Sepsis remains a leading cause of death worldwide, despite advances in critical care, and understanding of the pathophysiology and treatment strategies. No specific therapy or drugs are available for ...sepsis. Neutrophils play a critical role in controlling infection under normal conditions, and it is suggested that their migration and antimicrobial activity are impaired during sepsis which contribute to the dysregulation of immune responses. Recent studies further demonstrated that interruption or reversal of the impaired migration and antimicrobial function of neutrophils improves the outcome of sepsis in animal models. In this review, we provide an overview of the associated mediators and signal pathways involved which govern the survival, migration and antimicrobial function of neutrophils in sepsis, and discuss the potential of neutrophils as a target to specifically diagnose and/or predict the outcome of sepsis.
Cotton cultivars have evolved to produce extensive, long, seed-born fibers important for the textile industry, but we know little about the molecular mechanism underlying spinnable fiber formation. ...Here, we report how PACLOBUTRAZOL RESISTANCE 1 (PRE1) in cotton, which encodes a basic helix-loop-helix (bHLH) transcription factor, is a target gene of spinnable fiber evolution.
Differential expression of homoeologous genes in polyploids is thought to be important to plant adaptation and novel phenotypes. PRE1 expression is specific to cotton fiber cells, upregulated during their rapid elongation stage and A-homoeologous biased in allotetraploid cultivars. Transgenic studies demonstrated that PRE1 is a positive regulator of fiber elongation.
We determined that the natural variation of the canonical TATA-box, a regulatory element commonly found in many eukaryotic core promoters, is necessary for subgenome-biased PRE1 expression, representing a mechanism underlying the selection of homoeologous genes.
Thus, variations in the promoter of the cell elongation regulator gene PRE1 have contributed to spinnable fiber formation in cotton. Overexpression of GhPRE1 in transgenic cotton yields longer fibers with improved quality parameters, indicating that this bHLH gene is useful for improving cotton fiber quality.
The step-stress accelerated degradation test (SSADT) is a useful tool for assessing the lifetime distribution of highly reliable or expensive product. Some efficient SSADT plans have been proposed ...when the underlying degradation follows the Wiener process or Gamma process. However, how to design an efficient SSADT plan for the inverse Gaussian (IG) process is still a problem to be solved. The aim of this paper is to provide an optimal SSADT plan for the IG degradation process. A cumulative exposure model for the SSADT is adopted, in which the product degradation path depends only on the current stress level and the degradation accumulated, and has nothing to do with the way of accumulation. Under the constraint of the total experimental budget, some design variables are optimized by minimizing the asymptotic variance of the estimated p-quantile of the lifetime distribution of the product. Finally, we use the proposed method to deal with the optimal SSADT design for a type of electrical connector based on a set of stress relaxation data. The sensitivity and stability of the SSADT plan are studied, and we find that the optimal test plan is quite robust for a moderate departure from the values of the parameters.
•We propose an optimal SSADT plan for the IG degradation process.•A CE model is assumed in describing the degradation path of the SSADT.•The asymptotic variance of the estimated p-quantile is used as the objective function.•A set of stress relaxation data is analyzed and used for illustration of our method.
Background
How gastric cancer (GC) incidence is associated with changes in the gastric microbiome has not been firmly established. The present study therefore aims to investigate the microbial ...communities present within the gastric mucosa of patients with superficial gastritis (SG) or GC.
Methods
Paired tumor and paracancerous samples of the gastric mucosa were collected from 18 patients being surgically treated for GC and from 32 patients with SG being treated via gastroscopy. The gastric microbiome in these samples was then profiled via 16S rRNA sequencing, with a linear discriminant analysis effect size (LEfSe) approach used to identify and compare different bacteria, and with PICRUSt used for predictive functional analyses.
Results
GC patients exhibited a distinct gastric microbiota profile from that observed in SG patients. These changes were evident in both tumor and paracancerous tissues from GC patients. Specifically, we found that 6 bacterial genera were specifically enriched in GC tissue samples relative to SG samples, while 18 genera were depleted in these same samples. Based on the differential abundance of these bacteria, we were able to calculate microbial dysbiosis index (MDI) values, which were significantly higher in GC patients than in SG patients. In addition, MDI values were negatively correlated with gastric Shannon index and were positively correlated with relative
Helicobacter
spp. abundance. Importantly, these MDI values were readily able to discriminate between GC and SG patient samples. Functional analysis suggested that GC patients were more likely to harbor a nitrosating microbial community.
Conclusions
GC patients exhibited a gastric microbiome profile distinct from that observed in SG patients, with these differences being evident in both tumor and paracancerous tissues. Differences in the relative abundance of
Helicobacter
spp. may be the primary driver of gastric dysbiosis in GC patients.
Background
Pathogens capable of impacting gastrointestinal tract tumor development are located in the oral cavity, but whether these oral bacteria are able to colonize the gastric mucosa in gastric ...cancer (GC) patients and whether Helicobacter pylori infection can influence this process remains to be established.
Methods
Microbial 16S rDNA deep sequencing was conducted to characterize bacteria present in paired gastric mucosa and tongue coating samples in 27 patients with superficial gastritis (SG) and 11 GC patients.
Results
While the overall composition of the gastric mucosa and tongue coating microbiomes differed substantially, certain bacteria were present in both of these communities. The co‐occurrence of bacteria between the tongue coating and gastric mucosa differed significantly between SG and GC patients. Of the 15 most abundant shared oral bacteria genera (the core shared oral bacteria), which were associated with differences in microbiota composition between these tongue coating and gastric mucosa, three were enriched in the gastric mucosa of GC patients relative to SG patients, whereas, 12 were depleted in GC patient samples. Furthermore, the prevalence and relative abundance of these core shared oral bacteria in the gastric mucosa were also linked to H. pylori infection status, and the core shared oral bacteria were also associated with the overall composition of the gastric mucosal microbiome.
Conclusions
Helicobacter pylori infections are linked to the co‐occurrence of bacteria in the oral microbiome and the gastric mucosal microbiome. Ectopic colonization of oral microbes may be a primary driver of H. pylori‐induced gastric microbial dysbiosis in patients with GC.
The G-quadruplex ligands database (G4LDB, http://www.g4ldb.org) provides a unique collection of reported G-quadruplex ligands to streamline ligand/drug discovery targeting G-quadruplexes. ...G-quadruplexes are guanine-rich nucleic acid sequences in human telomeres and gene promoter regions. There is a growing recognition for their profound roles in a wide spectrum of diseases, such as cancer, diabetes and cardiovascular disease. Ligands that affect the structure and activity of G-quadruplexes can shed light on the search for G-quadruplex-targeting drugs. Therefore, we built the G4LDB to (i) compile a data set covering various physical properties and 3D structure of G-quadruplex ligands; (ii) provide Web-based tools for G-quadruplex ligand design; and (iii) to facilitate the discovery of novel therapeutic and diagnostic agents targeting G-quadruplexes. G4LDB currently contains >800 G-quadruplex ligands with ∼4000 activity records, which, to our knowledge, is the most extensive collection of its kind. It offers a user friendly interface that can meet a variety of data inquiries from researchers. For example, ligands can be searched for by name, molecular properties, structures, ligand activities and so on. Building on the reported data, the database also provides an online ligand design module that can predict ligand binding affinity in real time.
Plant cell growth involves a complex interplay among cell-wall expansion, biosynthesis, and, in specific tissues, secondary cell wall (SCW) deposition, yet the coordination of these processes remains ...elusive. Cotton fiber cells are developmentally synchronous, highly elongated, and contain nearly pure cellulose when mature. Here, we report that the transcription factor GhTCP4 plays an important role in balancing cotton fiber cell elongation and wall synthesis. During fiber development the expression of miR319 declines while GhTCP4 transcript levels increase, with high levels of the latter promoting SCW deposition. GhTCP4 interacts with a homeobox-containing factor, GhHOX3, and repressing its transcriptional activity. GhTCP4 and GhHOX3 function antagonistically to regulate cell elongation, thereby establishing temporal control of fiber cell transition to the SCW stage. We found that overexpression of GhTCP4A upregulated and accelerated activation of the SCW biosynthetic pathway in fiber cells, as revealed by transcriptome and promoter activity analyses, resulting in shorter fibers with varied lengths and thicker walls. In contrast, GhTCP4 downregulation led to slightly longer fibers and thinner cell walls. The GhHOX3–GhTCP4 complex may represent a general mechanism of cellular development in plants since both are conserved factors in many species, thus providing us a potential molecular tool for the design of fiber traits.
In cotton fiber, the high level of miR319 at the early stage of fiber development cleaves GhTCP4 transcripts, while GhTCP4 regulates the phase transition from elongation to wall thickening. GhTCP4 affects fiber cell elongation by repressing the transcriptional activity of an HD-ZIP IV protein, GhHOX3, activating the SCW biosynthesis genes required for cellulose deposition.
G-quadruplex has attracted considerable attention due to their prevalent distribution in functional genomic regions and transcripts, which can importantly influence biological processes such as ...regulation of telomere maintenance, gene transcription and gene translation. Artificial receptor study has been developed for accurate identification of G-quadruplex from DNA species, since it is important for the G-quadruplex related basic research, clinical diagnosis, and therapy. Herein, fluorescent dye ThT-E, a derivative of the known fluorescence probe Thioflavin T (ThT), was designed and synthesized to effectively differentiate various G-quadruplex structures from other nucleic acid forms. Compared with methyl groups in ThT, three ethyl groups were introduced to ThT-E, which leads to strengthened affinity, selectivity and little inducing effect on the G-quadruplex formation. More importantly, ThT-E could be served as a visual tool to directly differentiate G-quadruplex solution even with naked eyes under illumination of ultraviolet light. Thus, this probe reported herein may hold great promise for high-throughput assay to screen G-quadruplex, which may widely apply to G-quadruplex-based potential diagnosis and therapy.
The integration of constructed wetland-microbial fuel cell (CW-MFC) and anaerobic granular sludge (AGS) is an important way to promote its ammonification efficiency and decrease the land use scale. ...This study explored the integration of CW-MFC and AGS for nitrogen removal via the intensified ammonification-nitrification-denitrification processes with initial NH3–N, NO3–N, Org-N and total nitrogen (TN) concentrations of 10.5, 13.8, 21.4, and 45.7 mg L−1 in wastewater. Two reactors with AGS inoculated with a separated area (R1) and directly inoculated into gravel substrate (R2) were designed, respectively. Results showed that chemical oxygen demand (COD) removal efficiency could reach 85% in R1 and 81% in R2, and the conversion of Org-N to NH3–N and NO3–N to gaseous nitrogen were 80% and 90%, respectively. Although the conversion efficiency of NH3–N to NO2–N/NO3–N via nitrification process was only 18%, it could reach 45%, 94%, and 98% with the aeration rates of 50-, 100-, and 200-mL min−1. According to microstructural property and microbial community analyses, the separation gravel substrate and AGS areas in R1 availed for stable particle size of AGS, archaeal diversity, and metabolic activity even with a 1.5 times daily wastewater treatment capacity than that of R2. Overall, although the intensified ammonification-nitrification-denitrification processes for nitrogen removal could be achieved with supplementary aeration, further investigation is still needed to explore other substrate materials and high CW-MFC/AGS volume ratio for intensified nitrification process in CW-MFC associated with AGS.
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•High-rate nitrogen removal AGS CW-MFC was developed with 38 g N m−2 d−1 loading rate.•Ammonification in AGS CW-MFC reaches 80% with Org-N loading rate of 6–18 g N m−2 d−1.•Nitrification of AGS CW-MFC promotes by 76% with aeration rate of 100-mL min−1.•Denitrification in AGS CW-MFC reaches 90% via bio-metabolism and electrons transfer.•Separated gravel and AGS areas in CW-MFC availed for AGS stability and metabolism.
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