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Ionic liquids (ILs) are effective in pretreating cellulose for enhanced enzymatic saccharification, however ILs can inactivate cellulases. To guide the selection of ILs, the activity of cellulase was correlated with COSMO-RS calculations and descriptors of ILs including hydrogen bond (H-bond) basicity/acidity, polarity and ion size. Trends were deduced using an anion-series and a cation-series of ionic liquids in aqueous solutions. The activity in the cation-series was best correlated with the size of varied cations, whereas the activity in the anion-series showed a pronounced correlation to H-bond basicity and polarity of different anions. COSMO-RS was further used to predict the solubility of cellulose in ILs, which was correlated with cellulase activity on IL-pretreated cellulose. The best correlations were found between the enzyme activity in the anion-series ILs and the logarithmic activity coefficients, the H-bond energy, H-bond basicity and polarizability, underlining that the anion plays a crucial role in cellulose dissolution.

Diabetic sensory neuropathy leads to impairment of peripheral sensory nerves and downregulation of calcitonin gene-related peptide (CGRP) in a functionally specific subset of peripheral sensory neurons mediating pain. Whether CGRP plays a neuroprotective role in peripheral sensory nerve is unclear. We evaluated alterations in noxious thermal sensation and downregulation of CGRP in the 8 weeks after induction of diabetes in rats. We supplemented capsaicin in the diet of the animals to upregulate CGRP and reversed the downregulation of the neuropeptide in the dorsal root ganglion (DRG) neurons dissociated from the diabetic animals, via gene transfection and exogenous CGRP, to test disease-preventing and disease-limiting effects of CGRP. Significant preservation of the nociceptive sensation, CGRP in spinal cord and DRG neurons, and number of CGRP-expressing neurons was found in the diabetic animals given capsaicin. Improvement in the survival of the neurons and the outgrowth of neurites was achieved in the neurons transfected by LV-CGRP or by exogenous CGRP, paralleling the correction of abnormalities of intracellular reactive oxygen species and mitochondrial transmembrane potentials. The results suggest that downregulation of CGRP impairs viability, regeneration and function of peripheral sensory neurons while capsaicin normalizes the CGRP peptidergic DRG neurons and function of the sensory nerves.

The Loess Plateau, China, is the world’s largest apple-producing region, and over 80% of the orchards are in rainfed (dryland) areas. Desiccation of the deep soil layer under dryland apple orchards is the main stressor of apple production in this region. Fertilization is a factor that causes soil desiccation in dryland apple orchards. Given its applicability and precision validations, the Environmental Policy Integrated Climate (EPIC) model was used to simulate the dynamics of fruit yield and deep soil desiccation in apple orchards under six fertilization treatments. During the 45 years of study, the annual fruit yield under the fertilization treatments initially increased and then decreased in a fluctuating manner, and the average fruit yields were 24.42, 27.27, 28.69, 29.63, 30.49 and 29.43 t/ha in these respective fertilization treatments. As fertilization increased, yield of the apple orchards increased first and then declined,desiccation of the soil layers occurred earlier and extended deeper, and the average annual water consumption, over-consumption and water use efficiency increased as fertilization increased. In terms of apple yields, sustainable soil water use, and economic benefits, the most appropriate fertilization rate for drylands in Luochuan is 360–480 kg/ha N and 180–240 kg/ha P.

Nine synthetic amphiphilic phenolic lipids, varied in phenolic moiety (caffeoyl/dimethylcaffeoyl) and fatty acid chain lengths (8–18) were characterized by differential scanning calorimetry (DSC), temperature-ramp Fourier transform infra-red spectroscopy (FT-IR) and atomic force microscopy (AFM). FT-IR and DSC results revealed that the physical state and lateral packing of synthetic molecules were largely governed by fatty acyls. The critical micelle concentrations (CMC) of synthetic lipids was in the range of 0.1 mM to 2.5 mM, affording generation of stable oil-in-water emulsions; as evidenced by the creaming index (C12‒C16, and C12a‒C16a after 7 days’ storage. AFM analysis revealed that compound C14 formed stable double-layers films of 5.2 nm and 6.7 nm. Application studies showed that formulations stabilized by synthesized compounds containing 30% fish oil had superior physical and oxidative stability compared to formulations containing commercial emulsifiers or their mixtures with phenolic acids. Moreover, the synthetic compounds were non-toxic against in vitro transformed keratinocytes from histologically normal skin and Caco-2 cell lines. This study demonstrates the relevance of using a natural hydroxycarboxylic acid as a flexible linker between natural antioxidants, glycerol and fatty acids to generate multifunctional amphiphiles with potential applications in food, pharmaceutical and cosmetic industry.

Blood-based test has been considered as a promising way to diagnose and study Alzheimer’s disease (AD). However, the changed proportions of the leukocytes under disease states could confound the aberrant expression signals observed in mixed-cell blood samples. We have previously proposed a method, Ref-REO, to detect the leukocyte specific expression alterations from mixed-cell blood samples. In this study, by applying Ref-REO, we detect 42 and 45 differentially expressed genes (DEGs) between AD and normal peripheral whole blood (PWB) samples in two datasets, respectively. These DEGs are mainly associated with AD-associated functions such as Wnt signaling pathways and mitochondrion dysfunctions. They are also reproducible in AD brain tissue, and tend to interact with the reported AD-associated biomarkers and overlap with targets of AD-associated PWB miRNAs. Moreover, they are closely associated with aging and have severer expression alterations in the younger adults with AD. Finally, diagnostic signatures are constructed from these leukocyte specific alterations, whose area under the curve (AUC) for predicting AD is higher than 0.73 in the two AD PWB datasets. In conclusion, gene expression alterations in leukocytes could be extracted from AD PWB samples, which are closely associated with AD progression, and used as a diagnostic signature of AD.

Due to the invasiveness nature of tissue biopsy, it is common that investigators cannot collect sufficient normal controls for comparison with diseased samples. We developed a pathway enrichment tool, DRFunc, to detect significantly disease-disrupted pathways by incorporating normal controls from other experiments. The method was validated using both microarray and RNA-seq expression data for different cancers. The high concordant differentially ranked (DR) gene pairs were identified between cases and controls from different independent datasets. The DR gene pairs were used in the DRFunc algorithm to detect significantly disrupted pathways in one-phenotype expression data by combing controls from other studies. The DRFunc algorithm was exemplified by the detection of significant pathways in glioblastoma samples. The algorithm can also be used to detect altered pathways in the datasets with weak expression signals, as shown by the analysis on the expression data of chemotherapy-treated breast cancer samples.

Highly conserved short sequences help identify functional genomic regions and facilitate genomic annotation. We used Salmonella as the model to search the genome for evolutionarily conserved regions and focused on the tetranucleotide sequence CTAG for its potentially important functions. In Salmonella, CTAG is highly conserved across the lineages and large numbers of CTAG-containing short sequences fall in intergenic regions, strongly indicating their biological importance. Computer modeling demonstrated stable stem-loop structures in some of the CTAG-containing intergenic regions, and substitution of a nucleotide of the CTAG sequence would radically rearrange the free energy and disrupt the structure. The postulated degeneration of CTAG takes distinct patterns among Salmonella lineages and provides novel information about genomic divergence and evolution of these bacterial pathogens. Comparison of the vertically and horizontally transmitted genomic segments showed different CTAG distribution landscapes, with the genome amelioration process to remove CTAG taking place inward from both terminals of the horizontally acquired segment.

Red blood cell distribution width (RDW) is the coefficient of variation of red blood cell size, considered to be associated with cardiovascular disease (CVD). This study aimed to comprehensively synthesize previous studies on RDW and CVD outcomes through an overall and dose-response meta-analysis. PubMed, Embase and Web of Science were searched systematically for English and Chinese language publications up to November 30, 2015. We extracted data from publications matching our inclusion criteria for calculating pooled hazard ratio (HR), which was used to assess prognostic impact of RDW on CVD. Twenty-seven articles, consisting of 28 studies and 102,689 participants (mean age 63.9 years, 63,703 males/36,846 females, 2,140 gender-unmentioned subjects) were included in the present meta-analysis. The pooled HRs are 1.12 (95% CI = 1.09–1.15) for the association of all-cause mortality (ACM) per 1% increase of RDW, 1.12(95% CI = 1.08–1.17) for major adverse cardiac events (MACEs) per 1% increase of RDW. A dose-response curve relating RDW increase to its effect on CVD outcomes was established (pcurve

Titanium and its alloys with various porous structures are one of the most important metals used in orthopaedic implants due to favourable properties as replacement for hard tissues. However, surface modification is critical to improve the osteointegration of titanium and its alloys. In this study, a bioactive magnesium coating was successfully fabricated on porous Ti6Al4V by means of arc ion plating, which was proved with fine grain size and high film/substrate adhesion. The surface composition and morphology were characterized by X-ray diffraction and SEM equipped with energy dispersive spectroscopy. Furthermore, the in vitro study of cytotoxicity and proliferation of MC3T3-E1 cells showed that magnesium coated porous Ti6Al4V had suitable degradation and biocompatibility. Moreover, the in vivo studies including fluorescent labelling, micro-computed tomography analysis scan and Van-Gieson staining of histological sections indicated that magnesium coated porous Ti6Al4V could significantly promote bone regeneration in rabbit femoral condylar defects after implantation for 4 and 8 weeks, and has better osteogenesis and osteointegration than the bare porous Ti6Al4V. Therefore, it is expected that this bioactive magnesium coating on porous Ti6Al4V scaffolds with improved osteointegration and osteogenesis functions can be used for orthopedic applications.

To assess the role of time-intensity curves (TICs) of the normal peripheral zone (PZ) in the identification of biopsy-proven prostate nodules using contrast-enhanced transrectal ultrasound (CETRUS). This study included 132 patients with 134 prostate PZ nodules. Arrival time (AT), peak intensity (PI), mean transit time (MTT), area under the curve (AUC), time from peak to one half (TPH), wash in slope (WIS) and time to peak (TTP) were analyzed using multivariate linear logistic regression and receiver operating characteristic (ROC) curves to assess whether combining nodule TICs with normal PZ TICs improved the prediction of prostate cancer (PCa) aggressiveness. The PI, AUC (p p = 0.011 and 0.040 respectively) values of the malignant nodules were significantly higher than those of the benign nodules. Incorporating the PI and AUC values (both, p p = 0.076 and 0.159 respectively), significantly improved the AUC for prediction of malignancy (PI: 0.784–0.923; AUC: 0.758–0.891) and assessment of cancer aggressiveness (p

For patients with locally advanced rectal cancer (LARC) treated with preoperation chemoradiation (pCRT), identifying differentially expressed (DE) genes between non-responders and responders is a common approach for investigating mechanisms of chemoradiation resistance. However, some of such DE genes might be irrelevant to cancer itself but simply reflect the pharmacokinetic differences of the normal tissues. In this study, we adopted the RankComp algorithm to identify DE genes for each of LARC sample compared with its own normal state. Then, we identified genes with significantly different deregulation frequencies between the non-responders and responders, defined as cancer-related pCRT-response genes. Pathway enrichment and protein-protein interaction analyses showed that these genes specifically and intensively interacted with currently known effective genes of pCRT, involving in DNA replication, cell cycle and DNA repair. In contrast, after excluding the cancer-related pCRT-response genes, the other DE genes between non-responders and responders were enriched in many pathways of drug and protein metabolisms and transports, and interacted with both the known effective genes and pharmacokinetic genes. Hence, these two types of DE genes should be distinguished for investigating mechanisms of pCRT response in LARCs.

Identifying differentially expressed (DE) genes between cancer and normal tissues is of basic importance for studying cancer mechanisms. However, current methods, such as the commonly used Significance Analysis of Microarrays (SAM), are biased to genes with low expression levels. Recently, we proposed an algorithm, named the pairwise difference (PD) algorithm, to identify highly expressed DE genes based on reproducibility evaluation of top-ranked expression differences between paired technical replicates of cells under two experimental conditions. In this study, we extended the application of the algorithm to the identification of DE genes between two types of tissue samples (biological replicates) based on several independent datasets or sub-datasets of a dataset, by constructing multiple paired average gene expression profiles for the two types of samples. Using multiple datasets for lung and esophageal cancers, we demonstrated that PD could identify many DE genes highly expressed in both cancer and normal tissues that tended to be missed by the commonly used SAM. These highly expressed DE genes, including many housekeeping genes, were significantly enriched in many conservative pathways, such as ribosome, proteasome, phagosome and TNF signaling pathways with important functional significances in oncogenesis.

Transport-related genes significantly affect bacterial antibiotic resistance. However, the effects of these genes and their regulation of bacterial drug resistance in several mycobacterial species, including the fast-growing Mycobacterium smegmatis, the pathogen M. tuberculosis and M. avium have not been clearly characterized. We identified Ms4022 (MSMEG_4022) as a novel TetR family regulator that activates the expression of seven transport-related genes and affects drug resistance in M. smegmatis. Overexpression of Ms4022 inhibited M. smegmatis growth and enhanced mycobacterial resistance to the anti-tuberculosis drug rifampicin (RIF). By contrast, the Ms4022-deleted mycobacterial strain has shown sensitive to RIF. Ms4022 recognized three 19 bp non-palindromic motifs containing a 9 bp conserved region at their 5′ end and it directly regulated seven transport-related genes, which affects mycobacterial resistance to RIF. Overexpression of three of seven transport-related genes (Ms1448, Ms1613 and Ms5278) inhibited the growth of M. smegmatis. This study improves our understanding of the function of mycobacterial transport-related genes and their regulation of bacterial drug resistance.

To precisely diagnose metastasis state is important for tailoring treatments for gastric cancer patients. However, the routinely employed radiological and pathologic tests for tumour metastasis have considerable high false negative rates, which may retard the identification of reproducible metastasis-related molecular biomarkers for gastric cancer. In this research, using three datasets, we firstly shwed that differentially expressed genes (DEGs) between metastatic tissue samples and non-metastatic tissue samples could hardly be reproducibly detected with a proper statistical control when the metastatic and non-metastatic samples were defined by TNM stage alone. Then, assuming that undetectable micrometastases are the prime cause for recurrence of early stage patients with curative resection, we reclassified all the “non-metastatic” samples as metastatic samples whenever the patients experienced tumour recurrence during follow-up after tumour resection. In this way, we were able to find distinct and reproducible DEGs between the reclassified metastatic and non-metastatic tissue samples and concordantly significant DNA methylation alterations distinguishing metastatic tissues and non-metastatic tissues of gastric cancer. Our analyses suggested that the follow-up recurrence information for patients should be employed in the research of tumour metastasis in order to decrease the confounding effects of false non-metastatic samples with undetected micrometastases.

The drawbacks of traditional bone-defect treatments have prompted the exploration of bone tissue engineering. This study aimed to explore suitable β-tricalcium phosphate (β-TCP) granules for bone regeneration and identify an efficient method to establish β-TCP-based osteo-regenerators. β-TCP granules with diameters of 1 mm and 1–2.5 mm were evaluated in vitro. The β-TCP granules with superior osteogenic properties were used to establish in vivo bioreactors, referred to as osteo-regenerators, which were fabricated using two different methods. Improved proliferation of bone mesenchymal stem cells (BMSCs), glucose consumption and ALP activity were observed for 1–2.5 mm β-TCP compared with 1-mm granules (P

Emerging evidence substantiates the potential of porous titanium alloy (pTi) as an ideal bone-graft substitute because of its excellent biocompatibility and structural properties. However, it remains a major clinical concern for promoting high-efficiency and high-quality osseointegration of pTi, which is beneficial for securing long-term implant stability. Accumulating evidence demonstrates the capacity of low-amplitude whole-body vibration (WBV) in preventing osteopenia, whereas the effects and mechanisms of WBV on osteogenesis and osseointegration of pTi remain unclear. Our present study shows that WBV enhanced cellular attachment and proliferation and induced well-organized cytoskeleton of primary osteoblasts in pTi. WBV upregulated osteogenesis-associated gene and protein expression in primary osteoblasts, including OCN, Runx2, Wnt3a, Lrp6 and β-catenin. In vivo findings demonstrate that 6-week and 12-week WBV stimulated osseointegration, bone ingrowth and bone formation rate of pTi in rabbit femoral bone defects via μCT, histological and histomorphometric analyses. WBV induced higher ALP, OCN, Runx2, BMP2, Wnt3a, Lrp6 and β-catenin and lower Sost and RANKL/OPG gene expression in rabbit femora. Our findings demonstrate that WBV promotes osteogenesis and osseointegration of pTi via its anabolic effect and potential anti-catabolic activity and imply the promising potential of WBV for enhancing the repair efficiency and quality of pTi in osseous defects.

Isoniazid (INH), an anti-tuberculosis (TB) drug, has been widely used for nearly 60 years. However, the pathway through which Mycobacterium tuberculosis responds INH remain largely unclear. In this study, we characterized a novel transcriptional factor, InbR, which is encoded by Rv0275c and belongs to the TetR family, that is directly responsive to INH. Disrupting inbR made mycobacteria more sensitive to INH, whereas overexpressing inbR decreased bacterial susceptibility to the drug. InbR could bind specifically to the upstream region of its own operon at two inverted repeats and act as an auto-repressor. Furthermore, InbR directly bind with INH and the binding reduced InbR’s DNA-binding ability. Interestingly, susceptibilities were also changed by InbR for other anti-TB drugs, such as rifampin, implying that InbR may play a role in multi-drug resistance. Additionally, microarray analyses revealed a portion genes of the inbR regulon have similar expression patterns in inbR-overexpressing strain and INH-treated wild type strain, suggesting that these genes, for example iniBAC, may be responsible to the drug resistance of inbR-overexpressing strain. The regulation of these genes by InbR were further assessed by ChIP-seq assay. InbR may regulate multiple drug resistance of mycobacteria through the regulation of these genes.

Researchers usually measure only a few technical replicates of two types of cell line, resistant or sensitive to a drug and use a fold-change (FC) cut-off value to detect differentially expressed (DE) genes. However, the FC cut-off lacks statistical control and is biased towards the identification of genes with low expression levels in both cell lines. Here, viewing every pair of resistant-sensitive technical replicates as an experiment, we proposed an algorithm to identify DE genes by evaluating the reproducibility of the expression difference or FC between every two independent experiments without overlapping samples. Using four small datasets of cancer cell line resistant or sensitive to a drug, we demonstrated that this algorithm could efficiently capture reproducible DE genes significantly enriched in biological pathways relevant to the corresponding drugs, whereas many of them could not be found by the FC and other commonly used methods. Therefore, the proposed algorithm is an effective complement to current approaches for analysing small cancer cell line data.

Specific determination/monitoring of trace mercury ions (Hg(2+)) in environmental water is of significant importance for drinking safety. Complementarily to conventional inductively coupled plasma mass spectrometry and atomic emission/absorption spectroscopy, several methods, i.e., electrochemical, fluorescent, colorimetric, and surface enhanced Raman scattering approaches, have been developed recently. Despite great success, many inevitably encounter the interferences from other metal ions besides the complicated procedures and sophisticated equipments. Here we present a molecular-gap device for specific determination of trace Hg(2+) in both standardized solutions and environmental samples based on conductivity-modulated glutathione dimer. Through a self-assembling technique, a thin film of glutathione monolayer capped Au nanoparticles is introduced into 2.5 μm-gap-electrodes, forming numerous double molecular layer gaps. Notably, the fabricated molecular-gap device shows a specific response toward Hg(2+) with a low detection limit actually measured down to 1 nM. Theoretical calculations demonstrate that the specific sensing mechanism greatly depends on the electron transport ability of glutathione dimer bridged by heavy metal ions, which is determined by its frontier molecular orbital, not the binding energy.