Identification of essential proteins based on edge features and the fusion of multiple-source biological information

Abstract Background A major current focus in the analysis of protein–protein interaction (PPI) data is how to identify essential proteins. As massive PPI data are available, this warrants the design of efficient computing methods for identifying essential proteins. Previous studies have achieved considerable performance. However, as a consequence of the features of high noise and structural complexity in PPIs, it is still a challenge to further upgrade the performance of the identification methods. Methods This paper proposes an identification method, named CTF, which identifies essential proteins based on edge features including h-quasi-cliques and uv-triangle graphs and the fusion of multiple-source information. We first design an edge-weight function, named EWCT, for computing the topological scores of proteins based on quasi-cliques and triangle graphs. Then, we generate an edge-weighted PPI network using EWCT and dynamic PPI data. Finally, we compute the essentiality of proteins by the fusion of topological scores and three scores of biological information. Results We evaluated the performance of the CTF method by comparison with 16 other methods, such as MON, PeC, TEGS, and LBCC, the experiment results on three datasets of Saccharomyces cerevisiae show that CTF outperforms the state-of-the-art methods. Moreover, our method indicates that the fusion of other biological information is beneficial to improve the accuracy of identification

Effects of Supplementation of Branches and Leaves Trimmed from Tea Plant on Growth Performance, Rumen Fermentation and Meat Composition of Nanjiang Yellow Goats

Thirty-two 6-month-old, healthy Nanjiang Yellow goats (34.6 ± 4.16 kg) were randomly divided into four treatments to evaluate the supplementary effects of branches and leaves trimmed from tea tree (BLTT) on growth performance, rumen fermentation characteristics, and meat composition in fattening goats. The control goats were fed a basal diet. Treatments 1, 2 and 3 were fed 2%, 4% and 6% of BLTT respectively. After a 60 d feeding trial, blood samples were collected for the analysis of the antioxidant profile and goats were slaughtered to obtain the rumen fluid and carcass samples for determination of rumen fermentation characteristics and meat composition perameters. Increased final body weight was observed in goats fed 4% BLTT compared with control. The activity of superoxide dismutase was increased in the 4% BLTT-treated group, while glutathione peroxidase and malondialdehyde followed the quadratic curve. Quadratic curves were also observed for villus height, crypt depth and the ratio of villus height to crypt depth in the jejunum. The quadratic effect was obtained for total essential amino acids, and individual amino acids threonine and leucine. The saturated fatty acid C16:0 was decreased with 4% of BLTT supplementation, and a quadratic effect was observed for polyunsaturated fatty acid C18:3 (n−3). To sum up, our findings revealed that BLTT supplementation has a positive effect on body antioxidative status, gastrointestinal development, rumen fermentation characteristics and overall growth performance and meat quality in goats

Intensive cycles of neoadjuvant camrelizumab combined with chemotherapy in locally advanced esophageal squamous cell carcinoma: a single-arm, phase II trial

Abstract Background Two cycles of neoadjuvant PD-1 blockade plus chemotherapy induced favorable pathological response and tolerant toxicity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, approximately 25% of patients relapsed within 1 year after surgery, indicating that a short course of treatment may not be sufficient. Therefore, exploring the effects of intensive treatment is needed for optimal clinical outcomes. Methods Locally advanced ESCC patients were administered three cycles of camrelizumab plus nab-paclitaxel and capecitabine, followed by thoracoscopic esophagectomy. The primary endpoint was pathologic response. Secondary endpoints included safety, feasibility, radiologic response, survival outcomes, and immunologic/genomic correlates of efficacy. Results Forty-seven patients were enrolled in the study. Forty-two patients received surgery, and R0 resection was achieved in all cases. The complete and major pathological response rates were 33.3% and 64.3%, respectively, and the objective response rate was 80.0%. Three cycles of treatment significantly improved T down-staging compared to two cycles (P = 0.03). The most common treatment-related adverse events were grades 1–2, and no surgical delay was reported. With a median follow-up of 24.3 months, the 1-year disease-free survival and overall survival rates were both 97.6%, and the 2-year disease-free survival and overall survival rates were 92.3% and 97.6%, respectively. Three patients experienced disease recurrence or metastasis ranging from 12.5 to 25.8 months after surgery, and one patient died 6 months after surgery due to cardiovascular disease. Neither programmed death-ligand 1 expression nor tumor mutational burden was associated with pathological response. An increased infiltration of CD56 dim natural killer cells in the pretreatment tumor was correlated with better pathological response in the primary tumor. Conclusions It seems probable that intensive cycles of neoadjuvant camrelizumab plus nab-paclitaxel and capecitabine increased tumor regression and improved survival outcomes. Randomized controlled trials with larger sample sizes and longer follow-up periods are needed to validate these findings. Trial registration Chinese Clinical Trial Registry, ChiCTR2000029807, Registered February 14, 2020, https://www.chictr.org.cn/showproj.aspx?proj=49459

Total neoadjuvant treatment to increase the clinical complete response rate for distal locally advanced rectal cancer (TESS): A study protocol of a prospective, open‐label, multicenter, single‐arm, phase 2 trial

Abstract Background Standard treatment of locally advanced rectal cancer (LARC) was neoadjuvant chemoradiotherapy (CRT), followed by total mesorectal excision (TME). Total neoadjuvant treatment (TNT), a new concept, attempts to deliver both systemic chemotherapy and neoadjuvant CRT prior to surgery. Patients treated with neoadjuvant chemotherapy were more likely to show higher tumor regression. The objective of this trial was to increase complete clinical rate (cCR) for LARC patients by optimizing tumor response, using TNT regimen as compared to conventional chemoradiotherapy. TESS, a prospective, open‐label, multicenter, single‐arm, phase 2 study, is underway. Methods Main inclusion criteria include cT3‐4aNany or cT1‐4aN+ rectal adenocarcinoma aged 18‐70y; Eastern Cooperative Oncology Group (ECOG) performance 0–1; location ≤5 cm from anal verge. Ninety‐eight patients will receive 2 cycles of neoadjuvant chemotherapy Capeox (capecitabine + oxaliplatin) before, during, and after radiotherapy 50Gy/25 fractions, before TME (or other treatment decisions, such as Watch and Wait strategy) and adjuvant chemotherapy capecitabine 2 cycles. Primary endpoint is the cCR rate. Secondary endpoints include ratio of sphincter preservation strategy; pathological complete response rate and tumor regression grade distribution; local recurrence or metastasis; disease‐free survival; locoregional recurrence‐free survival; acute toxicity; surgical complications; long‐term anal function; late toxicity; adverse effect, ECOG standard score, and quality of life. Adverse events are graded per Common Terminology Criteria for Adverse Events V5.0. Acute toxicity will be monitored during antitumor treatment, and late toxicity will be monitored for 3 years from the end of the first course of antitumor treatment. Discussion The TESS trial aims to explore a new TNT strategy, which is expected to increase the rate of cCR and sphincter preservation rate. This study will provide new options and evidence for a new sandwich TNT strategy in patients with distal LARC

3D Digital Rock Modeling of the Fractal Properties of Pore Structures

Fractal parameters of porous media have been a focus of study in petroleum engineering and hydrogeology for several decades because they provide an effective way to describe the complexity of pore structure across a wide range of scales. This paper combines 3D process-driven digital rock modeling with fractal analysis in order to understand the effect of varying sorting, compaction, cementation, and the fine grain fraction of binary models on the fractal parameters and specific surface area of porous media. Digital rock models (DRMs) were constructed to simulate sandstone using a process-driven modeling technique which simulates sedimentation. The fractal parameters of the resulting pore geometry were calculated using the box-counting method on 2D and 3D representations of the DRMs. Our simulations indicate that increasing compaction or cementation lead to significant decreases in fractal dimension, specific surface area (SSp) and porosity, showing that these two diagenetic processes can affect the pore microstructure of the rock significantly. While interface fractal dimension (Di) and SSp both increase slightly with decreases in sorting (grain size variety), and porosity decreases slightly. Examining the behavior of binary models, the porosity of our digital models shows a V-shaped curve as fine grain fraction increases from 0 to 1, consistent with, but higher than the theoretical values, which we attribute to incomplete packing of the grains arising from the simplified packing algorithm and finite boundary of models. The value of both SSp and Di increase as the fine grain fraction increases. However, we must notice that the porosity may be underestimated, and the fractal dimension may be overestimated when we use models consisting of very fine spherical grains due to the effect of image resolution