A hybrid water quality prediction model based on variational mode decomposition and bidirectional gated recursive unit.

Water quality predicted accuracy is beneficial to river ecological management and water pollution prevention. Owing to water quality data has the characteristics of nonlinearity and instability, it is difficult to predict the change of water quality. This paper proposes a hybrid water quality prediction model based on variational mode decomposition optimized by the sparrow search algorithm (SSA-VMD) and bidirectional gated recursive unit (BiGRU). First, the sparrow search algorithm selects fuzzy entropy (FE) as the fitness function to optimize the two parameters of VMD, which improves the adaptability of VMD. Second, SSA-VMD is used to decompose the original data into several components with different center frequencies. Finally, BiGRU is employed to predict each component separately, which significantly improves predicted accuracy. The proposed model is validated using data about dissolved oxygen (DO) and the potential of hydrogen (pH) from the Xiaojinshan Monitoring Station in Qiandao Lake, Hangzhou, China. The experimental results show that the proposed model has superior prediction accuracy and stability when compared with other models, such as EMD-based models and other CEEMDAN-based models. The prediction accuracy of DO can reach 97.8% and pH is 96.1%. Therefore, the proposed model can provide technical support for river water quality protection and pollution prevention.

Giant dielectric tunability in ferroelectric ceramics with ultralow loss by ion substitution design.

Due to their responsiveness to modulation by external direct current fields, dielectric tunable materials are extensively utilized in integrated components, such as ferroelectric phase shifters. Barium strontium titanate ceramics have been considered the most potential tunable materials for a long time. However, the significant dielectric loss and high voltage drive have limited their further applications. Recently, Bi6Ti5WO22 ceramic has regained attention for its high dielectric tunability with low loss. In this study, we judiciously introduce Nb5+ with a larger ionic radius, replacing Ti4+ and W6+. This successful substitution enables the modulation of the phase transition temperature of Bi6Ti5WO22 ceramics to room temperature, resulting in superior tunable properties. Specifically, the 0.7Bi6Ti5WO22-0.3Bi6Ti4Nb2O22 ceramics exhibit giant tunability (~75.6%) with ultralow loss (<0.002) under a low electric field (1.5 kV/mm). This tunability is twice that of barium strontium titanate ceramics with a similar dielectric constant and only one-tenth of the loss. Neutron powder diffraction and transmission-electron-microscopy illustrate the nanodomains and micro-strains influenced by ion substitution. Density functional theory simulation calculations reveal the contribution of ion substitution to polarization. The research provides an ideal substitute for tunable material and a general strategy for adjusting phase transition temperature to improve dielectric properties.

Identification and analysis of prognostic immune cell homeostasis characteristics in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most invasive malignant tumor of the respiratory system. It is also the common pathological type leading to the death of LUAD. Maintaining the homeostasis of immune cells is an important way for anti-tumor immunotherapy. However, the biological significance of maintaining immune homeostasis and immune therapeutic effect has not been well studied. METHODS: We constructed a diagnostic and prognostic model for LUAD based on B and T cells homeostasis-related genes. Minimum absolute contraction and selection operator (LASSO) analysis and multivariate Cox regression are used to identify the prognostic gene signatures. Based on the overall survival time and survival status of LUAD patients, a 10-gene prognostic model composed of ABL1, BAK1, IKBKB, PPP2R3C, CCNB2, CORO1A, FADD, P2RX7, TNFSF14, and ZC3H8 was subsequently identified as prognostic markers from The Cancer Genome Atlas (TCGA)-LUAD to develop a prognostic signature. This study constructed a gene prognosis model based on gene expression profiles and corresponding survival information through survival analysis, as well as 1-year, 3-year, and 5-year ROC curve analysis. Enrichment analysis attempted to reveal the potential mechanism of action and molecular pathway of prognostic genes. The CIBERSORT algorithm calculated the infiltration degree of 22 immune cells in each sample and compared the difference of immune cell infiltration between high-risk group and low-risk group. At the cellular level, PCR and CKK8 experiments were used to verify the differences in the expression of the constructed 10-gene model and its effects on cell viability, respectively. The experimental results supported the significant biological significance and potential application value of the molecular model in the prognosis of lung cancer. Enrichment analyses showed that these genes were mainly related to lymphocyte homeostasis. CONCLUSION: We identified a novel immune cell homeostasis prognostic signature. Targeting these immune cell homeostasis prognostic genes may be an alternative for LUAD treatment. The reliability of the prediction model was confirmed at bioinformatics level, cellular level, and gene level.

Integrated Transcriptome and Proteome Analysis Reveals That Cell Wall Activity Affects Phelipanche aegyptiaca Parasitism.

Phelipanche aegyptiaca can infect many crops, causing large agricultural production losses. It is important to study the parasitism mechanism of P. aegyptiaca to control its harm. In this experiment, the P. aegyptiaca HY13M and TE9M from Tacheng Prefecture and Hami City in Xinjiang, respectively, were used to analyze the parasitical mechanism of P. aegyptiaca by means of transcriptome and proteome analyses. The parasitic capacity of TE9M was significantly stronger than that of HY13M in Citrullus lanatus. The results showed that the DEGs and DEPs were prominently enriched in the cell wall metabolism pathways, including "cell wall organization or biogenesis", "cell wall organization", and "cell wall". Moreover, the functions of the pectinesterase enzyme gene (TR138070_c0_g), which is involved in the cell wall metabolism of P. aegyptiaca in its parasitism, were studied by means HIGS. The number and weight of P. aegyptiaca were significantly reduced when TR138070_c0_g1, which encodes a cell-wall-degrading protease, was silenced, indicating that it positively regulates P. aegyptiaca parasitism. Thus, these results suggest that the cell wall metabolism pathway is involved in P. aegyptiaca differentiation of the parasitic ability and that the TR138070_c0_g1 gene plays an important role in P. aegyptiaca's parasitism.

ADCY4 promotes brain metastasis in small cell lung cancer and is associated with energy metabolism.

Brain metastasis (BMs) in small cell lung cancer (SCLC) has a very poor prognosis. This study combined WGCNA with the mfuzz algorithm to identify potential biomarkers in the peripheral blood of patients with BMs. By comparing the significantly differentially expressed genes present in BMs samples, we identified ADCY4 as a target for further study. Expression of ADCY4 was used to cluster mfuzz expression pattern, and 28 hub genes for functional enrichment. PPI network analysis were obtained by comparing with differentially expressed genes in BMs. GABRE, NFE4 and LMOD2 are highly expressed in patients with BMs and have a good diagnostic effect. Immunoinfiltration analysis showed that SCLC patients with BMs may be associated with memory B cells, Tregs, NK cell activation, macrophage M0 and dendritic cell activation. prophytic was used to investigate the ADCY4-mediated anti-tumor drug response. In conclusion, ADCY4 can be used as a promising candidate biomarker for predicting BMs, molecular and immune features in SCLC. PCR showed that ADCY4 expression was increased in NCI-H209 and NCI-H526 SCLC cell lines. In vitro experiments confirmed that the expression of ADCY4 was significantly decreased after anti-PD1 antibody treatment, while the expression of energy metabolism factors were significantly different. This study reveals a potential mechanism by which ADCY4 mediates poor prognosis through energy metabolism -related pathways in SCLC.

What role do biocontrol agents with Mg2+ play in the fate of antibiotic resistome and pathogenic bacteria in the phyllosphere?

The contamination of the plant phyllosphere with antibiotics and antibiotic resistance genes (ARGs), caused by application of antibiotics, is a significant environmental issue in agricultural management. Alternatively, biocontrol agents are environmentally friendly and have attracted a lot of interest. However, the influence of biocontrol agents on the phyllosphere resistome remains unknown. In this study, we applied biocontrol agents to control the wildfire disease in the Solanaceae crops and investigated their effects on the resistome and the pathogen in the phyllosphere by using metagenomics. A total of 250 ARGs were detected from 15 samples, which showed a variation in distribution across treatments of biocontrol agents (BA), BA with Mg2+ (T1), BA with Mn2+ (T2), and kasugamycin (T3) and nontreated (CK). The results showed that the abundance of ARGs under the treatment of BA-Mg2+ was lower than that in the CK group. The abundance of cphA3 (carbapenem resistance), PME-1 (carbapenem resistance), tcr3 (tetracycline antibiotic resistance), and AAC (3)-VIIIa (aminoglycoside antibiotic resistance) in BA-Mg2+ was significantly higher than that in BA-Mn2+ (P < 0.05). The abundance of cphA3, PME_1, and tcr3 was significantly negatively related to the abundance of the phyllosphere pathogen Pseudomonas syringae (P < 0.05). We also found that the upstream and downstream regions of cphA3 were relatively conserved, in which rpl, rpm, and rps gene families were identified in most sequences (92%). The Ka/Ks of cphA3 was 0 in all observed sequences, indicating that under the action of purifying selection, nonsynonymous substitutions are often gradually eliminated in the population. Overall, this study clarifies the effect of biocontrol agents with Mg2+ on the distribution of the phyllosphere resistome and provides evolutionary insights into the biocontrol process. IMPORTANCE: Our study applied metagenomics analysis to examine the impact of biocontrol agents (BAs) on the phyllosphere resistome and the pathogen. Irregular use of antibiotics has led to the escalating dissemination of antibiotic resistance genes (ARGs) in the environment. The majority of BA research has focused on the effect of monospecies on the plant disease control process, the role of the compound BA with nutrition elements in the phyllosphere disease, and the resistome is still unknown. We believe BAs are eco-friendly alternatives for antibiotics to combat the transfer of ARGs. Our results revealed that BA-Mg2+ had a lower relative abundance of ARGs compared to the CK group, and the phyllosphere pathogen Pseudomonas syringae was negatively related to three specific ARGs, cphA3, PME-1, and tcr3. These three genes also present different Ka/Ks. We believe that the identification of the distribution and evolution modes of ARGs further elucidates the ecological role and facilitates the development of BAs, which will attract general interest in this field.

Optimized strategy among diet, exercise, and pharmacological interventions for nonalcoholic fatty liver disease: A network meta-analysis of randomized controlled trials.

BACKGROUND: Emerging treatment methods, including exercise, diet, and drugs, for nonalcoholic fatty liver disease have been proposed. However, the differences in their efficacy have not been determined. We aimed to compare the effects of these treatments excluding surgery via a systematic review and network meta-analysis of randomized controlled trials. DATA SOURCE: The data sources included PubMed, Embase, Web of Science and Cochrane up to February 1st, 2023. The endpoints consisted of body mass index (BMI), serum markers of metabolism and liver injury markers, liver fat content, and stiffness. RESULTS: A total of 174 studies with 10,183 patients were included in this meta-analysis. In terms of improving BMI, Pan-agonist of peroxisome proliferator-activated receptors (PPAR) is the best treatment with the highest SUCRA (surface under the cumulative ranking) of 84.8% (mean = -3.40, 95% CI -5.55, -1.24) by the comparative effectiveness ranking. GLP-1 (glucagon-like peptide-1) has the best effect in improving the liver fat content based on the MRI-PDFF, steatosis score (SUCRA 99.7%, mean = -2.19, 95% CI -2.90, -1.48) and ballooning score (SUCRA 61.2%, mean = -0.82, 95% CI -4.46, 2.83). CONCLUSIONS: Pan-agonist of PPAR was the most efficacious regimen in lowering BMIs, whereas GLP-1R agonists achieved the highest efficacy of steatosis improvement in this network meta-analysis.

Integrated electrophysiological and genomic profiles of single cells reveal spiking tumor cells in human glioma.

Prior studies have described the complex interplay that exists between glioma cells and neurons, however, the electrophysiological properties endogenous to tumor cells remain obscure. To address this, we employed Patch-sequencing on human glioma specimens and found that one third of patched cells in IDH mutant (IDH mut ) tumors demonstrate properties of both neurons and glia by firing single, short action potentials. To define these hybrid cells (HCs) and discern if they are tumor in origin, we developed a computational tool, Single Cell Rule Association Mining (SCRAM), to annotate each cell individually. SCRAM revealed that HCs represent tumor and non-tumor cells that feature GABAergic neuron and oligodendrocyte precursor cell signatures. These studies are the first to characterize the combined electrophysiological and molecular properties of human glioma cells and describe a new cell type in human glioma with unique electrophysiological and transcriptomic properties that are likely also present in the non-tumor mammalian brain.

A hybrid prediction model of dissolved oxygen concentration based on secondary decomposition and bidirectional gate recurrent unit.

Dissolved oxygen is one of the important comprehensive indicators of river water quality, which reflects the degree of pollution in the water body. Monitoring and predicting dissolved oxygen are an important tool for water quality management, which helps to effectively maintain water ecological balance and prevent environmental problems. A single model cannot describe the dynamic characteristics of dissolved oxygen sequence, which affects the prediction accuracy. In order to obtain more accurate dissolved oxygen prediction results, decomposition techniques are commonly used to extract the main fluctuations and trends of water quality sequences. However, the high-frequency modes obtained from decomposition are still unstable. To solve this problem, this paper proposed a hybrid prediction model of dissolved oxygen concentration based on secondary decomposition and bidirectional gate recurrent unit. Firstly, dissolved oxygen sequence is preliminarily decomposed by complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and obtain several intrinsic mode functions (IMF). The fuzzy entropy (FE) is calculated to quantify the complexity of the IMF. Then, variational mode decomposition improved by northern goshawk optimization is used to decompose the IMF with higher entropy. The nonlinearity and instability of the sequence are further weakened. Finally, the bidirectional gate recurrent unit (BiGRU) neural network is used to predict each IMF component, and the final prediction result is obtained by reconstructing the prediction results of each component. In order to verify the effectiveness of the proposed model, this paper selects the dissolved oxygen data of Xin'anjiang Reservoir as the research object. The experimental results show that the RMSE, MAE, MAPE, and R2 of the proposed model are 0.1164, 0.0894, 1.0403%, and 0.9939, respectively, which is best among other comparative prediction models (BP, LSTM, GRU, BiGRU, EMD-BiGRU, CEEMDAN-BiGRU, VMD-BiGRU, and GNO-VMD-BiGRU). Therefore, this model effectively deals with high volatility and nonlinear dissolved oxygen data and provides reference for water environment management and ecological protection.

Activated hedgehog gene pattern correlates with dismal clinical outcome and tumor microenvironment heterogeneity in hepatocellular carcinoma.

Background: Activation of the Hedgehog signaling pathway is linked to the initiation and development of human hepatocellular carcinoma (HCC). However, its impact on clinical outcomes and the HCC microenvironment remains unclear. Methods: We performed comprehensive analyses of Hedgehog pathway genes in a large cohort of HCC patients. Specifically, we utilized univariate Cox regression analysis to identify Hedgehog genes linked to overall survival, and the LASSO algorithm was used to construct a Hedgehog-related gene pattern. We subsequently examined the correlation between the Hedgehog pattern and the HCC microenvironment employing the CIBERSORT and ssGSEA algorithms. Furthermore, Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and the anti-PD-L1 treatment dataset (IMvigor210) are used to evaluate the clinical response of the Hedgehog pattern in predicting immune checkpoint inhibitors. Results: We found that the Hedgehog activation score (HHAS), a prognostic score based on 11 Hedgehog genes, was significantly associated with HCC patient survival. Patients exhibiting high HHAS experienced markedly reduced survival rates compared to those with low HHAS, and HHAS emerged as an independent prognostic factor for HCC. Functional enrichment analysis unveiled the association of the HHAS phenotype with functions related to the immune system, and further investigation demonstrated that HCC patients exhibiting low HHAS displayed elevated levels of anti-tumor immune activation in CD8+ T cells, while high HHAS were linked to immune escape phenotypes and increased infiltration of immune suppressive cells. In addition, in the Immune Checkpoint Inhibitor (ICI) cohort of IMvigor210, patients with higher HHAS had worse ICI treatment outcomes and shortened survival time, indicating that the HHAS is a useful indicator for predicting patient response to immunotherapy. Conclusions: In summary, our study offers valuable insights for advancing research on Hedgehog and its impact on tumor immunity, which provides an opportunity to optimize prognosis and immune therapy for HCC.

Modeling future changes in potential habitats of five alpine vegetation types on the Tibetan Plateau by incorporating snow depth and snow phenology.

Although snow cover is a major factor affecting vegetation in alpine regions, it is rarely introduced into ecological niche models in alpine regions. Snow phenology over the Tibetan Plateau (TP) was estimated using a daily passive microwave snow depth dataset, and future datasets of snow depth and snow phenology were projected based on their sensitivity to temperature and precipitation. Furthermore, the potential habitats of five alpine vegetation types on the TP were predicted under two future climate scenarios (SSP245 and SSP585) by using a model with incorporated snow variables, and the driving factors of habitat change were analyzed. The results showed that the inclusion of snow variables improved the prediction accuracy of MaxEnt model, particularly in alpine meadow habitats. By the end of the 21st century, the potential habitats of steppes, meadows, shrubs, deserts, and coniferous forests on the TP will migrate to higher latitudes and altitudes, in which the potential habitats of alpine desert will recede (replaced by alpine steppe), and the potential habitats of other four vegetation types will expand. The random forest importance analysis showed that the recession of potential habitat was mainly driven by the increase in average annual temperature, and the expansion of potential habitat was mainly driven by the increase in precipitation. With the gradual increase in temperature and precipitation in the future, the snow depth and snow cover duration days will decrease, which may further lead to the transition of vegetation types from cold-adapted to warm-adapted on the TP. Our study highlights both that the prediction accuracy of alpine vegetation was improved by incorporating snow variables into the species distribution model, and that a changing climate will likely have a powerful influence on the distribution of alpine vegetation across the TP.

Molecular mechanism of CCDC106 regulating the p53-Mdm2/MdmX signaling axis.

The tumor suppressor p53 (p53) is regulated by murine double minute 2 (Mdm2) and its homologous MdmX in maintaining the basal level of p53. Overexpressed Mdm2/MdmX inhibits cellular p53 activity, which is highly relevant to cancer occurrence. Coiled-coil domain-containing protein 106 (CCDC106) has been identified as a p53-interacting partner. However, the molecular mechanism of the p53/Mdm2/MdmX/CCDC106 interactions is still elusive. Here, we show that CCDC106 functions as a signaling regulator of the p53-Mdm2/MdmX axis. We identified that CCDC106 directly interacts with the p53 transactivation domain by competing with Mdm2 and MdmX. CCDC106 overexpression downregulates the cellular level of p53 and Mdm2/MdmX, and decreased p53 reversibly downregulates the cellular level of CCDC106. Our work provides a molecular mechanism by which CCDC106 regulates the cellular levels of p53 and Mdm2/MdmX.

Synthesis, molecular docking studies of formononetin derivatives as potent Bax agonists for anticancer activity.

Formononetin as a Bax agonist exhibits anticancer effects. To identify novel Bax agonist, 18 new structurally modified formononetin derivatives were synthesised and their anticancer activities were evaluated in the A549 and Beas-2b cell lines. The results indicated that 7a elicited the most potent inhibitory effect against the A549 cell line, with an IC50 value of 0.87 µM, and no obvious toxicity to Beas-2b cells. These results indicated that 7a was 40-fold and 6.94-fold more efficacious than Formononetin and Doxorubicin, respectively. Additionally, western blot and immunofluorescence assays demonstrated that 7a downregulated the protein expression of Bcl-2 and upregulated the expressions of Bax to promote A549 apoptosis, the obtained results also suggested that 7a had the potential to be developed into a lead compound that can be applied in the prevention and treatment of lung cancer.

The Association Between Sleep Duration and Sleep-Related Gene Methylation with Osteoporosis in Chinese Postmenopausal Women.

This study aims to investigate the association between sleep duration and osteoporosis. In addition, sleep-related gene methylation was also detected in this study and we explored its relationship with osteoporosis. The epidemiological investigation section of this study was designed as a retrospective cross-sectional study. We gathered 148 postmenopausal women from two communities and used questionnaires to collect data of sleep duration and other sleep patterns. Biochemical variables were tested, and bone mineral density was measured by dual-energy X-ray absorptiometry. In addition, sleep-related gene (PER2 and PER3) methylation was tested, and the association with osteoporosis was further studied. Twenty-nine of the 148 participants (aged from 65 to 86 years) who suffered from osteoporosis were tested for osteopenia. A significant difference was observed in the association between sleep duration and osteoporosis; the p-value was 0.013. In addition, in our study, we found that short sleep duration (<7 hours) may increase the risk of osteoporosis compared with longer sleep duration. Moreover, sleep-related genes such as PER2 and PER3 and their CpG island methylation were tested, and there was no significant difference between PER2 and PER3 CpG island methylation and osteoporosis. Short sleep duration may increase the risk of osteoporosis. However, the association between sleep-related gene methylation and osteoporosis was not found.

Oxygen enrichment protects against intestinal damage and gut microbiota disturbance in rats exposed to acute high-altitude hypoxia.

Acute high-altitude hypoxia can lead to intestinal damage and changes in gut microbiota. Sustained and reliable oxygen enrichment can resist hypoxic damage at high altitude to a certain extent. However, it remains unclear whether oxygen enrichment can protect against gut damage and changes in intestinal flora caused by acute altitude hypoxia. For this study, eighteen male Sprague-Dawley rats were divided into three groups, control (NN), hypobaric hypoxic (HH), and oxygen-enriched (HO). The NN group was raised under normobaric normoxia, whereas the HH group was placed in a hypobaric hypoxic chamber simulating 7,000 m for 3 days. The HO group was exposed to oxygen-enriched air in the same hypobaric hypoxic chamber as the HH group for 12 h daily. Our findings indicate that an acute HH environment caused a fracture of the crypt structure, loss of epithelial cells, and reduction in goblet cells. Additionally, the structure and diversity of bacteria decreased in richness and evenness. The species composition at Phylum and Genus level was characterized by a higher ratio of Firmicutes and Bacteroides and an increased abundance of Lactobacillus with the abundance of Prevotellaceae_NK3B31_group decreased in the HH group. Interestingly, after oxygen enrichment intervention, the intestinal injury was significantly restrained. This was confirmed by an increase in the crypt depth, intact epithelial cell morphology, increased relative density of goblet cells, and higher evenness and richness of the gut microbiota, Bacteroidetes and Prevotellaceae as the main microbiota in the HO group. Finally, functional analysis showed significant differences between the different groups with respect to different metabolic pathways, including Amino acid metabolism, energy metabolism, and metabolism. In conclusion, this study verifies, for the first time, the positive effects of oxygen enrichment on gut structure and microbiota in animals experiencing acute hypobaric hypoxia.

GRB2 serves as a viable target against skin fibrosis in systemic sclerosis by regulating endothelial cell apoptosis.

BACKGROUND: Systemic Sclerosis (SSc) is an autoimmune disease characterized by vascular and immune system dysfunction, along with tissue fibrosis. Our previous study found GRB2 was downregulated by salvianolic acid B, a small molecule drug that attenuated skin fibrosis of SSc. OBJECTIVES: Here we aim to investigate the role of GRB2 in SSc. METHODS: The microarray data of SSc skin biopsies in Caucasians were obtained from the Gene Expression Omnibus (GEO) database. The expression of GRB2 was further detected in Chinese SSc and healthy controls. Bleomycin (BLM)-induced skin fibrosis mice were used to explore how GRB2 downregulation affected fibrosis. The apoptosis of EA.hy926 endothelial cells was induced by H2O2 and apoptosis ratio was measured by flow cytometric. Transcriptome and phosphoproteomic analyses were performed to explore the regulated pathway. RESULTS: The expression of GRB2 was significantly enhanced in SSc patient skin, 1.51-fold in Caucasians and 1.40-fold in Chinese. Double immunofluorescence staining showed the endothelial cells of SSc patient's skin highly expressed GRB2. The in vivo study revealed that GRB2 knockdown alleviated skin fibrosis and apoptosis of endothelial cells in BLM mouse skin. The in vitro study showed that GRB2 downregulation inhibited the apoptosis of EA.hy926 and protected them from H2O2-induced hyperpermeability. Moreover, transcriptome and phosphoproteomic analysis suggested the focal adhesion pathway was enriched in GRB2 siRNA transfected endothelial cells. CONCLUSIONS: Our results demonstrated GRB2 highly expressed in endothelial cells of SSc skin, and inhibiting GRB2 could effectively attenuate BLM-induced skin fibrosis and endothelial cell apoptosis. GRB2 is expected to be a new therapeutic target for SSc.

Alanine dehydrogenases from four different microorganisms: characterization and their application in L-alanine production.

BACKGROUND: Alanine dehydrogenase (AlaDH) belongs to oxidoreductases, and it exists in several different bacteria species and plays a key role in microbial carbon and nitrogen metabolism, spore formation and photosynthesis. In addition, AlaDH can also be applied in biosynthesis of L-alanine from cheap carbon source, such as glucose. RESULTS: To achieve a better performance of L-alanine accumulation, system evaluation and comparison of different AlaDH with potential application value are essential. In this study, enzymatic properties of AlaDH from Bacillus subtilis 168 (BsAlaDH), Bacillus cereus (BcAlaDH), Mycobacterium smegmatis MC2 155 (MsAlaDH) and Geobacillus stearothermophilus (GsAlaDH) were firstly carefully investigated. Four different AlaDHs have few similarities in optimum temperature and optimum pH, while they also exhibited significant differences in enzyme activity, substrate affinity and enzymatic reaction rate. The wild E. coli BL21 with these four AlaDHs could produce 7.19 g/L, 7.81 g/L, 6.39 g/L and 6.52 g/L of L-alanine from 20 g/L glucose, respectively. To further increase the L-alanine titer, competitive pathways for L-alanine synthesis were completely blocked in E. coli. The final strain M-6 could produce 80.46 g/L of L-alanine with a yield of 1.02 g/g glucose after 63 h fed-batch fermentation, representing the highest yield for microbial L-alanine production. CONCLUSIONS: Enzyme assay, biochemical characterization and structure analysis of BsAlaDH, BcAlaDH, MsAlaDH and GsAlaDH were carried out. In addition, application potential of these four AlaDHs in L-alanine productions were explored. The strategies here can be applied for developing L-alanine producing strains with high titers.

First Report of Karelinia caspia (Pall.) Less as a new host of Orobanche cumana Wallr. in Xinjiang, China.

Sunflower broomrape (Orobanche cumana Wallr.) is a holoparasitic plant species which mainly parasitizes a few species of the Asteraceae in the wild and is exclusively found growing on sunflower in agricultural fields (Fernández-Martínez et al. 2015). O. cumana is a serious threat to sunflower production in Xinjiang and Inner Mongolia (Shi et al. 2015). Karelinia caspia (Pall.) Less. (Asteraceae) is an ecologically important plant species occurring across the desert ecosystems of Russia, Central Asia, and northwest China. It plays an important role in reducing wind erosion and desertification (Xu et al. 2018). During the 2018 and 2019 growing seasons, sunflower broomrape was observed parasitizing K. caspia in non-cultivated areas adjacent to sunflower fields near Beitun city (87°51'E, 47°15'N) in Xinjiang, China. Sunflower broomrape plants were identified morphologically as O. cumana according to Pujadas-Salvà and Velasco (2000). The host plants were identified morphologically as K. caspia according to Lin et al (1979). The ribosomal DNA internal transcribed spacer (ITS) and the trnL-F region of the parasite were amplified by PCR using primer pairs ITS1/ITS4 and trnL-FF/trnL-FR, respectively (Taberlet et al. 1991; Anderson et al. 2004). The ITS sequence of the parasite (Accession No. MT795725.1) showed 100% identity (675bp out of 689bp) to that of O. cernua var. cumana (KC811228.1). The trnl-F sequence of the parasite (Accession No. ON843707) showed 98% identity (675 of 689 bp) to O.cernua var. cumana (KT387722.1). Multi-locus phylogenetic analysis of the two sequences showed clustering with sunflower broomrape. The ITS region of the parasite and host was were amplified by PCR using the primer pair ITS1F/ITS4R (Taberlet et al.1991), and the ITS sequences of the host (Accession No. MT791995.1) showed 99.86% identity (728bp of 802bp) to that of K. caspia (LN607483.1). Rhizotron and pot experiments were carried out to assess the parasitic relationship between O. cumana and K. caspia. In the rhizotron experiment, 2-week-old seedlings of K. caspia were inoculated with sterilized 400 O. cumana seeds in a 15-cm petri dish filled with a sponge overlaid with glass fiber filter paper. The parasitic state of O. cumana was observed 9 days after inoculation. In another trial, seeds of K. caspia were sowed in 2-L and 4-L pots containing sand-vermiculite-compost (1:1:1 v:v:v). These pots were artificially inoculated with 50 mg of O. cumana seeds per 1 kg of substrate. After 20 and 70 days, corresponding to the early parasitic and flowering stages, respectively, of O. cumana, K. caspia plants were uprooted from the media and washed carefully. The parasitic relationship was confirmed by the attachment position of the broomrape to the K. caspia root. To our knowledge, this is the first report of O. cumana parasitizing K. caspia in Xinjiang, China. This phenomenon means that sunflower broomrape can raise up seed on a newly recognized host. Weed eradication in and near sunflower fields is a key measure to control sunflower broomrape.

Elaboration and characterization of ε-polylysine­sodium alginate nanoparticles for sustained antimicrobial activity.

The ε-polylysine (ε-PL) is a food-grade antimicrobial substance. The cationic ε-PL molecules may interact with anionic components of food matrix causing turbidity, sedimentation, and hampering the antimicrobial activity. Herein, sodium alginate (SA) was used as wall material to encapsulate ε-PL, thereby to synthesize ε-PL-SA nanoparticles (ε-PL-SA-NPs). Monosaccharide composition and molecular weight of SA were characterized. The synthetic scheme is optimized and physicochemical characteristics and antimicrobial potential was investigated. Findings indicate that SA primarily consisted of mannuronic acid (95.25 %), weight average molecular weight (Mw) of SA was 176.464 kDa, and the molecular configuration of SA was irregular line clusters. The encapsulation efficiency (EE) of ε-PL in ε-PL-SA-NPs made under optimum strategy (at pH 6.0, mass ratio of ε-PL to SA is 0.14, and SA concentration is 6 mg/mL) is about 99.74 %. The particle size of ε-PL-SA-NPs is ∼541.86 nm. The SEM image showed that the ε-PL-SA-NPs had a nearly spherical morphology. Zeta-potential and FTIR data reveal the interaction between ε-PL and SA was electrostatic and the hydrogen bonding. Agar diffusion assay exhibit that ε-PL-SA-NPs had antimicrobial activity against Escherichia coli and Staphylococcus aureus. The salmon preservation experiments reveal sustained antimicrobial efficacy of ε-PL-SA-NPs.

Aflatoxin B1-induced early developmental hepatotoxicity in larvae zebrafish.

Aflatoxin B1 (AFB1) is a ubiquitous mycotoxin that causes oxidative damage in various organs. At present, the research studies on AFB1 are primarily focused on its effects on the terrestrial environment and animals. However, its toxicity mechanism in aquatic environments and aquatic animals has not been largely explored. Thus, in this study, zebrafish was used as a model to study the toxicity mechanism of AFB1 on the liver of developing larvae. The results showed that AFB1 exposure inhibited liver development and promoted fat accumulation in the liver. Transcriptome sequencing analysis showed that AFB1 affected liver redox metabolism and oxidoreductase activity. KEGG analysis showed that AFB1 inhibited the expression of gsto1, gpx4a, mgst3a, and idh1 in the glutathione metabolizing enzyme gene pathway, resulting in hepatic oxidative stress. At the same time, AFB1 also inhibited the expression of acox1, acsl1b, pparα, fabp2, and cpt1 genes in peroxidase and PPAR metabolic pathways, inducing hepatic steatosis and lipid droplet accumulation. Antioxidant N-Acetyl-l-cysteine (NAC) preconditioning up-regulated gsto1, gpx4a and idh1 genes, and improved the AFB1-induced lipid droplet accumulation in the liver. In summary, AFB1 induced hepatic oxidative stress and steatosis, resulting in abnormal liver fat metabolism and accumulation of cellular lipid droplets. NAC could be used as a potential preventative drug to improve AFB1-induced fat accumulation.