Prognostic value of the Naples prognostic score in patients with intrahepatic cholangiocarcinoma after hepatectomy.

BACKGROUND: The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. METHODS: Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022-3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259-4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184-3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519-4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. CONCLUSIONS: NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.

Resource-efficient channel estimation for DCO-OFDM based VLC systems.

We consider a resource-efficient pilot design for visible light communication (VLC) system employing direct-current offset orthogonal frequency division multiplexing (DCO-OFDM). Firstly, we experimentally verify that the normalized channel gain vectors remain approximately the same at different locations under a line-of-sight (LOS) path between the transmitter and the receiver. Then, under the constant normalized subcarrier gain assumption, it is proved that a single pilot subcarrier is optimal to maximize the achievable rate without signal clipping. The impact of power budget and statistical channel characteristics is investigated regarding the optimal pilot position and the related achievable rate. We extend the pilot position optimization to a general case considering the light-emitting diode (LED) and power amplifier (PA) with a limited linear dynamic range. Assuming double-sided clipping, the impact of LED upper saturation voltage and statistical channel characteristics on the optimal pilot position and the achievable rate is investigated via the Bussgang theorem. Finally, under constant normalized link gain assumption, we propose a blind channel estimation approach based on the covariance of frequency-domain outputs. The convergence of the proposed channel estimation approaches based on constant normalized link gain is verified experimentally.

Tris(1,3-dichloro-2-propyl) Phosphate Inhibits Early Embryonic Development by Binding to Gsk-3ß Protein in Zebrafish.

Recently, several studies have reported that exposure to tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) results in abnormal development of zebrafish embryos in blastocyst and gastrula stages, but molecular mechanisms are still not clear. This lacking strongly affects the interspecific extrapolation of embryonic toxicity induced by TDCIPP and hazard evaluation. In this study, zebrafish embryos were exposed to 100, 500 or 1000 µg/L TDCIPP, and 6-bromoindirubin-3'-oxime (BIO, 35.62 µg/L) was used as a positive control. Results demonstrated that treatment with TDCIPP or BIO caused an abnormal stacking of blastomere cells in mid blastula transition (MBT) stage, and subsequently resulted in epiboly delay of zebrafish embryos. TDCIPP and BIO up-regulated the expression of ß-catenin protein and increased its accumulation in nuclei of embryonic cells. This accumulation was considered as a driver for early embryonic developmental toxicity of TDCIPP. Furthermore, TDCIPP and BIO partly shared the same modes of action, and both of them could bind to Gsk-3ß protein, and then decreased the phosphorylation level of Gsk-3ß in TYR·216 site and lastly inhibited the activity of Gsk-3ß kinase, which was responsible for the increased concentrations of ß-catenin protein in embryonic cells and accumulation in nuclei. Our findings provide new mechanisms for clarifying the early embryonic developmental toxicity of TDCIPP in zebrafish.

Identification of DNA methylation and genetic alteration simultaneously from a single blood biopsy.

BACKGROUND: High-throughput sequencing of blood cell-free DNA (cfDNA) techniques offer an opportunity to characterize and monitor cancer rapidly in a non-invasive and real-time manner. Nonetheless, there lacks a tool within therapeutic arsenal to identify multi-omics alterations simultaneously from a single biopsy. In current times, bisulfite-based sequencing detects 5mC and 5hmC at single-base resolution is the golden standard of DNA methylation, while the degradation of DNA and biased sequencing data are the problems of this method. OBJECTIVE: To identify the consistency analysis of methylation and genetic variation with single library, we presented a platform detecting multi-omics data simultaneously from a single blood biopsy using bisulfite-free method of genomic methylation sequencing (GM-seq) mediated by TET enzyme. METHODS: We detected methylomic and genetic changes simultaneously from a single blood biopsy in NA12878 and randomly chose ten blood biopsies from colorectal cancer or lung cancer patients to validate the ability of GM-seq. RESULTS: Similar cytosine methylation level between whole genome bisulfite sequencing (WGBS) and GM-seq were identified in NA12878. Moreover, longer insert size, CpGs coverage and GC distribution were outperformed than WGBS. In addition, the comparison of the single nucleotide polymorphism (SNP), insertion-deletion (Indel) and copy number variation (CNV) in NA12878 or ctDNA from liver cancer between GM-seq and whole genome sequencing (WGS) show a good consistency, indicating that this method is feasible for detecting genetic variation in blood. CONCLUSION: In conclusion, our work demonstrated a method for identification of the methylated modification and genetic variations simultaneously from a single blood biopsy.

Reduced Biofilm Formation at the Air-Liquid-Solid Interface via Introduction of Surfactants.

Reduced biofilm formation is highly desirable in applications ranging from transportation to separations and healthcare. Biofilms often form at the three-phase interface where air, liquid, and solid coexist due to the close proximity to nutrients and oxygen. Reducing biofilm formation at the triple interface presents challenges because of the conflicting requirements for hydrophobicity at the air-solid interface (for self-cleaning properties) and for hydrophilicity at the liquid-solid interface (for reduced foulant adhesion). Meeting those needs simultaneously likely entails a dynamic surface, capable of shifting the surface energy landscape in response to wetting conditions and thus enabling hydrophobicity in air and hydrophilicity in water. Here, we designed a facile approach to render existing surfaces resistant to biofilm formation at the triple interface. By adding trace amounts (∼0.1 mM) of surfactants, biofilm formation of Pseudomonas aeruginosa (known to form biofilm at the triple interface) was reduced on all surfaces tested, ranging from hydrophilic to hydrophobic, polar to nonpolar. That reduced fouling was not a result of the known antimicrobial effects. Instead, it was attributed to the surface-adsorbed surfactants that dynamically control surface energy at the triple interface. To further understand the effect of surfactant-surface interactions on biofilm reduction, we systematically varied the surfactant charge type and surface properties (surface energy and charge). Electrostatic interactions between surfactants and surfaces were identified as an influential factor when predicting the relative fouling reduction upon introduction of surfactants. Nevertheless, biofilm formation was reduced even on the charge-neutral, fluorinated surface made of poly(1H, 1H, 2H, 2H-perfluorodecyl acrylate) by more than 2-fold simply via adding 0.2 mM dodecyl trimethylammonium chloride or 0.3 mM sodium dodecyl sulfate. Given its robustness, this strategy is broadly applicable for reducing fouling on existing surfaces, which in turn improves the cost-effectiveness of membrane separations and mitigates contaminations and nosocomial infections in healthcare.

Metabolic engineering of Escherichia coli for efficient production of L-5-hydroxytryptophan from glucose.

BACKGROUND: 5-hydroxytryptophan (5-HTP), the direct biosynthetic precursor of the neurotransmitter 5-hydroxytryptamine, has been shown to have unique efficacy in the treatment of a variety of disorders, including depression, insomnia, and chronic headaches, and is one of the most commercially valuable amino acid derivatives. However, microbial fermentation for 5-HTP production continues to face many challenges, including low titer/yield and the presence of the intermediate L-tryptophan (L-Trp), owing to the complexity and low activity of heterologous expression in prokaryotes. Therefore, there is a need to construct an efficient microbial cell factory for 5-HTP production. RESULTS: We describe the systematic modular engineering of wild-type Escherichia coli for the efficient fermentation of 5-HTP from glucose. First, a xylose-induced T7 RNA polymerase-PT7 promoter system was constructed to ensure the efficient expression of each key heterologous pathway in E. coli. Next, a new tryptophan hydroxylase mutant was used to construct an efficient tryptophan hydroxylation module, and the cofactor tetrahydrobiopterin synthesis and regeneration pathway was expressed in combination. The L-Trp synthesis module was constructed by modifying the key metabolic nodes of tryptophan biosynthesis, and the heterologous synthesis of 5-HTP was achieved. Finally, the NAD(P)H regeneration module was constructed by the moderate expression of the heterologous GDHesi pathway, which successfully reduced the surplus of the intermediate L-Trp. The final engineered strain HTP11 was able to produce 8.58 g/L 5-HTP in a 5-L bioreactor with a yield of 0.095 g/g glucose and a maximum real-time productivity of 0.48 g/L/h, the highest values reported by microbial fermentation. CONCLUSION: In this study, we demonstrate the successful design of a cell factory for high-level 5-HTP production, combined with simple processes that have potential for use in industrial applications in the future. Thus, this study provides a reference for the production of high-value amino acid derivatives using a systematic modular engineering strategy and a basis for an efficient engineered strain development of 5-HTP high-value derivatives.

Application of DNA barcoding in fish identification of supermarkets in Henan province, China: More and longer COI gene sequences were obtained by designing new primers.

In recent years, DNA barcode technology has been widely used in food identification, especially in the identification of fish. In China, there are few studies on the authenticity of fish products in Henan province of China. In this study, 179 fish samples were collected from supermarkets in Zhengzhou city and Xinxiang city in Henan province, China. COI gene sequences were obtained with PCR technology by designing specific primers and universal primers. COI gene sequences of all samples were obtained to identify species, which is used to investigate species substitution and mislabeling of the fish sold in the two regional markets. The molecular identification results showed that 28.49% (51/179) fish samples were not consistent with the labels. Substitution of high-price fish by low-price fish was prevalent. For example, halibut (Pleuronectiformes) and cod (Gadus) are replaced by striped catfish (Pangasianodon hypophthalmus), and some merchants label bighead carp (Hypophthalmichthys nobilis) as cod (Gadus), there are also accidental labeling errors (such as labels for greenfin horse-faced filefish (Thamnaconus septentrionalis) have been identified as grass carp (Ctenopharyngodon idella) and Wuchang bream (Megalobrama amblycephala) etc. Most of the samples labeled correctly are the fish of low economic value and the fresh fish. This study shows that almost all the commercial fish can be identified by COI DNA barcoding by newly designed primers. Finally, this study also gives a reference of real species of fish fillet in Henan province in China.

Detection of C1236T, G2677T/A, and C3435T polymorphism of MDR1 by amplification refractory mutation system PCR.

C1236T, G2677T/A, and C3435T polymorphism of the multidrug resistance (MDR1) gene have substantial impact on expression or activity of P-glycoprotein (P-gp). We developed new methods based on amplification refractory mutation system (ARMS) to detect these polymorphisms. Tetra-primers amplification in a single tube was established to detect C1236T and C3435T polymorphism. For G2677T/A polymorphism, a two-step allele-specific amplification method was used. MDR1 genotypes of 177 Chinese subjects were determined by the methods we established. The methods we established were verified with gene sequencing. Gene frequencies of 1236C and 1236T were 37.8 and 62.2%, respectively; gene frequencies of 2677G, 2677T and 2677A were 44.1, 38.4 and 17.5%, respectively; the gene frequencies of 3435C and 3435T were 65.0 and 35.0%, respectively. The results were similar with other studies on Oriental subjects. The methods we established are simple, accurate, and economical, and can provide reliable approaches for determining MDR1 polymorphism.