Statistical Inference Methods for Two Crossing Survival Curves: A Comparison of Methods

A common problem that is encountered in medical applications is the overall homogeneity of survival distributions when two survival curves cross each other. A survey demonstrated that under this condition, which was an obvious violation of the assumption of proportional hazard rates, the log-rank test was still used in 70% of studies. Several statistical methods have been proposed to solve this problem. However, in many applications, it is difficult to specify the types of survival differences and choose an appropriate method prior to analysis. Thus, we conducted an extensive series of Monte Carlo simulations to investigate the power and type I error rate of these procedures under various patterns of crossing survival curves with different censoring rates and distribution parameters. Our objective was to evaluate the strengths and weaknesses of tests in different situations and for various censoring rates and to recommend an appropriate test that will not fail for a wide range of applications. Simulation studies demonstrated that adaptive Neyman’s smooth tests and the two-stage procedure offer higher power and greater stability than other methods when the survival distributions cross at early, middle or late times. Even for proportional hazards, both methods maintain acceptable power compared with the log-rank test. In terms of the type I error rate, Renyi and Cramér—von Mises tests are relatively conservative, whereas the statistics of the Lin-Xu test exhibit apparent inflation as the censoring rate increases. Other tests produce results close to the nominal 0.05 level. In conclusion, adaptive Neyman’s smooth tests and the two-stage procedure are found to be the most stable and feasible approaches for a variety of situations and censoring rates. Therefore, they are applicable to a wider spectrum of alternatives compared with other tests.     

Elaborate differences between trees and understory plants in the deployment of fine roots

Plant and Soil - Leaf-litter decomposition rate (k L ) regulates nutrient dynamics and is affected at microsite level by species traits, soil biota and microclimate conditions. Fallen fruits form...     

Biocatalysis for the synthesis of pharmaceuticals and pharmaceutical intermediates

Biocatalysis has been increasingly used for pharmaceutical synthesis in an effort to make manufacturing processes greener and more sustainable. Biocatalysts that possess excellent activity, specificity, thermostability and solvent-tolerance are highly sought after to meet the requirements of practical applications. Generating biocatalysts with these specific properties can be achieved by either discovery of novel biocatalysts or protein engineering. Meanwhile, chemoenzymatic routes have also been designed and developed for pharmaceutical synthesis on an industrial scale. This review discusses the recent discoveries, engineering, and applications of biocatalysts for the synthesis of pharmaceuticals and pharmaceutical intermediates. Key classes of biocatalysts include reductases, oxidases, hydrolases, lyases, isomerases, and transaminases.     

Purification of Chinese Sacbrood Virus (CSBV), Gene Cloning and Prokaryotic Expression of its Structural Protein VP1

The aim of this study was to purify the Chinese Sacbrood Virus Beijing Miyun (BJMY-CSBV) from infected Apis cerana larvae, clone structural protein gene VP1 (named BJMY-CSBV-VP1), and investigate its biological information. The result indicated that the capsid of CSBV is of spherical shape. Gene clone experiment showed that the BJMY-CSBV-VP1 gene sequence comprised 945 bp, encoding 315 amino acids with relative molecular weight of 35.59 kDa and isoelectric point 9.38 pI. Phylogenetic analysis of amino acid sequences showed that the BJMY-CSBV-VP1 and LNDD_2015 were grouped together. Protein secondary structure prediction showed that the gene contained two α-helices, thirteen β-folds, six polypeptide binding sites, and no disulfide bridge. Simultaneously, the BJMY-CSBV-VP1 was ligated to the expression vector pET32a(+) and then transformed into the Escherichia coli BL21 (DE3) for prokaryotic expression. The optimal expression experiment revealed that the protein was found in the inclusion body. The recombinant protein was successfully purified by washing buffer combined with supersonic fragmentation. In this study, we obtained the purified BJMY-CSBV particles, cloned BJMY-CSBV-VP1 gene, investigated the detailed information of the gene by analyzing the sequence, and obtained the purified recombinant protein, which could help for further understanding of the function of the structural protein gene VP1.     

Upregulation of the solute carrier family 7 genes is indicative of poor prognosis in papillary thyroid carcinoma

Background

The solute carrier (SLC) 7 family genes comprise 14 members and function as cationic amino acid/glycoprotein transporters in many cells, they are essential for the maintenance of amino acid nutrition and survival of tumor cells. This study was conducted to analyze the associations of SLC7 family gene expression with mortality in papillary thyroid carcinoma (PTC).

Methods

Clinical features, somatic mutations, and SLC7 family gene expression data were downloaded from The Cancer Genome Atlas database. Linear regression model analysis was performed to analyze the correlations between SLC7 family gene expression and clinicopathologic features. Kaplan-Meier survival and logistic regression analyses were performed to characterize the associations between gene expression and patients’ overall survival.

Results

Patient mortality was negatively associated with age and tumor size but positively increased cancer stage and absence of thyroiditis in PTC patients. Kaplan-Meier survival analysis indicated that patients with high SLC7A3, SLC7A5, and SLC7A11 expression levels exhibited poorer survival than those with low SLC7A3, SLC7A5, and SLC7A11 expression levels (P?<?0.05 for all cases). Logistic regression analysis showed that SLC7A3, SLC7A5, and SLC7A11 were associated with increased mortality (odds ratio [OR] 8.61, 95% confidence interval [CI] 2.3–55.91; OR 3.87, 95% CI 1.18–17.31; and OR 3.87, 95% CI 1.18–17.31, respectively.

Conclusion

Upregulation of SLC7A3, SLC7A5, and SLC7A11 expression was associated with poor prognosis in PTC patients, and SLC7 gene expression levels are potentially useful prognostic biomarkers.

     

In vivo biosensors: mechanisms,development, and applications

In vivo biosensors can recognize and respond to specific cellular stimuli. In recent years, biosensors have been increasingly used in metabolic engineering and synthetic biology, because they can be implemented in synthetic circuits to control the expression of reporter genes in response to specific cellular stimuli, such as a certain metabolite or a change in pH. There are many types of natural sensing devices, which can be generally divided into two main categories: protein-based and nucleic acid-based. Both can be obtained either by directly mining from natural genetic components or by engineering the existing genetic components for novel specificity or improved characteristics. A wide range of new technologies have enabled rapid engineering and discovery of new biosensors, which are paving the way for a new era of biotechnological progress. Here, we review recent advances in the design, optimization, and applications of in vivo biosensors in the field of metabolic engineering and synthetic biology.     

Synthetic biology advances and applications in the biotechnology industry: a perspective

Synthetic biology is a logical extension of what has been called recombinant DNA (rDNA) technology or genetic engineering since the 1970s. As rDNA technology has been the driver for the development of a thriving biotechnology industry today, starting with the commercialization of biosynthetic human insulin in the early 1980s, synthetic biology has the potential to take the industry to new heights in the coming years. Synthetic biology advances have been driven by dramatic cost reductions in DNA sequencing and DNA synthesis; by the development of sophisticated tools for genome editing, such as CRISPR/Cas9; and by advances in informatics, computational tools, and infrastructure to facilitate and scale analysis and design. Synthetic biology approaches have already been applied to the metabolic engineering of microorganisms for the production of industrially important chemicals and for the engineering of human cells to treat medical disorders. It also shows great promise to accelerate the discovery and development of novel secondary metabolites from microorganisms through traditional, engineered, and combinatorial biosynthesis. We anticipate that synthetic biology will continue to have broadening impacts on the biotechnology industry to address ongoing issues of human health, world food supply, renewable energy, and industrial chemicals and enzymes.     

Propagation Properties of Nanoscale Three-Dimensional Plasmonic Waveguide Based on Hybrid of Two Fundamental Planar Optical Metal Waveguides

In this paper, a nanoscale three-dimensional plasmonic waveguide (TDPW), created by depositing an Ag stripe on a SiO₂ layer with an Ag substrate, is introduced and theoretically investigated at visible and telecom wavelengths. By applying the effective index method and finite-difference time-domain numerical simulations, the authors find that the propagation properties of surface plasmon polaritons (SPPs) in the TDPW, including the propagation length and beam width, are mainly decided by the core (the SiO₂ layer just under the Ag stripe) itself, due to the much stronger localization of SPPs in the core than in the two side claddings (the SiO₂ layer without the covered Ag stripe). And propagating SPPs in the TDPW are strongly confined in the core region, even with a very small waveguide cross section. Furthermore, based on the stronger localization of propagation SPPs in the TDPW, two kinds of bending waveguides, oblique bending and 90° circular bending waveguides, are also investigated. For wavelength of 1550 nm, the 90° circular bending guide with a minimum radius as small as 2.6 μm show nearly zero radiation loss, even with a small waveguide cross section of 70?×?80 nm². The proposed TDPW is suitable for planar integration and provides a possible way for constructing various nanoscale counterparts of conventional integrated devices such as splitter, resonator, sensor, and optical switch.     

Molecular mechanisms governing plant responses to high temperatures

The increased prevalence of high temperatures(HTs) around the world is a major global concern, as they dramatically affect agronomic productivity. Upon HT exposure, plants sense the temperature change and initiate cellular and metabolic responses that enable them to adapt to their new environmental conditions.Decoding the mechanisms by which plants cope with HT will facilitate the development of molecular markers to enable the production of plants with improved thermotolerance. In recent decades, genetic, physiological, molecular, and biochemical studies have revealed a number of vital cellular components and processes involved in thermoresponsive growth and the acquisition of thermotolerance in plants. This review summarizes the major mechanisms involved in plant HT responses, with a special focus on recent discoveries related to plant thermosensing, heat stress signaling, and HT-regulated gene expression networks that promote plant adaptation to elevated environmental temperatures.     

Adoptive transfer of natural killer cells in combination with chemotherapy improves outcomes of patients with locally advanced colon carcinoma

Background

Despite the availability of multiple treatment strategies, patients with advanced colon carcinoma (CC) have poor prognoses. The aim of this study was to evaluate the efficacy and safety of natural killer (NK) cell therapy in combination with chemotherapy in patients with locally advanced CC.