Fabrication of well-aligned Co-MOF arrays through a controlled and moderate process for the development of a flexible tetrabromobisphenol A sensor.

Tetrabromobisphenol A (TBBPA) has attracted a great deal of attention due to its side effects and potential bioaccumulation properties. It is of great importance to construct and develop novel electrochemical sensors for the sensitive and selective detection of TBBPA. In the present study, cobalt (Co) based metal-organic frameworks (MOFs) were synthesized on carbon cloth (CC) by using cobalt nitrate hexahydrate and 2-methylimidazole. The morphological characterization was carried out by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). The results showed that Co-MOFs/CC have a leaf-like structure and abundant surface functional groups. The electrochemical properties of the sensor were investigated by differential pulse voltammetry (DPV). The effects of different ratios of metal ions to organic ligands, reaction temperature, time, concentration, pH value of the electrolyte, and incubation time on the oxidation peak current of TBBPA were studied. Under the optimal conditions, the linear range of the designed sensor was 0.1 µM-100 µM, and the limit of detection was 40 nM. The proposed sensor is simple, of low cost and efficient, which can greatly facilitate the detection tasks of environmental monitoring workers.

Hsa_circ_0001740 mediates trophoblast cell function via regulating miR-188-3p/ARRDC3.

Preeclampsia is an obstetric disorder and remains the leading contributor to maternal and fetal morbidity and mortality. This study was designed to explore the role of hsa_circ_0001740 in preeclampsia as well as its underlying mechanism. Real-time quantitative polymerase chain reaction was performed to examine hsa_circ_0001740 and miR-188-3p levels in trophoblast cell line HTR-8/SVneo. The proliferation, migration, invasion, and apoptosis of HTR-8/SVneo cells were detected using cell counting kit-8, colony formation, wound healing, transwell, and terminal-deoxynucleoitidyl transferase mediated nick end labeling assays, respectively. The expression of apoptosis- and Hippo signaling-related proteins were assessed by western blot. Moreover, the binding relationship between hsa_circ_0001740 and miR-188-3p, miR-188-3p and ARRDC3 were verified by luciferase report assay. The results showed that hsa_circ_001740 overexpression inhibited the proliferation, migration, and invasion, and promoted apoptosis of HTR-8/SVneo cells. Hsa_circ_0001740 was verified to bind to miR-188-3p, and ARRDC3 was demonstrated to be a target of miR-188-3p. miR-188-3p overexpression partially counteracted the suppressive effects of hsa_circ_001740 overexpression on the proliferation, migration, and invasion of HTR-8/SVneo cells. What's more, ARRDC3 expression was upregulated by hsa_circ_001740-overexpression but was downregulated by miR-188-3p overexpression. Hsa_circ_001740/miR-188-3p also mediated Hippo signaling. To summarize, hsa_circ_0001740 could maintain trophoblast cell function via downregulating miR-188-3p, providing a potential biomarker for the diagnosis and treatment of preeclampsia.

Acetylation of H3K27 activated lncRNA NEAT1 and promoted hepatic lipid accumulation in non-alcoholic fatty liver disease via regulating miR-212-5p/GRIA3.

Non-alcoholic fatty liver disease (NAFLD) was a world-wide health burden. H3K27 acetylation, long non-coding RNA (lncRNA), and miRNA were all implicated in NAFLD regulation, yet the detailed regulatory mechanism was not well understood. LncRNA NEAT1, miR-212-5p, and GRIA3 expression were detected both in high fatty acid-treated hepatocytes cells and NAFLD patients. Lipid droplets were stained and analyzed by oil red O staining. Expression of fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), and GRIA3 was detected by qRT-PCR and western blot. RNA level of lncRNA NEAT1 and miR-212-5p was analyzed by qRT-PCR. The binding sequences of lncRNA NEAT1/miR-212-5p and miR-212-5p/GRIA3 were predicted bioinformatically and validated through luciferase assay. ChIP was performed to analyze H3K27 acetylation on the promoter of lncRNA NEAT1. LncRNA NEAT1 and GRIA3 was upregulated, while miR-212-5p was downregulated in NAFLD patients. FFA promoted lncRNA NEAT1 and GRIA3 expression while suppressing miR-212-5p and promoted lipid accumulation as indicated by increased oil red O staining and FAS and ACC expression. ChIP indicated enrichment of H3K27 on NEAT1 promoter. Inhibition of H3K27 acetylation suppressed lncRNA NEAT1 level. Luciferase results indicated direct interaction of NEAT1/miR-212-5p (which was confirmed by RIP) and miR-212-5p/GRIA3. LncRNA NEAT1 knockdown upregulated miR-212-5p level and inhibited FFA-induced lipid accumulation while suppressing GRIA3 expression. Such function was antagonized by miR-212-5p inhibition and GRIA3 knockdown counteracted with miR-212-5p inhibition. H3K27 acetylation was enriched within the promoter of lncRNA NEAT1 and promoted lncRNA NEAT1 transcription. LncRNA NEAT1 could then interact with miR-212-5p and suppress its cellular concentration.

Prognostic value of a nomogram based on peripheral blood immune parameters in unresectable hepatocellular carcinoma after intensity-modulated radiotherapy.

BACKGROUND: For patients with unresectable hepatocellular carcinoma (uHCC), intensity-modulated radiotherapy (IMRT) has become one of the options for clinical local treatment. Immune parameters, including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic immune inflammatory (SII), predict survival in various cancers. This study aimed to determine whether peripheral immune parameters can predict survival in patients with uHCC undergoing IMRT and establish a clinically useful prognostic nomogram for survival prediction. METHODS: The clinical data of 309 HCC patients were retrospectively analyzed and randomly divided into training (n = 216) and validation (n = 93) cohorts. PLR, NLR and SII were collected before and after IMRT. Univariate and multivariate Cox analyses were performed to identify independent prognostic factors affecting survival, which were used to generate a nomogram. RESULTS: The median survival was 16.3 months, and significant increases in PLR, NLR, and SII were observed after IMRT (P < 0.001). High levels of immune parameters were associated with poor prognosis (P < 0.001); enlarged spleen, Barcelona clinic liver cancer stage (B and C), post-SII, and delta-NLR were independent risk factors for survival and were included in the nomogram, which accurately predicted 3- and 5-year survival. The nomogram was well verified in the validation cohort. CONCLUSIONS: High levels of immune parameters are associated with poor prognosis in uHCC patients receiving IMRT. Our nomogram accurately predicts the survival of patients with uHCC receiving IMRT.

Acclimation of copper absorption ability of Candida utilis.

The use of inorganic copper in feed is hazardous. As probiotics of animals, Candida utilis can absorb copper ions and transform them to organic copper. This study aimed to domesticate the ability of C. utilis (CICC 32211) to absorb and transform copper ions. So, C. utilis (CICC 32211) was cultured in media with different concentrations of copper ions for 24, 48 and 72 h to identify the optimum copper ion concentration. C. utilis (CICC 32211) strains were domesticated for three generations, then the absorption and distribution of copper ions in the yeast cells were studied. We found that the optimum concentration of copper ions was 110 µg/mL. After 48 h, the number of yeast cells was low, but copper ion absorption efficiency was maximized (43.83%). Most of the enriched copper ions were distributed in the yeast cell wall (up to 30.58% when grown in the medium with 110 µg/mL copper ions), while the intracellular copper ion content was low (2.095%). High concentrations of copper ions affected the morphological structure, element content and distribution of yeast cells.

Pediatric Antibiotic Prescribing in China According to the 2019 World Health Organization Access, Watch, and Reserve (AWaRe) Antibiotic Categories.

OBJECTIVES: To assess clinical indication-specific antibiotic prescribing in pediatric practice in China based on the World Health Organization (WHO) Access, Watch, and Reserve (AWaRe) metrics and to detect potential problem areas. STUDY DESIGN: Pediatric prescription records on the 16th of each month during 2018 were sampled for all encounters at outpatient and emergency departments of 16 tertiary care hospitals via hospital information systems. Antibiotic prescribing patterns were analyzed across and within diagnostic conditions according to WHO AWaRe metrics and Anatomical Therapeutic Chemical (ATC) classification. RESULTS: A total of 260 001 pediatric encounters were assessed, and antibiotics were prescribed in 94 453 (36.3%). In 35 167 encounters (37.2%), at least 1 intravenous antibiotic was administered. WHO Watch group antibiotics accounted for 82.2% (n = 84 176) of all antibiotic therapies. Azithromycin (n = 15 791; 15.4%) was the most commonly prescribed antibiotic, and third-generation cephalosporins (n = 44 387; 43.3%) were the most commonly prescribed antibiotic class. In at least 66 098 encounters (70.0%), antibiotics were prescribed for respiratory tract conditions, mainly for bronchitis/bronchiolitis (n = 25 815; 27.3%), upper respiratory tract infection (n = 25 184; 26.7%), and pneumonia (n = 13 392; 14.2%). CONCLUSIONS: Overuse and misuse of WHO Watch group antibiotics for respiratory tract conditions and viral infectious diseases is common in pediatric outpatients in China. Pediatric antimicrobial stewardship should be strengthened using WHO AWaRe metrics.

[Currency Survey and Influencing Factors Analysis on the Knowledge and Behavior Related to Brucellosis among Occupational Workers in Jianyang City].

OBJECTIVE: To investigate the status and influencing factors of the knowledge and behavior related to brucellosis among occupational workers in Jianyang city, and to provide basic information for developing regional specific strategies for brucellosis prevention and control. METHODS: With multistage cluster random sampling, occupational workers aged ≥18 yr. who had been in contact with sheep and their products were interviewed through a questionnaire about demographic characteristic, knowledge, and behavior related to brucellosis. The knowledge and practice scores were described as frequency and percentage, and the awareness rate of knowledge about brucellosis was calculated. Unconditional logistic regression model was used to analyze the influencing factors of knowledge and behavior related to brucellosis. RESULTS: In total, 378 workers were recruited. The minority (25.1%) of the workers had heard of brucellosis, and the awareness rate of brucellosis was 22.0%. Occupational protective behaviors were poor, and the scoring rates of wearing protective clothes, mask and gloves were 58.7%, 76.5%, 71.7% respectively. The results of multivariate logistic regression analysis revealed that the awareness rate of knowledge about brucellosis decreased with age, while the low educational level was found to be associated with low awareness of knowledge about brucellosis, and occupation type had association with the awareness rate of knowledge. Besides, the awareness of knowledge about brucellosis was a protective factor and occupation type were associated with the behavior related to brucellosis. CONCLUSIONS: The knowledge and behavior related to brucellosis are poor among occupational workers in Jianyang. It is necessary to continuously implement targeted health education and health promotion programs in this region, and the people with low education level and livestock farmers should be paid special attention to.

[Evolution and the flanking sequences of Β-lactamase resistance gene blaOKP].

blaOKP genes are chromosomally encoded beta-lactamases that mediate several classes of antibiotics resistance. To investigate the evolution and flanking sequences of OKP beta-lactamase gene, the gene blaOKP and its flanking sequences from a newly isolated Klebsiella pneumoniae were studied using whole genome sequencing. The flanking sequences of different variant blaOKP genes and blaSHV, another plasmid-encoded beta-lactamase gene, were then compared. These studies show that the blaOKP and blaSHV genes evolve differently and belong to two different evolution branches. The blaOKP gene variants can be divided into subgroups: blaOKP-A and blaOKP-B. Although both blaOKP and blaSHV genes have no mobile genetic elements in their flanking sequences, their genetic environments are quite different. The blaOKP gene is adjacent to KdpC while blaSHV gene is flanked by RecF and ygbN-ygbM-ygbK. Furthermore, there are a variety of mobile genetic elements in the neighboring sequence plasmid-encoded blaSHV genes that are absent in blaOKP genes. These structural differences may slow the evolution of blaOKP gene. Collectively, we demonstrate that the evolution and flanking sequence of blaOKP gene are different from those of the blaSHV gene, which could be an important reason for its relatively slow evolution.

The important role of the receptor for activated C kinase 1 (RACK1) in nasopharyngeal carcinoma progression.

BACKGROUND: The receptor for activated C kinase 1 (RACK1) is involved in various cancers, but its roles in nasopharyngeal carcinoma (NPC) have not yet been fully elucidated. METHODS: Initially, RACK1 expression was analyzed by immunohistochemistry in NPC and normal nasopharyngeal (NP) tissues. It was also detected by qPCR and Western blot in NPC cells. Confocal microscope and immunofluorescence were performed to detect the subcellular compartmentalization of RACK1. Subsequently, after up- or down-regulating RACK1 in NPC cells, cell proliferation and migration/invasion were tested using in vitro assays including MTT, EdU, colony formation, Transwell and Boyden assays. Furthermore, several key molecules were detected by Western blot to explore underlying mechanism. Finally, clinical samples were analyzed to confirm the relationship between RACK1 expression and clinical features. RESULTS: Receptor for activated C kinase 1 expression was much higher in NPC than NP tissues. And RACK1 was mainly located in the cytoplasm. Overexpression of RACK1 promoted NPC cell proliferation and metastasis/invasion, whereas depletion of this protein suppressed NPC cell proliferation and metastasis/invasion. Mechanistically, RACK1 deprivation obviously suppressed the activation of Akt and FAK, suggesting the PI3K/Akt/FAK pathway as one of functional mechanisms of RACK1 in NPC. Furthermore, clinical sample analysis indicated a positive correlation between in vivo expression of RACK1 with lymph node invasion and clinical stage of NPC. CONCLUSION: Our results demonstrate that RACK1 protein plays an important role in NPC development and progression. The upregulation of RACK1 can promote the proliferation and invasion of NPC by regulating the PI3K/Akt/FAK signal pathway. Thus, this study contributes to the discovery of a potential therapeutic target for NPC.

Inhibition of proliferation and induction of apoptosis in RB116 retinoblastoma cells by afatinib treatment.

The present study investigates the effect of afatinib on the growth, induction of apoptosis in RB116 cells, and reduction of carcinoma growth in the mice transplanted with RB116 cells. The results from MTT assay revealed that afatinib inhibited the growth of RB116 cells in a dose-dependent manner. Proliferation of RB116 cells was reduced to 64 % on treatment with 200 µM concentration of afatinib after 48 h. Afatinib treatment of RB116 cells at 200 µM concentration induced apoptosis and necrosis in 49.7 and 9.4 %, respectively, after 48 h. In the RB116-transplanted mice, treatment with afatinib at 10-mg/kg doses for 45 days caused a significant (p < 0.005) reduction in the tumor volume compared to the control group. The tissue lysates of the mice containing RB116 transplant showed a significant decrease in the expressions of Ki67 and p53 in the afatinib treatment group after 45 days. However, the expression of caspase-3 was increased and of Bcl-2 remained unaltered on treatment with afatinib. Measurement of the body weight of afatinib-treated animals showed no reduction during the study. Thus, afatinib can be of therapeutic value for the treatment of retinoblastoma.

Antibiotic and disinfectant resistance of Salmonella isolated from egg production chains.

To investigate the contamination of Salmonella and its drug resistance in egg production chains, 111 Salmonella strains of different serotypes isolated from egg production chains were used in the study. The minimum inhibitory concentrations (MICs) of antibiotics and disinfectants against Salmonella isolates were determined, meanwhile, antibiotic and disinfectant resistance genes were amplified. The results showed that the resistance frequency of trimethoprim (TMP, N=100, P=90.09%) was highest among Salmonella isolates and all isolates were sensitive to amoxicillin and clavulanate (AMC), ceftiofur sodium (CFS) and gentamicin (CN), respectively. There were six different antibiotic resistance profiles, and TMP profile was the most prevalent type (N=36, P=32.43%). 52.25% of Salmonella isolates appeared multi-drug resistance. The MICs of benzalkonium chloride (BC) and cetylpyridinium chloride (CPC) against Salmonella strains ranged from 8 to 128 µg/mL and 8 to 256 µg/mL, respectively. Compared to quality control strain Escherichia coli ATCC10536, 101 Salmonella isolates (P=90.99%) had dual resistances to BC and CPC. 109 Salmonella (P=98.20%) were co-resistant to antibiotic and disinfectant. Detection of drug resistance genes showed that blaTEM gene was dominant (N=49, P=44.14%). The qnrA, qnrB and qepA genes were not detected. Only qacEΔ1 gene (N=63, P=56.76%) was detected among the disinfectant resistance genes. There was a significant correlation between sul1 gene and qacEΔ1 gene (P < 0.01). S. Derby showed multi-resistances to TMP, oxytetracycline (OTC), amoxicillin (AML) and ciprofloxacin (CIP). Eleven antibiotic resistance genes were found in S. Derby, in which the prevalence of qacEΔ1 gene was 81.25% (N=52). Besides, the drug resistance frequency and the prevalence of drug resistance genes in internal farm environment were higher than those in external environment. High frequency of drug resistances and high prevalence of drug resistance genes were detected in all links of the egg production chains, including package, storage and sale. Our results showed that severe antibiotic and disinfectant resistances existed in egg production chains. Therefore, further hygiene supervision should be implemented to prevent and control Salmonella, and standardize the use of antibiotics and disinfectants.

Accuracy of visual inspection with acetic acid and with Lugol's iodine for cervical cancer screening: Meta-analysis.

The aim of this review was to provide an updated summary estimation of the accuracy of visual inspection with acetic acid (VIA) and with Lugol's iodine (VILI) in detecting cervical cancer and precancer. Studies on VIA/VILI accuracy were eligible in which VIA/VILI was performed on asymptomatic women who all underwent confirmatory testing of histology, combination of colposcopy and histology, or combination of multiple screening tests, colposcopy and histology, to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+ or CIN3+). A bivariate model was fitted to estimate the accuracy of VIA/VILI and provide estimates of heterogeneity. Subgroup analysis was used to investigate the source of heterogeneity. A total of 29 studies on VIA and 19 studies on VILI were included finally in the meta-analysis. The summary sensitivity and specificity of VIA for CIN2+ were 73.2% (95%CI: 66.5-80.0%) and 86.7% (95%CI: 82.9-90.4%), respectively, and those for VILI were 88.1% (95%CI: 81.5-94.7%) and 85.9% (95%CI: 81.7-90.0%), respectively. VIA and VILI were both more sensitive in detecting more severe outcome, although there was a slight loss in specificity. Apparent heterogeneity existed in sensitivity and specificity for both VIA and VILI. High sensitivity of both VIA and VILI for CIN2+ was found when a combination of colposcopy and histology was used as disease confirmation. VIA, VILI, even a combination of them in parallel, could be good options for cervical screening in low-resource settings. Significant differences in sensitivity between different gold standards might provide a proxy for optimization of ongoing cervical cancer screening programs.

[CecropinA-magainin, a new hybrid antibacterial peptide against meticillin-resistant Staphylococcus aureus].

OBJECTIVE: To study the mechanism of cecropinA-mangainin treatment on the meticillin-resistant Staphylococcus anreus biofilms. METHODS: The activity of the hybrid antibacterial peptide against Staphylococcus anreus was evaluated by the minimum inhibitory concentration (MIC) test and its effect on the bacteria membrane changes were observed through transmission electron microscope. The concentration of K+ of the tested bacterial liquid after interact with antibacterial peptide was detected with atomic absorption spectrometer. The changes of the treated bacteria biofilm was also evaluated by using flow cytometry. RESULTS: The results demonstrated that the MIC of the peptide against Staphylococcus aureus was 64 microg/mL. The ultrastructure changes of the meticillin-resistant Staphylococcus anreus membrane and the rising concentration of intracellular K+ were observed. And increased number of PI positive cells was also observed after hybrid antibacterial peptide treatmennt. CONCLUSION: The hybrid antibacterial peptide could kill the meticillin-resistant Staphylococcus anreus by damage the treated bacteria membrane.

[Assessing quality of life of patients with stroke using EQ-5D and SF-12].

OBJECTIVE: To compare.the results of EQ-SD and SF-12 for assessing health-related quality of life in stroke patients. METHODS: EQ-5D and SF-12 were administered to 598 ischemic stroke patients through face-to-face interviews. Differences in PCS-12 and MCS-12 scores across different levels of EQ-5D dimensions were tested using analysis of variance (ANOVA). The EQ-5D index and visual analogue scale/score (VAS) scores of respondents were compared between those with higher than and lower than median SF-12 scores using student t-test. Pearson correlations between PCS-12 and EQ-5D scores were tested. RESULTS: PCS-12 and MCA-12 scores varied across different levels of EQ-5D dimensional scores, except for pain/discomfort. EQ-5D and VAS scores varied between those with high and low SF-12 scores. No significant differences in EQ-5D index and VAS scores were found in the EQ-5D indicated healthy respondents between those with high and low SF-12 scores (P>0.05). PCS-12 was positively correlated with EQ-5D index and VAS scores, with r=0.15 (P<0.001) and r=0.33 (P< 0.001), respectively. MCS-12 was also positively correlated with EQ-5D index and VAS score, with r=0.17 (P<0.001) and r = 0.13 (P<0.001), respectively. CONCLUSION: Both instruments are valid measurements for assessing quality of life. The SF-12 appeared to be more sensitive to differences in health status. EQ-5D is preferable if both quality of life assessment and health economics study are to be conducted.

[Changes in health-related quality of life in incipient stroke survivors].

OBJECTIVE: To assess the long-term changes in quality of life of stroke patients. METHODS: A total of 467 stroke survivors were recruited for this study. The participants completed the 12-Item Short Form Health Survey (SF-12) at a three-month interval over two years. Multi-level modelling was performed to identify the trend of changes and associated demographic characteristics. RESULTS: The participants had (31.50 +/- 10.49) PCS and (51.92 +/- 10.03) MCS at the baseline survey. Overall, PCS and MCS scores increased over time, but MCS scores declined slightly 15 months later. Men had higher PCS scores than women. The multi-level model revealed similar trends of PCS changes in those with different gender and education. Older patients had slower changes in quality of life over time (beta9 = -0.013, P = 0.03) compared with their younger counterparts. The trends of MCS changes were similar among those with different age, gender and education. CONCLUSION: Support should be strengthened for female stroke survivors and those with older age and lower levels of education.

Air-stable (phenylbuta-1,3-diynyl)palladium(II) complexes: highly active initiators for living polymerization of isocyanides.

A family of air-stable (phenylbuta-1,3-diynyl)palladium(II) complexes were designed and prepared in a facile synthetic procedure. Their structures were characterized by (1)H and (13)C NMR, MS, and X-ray analysis. These Pd complexes were revealed to efficiently initiate the polymerization of phenyl isocyanides in a living/controlled chain growth manner, which led to the formation of poly(phenyl isocyanide)s with controlled molecular weights and narrow molecular weight distributions. (13)C NMR analysis indicated the isolated poly(phenyl isocyanide) was of high stereoregularity. The Pd unit at the end of the polymer chain could undergo further copolymerization with phenyl isocyanide monomers to give block copolymers. It was also found that incorporation of an electron-donating group on the phenyl group of the Pd complex could improve the catalytic activities. Furthermore, these Pd complexes were tolerant to most organic solvents and applicable to a wide range of isocyanide monomers including alkyl and phenyl isocyanides and even phenyl isocyanide with bulky substituents at the ortho position and diisocyanide monomers. Therefore, this polymerization system is versatile in the preparation of well-defined polyisocyanides with controlled sequence. Bi- and trifunctional Pd complexes with two and three Pd units incorporated onto the same phenyl ring were designed and synthesized. They were also able to initiate the living polymerization of phenyl isocyanide to afford telechelic linear and star-shaped polyisocyanides with controlled molecular weights and narrow molecular weight distributions.

Inhibition of tumor necrosis factor alpha reduces the outgrowth of hepatic micrometastasis of colorectal tumors in a mouse model of liver ischemia-reperfusion injury.

BACKGROUND: Patients with colorectal cancer (CRC) often develop liver metastases, in which case surgery is considered the only potentially curative treatment option. However, liver surgery is associated with a risk of ischemia-reperfusion (IR) injury, which is thought to promote the growth of colorectal liver metastases. The influence of IR-induced tumor necrosis factor alpha (TNF-α) elevation in the process still is unknown. To investigate the role of TNF-α in the growth of pre-existing micrometastases in the liver following IR, we used a mouse model of colorectal liver metastases. In this model, mice received IR treatment seven days after intrasplenic injections of colorectal CT26 cells. Prior to IR treatment, either TNF-α blocker Enbrel or low-dose TNF-α, which could inhibit IR-induced TNF-α elevation, was administered by intraperitoneal injection. RESULTS: Hepatic IR treatment significantly promoted CT26 tumor growth in the liver, but either Enbrel or low-dose TNF-α pretreatment reversed this trend. Further studies showed that the CT26 + IR group prominently increased the levels of ALT and AST, liver necrosis, inflammatory infiltration and the expressions of hepatic IL-6, MMP9 and E-selectin compared to those of CT26 group. Inhibition of TNF-α elevation remarkably attenuated the increases of these liver inflammatory damage indicators and tumor-promoting factors. CONCLUSION: These findings suggested that inhibition of TNF-α elevation delayed the IR-enhanced outgrowth of colorectal liver metastases by reducing IR-induced inflammatory damage and the formation of tumor-promoting microenvironments. Both Enbrel and low-dose TNF-α represented the potential therapeutic approaches for the protection of colorectal liver metastatic patients against IR injury-induced growth of liver micrometastases foci.

A two dimensional Co(OH)2 catalytic gravity-driven membrane for water purification: a green and facile fabrication strategy and excellent water decontamination performance.

Cobalt-based materials are reported to be the most efficient catalysts in sulfate radical advanced oxidation processes (SR-AOPs). A green and facile method was developed in this work to prepare uniform Co(OH)2 hexagonal nanosheets, which was void of any organic solvents via mere ambient temperature stirring. The obtained nanosheets were assembled into a catalytic gravity-driven membrane, through which the removal efficiency of a typical pharmaceutical contaminant, ranitidine (RNTD), could reach ∼100% within 20 min. Meanwhile, the catalytic membrane also demonstrated effective removal performance towards various pollutants. In order to augment the long-term stability of catalytic membranes, Co(OH)2/rGO composites were fabricated using the same strategy, and a Co(OH)2/rGO catalytic membrane was prepared correspondingly. The Co(OH)2/rGO membrane could maintain a ∼100% removal of RNTD over a constant reaction period lasting for up to 165 hours, which was approximately 11 times that of the sole Co(OH)2 membrane (15 h). Analysis of element chemical states, metal ion concentration in filtrates, and quenching experiments suggested that the combination with rGO could promote the electron transfer to accelerate the Co(II) regeneration, restrain the cobalt dissolution to alleviate the active site loss, and contribute to the production of 1O2via synergistic effects of oxygen-containing groups in rGO. Toxicity assessment was performed on RNTD and its degradation intermediates to confirm the reduction in ecotoxicity of the treated feed. Overall, this work not only offered guidance for the application of nanosheets in AOP membranes, but also had implications for the environmentally-friendly preparation protocol to obtain functional metal hydroxides.

LncRNA MEG3 Restrains Hepatic Lipogenesis via the FOXO1 Signaling Pathway in HepG2 Cells.

Nonalcoholic fatty liver disease (NAFLD) become a main public health concern, and is characterized by lipid accumulation in the hepatocytes. We found that overexpression of lncRNA MEG3 significantly reduced the expression of FOXO1, ACC1, and FAS, and subsequently decreased the lipid accumulation in HepG2 cells. Moreover, inhibition of lncRNA MEG3 could increase the lipid accumulation and the mRNA and protein levels of FOXO1, ACC1, and FAS. Further study showed that lncRNA MEG3 regulates the lipogenesis process by inhibiting the entry of FOXO1 into the nucleus translocation. Our study demonstrated that lncRNA MEG3 regulates de novo lipogenesis by decreasing the expression and nucleus translocation of FOXO1 in HepG2 cells, suggesting that lncRNA MEG3 could be a promising therapeutic target in lipid metabolic disorders.

Unzippable Siamese Nanoparticles for Programmed Two-Stage Cancer Immunotherapy.

Epigenetic drugs (epi-drugs) can destruct cancer cells and initiate both innate and adaptive immunity, yet they have achieved very limited success in solid tumors so far, partly attributing to their concurrent induction of the myeloid-derived suppressor cell (MDSC) population. Here, dissociable Siamese nanoparticles (SIANPs) are developed for tumor cell-targeted delivery of epi-drug CM-272 and MDSC-targeted delivery of small molecule inhibitor Ibrutinib. The SIANPs are assembled via interparticle DNA annealing and detached via tumor microenvironment-triggered strand separation. Such binary regulation induces endogenous retrovirus expression and immunogenic cell death in tumor cells while restraining the immunosuppressive effects of MDSCs, and synergistically promotes dendritic cell maturation and CD8+ T cell activation for tumor inhibition. Significantly, immune microenvironment remodeling via SIANPs further overcomes tumor resistance to immune checkpoint blockade therapy. This study represents a two-pronged approach for orchestrating immune responses, and paves a new way for employing epi-drugs in cancer immunotherapy.