Highly-tumor-targeted PAD4 inhibitors with PBA modification inhibit tumors in vivo by specifically inhibiting the PAD4-H3cit-NETs pathway in neutrophils.

As a new target for tumor therapy, PAD4 protein, shows excellent antitumor activity, and phenylboronic acid (PBA) could combine with sialic acid on the tumor surface to achieve dual targeting in situ and for metastatic tumors. The purpose of this study was therefore to modify PAD4 protein inhibitors with different phenylboronic acid groups in order to obtain highly-targeted PAD4 inhibitors. The activity and mechanism of these PBA-PAD4 inhibitors were studied in vitro by MTT assay, laser confocal analysis, and flow cytometry. The effects of the compounds on primary tumor and lung metastasis in mice were evaluated in vivo using a S180 sarcoma model and a 4T1 breast cancer model. In addition, cytometry mass (CyTOF) was used to analyze the immune microenvironment, and the results show that the PAD4 inhibitor 5i modified by m-PBA at the carboxyl terminal of ornithine skeleton had the best antitumor activity. In vitro evaluation of this activity revealed that 5i could not directly kill tumor cells but had a significant inhibitory effect on tumor cell metastasis. Further mechanism studies showed that 5i could be taken up by 4T1 cells in a time-dependent manner and distributed around the cell membrane but could not be taken up by normal cells. In addition, although 5i was distributed in the cytoplasm of tumor cells while in the nucleus of neutrophils, it could both decrease the histone 3 citrullination (H3cit) in the nucleus. In vivo 4T1 tumor-bearing mouse models, 5i inhibited breast cancer growth and metastasis in a concentration-dependent manner, and NET formation in tumor tissues was significantly reduced. In conclusion, PBA-PAD4 inhibitors show high targeting of tumor cells and good safety in vivo. By specifically inhibiting PAD4 protein in the neutrophil nucleus, PBA-PAD4 inhibitors also show excellent antitumor activity toward growth and metastasis in vivo, which provides a new idea for the design of highly-targeted PAD4 inhibitors.

Chromosome-level genome assembly of the endangered plant Tetraena mongolica.

Tetraena mongolica is an endangered xerophytic shrub with high ecological value for the restoration of desert vegetation because of its high tolerance to drought and heat stress. Here, we generated a high-quality chromosome-level reference genome of T. mongolica by combining PacBio HiFi data and Hi-C sequencing technologies, which was approximately 1.12 Gb (contig N50 of 25.5 Mb) in size and contained 61,888 protein-coding genes; repetitive sequences comprised 44.8% of the genome. This genome of T. mongolica is the first published genome sequence of a member of the order Zygophyllales. Genome analysis showed that T. mongolica has undergone a recent whole genome duplication event, and a recent burst of long terminal repeat insertions afterward, which may be responsible for its genome size expansion and drought adaptation. We also conducted searches for gene homologues and identified terpene synthase (TPS) gene families and candidate genes involved in triacylglycerol biosynthesis. The T. mongolica genome sequence could aid future studies aimed at functional gene identification, germplasm resource management, molecular breeding efforts, as well as evolutionary studies of Fabids and angiosperm taxa.

Allelopathic inhibition effects and mechanism of phenolic acids to Microcystis aeruginosa.

Allelochemicals are essential agents for the biological control of harmful blooms. It is crucial to identify efficient algal suppressors and understand their mechanisms. This study reports the inhibition of Microcystis aeruginosa growth by 6 phenolic acids derived from plants' secondary metabolites. The inhibitory effect of phenolic acids was significantly influenced by exposure dose and phenolic acid species. Caffeic acid has the most efficient algal inhibition ability (96 h-EC50 of 5.8 mg/L). In contrast, the other 5 analogs (cinnamic acid, p-coumaric acid, 3-hydroxycinnamic acid, ferulic acid, and isoferulic acid) showed a weak inhibition effect or promotion effect with the exposure dose of 5-100 mg/L. ROS and chlorophyll a content tests combined with metabolomics analysis revealed that caffeic acid could induce the ROS accumulation of M. aeruginosa. They mainly disturbed nucleotide, amino acid, and fatty acid metabolism, leading to the downregulation of most metabolites, including toxins of microcystin LR and cyanopeptolin A, and the precursors of some unpleasant terpenoids. It has been suggested that caffeic acid is an effective agent for controlling M. aeruginosa blooms.

Sludge disintegration and phosphorus migration in anaerobic fermentation of waste activated sludge by the addition of EDTA-2Na.

The effects of the addition of EDTA-2Na on sludge disintegration and phosphorus (P) migration during anaerobic fermentation (AF) of waste activated sludge (WAS) are investigated. The efficiency of sludge disintegration was positively correlated with the dose of EDTA-2Na from 0.5-2.0 g/g SS, and an enormous quantity of P was liberated into the aqueous phase, accompanied by sludge disintegration. The proper dose of EDTA-2Na for P release from WAS was 1.5 g/g SS, with an orthophosphate concentration of 394.72 mg/L. P release was more consistent with the pseudo second-order kinetic model. The migration of P species during AF with EDTA-2Na addition was also studied. Orthophosphate was the main species in both of the liquid phase and the loosely bound extracellular polymeric substances (EPS), but organic P (OP) was much more abundant in tightly bound EPS. Inorganic P (IP) was the dominant P speciation in the solid and was mainly distributed in the fraction of non-apatite IP, which accounted for more than 62.8% of IP in the presence of EDTA-2Na. In addition, both IP and OP in the solid contributed to the accumulation of P and the former was outperformed. Furthermore, the increased total dissolved P mainly came from cells. However, the fermented sludge tended to be smaller and to have low compressibility, which is detrimental to its further treatment.

The Promoting Role of HK II in Tumor Development and the Research Progress of Its Inhibitors.

Increased glycolysis is a key characteristic of malignant cells that contributes to their high proliferation rates and ability to develop drug resistance. The glycolysis rate-limiting enzyme hexokinase II (HK II) is overexpressed in most tumor cells and significantly affects tumor development. This paper examines the structure of HK II and the specific biological factors that influence its role in tumor development, as well as the potential of HK II inhibitors in antitumor therapy. Furthermore, we identify and discuss the inhibitors of HK II that have been reported in the literature.

Re-vegetation Improves Soil Quality by Decreasing Soil Conductivity and Altering Soil Microbial Communities: A Case Study of an Opencast Coal Mine in the Helan Mountains.

Microbial communities constitute a diverse genetic resource pool in the soil and are key indicators of soil health and quality. How re-vegetation affects soil microbial diversity and community composition at the dump of an opencast coal mine is largely unknown. Using high-throughput sequencing, we performed a comparative study of the bacterial and fungal communities from non-vegetated (bare land) soil and from areas re-vegetated by Astragalus laxmannii, Halogeton arachnoideus, and Artemisia desertorum at an opencast coal mine in the Helan Mountains in western China. These results indicated that re-vegetation significantly reduced soil conductivity. The soils re-vegetated by all three plant species showed greater richness of bacterial species than the bare land, and soils re-vegetated with A. desertorum and A. laxmannii showed significantly greater richness of fungal species than bare land. The bacterial and fungal ß-diversity values differed significantly between vegetated and non-vegetated soil, and these differences were more pronounced for bacterial communities than for fungal communities. Re-vegetation significantly increased the relative abundances of Proteobacteria and Bacteroidota and decreased the relative abundance of Chloroflexi. The decreasing soil conductivity that occurred with re-vegetation was found to be an important environmental determinant of the soil microbial community. This study provides evidence that re-vegetation may enhance soil quality via decreasing soil conductivity and altering the soil microbial community, and A. laxmannii was found to be a more effective species than H. arachnoideus or A. desertorum with respect to decreasing soil conductivity and altering the soil microbial communities in the Opencast Coal Mine arid region. This work may provide a helpful guideline for selection of plant species for re-vegetation projects.

Mechanism of bio-electrokinetic remediation of pyrene contaminated soil: Effects of an electric field on the degradation pathway and microbial metabolic processes.

In this study, the mechanism of bio-electrokinetic (BIO-EK) remediation to improve the degradation of pyrene was evaluated based on an analysis of the intermediate products and the microbial community. The results show that BIO-EK remediation has a higher pyrene degradation efficiency on pyrene and its intermediate products than the bioremediation and electrokinetic (EK) remediation processes. A series of intermediate products were detected. According to the type of the intermediate products, two degradation pathways, biological metabolism and electrochemical oxidation, are proposed in the BIO-EK remediation of pyrene. Furthermore, the primary microbial taxa involved in the pollutant degradation changed, which led to variations in the functional gene components. The abundant and functional genes related to metabolism were specifically analyzed. The results indicate that the electric field promotes the expression of metabolisms associated with 14 carbohydrates, 13 lipids, 13 amino acids, five energies, and in particular, 11 xenobiotics. These results suggest that in addition to the promotion effect on the microbial metabolism caused by the electric field, BIO-EK remediation can promote the degradation of pollutants due to the coexistence of a microbial metabolic pathway and an electrochemical oxidation pathway.

Enhancements of short-chain fatty acids production via anaerobic fermentation of waste activated sludge by the combined use of persulfate and micron-sized magnetite.

The combination of persulfate (PDS) with micron-sized magnetite (Fe3O4) was introduced into the process of anaerobic fermentation (AF) to scrutinize the short chain fatty acid (SCFA) production from waste activated sludge for the first time. The synergetic effect of PDS and Fe3O4 results in the promotion of intracellular and extracellular substance liberation, augment in key hydrolases activities, and enrichment of hydrolytic and acidifying microbial population. Meanwhile, carbohydrate, amino acid, and energy metabolism as well as enzymes, are considerably accelerated. Consequently, the maximum SCFAs yield is significantly enhanced to 391.25 mg COD/L on day 8 of AF with the addition of 0.3 g Fe3O4/g SS and 0.5 g PDS/g SS, which was 2.39-folds than that of the control. The relative abundance of Actinobacteria were highly enriched and reached to 35.76% at the class level. This work affords an effective avenue to evidently boost the production of SCFAs from WAS via AF.

One-step fabrication of trimetallic alloy nanozyme catalyzer for luminol-H2O2 chemiluminescence and its application for miRNA-21 detection coupled with miRNA walking machine.

PtCuCo trimetallic alloys (PtCuCo-TAs) are synthesized by one-step reduction. The chemiluminescence (CL) properties of PtCuCo-TAs are studied systemically. PtCuCo-TAs show good catalyzing for luminol-H2O2 system. A CL platform is developed for the detection of miRNA-21 using PtCuCo-TAs as nanozyme catalyzer. In the CL detection platform, H1 (Hairpin DNA1) is immobilized onto magnetic beads (MBs) firstly. In the presence of miRNA-21, H1 is opened. H2 (Hairpin DNA2) then hybridizes with H1. Meanwhile, a "cleat" in the end of miRNA-21 with a fewer bases complementary is formed to prevent miRNA-21 dissociating from H1. This miRNA-21 hybridizes to another H1. When cpDNA-PtCuCo-TAs which consisted with cDNA (Complementary strand of probe DNA) and pDNA-PtCuCo-TAs (PtCuCo-TAs labeled with probe DNA) are added, the ssDNA region of H1 reacts with the toehold domain of probe DNA and cDNA is released resulting pDNA-PtCuCo-TAs being captured. With this process repeatedly, a lot of pDNA-PtCuCo-TAs are captured onto MBs. After separation and washing, the precipitate and H2O2 are put into the 96-well and luminol solution is injected. The CL signal is produced by PtCuCo-TAs catalyzing luminol-H2O2 system. The amount of miRNA-21 is detected with CL signal. This CL platform performs with limit of detection 0.167 fM and has good selectivity over other RNA.

Testing relationship between plant productivity and diversity in a desertified steppe in Northwest China.

The rapid global plant diversity and productivity loss has resulted in ecosystem functional degeneration in recent decades, and the relationship between plant diversity and productivity is a pressing issue around the world. Here, we sampled six plant communities that have not been grazed for 20 years, i.e., Agropyron mongolicum, Stipa bungeana, Cynanchum komarovii, Glycyrrhiza uralensis, Sophora alopecuroides, Artemisia ordosica, located in a desertified steppe, northwestern China, and tested the relationship between plant diversity and productivity in this region. We found a positive linear relationship between AGB (above-ground biomass) and BGB (below-ground biomass), and the curves between plant diversity and AGB were unimodal (R 2 = 0.4572, p < 0.05), indicating that plant productivity increased at a low level of diversity but decreased at a high level of diversity. However, there was no significant relationship between BGB and plant diversity (p > 0.05). Further, RDA (redundancy analysis) indicated that soil factors had a strong effect on plant diversity and productivity. Totally, GAMs (generalized additive models) showed that soil factors (especially total nitrogen TN, total carbon TC, soil microbial biomass nitrogen SMB-N, soil microbial biomass carbon SMB-C) explained more variation in plant diversity and productivity (78.24%), which can be regarded as the key factors driving plant diversity and productivity. Therefore, strategies aiming to increase plant productivity and protect plant diversity may concentrate on promoting soil factors (e.g., increasing TC, TN, SMB-N and SMB-C) and plant species, which can be regarded as an effective and simple strategy to stabilize ecosystems to mitigate aridity in desertified steppes in northwestern China.

Rigid and elastic registration for coronary artery IVUS images.

BACKGROUND: Intravascular ultrasound (IVUS) has been widely used in diagnosis and interventional treatment of cardiac vessel diseases. The coronary artery IVUS images are usually polluted by motion artifacts caused by cardiac motion, pulsatile blood and catheter twist during continuous pullback acquisition. OBJECTIVE: Strategies for rigid and elastic registration of coronary artery IVUS studies are developed to suppress the longitudinal motion and misalignment between successive frames. METHODS: Rigid registration is performed by searching for the optimal matching for each frame in other cycles based on the cyclic variation of gray-scale features. The image sequence is gated to properly identify the frames in each cardiac phase. Then, elastic registration between frames is achieved through an optimization algorithm based on thin plate spline (TPS) to correct the misalignment of successive slices. RESULTS: Experimental results with in vivo image data shows that the rigid registration performs better than the offline ECG gating. The elastic mapping relation between lumen contours in successive frames is smooth and continuous. CONCLUSION: The serrated vessel wall borders in longitudinal cuts are smoothed after rigid registration while image segmentation and feature extraction are required. The point-to-point correspondence between lumen contours detected from two matched frames is obtained with elastic registration.

[Effects of short-term fencing on organic carbon fractions and physical stability of sandy sierozem in desert steppe of Northwest China].

In order to explore the change patterns of organic carbon fractions and physical stability of sandy sierozem in desert steppe at the early stage of fencing, 0-40 cm soil samples were collected from a 5-year fenced desert steppe (inside the fence) and a free grazing steppe (outside the fence) in Yanchi County of Ningxia, Northwest China, with the soil organic carbon, labile organic carbon, and particulate organic carbon contents and soil particle composition analyzed. No significant differences were observed in the soil organic carbon content and soil particle composition inside and outside the fence. The average soil organic carbon inside and outside the fences was 3.25 g x kg(-1), the percentages of sand, silt, and clay were averagely 72%, 16%, and 12%, respectively, and the soil physical stability index was 1.30% -1.31%. The soil active organic carbon showed a significant change in 10-20 cm layer. The soil labile organic carbon content was 0.80 g x kg(-1) inside the fence, which was significantly higher than that outside the fence (0.62 g x kg(-1)). The percentage of soil particulate organic carbon was 50.9% inside the fence, which was also significantly higher than that outside the fence (31.7%). The soil texture inside the fence changed from sandy to loam, and the soil labile organic carbon content increased gradually; while the soil texture outside the fence was sandy, and its vertical change was relatively smooth. The organic carbon of sandy si- erozem in the desert steppe under the conditions of short-term fencing was still in a balance between consumption and accumulation, the soil texture was relatively stable, and the soil physical stability changed little. It was suggested that the soil active organic carbon content and its relative percentage in 10-20 cm layer could be used as the indicators of early soil quality change of desert steppe.

[Changes of plant community biomass and soil nutrients during the vegetation succession on abandoned cultivated land in desert steppe region].

By the method of substituting temporal serial with spatial serial, and taking five abandoned cultivated lands with different ages (1, 4, 9, 12, and 20 years) in desert steppe region as test objects, this paper studied the change characteristics of plant community biomass and soil nutrients during vegetation succession. With the increasing abandoned years, the plant community aboveground biomass on the abandoned lands increased after an initial decrease, whereas the total nitrogen, total phosphorus, organic carbon contents, and carbon density in 0-60 cm soil layer increased first, decreased then, and increased again, with the maximum values of soil total nitrogen and phosphorus contents appeared on the abandoned lands with the ages 4 and 20 years. During vegetation succession, the effects of soil total nitrogen and organic carbon on plant community biomass were greater than those of soil total phosphorus and soil bulk density.