Aminopeptidase MNP-1 triggers intestine protease production by activating daf-16 nuclear location to degrade pore-forming toxins in Caenorhabditis elegans.

Pore-forming toxins (PFTs) are effective tools for pathogens infection. By disrupting epithelial barriers and killing immune cells, PFTs promotes the colonization and reproduction of pathogenic microorganisms in their host. In turn, the host triggers defense responses, such as endocytosis, exocytosis, or autophagy. Bacillus thuringiensis (Bt) bacteria produce PFT, known as crystal proteins (Cry) which damage the intestinal cells of insects or nematodes, eventually killing them. In insects, aminopeptidase N (APN) has been shown to act as an important receptor for Cry toxins. Here, using the nematode Caenorhabditis elegans as model, an extensive screening of APN gene family was performed to analyze the potential role of these proteins in the mode of action of Cry5Ba against the nematode. We found that one APN, MNP-1, participate in the toxin defense response, since the mnp-1(ok2434) mutant showed a Cry5Ba hypersensitive phenotype. Gene expression analysis in mnp-1(ok2434) mutant revealed the involvement of two protease genes, F19C6.4 and R03G8.6, that participate in Cry5Ba degradation. Finally, analysis of the transduction pathway involved in F19C6.4 and R03G8.6 expression revealed that upon Cry5Ba exposure, the worms up regulated both protease genes through the activation of the FOXO transcription factor DAF-16, which was translocated into the nucleus. The nuclear location of DAF-16 was found to be dependent on mnp-1 under Cry5Ba treatment. Our work provides evidence of new host responses against PFTs produced by an enteric pathogenic bacterium, resulting in activation of host intestinal proteases that degrade the PFT in the intestine.

Prognostic Role of Serum Soluble Tim-3 in Severe Traumatic Brain Injury: A Prospective Observational Study.

Objective: T cell immunoglobulin and mucin domain-3 (Tim-3) may be implicated in neuroinflammation. Herein, we attempted to discern the role of serum soluble (s) Tim-3 as an inflammatory prognostic biomarker of severe traumatic brain injury (sTBI). Methods: In this prospective observational study of 112 sTBI patients and 112 controls, serum sTim-3 levels were determined, Rotterdam computed tomography (CT) classification and Glasgow coma scale (GCS) were selected as the two severity indicators, serum C-reactive protein (CRP) was regarded as an inflammatory biomarker, and poor prognosis was referred to as extended Glasgow outcome scale (GOSE) scores 1-4 at 180 days after trauma. Results: Serum sTim-3 levels were markedly higher in patients than in controls (median, 4.2 ng/mL versus 0.7 ng/mL; P<0.001). Serum sTim-3 levels of patients were independently related to Rotterdam CT scores (ß=1.126), GCS scores (ß=-0.589), serum CRP levels (ß=0.155) and GOSE scores (ß=-0.211). Serum sTim-3 appeared as an independent predictor of post-traumatic 180-day mortality (odds ratio=1.289), overall survival (hazard ratio=1.208) and poor prognosis (odds ratio=1.293). Serum sTim-3 levels discriminated patients at risk of post-injury 180-day mortality and poor prognosis with areas under curve (AUCs) at 0.753 and 0.782, respectively. Serum sTim-3 levels combined with GCS scores and Rotterdam CT scores (AUC=0.869) exhibited significantly higher AUC than Rotterdam CT scores (P=0.026), but not than GCS scores (P=0.181) for death prediction and their combination (AUC=0.895) had significantly higher AUC than GCS scores (P=0.036) or Rotterdam CT scores (P=0.005) for outcome prediction. Conclusion: Elevated serum sTim-3 levels, in close correlation with traumatic severity and inflammation, are substantially associated with long-term death and poor outcome, indicating that serum sTim-3, as an inflammatory biomarker, may be of clinical significance in severity assessment and prediction of prognosis following sTBI.

Composition-Aware Image Steganography Through Adversarial Self-Generated Supervision.

Steganography is an important and prevailing information hiding tool to perform secret message transmission in an open environment. Existing steganography methods can mainly fall into two categories: predefined rule-based and data-driven methods. The former is susceptible to the statistical attack, while the latter adopts the deep convolution neural networks to promote security. However, deep learning-based methods suffer from perceptible artificial artifacts or deep steganalysis. In this article, we introduce a novel composition-aware image steganography (CAIS) to guarantee both visual security and resistance to deep steganalysis through the self-generated supervision. The key innovation is an adversarial composition estimation module, which has integrated the rule-based composition method and generative adversarial network to help synthesize steganographic images with more naturalness. We first perform a rule-based image blending method to obtain infinite synthetically data-label pairs. Then, we utilize an adversarial composition estimation branch to recognize the message feature pattern from the composite image based on these self-generated data-label pairs. Through the adversarial training, we force the steganography function to synthesize steganographic images, which can fool the composition estimation network. Thus, the proposed CAIS can achieve better information hiding and higher security to resist deep steganalysis. Furthermore, an effective global-and-part checking is designed to alleviate visual artifacts caused by hiding secret information. We conduct a comprehensive analysis of CAIS from various aspects (e.g., security and robustness) to verify the superior performance of the proposed method. Comprehensive experimental results on three large-scale widely used datasets have demonstrated the superior performance of our CAIS compared with several state-of-the-art approaches.

Synthesis of Fe3O4@CdS@CQDs ternary core-shell heterostructures as a magnetically recoverable photocatalyst for selective alcohol oxidation coupled with H2O2 production.

Photocatalytic aerobic oxidation of aromatic alcohols to corresponding aldehydes coupled with producing hydrogen peroxide (H2O2) represents one of the most efficient strategies for converting solar energy into chemical energy. In this work, a magnetically recoverable photocatalyst of Fe3O4@CdS@CQDs ternary core-shell heterostructures is elaborately fabricated through the hydrothermal growth of CdS on Fe3O4 nanospheres with in-situ incorporation of carbon quantum dots (CQDs) and used for selective alcohol oxidation coupled with H2O2 production. The Fe3O4@CdS@CQDs photocatalyst possess distinct advantages of full solar spectral absorption, efficient charge separation, and high stability. The Fe3O4-nanosphere cores not only endow photocatalyst with the characteristics of magnetic recovery but also form Fe3O4@CdS Z-scheme heterojunction to prevent CdS from photocorrosion. The in-situ modified CQDs act as charge mediators to accelerate the photogenerated electron-hole separation and afford active sites to facilitate H2O2 production. As a result, the Fe3O4@CdS@CQDs photocatalyst exhibits excellent performance in selectively converting benzyl alcohol to benzaldehyde accompanied with H2O2 production. The generation rates of benzaldehyde and H2O2 reach up to 57.22 and 27.06 mmol·gCdS-1·h-1, respectively. This work highlights a rational construction of magnetic heterostructure photocatalyst and its application in the photo-redox coupling reactions.

Effects of cimetidine on ciclosporin population pharmacokinetics and initial dose optimization in aplastic anemia patients.

The present study aimed to explore the effects of cimetidine on ciclosporin population pharmacokinetics and initial dose optimization in aplastic anemia patients. Aplastic anemia patients were used to establish a population pharmacokinetic model by the nonlinear mixed effect (NONMEM), and concentrations of ciclosporin were simulated by Monte Carlo method. With the same weight, the ciclosporin clearance rates were 0.387:1 in patients with or without cimetidine, respectively. In the measured ciclosporin concentrations, compared to aplastic anemia patients without cimetidine, ciclosporin concentrations were higher in patients with cimetidine (P < 0.01). Further research found that at the same body weight and same dose, ciclosporin concentrations in aplastic anemia patients with cimetidine were indeed higher than those in patients without cimetidine (P < 0.01). The initial recommended ciclosporin dose for patients without cimetidine were 7mg/kg splited into two doses for weight of 40-60kg, and 6mg/kg splited into two doses for weight of 60-100kg. The patients with cimetidine were recommended to take 3mg/kg ciclosporin splited into two doses for weight of 40-100kg. It was the first time to explore the effects of cimetidine on ciclosporin population pharmacokinetics and initial dose optimization in aplastic anemia patients. Patients coadministration of cimetidine, may need low ciclosporin dose.

Draft Genome Sequence of Bacillus wiedmannii Biovar thuringiensis ZZQ-138, Isolated from a Saline Lake.

Ecologically sound approaches to control mosquitoes like Anopheles stephensi, which are obligatory vectors for malaria transmission, are urgently needed because of increasing insecticide resistance. Bacteria from Bacillus are important resources. Here, we report the whole-genome sequence of Bacillus wiedmannii biovar thuringiensis ZZQ-138, which was isolated from sediment from a saline lake.

Draft Genome Sequence of Bacillus thuringiensis ZZQ-130 with Multiple Pesticidal Genes, Isolated from Caka Salt Lake, China.

Bacillus thuringiensis is a typical pesticide, with global application for over 40 years. Here, we report the draft genome sequence of B. thuringiensis ZZQ-130 from a salt lake; this strain has 31 pesticidal genes, including five cry genes, one vip gene, two vpa genes, and two vpb genes.

Not every sample is efficient: Analogical generative adversarial network for unpaired image-to-image translation.

Image translation is to learn an effective mapping function that aims to convert an image from a source domain to another target domain. With the proposal and further developments of generative adversarial networks (GANs), the generative models have achieved great breakthroughs. The image-to-image (I2I) translation methods can mainly fall into two categories: Paired and Unpaired. The former paired methods usually require a large amount of input-output sample pairs to perform one-side image translation, which heavily limits its practicability. To address the lack of the paired samples, CycleGAN and its extensions utilize the cycle-consistency loss to provide an elegant and generic solution to perform the unpaired I2I translation between two domains based on unpaired data. This thread of dual learning-based methods usually adopts the random sampling strategy for optimizing and does not consider the content similarity between samples. However, not every sample is efficient and effective for the desired optimization and leads to optimal convergence. Inspired by analogical learning, which is to utilize the relationships and similarities between sample observations, we propose a novel generic metric-based sampling strategy to effectively select samples from different domains for training. Besides, we introduce a novel analogical adversarial loss to force the model to learn from the effective samples and alleviate the influence of the negative samples. Experimental results on various vision tasks have demonstrated the superior performance of the proposed method. The proposed method is also a generic framework that can be easily extended to other I2I translation methods and result in a performance gain.

Synthesis of Ni modified Au@CdS core-shell nanostructures for enhancing photocatalytic coproduction of hydrogen and benzaldehyde under visible light.

The development of visible light responsive photocatalysts for simultaneous production of hydrogen (H2) fuel and value-added chemicals is greatly promising to solve the energy and environmental issues by improving the utilization efficiency of solar energy. Herein, the three-component Ni/(Au@CdS) core-shell nanostructures were constructed by the hydrothermal synthesis followed with photodeposition. The intimate integration of plasmonic Au nanospheres and visible-light responsive CdS shells modified with Ni cocatalyst facilitated the generation and separation of electron-hole pairs as well as reduced the overpotential of hydrogen evolution. The Ni/(Au@CdS) photocatalyst exhibited excellent performance toward the selective transformation of benzyl alcohol under anaerobic conditions, and the yields of H2 and benzaldehyde reached up to 3882 and 4242 µmol·g-1·h-1, respectively. The apparent quantum efficiency (AQE) was determined to be 4.09% under the irradiation of 420 nm. The systematic studies have verified the synergy of plasmonic effect and metal cocatalyst on enhancing the photocatalysis. This work highlights the desirable design and potential application of plasmonic photocatalysts for solar-driven coproduction of H2 fuel and high-value chemicals.

Serum hypoxia-inducible factor 1alpha emerges as a prognostic factor for severe traumatic brain injury.

BACKGROUND: Hypoxia-inducible factor 1alpha (HIF-1α) is implicated in the cell's response to hypoxia. We investigated whether serum HIF-1α concentrations are correlated with the severity and clinical outcome of severe traumatic brain injury (sTBI). METHODS: Serum HIF-1α concentrations were quantified in 104 sTBI patients and 80 healthy controls. Trauma severity was assessed using Glasgow coma scale (GCS). Glasgow outcome scale (GOS) score of 1-3 at post-trauma 90 days was defined as a poor outcome. Multivariate analyses were performed to discern the relationship between serum HIF-1α concentrations and outcome. RESULTS: Patients displayed significantly higher serum HIF-1α concentrations than controls (median, 294.9 versus 102.7 pg/ml). HIF-1α concentrations were intimately related to GCS scores (r = -0.62) and GOS scores (r = -0.64). 48 patients (46.2%) experienced a poor outcome. Serum HIF-1α concentrations > 280.2 pg/ml significantly distinguished patients with the development of poor outcome with 77.1% sensitivity and 69.6% specificity (AUC, 0.750; 95% CI: 0.655-0.829). Serum HIF-1α concentrations > 280.2 pg/ml emerged as an independent predictor for poor outcome (OR: 4.179; 95% CI: 1.024-17.052). CONCLUSIONS: Serum HIF-1α concentrations are tightly associated with trauma severity and poor 90-day outcome, substantializing serum HIF-1α as a promising prognostic biomarker for sTBI.

Generative Adversarial Network with Multi-branch Discriminator for imbalanced cross-species image-to-image translation.

There has been an increased interest in high-level image-to-image translation to achieve semantic matching. Through a powerful translation model, we can efficiently synthesize high-quality images with diverse appearances while retaining semantic matching. In this paper, we address an imbalanced learning problem using a cross-species image-to-image translation. We aim to perform the data augmentation through the image translation to boost the recognition performance of imbalanced learning. It requires a strong ability of the model to perform a biomorphic transformation on a semantic level. To tackle this problem, we propose a novel, simple, and effective structure of Multi-Branch Discriminator (termed as MBD) based on Generative Adversarial Networks (GANs). We demonstrate the effectiveness of the proposed MBD through theoretical analysis as well as empirical evaluation. We provide theoretical proof of why the proposed MBD is an effective and optimal case to achieve remarkable performance. Comprehensive experiments on various cross-species image translation tasks illustrate that our MBD can dramatically promote the performance of popular GANs with state-of-the-art results in terms of both objective and subjective assessments. Extensive downstream image recognition evaluations at a few-shot setting have also been conducted to demonstrate that the proposed method can effectively boost the performance of imbalanced learning.

Modulating oxygen vacancies on bismuth-molybdate hierarchical hollow microspheres for photocatalytic selective alcohol oxidation with hydrogen peroxide production.

Photocatalytic selective oxidation of alcohols into high value-added carbonyl compounds accompanied by producing hydrogen peroxide (H2O2) is undoubtedly a more efficient solar energy conversion strategy with high atom economy. Herein, we have developed an efficient photocatalyst of bismuth-molybdate (Bi2MoO6) hierarchical hollow microspheres with tunable surface oxygen vacancies (OVs) for promoting the photocatalytic selective alcohol oxidation with H2O2 production. The effect of surface OVs on the photocatalytic efficiency is studied systematically by comparing the performance of different photocatalysts. The benzaldehyde and H2O2 production rates over the OV-rich Bi2MoO6 photocatalyst reach up to 1310 and 67.2 µmol g-1 h-1, respectively, which are 2.3 and 4.0 times those generated from the OV-poor Bi2MoO6 hollow microspheres. The roles of various active radicals in the photocatalytic reaction are probed by a series of controlled experiments and in situ ESR measurements, revealing that both superoxide radical (•O2-) and carbon-centered radical are the key active intermediates. The introduction of surface OVs on Bi2MoO6 hollow microspheres accelerates the separation and transfer of photo-generated charge carriers as well as enhances the adsorption and activation of reactant molecules, thereby greatly promoting the photocatalytic selective oxidation of alcohols along with H2O2 production. This work not only demonstrates a facile strategy for the preparation of high-efficiency photocatalysts by simultaneous modulations of morphology and surface defects, but also offers insight into developing the dual-functional photocatalytic reactions for the full utilizations of photoinduced electrons and holes.

Imine bond transformation of a dynamic Sm(III) macrocycle-based chemosensor: The indirect approach for detecting cyanuric chloride.

Herein, we report our strategy to develop the efficient chemosensor and real-time monitoring technique for cyanuric chloride (TCT) detection. A luminescent macrocyclic mononuclear Sm(III) complex Sm-2k bearing with two dynamic imine bonds has been constructed via the template synthesis between dialdehyde H2Qk and matched diamine 1,2-bis(2-aminoethoxy)ethane. Sensing experiments reveal that complex Sm-2k exhibits the turn-off fluorescent and colorimetric response for TCT in CH3OH. It is especially encouraging that this optical sensing process is not only rapid within 60 s but also high-efficient in the presence of TCT analogues as well as sensitive with the low limit of detection (LOD, 1.74 µM) and wide linear sensing range. Mechanism studies demonstrate that TCT sensing is mainly based on the imine bond transformation of probe Sm-2k, which is due to the increased acidity induced by TCT. Meanwhile, a smartphone-based analytical method was developed to make complex Sm-2k accessible for the real-time TCT detection by RGB value outputs. It is believed that this work can shed some constructive lights on design of chemosensors and convenient detection technique for highly reactive analytes.

The CRISPR-Cas systems were selectively inactivated during evolution of Bacillus cereus group for adaptation to diverse environments.

CRISPR-Cas systems are considered as barriers to horizontal gene transfer (HGT). However, the influence of such systems on HGT within species is unclear. Also, little is known about the impact of CRISPR-Cas systems on bacterial evolution at the population level. Here, using Bacillus cereus sensu lato as model, we investigate the interplay between CRISPR-Cas systems and HGT at the population scale. We found that only a small fraction of the strains have CRISPR-Cas systems (13.9% of 1871), and most of such systems are defective based on their gene content analysis. Comparative genomic analysis revealed that the CRISPR-Cas systems are barriers to HGT within this group, since strains harboring active systems contain less mobile genetic elements (MGEs), have lower fraction of unique genes and also display limited environmental distributions than strains without active CRISPR-Cas systems. The introduction of a functional CRISPR-Cas system into a strain lacking the system resulted in reduced adaptability to various stresses and decreased pathogenicity of the transformant strain, indicating that B. cereus group strains could benefit from inactivating such systems. Our work provides a large-scale case to support that the CRISPR-Cas systems are barriers to HGT within species, and that in the B. cereus group the inactivation of CRISPR-Cas systems correlated with acquisition of MGEs that could result in better adaptation to diverse environments.

Complete genome sequence of Bacillus velezensis ZY-1-1 reveals the genetic basis for its hemicellulosic/cellulosic substrate-inducible xylanase and cellulase activities.

Bacillus velezensis ZY-1-1 was isolated from the larval gut of the lignocellulose-rich diet-fed scarab beetle, Holotrichia parallela, and confirmed to possess extremely high xylanase (48153.8 ± 412.1 U/L) and relatively moderate cellulase activity (610.1 ± 8.2 U/L). Notably, these xylanase and cellulase activities were enhanced by xylan (1.4 and 5.8-fold, respectively) and cellulose (1.1 and 3.5-fold, respectively), which indicated the hemicellulosic/cellulosic substrate-inducible lignocellulolytic activities of this strain. The complete genome of B. velezensis ZY-1-1 comprises of 3,899,251 bp in a circular chromosome with a G + C content of 46.6%. Among the predicted 3688 protein-coding genes, 24 genes are involved in the degradation of lignocellulose and other polysaccharides, including 8, 7 and 2 critical genes for the degradation of xylan, cellulose and lignin, respectively. This genome-based analysis will facilitate our understanding of the mechanism underlying the biodegradation of lignocellulose and the biotechnological application of this novel lignocellulolytic bacteria or related enzymes.

Disturbance of Mammary UDP-Glucuronosyltransferase Represses Estrogen Metabolism and Exacerbates Experimental Breast Cancer.

The progression of breast cancer is closely related to the levels of estrogens within the body. UDP-glucuronosyltransferase (UGT) is an important class of phase II metabolizing enzymes, playing a pivotal role in detoxifying steroid hormone. In the present study, we aim at uncovering the potential dysregulation pattern of UGT and its role in estrogen metabolism and in the pathogenesis of breast cancer. Female Sprague-Dawley rats were treated with 100 mg/kg dimethylbenz(a)anthracene (DMBA) to induce breast cancer. Our results showed that the expression and activity of UGT in mammary tissues were downregulated significantly in DMBA rats. Consistent with this, levels of estradiol, 4-hydroxylated estradiol, and 2-hydroxylated estradiol were increased in both mammary tissues and serum, supporting a notable accumulation of toxic estrogen species in the target tissue of breast cancer. In addition, we also observed the decreased cell migration, cell proliferation, and DNA damage in UGT-transfected MCF-7 cells, suggesting a protective role of UGT against estrogen-induced mammary carcinogenesis. Taken together, these results indicated that accumulation of estrogens induced by UGT deficiency is a critical factor to induce the development of breast cancer. UGT contributes to estrogen elimination, and its glucuronidation capacity influences the estrogen signaling pathway and the pathogenesis of breast cancer.

Complete genome sequence of Fictibacillus arsenicus G25-54, a strain with toxicity to nematodes.

Root-knot nematodes (RKNs) can infect almost all crops and cause huge economic losses in agriculture worldwide. An in-depth understanding of bacteria with nematicidal activity is essential for an effective and environmentally friendly control of RKNs. Fictibacillus arsenicus G25-54, a gram-positive and spore-forming bacterium isolated from a submerged sand bank, shows nematicidal activity against free-living Caenorhabditis elegans and RKNs. Here, we report the complete genome of F. arsenicus G25-54, which contains a circular chromosome and encodes ten potential nematicidal factors with twelve secondary metabolite gene clusters. Additionally, it encodes five arsenic resistance and transformation related proteins, which may provide the potential arsenic-resistance activity.

Complete genome sequence of Fictibacillus phosphorivorans G25-29, a strain toxic to nematodes.

Root-knot nematodes (RKNs) which can infect almost all crops lead to huge economic losses in agriculture around the world. Unavailability of effective and environmentally friendly control of RKNs provides an opportunity to nematicidal bacteria. Fictibacillus phosphorivorans G25-29 is a gram-positive and spore-forming bacterium with nematicidal capability against root-knot nematodes and free-living nematode Caenorhabditis elegans. Here, we report the complete genome of F. phosphorivorans G25-29, containing a circular chromosome and encoding nine potential nematicidal factors which may contribute to its nematicidal activity.

Nematicidal spore-forming Bacilli share similar virulence factors and mechanisms.

In the soil environment, Bacilli can affect nematode development, fecundity and survival. However, although many Bacillus species can kill nematodes, the virulence mechanisms Bacilli utilize remain unknown. In this study, we collected 120 strains comprising 30 species across the Bacillaceae and Paenibacillaceae families of the Bacillales order and measured their nematicidal activities in vitro. Comparison of these strains' nematicidal capacities revealed that nine species, including Bacillus thuringiensis, B. cereus, B. subtilis, B. pumilus, B. firmus, B. toyonensis, Lysinibacillus sphaericus, Brevibacillus laterosporus and B. brevis, were highly nematicidal, the first of which showed the highest activity. Genome sequencing and analysis identified many potential virulence factors, which grouped into five types. At least four possible mechanisms were deduced on the basis of the combination of these factors and the bacterial nematicidal activity, including a pore-forming mechanism of crystal proteins, an inhibition-like mechanism of thuringiensin and a degradation mechanism of proteases and/or chitinases. Our results demonstrate that 120 spore-forming Bacilli across different families share virulence factors that may contribute to their nematicidal capacity.

The complete genome sequence of Alcaligenes faecalis ZD02, a novel potential bionematocide.

Root-knot nematodes (RKNs) can infect almost all crops, and result in huge economic losses in agriculture. There is no effective and environmentally safe means available to control RKNs. Alcaligenes faecalis ZD02 isolated from free living nematode Caenorhabditis elegans cadavers shows toxicity against RKN Meloidogyne incognita, that makes this strain to be a good bionematicide candidate for controlling of RKNs. Here, we firstly report the complete genome of A. faecalis ZD02 and describe its features. Additionally, we found two potential virulence factors in this genome, which play important roles for the nematocidal activity of A. faecalis ZD02.