, with less adverse events and injection pain. Clinical trial registration: ClinicalTrials.gov, identifier NCT04958746.

Association between CHRNA3 rs1051730 genotype and lung cancer risk in Chinese Han population: a case-control study.

Recent population-based genome wide association studies have revealed potential susceptibility loci of lung cancer at the region of chromosome 15q25.1 containing nicotinic acetylcholine receptor genes. The loci increasing lung cancer risk has been widely identified in Caucasians, but whether this association also exists in Asians and whether this association is a direct role or mediated via tobacco smoking indirectly has not been fully established. We conducted a case-control study comprising of 210 histologically confirmed lung cancer cases and 200 healthy controls to examine rs1051730 genotyping, a single nucleotide polymorphism receiving much attention recently, and its influence on lung cancer risk as well as nicotine dependence in a Chinese Han population. Our results showed that the heterozygous C/T genotype and minor allele T conferred a significant higher risk of lung cancer than the CC homozygotes and allele C (adjusted OR=2.25, 95% CI=1.04-4.89, P=0.040 and OR=2.18, 95% CI=1.02-4.67, P=0.045 respectively). However, no association between the smoking habit and the CHRNA3 rs1051730 polymorphism was observed in this study. The results suggested that the rs1051730 polymorphism may modify susceptibility to lung cancer via a smoking-independent manner among Chinese Han population. Additional studies in vitro and in vivo are warranted to further elucidate the impact of rs1051730 on lung cancer susceptibility.

Correlation between increased circulating endothelial progenitor cells and stage of non-Hodgkin lymphoma.

This study aims to examine the levels of circulating endothelial progenitor cells (cEPCs) in the peripheral blood of patients with non-Hodgkin lymphoma (NHL) and their correlation with the tumor stage. Forty-one patients with biopsy-proven NHL and 16 healthy individuals were recruited. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation, and cEPCs were characterized by triple staining using antibodies against CD133, CD34 and vascular endothelial growth factor receptor-2 (VEGFR-2, CD309) and quantified by flow cytometry. In NHL patients, the number of cEPCs was significantly greater than in control group (P=0.000). The cEPCs counts in patients with NHL of stage III-IV were significantly greater than in stage I-II (P=0.010). FACS analysis revealed that the number of cEPCs in NHL patients had no correlation with the gender (P=0.401) or the pathological category (P=0.852). It was suggested that the over-expression of cEPCs in NHL patients may serve as a novel biomarker for disease progression in NHL.

Suppression of low-dose hyper-radiosensitivity in human lung cancer cell line A549 by radiation-induced autophagy.

This study explored the role of radiation-induced autophagy in low-dose hyperradiosensitivity (HRS) in the human lung cancer cell line A549. A549 cells, either treated with an autophagic inhibitor 3-methyladenine (3-MA), or with a vehicle control, were irradiated at different low doses (≤0.5 Gy). The generation of autophagy was examined by laser scanning confocal microscopy. Western blotting was used to detect the expression of microtubule-associated protein l light chain 3B II (LC3B-II). Flow cytometry (FCM) and clonogenic assays were used to measure the fraction of surviving cells at the low irradiation doses. Our results showed that there was a greater inhibition of autophagic activity, but a higher degree of low-dose HRS in A549 cells treated with 3-MA than in control group. Our data demonstrated that radiation-induced autophagy is correlated with HRS in A549 cells, and is probably one of the mechanisms underlying HRS.

Effects of biofilms on the retention and transport of PFOA in saturated porous media.

Understanding the fate and transport of perfluorooctanoic acid (PFOA) in soil and groundwater is essential to reliable assessments of its risks. This study investigated the impacts of Gram-positive Bacillus subtilis (BS), Gram-negative Pseudomonas aeruginosa (PA) and wild microbiota (WM) biofilm on the transport of PFOA in saturated sand columns at two ionic strengths (i.e., 1.0 and 20.0 mM NaCl). The retention of PFOA in biofilm-coated sand columns was higher than that in uncoated sand columns, due to biofilm-induced reinforced hydrophobic interactions and surface roughness, and decreased zeta potential. However, the retention effects varied among biofilm bacterial species with PFOA retardation factors in PA, WM and BS columns of 1.29-1.38, 1.21-1.29 and 1.11-1.15, respectively. Notably, PA biofilm had the most pronounced effect on PFOA retention. While increasing ionic strength promoted the retention of PFOA in BS biofilm-coated sand, it had no significant impact on PFOA transport in PA and WM biofilm-coated sand. This could be attributed to the differences in biofilm composition, deviating the ionic strengths effects on electrostatic double layer compression. The advection dispersion equation coupled with two-site kinetic retention model well described the transport of PFOA in all saturated columns. Our findings reveal that biofilm plays important roles in PFOA transport in porous media, instructive for risk assessment and remediation of PFOA contamination.