Comparative analysis of chlorine-resistant bacteria after chlorination and chloramination in drinking water treatment plants.

Chlorine-resistant bacteria (CRB) in drinking water treatment plants (DWTPs) jeopardize water quality and pose a potential risk to human health. However, the specific response of CRB to chlorination and chloramination remains uncharacterized. Therefore, we analyzed 16 S rRNA sequencing data from water samples before and after chlorination and chloramination taken between January and December 2020. Proteobacteria and Firmicutes dominated all finished water samples. After chloramination, Acinetobacter, Pseudomonas, Methylobacterium, Ralstonia, and Sphingomonas were the dominant CRB, whereas Ralstonia, Bacillus, Acinetobacter, Pseudomonas, and Enterococcus were prevalent after chlorination. Over 75% of the CRB e.g. Acinetobacter, Pseudomonas, Bacillus, and Enterococcus were shared between the chlorination and chloramination, involving potentially pathogens, such as Acinetobacter baumannii and Pseudomonas aeruginosa. Notably, certain genera such as Faecalibacterium, Geobacter, and Megasphaera were enriched as strong CRB after chloramination, whereas Vogesella, Flavobacterium, Thalassolituus, Pseudoalteromonas, and others were enriched after chlorination according to LEfSe analysis. The shared CRB correlated with temperature, pH, and turbidity, displaying a seasonal pattern with varying sensitivity to chlorination and chloramination in cold and warm seasons. These findings enhance our knowledge of the drinking water microbiome and microbial health risks, thus enabling better infectious disease control through enhanced disinfection strategies in DWTPs.

To Assess the Role of microRNA-451 in the Progression and Metastasis of Colorectal Cancer.

The study aimed to determine the expression of miR451 in colorectal cancer (CRC) subjects with CRC cells, and the role of miR451 in colorectal cancer cells. In October 2020, ATC purchased CRC and normal mucosal cell lines of CRC and implanted them in DMEM with 10% fetal serum. The suitability of the HT29 cell line is verified using the STR profile. In an incubator with 5% CO2, enlarged cells were placed at 37 °C. TCGA data was used to select the top 120 patients with a high voice and the lowest 120 patients with a low voice. Cells were collected and coated with Annexin V and PE according to the manufacturer's instructions after 24.0 h. After that, the cells were separated. Cells were also tested using flow cytometry. HCT-120 cells were transplanted into a concentration of 5×105/ml cells in 6-source plates. HCT120 cells in the experimental group were combined with miR451 mimics, miR451 inhibitors, or miR451 miR + SMAD4B for 12 h at 37 °C, and cells were collected 24 h later at 37 °C. The sample was injected with 5 ml of Annexin VFITC and PE. Compared with normal colorectal mucosal cells, CRC cell lines decreased miR451 expression levels (fetal human cells (FHC) and HCoEpiC). Then, the HCT120 cells were transfected with miR451 inhibitors, and 72 h after transfection, say of miR451 was normal. There was a significant decrease in cell function in the miR451mimic groups, but an increase when the miR451 was blocked. The proliferation of cancer cells was prevented and chemotherapy was effective when miR451 was overexpressed. The SMAD4 gene provides instructions for making a protein involved in transmitting chemical signals from the cell surface to the nucleus. The SMAD4B expression was tested by RT-qPCR and Western blotting after 72.0 h of transmission. The mRNA and protein expression of SMAD4B decreased significantly when miR451 was significantly higher than when inhibited, as revealed in the results of this study. Seventy-two hours after transplantation, mRNA levels and SMAD4B proteins were measured in HCT120 cells. In addition, the researchers in this study investigated whether miR451 was associated with SMAD4B-directed control of CRC growth and migration. It was found that SMAD4B is highly expressed in both CRC and para-cancer tissues while using the TCGA database to detect SMAD4B expression. Patients with CRC with SMAD4B have a severe prognosis. MiR451 is sensitive to depressive disorders by targeting SMAD4B, according to these studies. We found that miR451 inhibited cell growth and migration, made CRC cells more readily available in chemotherapy, and did so by targeting SMAD4B. The findings suggest that miR451 and its genetic predisposition, SMAD4B, may help predict the prognosis and course of cancer patients. Treatments that target the miR451/SMAD4B axis may be helpful to people with CRC.

Spatial and temporal analysis of the seasonal dynamics of antibiotic resistance gene occurrence in recreational marine water.

People who engage in water sports in recreational marine water may be at high risk of exposure to hazardous antibiotic-resistant bacteria (ARB). However, information on the contribution of specific sources to ARB contamination in recreational marine water is still lacking. Here, we carried out monthly analyses of antibiotic resistance genes (ARGs), pathogenic bacteria and 16S rRNA sequencing data at the First Bathing Beach in Qingdao. The sampling sites were divided into four areas: swimming area, intermediate area, polluted area, and sewage outlet. Correlations between ARGs and bacterial communities among sampling sites were explored by spatial and temporal analysis. We found that all of 21 important ARG types were detected in the swimming area, with aadA (1.3 × 106 ± 2.7 × 106 genomic copies/L) and sul2 (4.3 × 105 ± 5.9 × 105 genomic copies/L) at the highest concentration. Most ARGs were detected at highest frequency and concentration in the sewage outlet and decreased from there to the swimming area. ARG correlation between these two areas was positive only in the cold season, suggesting that sewage was the main source of ARG pollution in the swimming area during that period. The ARGs ermA(1) and vanA were detected at highest frequency and concentration in the swimming area and were significantly correlated with the intestinal pathogen Enterococcus, which was more abundant here than in the surrounding areas during the warm season. Co-occurrence analysis of bacterial genera and ARGs showed that six genera were commonly correlated with ARGs in all sampling areas in the cold season, while none were found in the warm season. Our findings indicate that ARG pollution in the swimming area was also driven by sources other than sewage, especially in the warm season, which is the peak tourist season in Qingdao. These results provide a valuable basis for the implementation of effective strategies to control ARG risks in recreational waters.

Long Noncoding RNA LINC00578 Inhibits Ferroptosis in Pancreatic Cancer via Regulating SLC7A11 Ubiquitination.

Background: Pancreatic cancer is a highly aggressive malignancy worldwide with rapid development and an exceedingly poor prognosis. lncRNAs play crucial roles in regulating the biological behaviors of tumor cells. In this study, we discovered that LINC00578 acted as a regulator of ferroptosis in pancreatic cancer. Methods: A series of loss- and gain-of-function experiments in vitro and in vivo were performed to explore the oncogenic role of LINC00578 in pancreatic cancer development and progression. Label-free proteomic analysis was performed to select LINC00578-related differentially expressed proteins. Pull-down and RNA immunoprecipitation assays were carried out to determine and validate the binding protein of LINC00578. Coimmunoprecipitation assays were used to investigate the association of LINC00578 with SLC7A11 in ubiquitination and to confirm the interaction between ubiquitin-conjugating enzyme E2 K (UBE2K) and SLC7A11. An immunohistochemical assay was used to confirm the correlation between LINC00578 and SLC7A11 in the clinic. Results: LINC00578 positively regulated cell proliferation and invasion in vitro and tumorigenesis in vivo in pancreatic cancer. LINC00578 can obviously inhibit ferroptosis events, including cell proliferation, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP) depolarization. In addition, the LINC00578-induced inhibitory effect on ferroptosis events was rescued by SLC7A11 knockdown. Mechanistically, LINC00578 directly binds UBE2K to decrease the ubiquitination of SLC7A11, thus accelerating SLC7A11 expression. In the clinic, LINC00578 is closely associated with clinicopathologic factors and poor prognosis and correlated with SLC7A11 expression in pancreatic cancer. Conclusions: This study elucidated that LINC00578 acts as an oncogene to promote pancreatic cancer cell progression and suppress ferroptosis by directly combining with UBE2K to inhibit the ubiquitination of SLC7A11, which provides a promising option for the diagnosis and treatment of pancreatic cancer.

Hepatocyte-derived MANF mitigates ethanol-induced liver steatosis in mice via enhancing ASS1 activity and activating AMPK pathway.

Hepatic steatosis plays a detrimental role in the onset and progression of alcohol-associated liver disease (ALD). Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an evolutionarily conserved protein related to the unfolded protein response. Recent studies have demonstrated that MANF plays an important role in liver diseases. In this study, we investigated the role of MANF in ethanol-induced steatosis and the underlying mechanisms. We showed that the hepatic MANF expression was markedly upregulated in mouse model of ALD by chronic-plus-single-binge ethanol feeding. Moreover, after chronic-plus-binge ethanol feeding, hepatocyte-specific MANF knockout (HKO) mice displayed more severe hepatic steatosis and liver injury than wild-type (WT) control mice. Immunoprecipitation-coupled MS proteomic analysis revealed that arginosuccinate synthase 1 (ASS1), a rate-limiting enzyme in the urea cycle, resided in the same immunoprecipitated complex with MANF. Hepatocyte-specific MANF knockout led to decreased ASS1 activity, whereas overexpression of MANF contributed to enhanced ASS1 activity in vitro. In addition, HKO mice displayed unique urea cycle metabolite patterns in the liver with elevated ammonia accumulation after ethanol feeding. ASS1 is known to activate AMPK by generating an intracellular pool of AMP from the urea cycle. We also found that MANF supplementation significantly ameliorated ethanol-induced steatosis in vivo and in vitro by activating the AMPK signaling pathway, which was partly ASS1 dependent. This study demonstrates a new mechanism in which MANF acts as a key molecule in maintaining hepatic lipid homeostasis by enhancing ASS1 activity and uncovers an interesting link between lipid metabolism and the hepatic urea cycle under excessive alcohol exposure.

Comprehensive insights into profiles and bacterial sources of intracellular and extracellular antibiotic resistance genes in groundwater.

Antibiotic resistance genes (ARGs), especially last-resort ARGs (LARGs), are receiving extensive attention as emerging environmental contaminants in groundwater. However, their prevalent intracellular and extracellular patterns and bacterial sources in groundwater remain unclear. Herein, groundwater samples were collected in Tianjin, and characterized based on the profiles of intracellular ARGs (iARGs) and extracellular ARGs (eARGs), as well as the resident bacterial communities and extracellular DNA (eDNA)-releasing bacterial communities. The quantitative real-time PCR assays showed that eARGs presented fewer subtypes than iARGs and generally displayed lower detection frequencies than the corresponding iARGs. Similarly, LARGs exhibited lower detection frequencies than common ARGs, but the total abundance showed no significant differences between them. Genes vanA and blaVIM were the observed dominant LARGs, and aadA was the observed common ARG independent of location inside or outside the bacteria. Furthermore, the top 10 phyla showed much difference between the main eDNA-releasing bacteria and the dominant resident bacteria. Proteobacteria was the predominant resident bacterial phyla while dominating the source of eDNA in groundwater. Despite representing a minor portion of the abundance in the resident bacteria, Actinobacteriota, Acidobacteriota, and Chloroflex surprisingly accounted for a large majority of eDNA release. Co-occurrence patterns among persistent ARGs, the resident bacteria, and eDNA-releasing bacteria revealed that the dominant common iARG aadA and intracellular LARGs blaVIM and vanA had significant positive correlations with Methylobacterium_Methylorubrum and Shewanella. Meanwhile, the dominant extracellular LARG blaVIM may be released by bacteria belonging to at least five genera, including Ellin6067, Bifidobacterium, Blautia, Veillonella, and Dechloromonas. Collectively, the findings of this study extend our understanding regarding the distribution of ARGs and their bacterial sources in groundwater, and indicate the serious pollution of LARGs in groundwater, which poses potential risks to public health.

Emerging pollutant metformin in water promotes the development of multiple-antibiotic resistance in Escherichia coli via chromosome mutagenesis.

Antibiotics are known to be key drivers of antibiotic resistance and antibiotic resistance gene transmission. However, the contribution of the emerging pollutant metformin in facilitating antibiotic resistance remains unclear. In this study, Escherichia coli K12 (E. coli) was exposed to metformin at concentrations ranging from 10-7 to 200 mg/L, and antibiotic susceptibility test of isolated mutants was evaluated. DNA and RNA sequencing and real-time quantitative PCR (qPCR) were performed to identify the underlying mechanisms. The results showed metformin concentrations ranging from 10-6 to 200 mg/L caused multiple-antibiotic resistance in E. coli. After 1 day exposure to metformin at 1 ng/L, the mutation frequency in E. coli increased to 1.24 × 10-8, and it further increased to 7.13 × 10-8 when prolonged to 5 days. And the mutants showed multiple-antibiotic resistance. Whole-genome DNA analysis of mutants showed chromosome mutagenesis in marR, tonB, and fhuA. Global transcriptional analysis and qPCR revealed the expressions of emrK, emrY, cusB, cusC, hycA, cecR, marA, acrA, and acrB were upregulated and those of tonB and fhuA were significantly downregulated. Thus, an increase in efflux systems AcrAB-TolC, EmrKY-TolC, and CusCFBA together with a decrease in FhuA-TonB protein complex play vital roles in the multiple-antibiotic resistance induced by metformin.

Integrative analysis of TNFRSF6B as a potential therapeutic target for pancreatic cancer.

BACKGROUND: Pancreatic cancer is one of the most lethal malignant tumors worldwide with poor outcomes. Previous studies have shown that tumor necrosis factor receptor superfamily member 6b (TNFRSF6B) plays an important role in cancer progression and immunosuppression. However, the mechanisms by which TNFRSF6B influence pancreatic cancer, and the regulatory networks involved remain to be further studied. METHODS: This study analyzed the mRNA information and clinical data of patients from The Cancer Genome Atlas (TCGA) and the ONCOMINE databases. The gene co-expression data regarding TNFRSF6B was obtained from the c-BioPortal and used to explore the functional network of TNFRSF6B in pancreatic cancer, as well as its function in tumor immunity. Short hairpin (sh) RNA knock-down experiments were performed to examine the functional roles of TNFRSF6B in pancreatic cancer cell lines. RESULTS: The expression of TNFRSF6B was elevated in pancreatic cancer tissues compared to normal pancreatic tissues, and its high expression was associated with poor prognosis of patients with pancreatic cancer. TNFRSF6B was found to be widely involved in cell cycle processes, apoptosis, apoptosis signaling pathways, immune responses, and responses to interferon. Knock-down of TNFRSF6B expression inhibited pancreatic cancer cell proliferation and invasion in vitro. Moreover, carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) was found to be co-expressed with TNFRSF6B, and there was a positive correlation between these molecules in pancreatic cancer cells. CONCLUSIONS: This report suggested that TNFRSF6B has a critical role in the progression and metastasis of pancreatic cancer. These findings provide novel insights into the role of TNFRSF6B in the functional network of pancreatic cancer, and suggest that TNFRSF6B may be a potential therapeutic target.

Why MUC16 mutations lead to a better prognosis: A study based on The Cancer Genome Atlas gastric cancer cohort.

BACKGROUND: MUC16, encoding cancer antigen 125, is a frequently mutated gene in gastric cancer. In addition, MUC16 mutations seem to result in a better prognosis in gastric cancer. However, the mechanisms that lead to a better prognosis by MUC16 mutations have not yet been clarified. AIM: To delve deeper into the underlying mechanisms that explain why MUC16 mutations signal a better prognosis in gastric cancer. METHODS: We used multi-omics data, including mRNA, simple nucleotide variation, copy number variation and methylation data from The Cancer Genome Atlas, to explore the relationship between MUC16 mutations and prognosis. Cox regression and random survival forest algorithms were applied to search for hub genes. Gene set enrichment analysis was used to elucidate the molecular mechanisms. Single-sample gene set enrichment analysis and "EpiDISH" were used to assess immune cells infiltration, and "ESTIMATE" for analysis of the tumor microenvironment. RESULTS: Our study found that compared to the wild-type group, the mutation group had a better prognosis. Additional analysis indicated that the MUC16 mutations appear to activate the DNA repair and p53 pathways to act as an anti-tumor agent. We also identified a key gene, NPY1R (neuropeptide Y receptor Y1), which was significantly more highly expressed in the MUC16 mutations group than in the MUC16 wild-type group. The high expression of NPY1R predicted a poorer prognosis, which was also confirmed in a separate Gene Expression Omnibus cohort. Further susceptibility analysis revealed that NPY1R might be a potential drug target for gastric cancer. Furthermore, in the analysis of the tumor microenvironment, we found that immune cells in the mutation group exhibited higher anti-tumor effects. In addition, the tumor mutation burden and cancer stem cells index were also higher in the mutation group than in the wild-type group. CONCLUSION: We speculated that the MUC16 mutations might activate the p53 pathway and DNA repair pathway: alternatively, the tumor microenvironment may be involved.

Enhancement of sludge electro-dewatering by anthracite powder modification.

Electro-dewatering of sludge has received considerable attention due to its low energy consumption for sludge deep-dewatering. However, prior studies have shown the resistance of dried sludge near anode significantly hinders electro-dewatering. The dewatering performance may be improved by reducing the resistance with the addition of conductive material into sludge. We conditioned municipal sludge by anthracite powder, an inexpensive product, to increase solid conductivity, followed by electro-dewatering. After running for 20 min under a constant voltage of 30 V, when the anthracite powder mass was 10%-22% of raw sludge dry solids mass (DS), the final dry solids content of the mud cake after dehydration was 6.2%-12.9% higher than that from dehydration of unconditioned sludge. The average filtrate flow rate ranged from 0.0243 to 0.0285 g s-1. The lowest unit energy consumption, 0.19 kW h·kgwater-1, which was 14% lower than that of control, was reached when 18% DS of anthracite was added. Our theoretical analysis indicates that properly increasing solid conductivity of sludge can reduce the adverse effect caused by the high electrical resistance of sludge near anode. The experimental results, along with the theoretical analysis, show that using anthracite powder for sludge modification is an economical approach to improve sludge dewatering rate and reduce energy consumption.

Signature of gene aberrant alternative splicing events in pancreatic adenocarcinoma prognosis.

Alternative splicing (AS), as an effective and universal mechanism of transcriptional regulation, is involved in the development and progression of cancer. Therefore, systematic analysis of alternative splicing in pancreatic adenocarcinoma (PAAD) is warranted. The corresponding clinical information of the RNA-Seq data and PAAD cohort was downloaded from the TCGA data portal. Then, a java application, SpliceSeq, was used to evaluate the RNA splicing pattern and calculate the splicing percentage index (PSI). Differentially expressed AS events (DEAS) were identified based on PSI values between PAAD cancer samples and normal samples of adjacent tissues. Kaplan-Meier and Cox regression analyses were used to assess the association between DEAS and patient clinical characteristics. Unsupervised cluster analysis used to reveal four clusters with different survival patterns. At the same time, GEO and TCGA combined with GTEx to verify the differential expression of AS gene and splicing factor. After rigorous filtering, a total of 45,313 AS events were identified, 1,546 of which were differentially expressed AS events. Nineteen DEAS were found to be associated with OS with a five-year overall survival rate of 0.946. And the subtype clusters results indicate that there are differences in the nature of individual AS that affect clinical outcomes. Results also identified 15 splicing factors associated with the prognosis of PAAD. And the splicing factors ESRP1 and RBM5 played an important role in the PAAD-associated AS events. The PAAD-associated AS events, splicing networks, and clusters identified in this study are valuable for deciphering the underlying mechanisms of AS in PAAD and may facilitate the establishment of therapeutic goals for further validation.

A 3-armed multicenter randomized controlled trial: Placental Transfusion in Very Preterm Infants (PT-VPI).

Preterm infants constitute an important proportion of neonatal deaths and various complications, and very preterm infants (VPI) are more likely to develop severe complications, such as intraventricular hemorrhage (IVH), anemia, and sepsis. It has been confirmed that placental transfusion can supplement blood volume in infants and reduce preterm-associated complications, which is further conducive to the development of the nervous system and a better long-term prognosis. Based on these advantages, placental transfusion has been widely used in VPI. There are three main types of placental transfusion: delayed cord clamping (DCC), intact umbilical cord milking (I-UCM), and cut umbilical cord milking (C-UCM). However, the optimal method for PT-VPI remains controversial, and it is urgent to identify the best method of placental transfusion. We plan to fully evaluate the safety and effectiveness of these three placental transfusion methods in VPI in a 3-arm multicenter randomized controlled trial: Placental Transfusion in Very Preterm Infants (PT-VPI). Trial registration: chictr.org.cn, number ChiCTR2000030953.

Correction of the tumor suppressor Salvador homolog-1 deficiency in tumors by lycorine as a new strategy in lung cancer therapy.

Salvador homolog-1 (SAV1) is a tumor suppressor required for activation of the tumor-suppressive Hippo pathway and inhibition of tumorigenesis. SAV1 is defective in several cancer types. SAV1 deficiency in cells promotes tumorigenesis and cancer metastasis, and is closely associated with poor prognosis for cancer patients. However, investigation of therapeutic strategies to target SAV1 deficiency in cancer is lacking. Here we found that the small molecule lycorine notably increased SAV1 levels in lung cancer cells by inhibiting SAV1 degradation via a ubiquitin-lysosome system, and inducing phosphorylation and activation of the SAV1-interacting protein mammalian Ste20-like 1 (MST1). MST1 activation then caused phosphorylation, ubiquitination, and degradation of the oncogenic Yes-associated protein (YAP), therefore inhibiting YAP-activated transcription of oncogenic genes and tumorigenic AKT and NF-κB signal pathways. Strikingly, treating tumor-bearing xenograft mice with lycorine increased SAV1 levels, and strongly inhibited tumor growth, vasculogenic mimicry, and metastasis. This work indicates that correcting SAV1 deficiency in lung cancer cells is a new strategy for cancer therapy. Our findings provide a new platform for developing novel cancer therapeutics.

Electro-dewatering of sewage sludge: Effect of near-anode sludge modification with different dosages of calcium oxide.

The efficiency of common sludge electro-dewatering (EDW) is restrained by the following issues: 1, the near-anode sludge dries out quickly, causing a rapid increase in electrical resistance; 2, the pH at anode decreases by the accumulation of H+ from the electrolysis of moisture, resulting in a decrease in Zeta potential (ζ). Alleviating the negative impact of these problems is the key to improving the dewatering efficiency of EDW. Therefore, in this study, calcium oxide (CaO) was used for near-anode sludge modification to increase its pH and electrical conductivity. With increasing CaO dosage, pH rose from 6.0 to 12.2, electrical conductivity increased from 368 ± 16 µS/cm to 6285 ± 21 µS/cm and the ζ declined from -15.3 ± 0.6 mV to -8.8 ± 0.4 mV. The EDW tests were conducted at 30 V and 25.5 kPa. The results indicate near-anode sludge modification with CaO weighing 3%-5% mass of raw sludge (mu(RS)) improved the EDW effect, while the energy consumption increased slightly. When 3%-5% mu(RS) of CaO was added, the final moisture content of sludge was 54.5%-44.3%, below that of the blank group (no CaO added), which was 57.9%; the time to obtain target moisture content (60%) was 910 s-590 s, lower than the blank group's 1060 s; and the energy consumption to obtain target moisture content was 0.233 kW h/kg H2O-0.271 kW h/kg H2O, higher than the blank group's 0.157 kW h/kg H2O. A quantitative criterion (KsiEDW) was adopted to assess the feasibility of EDW. Economically and energetically, the experiment with 4% mu(RS) of CaO added for near-anode modification was the optimal condition in this research, due to its second smallest KsiEDW, the best sludge reduction effect (67.2%), lower final moisture content (46.2%) and less time (640 s) to obtain target moisture content. The results show some mechanisms of EDW and provide experience for practical application.

Novel risk scoring system for prediction of pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: The available prediction models for clinically relevant postoperative pancreatic fistula (CR-POPF) do not incorporate both preoperative and intraoperative variables. AIM: To construct a new risk scoring system for CR-POPF that includes both preoperative and intraoperative factors. METHODS: This was a retrospective study of patients who underwent pancreaticoduodenectomy (PD) or pylorus-preserving PD (PPPD) between January 2011 and December 2016 at the First Affiliated Hospital of Soochow University. Patients were divided into a study (01/2011 to 12/2014) or validation (01/2015 to 12/2016) group according to the time of admission. POPF severity was classified into three grades: Biochemical leak (grade A) and CR-POPF (grades B and C). Logistic regression was used to create a predictive scoring system. RESULTS: Preoperative serum albumin ≥ 35 g/L [P = 0.032, odds ratio (OR) = 0.92, 95% confidence interval (CI): 0.85-0.99], hard pancreatic texture (P = 0.004, OR = 0.25, 95%CI: 0.10-0.64), pancreatic duct diameter ≥ 3 mm (P = 0.029, OR = 0.50, 95%CI: 0.27-0.93), and intraoperative blood loss ≥ 500 mL (P = 0.006, OR = 1.002, 95%CI: 1.001-1.003) were independently associated with CR-POPF. We established a 10-point risk scoring system to predict CR-POPF. The area under the curve was 0.821 (95%CI: 0.736-0.905) and the cut-off value was 3.5. Including drain amylase levels improved the predictive power of the model. CONCLUSION: This study established a 10-point scoring system to predict CR-POPF after PD/PPPD using preoperative and intraoperative parameters. Ultimately, this system could be used to distinguish between high- and low-risk populations in order to facilitate timely interventions after PD.

Electro-dewatering of sewage sludge: Influence of combined action of constant current and constant voltage on performance and energy consumption.

In this study, mechanically-dewatered sludge was used to investigate the effect of electro-dewatering (EDW) under two electrical modes, which are constant current mode followed by constant voltage mode (CV-EDW), and constant voltage mode followed by constant current mode (VC-EDW). The effect of current and voltage changes on dewatering efficiency and energy consumption of sludge electroosmosis under CV-EDW and VC-EDWs was evaluated The results show that compared with constant current mode (C-EDW), CV-EDW can improve the final dry solids content and reduce the heating rate, and the final dry solids content and unit energy consumption increase with the decrease of current and the increase of voltage. Under CV-EDW, when the dry solids content is 32%, the energy consumption can be reduced by changing to the constant voltage stage, and the energy consumption is 0.093-0.113 kWh/kgwater. Compared with constant voltage mode (V-EDW), VC-EDW significantly improves sludge dewatering rate. Under VC-EDW, the final dry solids content of sludge increases with the decrease of current and voltage. When the voltage is decreased by 10 V, the unit energy consumption is reduced by 27.15 ±â€¯1.77% on average, and the energy consumption is 0.132-0.163 kWh/kgwater. Compared with CV-EDW, the dehydration rate of VC-EDW is increased by 72.9% on average. However, the unit energy consumption required for dehydration increases by 43.09% when the dry solids content is less than 45%.

DcR3 promotes proliferation and invasion of pancreatic cancer via a DcR3/STAT1/IRF1 feedback loop.

Pancreatic cancer (PC) is one of the most common gastrointestinal malignancies that are highly aggressive with a low 5-year survival rate. Accumulated evidence has indicated that decoy receptor 3 (DcR3) is involved in several pathologic processes and various cancers. However, the mechanisms underlying dysregulated DcR3 expression and activation in PC remain to be fully established. In this study, we investigate the function and regulatory network of DcR3 in PC. We found that DcR3 was upregulated in PC tissues and serum. High DcR3 expression was associated with aggressive clinicopathological features and poor prognosis. Functionally, DcR3 not only increased cell migration and invasion in vitro but also promoted tumour growth both in vitro and in vivo by loss-of-function and gain-of-function experiments. Mechanistically, DcR3 promoted the phosphorylation of signal transducers and activators of transcription 1 (STAT1), leading to a dramatic increase in interferon regulatory factor 1 (IRF1). IRF1 then increased the transcriptional activity of DcR3, forming a positive feedback loop to reinforce DcR3 expression. In addition, DcR3 promoted carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) expression through activated IRF1. In conclusion, our findings provided novel insights into the function and mechanism of DcR3 in the pathogenesis of PC, which may be a potential therapeutic target for PC.

Inhibition of colon cancer cell growth by nanoemulsion carrying gold nanoparticles and lycopene.

Lycopene (LP), an important functional compound in tomatoes, and gold nanoparticles (AN), have received considerable attention as potential candidates for cancer therapy. However, the extreme instability and poor bioavailability of LP limits its in vivo application. This study intends to develop a nanoemulsion system incorporating both LP and AN, and to study the possible synergistic effects on the inhibition of the HT-29 colon cancer cell line. LP-nanogold nanoemulsion containing Tween 80 as an emulsifier was prepared, followed by characterization using transmission electron microscopy (TEM), dynamic light scattering (DLS) analysis, ultraviolet spectroscopy, and zeta potential analysis. The particle size as determined by TEM and DLS was 21.3±3.7 nm and 25.0±4.2 nm for nanoemulsion and 4.7±1.1 nm and 3.3±0.6 nm for AN, while the zeta potential of nanoemulsion and AN was -32.2±1.8 mV and -48.5±2.7 mV, respectively. Compared with the control treatment, both the combo (AN 10 ppm plus LP 12 µM) and nanoemulsion (AN 0.16 ppm plus LP 0.4 µM) treatments resulted in a five- and 15-fold rise in early apoptotic cells of HT-29, respectively. Also, the nanoemulsion significantly reduced the expressions of procaspases 8, 3, and 9, as well as PARP-1 and Bcl-2, while Bax expression was enhanced. A fivefold decline in the migration capability of HT-29 cells was observed for this nanoemulsion when compared to control, with the invasion-associated markers being significantly reversed through the upregulation of the epithelial marker E-cadherin and downregulation of Akt, nuclear factor kappa B, pro-matrix metalloproteinase (MMP)-2, and active MMP-9 expressions. The TEM images revealed that numerous nanoemulsion-filled vacuoles invaded cytosol and converged into the mitochondria, resulting in an abnormally elongated morphology with reduced cristae and matrix contents, demonstrating a possible passive targeting effect. The nanoemulsion containing vacuoles were engulfed and internalized by the nuclear membrane envelop for subsequent invasion into the nucleoli. Taken together, LP-nanogold nanoemulsion could provide synergistic effects at AN and LP doses 250 and 120 times lower than that in the combo treatment, respectively, demonstrating the potential of nanoemulsion developed in this study for a possible application in colon cancer therapy.

Factors influencing the decision to retain or remove the bone flap of adult patients with traumatic brain injury: a retrospective study.

AIM: To investigate clinical factors that may influence the decision to preserve or remove the bone flap during the craniectomy surgery for patients of traumatic brain injury. MATERIAL AND METHODS: Clinical data from 2256 TBI patients were quantitatively analyzed and scored based on multiple clinical factors, including preoperative Glasgow Coma Scale (GCS) score, changes in pupil size, hematoma volume, time interval between injury and surgery, midline shift on CT scan, hematoma location and type, cortical collapse and the lateral ventricular shift deformation. RESULTS: We identified several independent factors in the decision to preserve the bone flap: GCS score and pupil changes before the operation, cortical collapse, injury/surgery time interval and hematoma location. The results suggested that for patients with a combined score of ≥ 55, their bone flap was generally retained. For cases with a score of 50-55, the surgical decision was based on the patient level of preconscious status, changes in pupil size and the extent of postoperative cortical collapse, and for patients with a score < 50, the bone flap was generally removed. CONCLUSION: Our scoring scheme is to identify factors that may be helpful when determining whether to remove or retain bone flap of TBI patients.

Apolipoprotein E gene polymorphism and the risk of intracerebral hemorrhage: a meta-analysis of epidemiologic studies.

BACKGROUND: Studies investigating the association between the apolipoprotein E (APOE) gene polymorphism and the risk of intracerebral hemorrhage (ICH) have reported conflicting results. We here performed a meta-analysis based on the evidence currently available from the literature to make a more precise estimation of this relationship. METHODS: Published literature from the National Library of Medline and Embase databases were retrieved. Odds ratio (OR) and 95% confidence interval (CI) were calculated in fixed- or random-effects models when appropriate. Subgroup analyses were performed by race. RESULTS: This meta-analysis included 11 case-control studies, which included 1,238 ICH cases and 3,575 controls. The combined results based on all studies showed that ICH cases had a significantly higher frequency of APOE ϵ4 allele (OR= 1.42, 95% CI= 1.21,1.67, P<0.001). In the subgroup analysis by race, we also found that ICH cases had a significantly higher frequency of APOE ϵ4 allele in Asians (OR= 1.52, 95% CI= 1.20,1.93, P<0.001) and in Caucasians (OR= 1.34, 95% CI= 1.07,1.66, P=0.009). There was no significant relationship between APOE ϵ2 allele and the risk of ICH. CONCLUSION: Our meta-analysis suggested that APOE ϵ4 allele was associated with a higher risk of ICH.