Machine learning assisted rational design of antimicrobial peptides based on human endogenous proteins and their applications for cosmetic preservative system optimization.

Preservatives are essential components in cosmetic products, but their safety issues have attracted widespread attention. There is an urgent need for safe and effective alternatives. Antimicrobial peptides (AMPs) are part of the innate immune system and have potent antimicrobial properties. Using machine learning-assisted rational design, we obtained a novel antibacterial peptide, IK-16-1, with significant antibacterial activity and maintaining safety based on ß-defensins. IK-16-1 has broad-spectrum antimicrobial properties against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans, and has no haemolytic activity. The use of IK-16-1 holds promise in the cosmetics industry, since it can serve as a preservative synergist to reduce the amount of other preservatives in cosmetics. This study verified the feasibility of combining computational design with artificial intelligence prediction to design AMPs, achieving rapid screening and reducing development costs.

Relationship between Occupational Metal Exposure and Hypertension Risk Based on Conditional Logistic Regression Analysis.

Occupational exposure is a significant source of metal contact; previous studies have been limited regarding the effect of occupational metal exposure on the development of hypertension. This study was conducted to assess the levels of exposure of certain metals (chromium (Cr), iron (Fe), manganese (Mn), and nickel (Ni)) in hypertensive and non-hypertensive workers and to assess the relationship between the risk of hypertension and metal exposure level. Our study included 138 hypertensive patients as case groups and 138 non-hypertensive participants as controls. The exposure risk level was divided according to the limit value after collecting and testing the metal dust in the workshop. Considering the influence of single- and poly-metal, single factor analysis and conditional logistic regression analysis of poly-metal were carried out. The results of the model indicated that the incidence of hypertension increased with an increase in Cr exposure level, and the risk of hypertension was 1.85 times higher in the highest exposure than in the lowest exposure (95% CI: 1.20−2.86, p < 0.05). Mn has the same effect as Cr. There was no significant correlation between Fe or Ni and hypertension. Our findings suggested that Cr and Mn exposure in the work environment might increase the risk of hypertension, while no effect of Fe and Ni on blood pressure was found. Prospective study designs in larger populations are needed to confirm our findings.

Highly Efficient Organic Dyes Capture Using Thiol-Functionalized Porous Organic Polymer.

It is of great significance to develop new materials for efficient capture cationic dyes methylene blue (MB) and malachite green (MG). In this work, a novel triptycene-based porous organic polymer with abundant thiol groups (TPP-SH) was prepared successfully by postmodification with a high surface area and robust triptycene-based porous organic polymer (TPP). The obtained TPP-SH exhibited a high surface area, good porosity, and good thermal stability. In addition, TPP-SH was highly effective at capturing MB and MG from aqueous solution because of the abundant thiols in its hierarchical structure. Under optimal adsorption conditions, the maximum adsorption capacities of MB and MG calculated by the Langmuir model at room temperature were 1146.3 and 689.6 mg g-1, respectively. These values are higher than those of many reported materials. The MB and MG adsorption rates were 0.0154 and 6.69 × 10-4 mg g-1 min-1, respectively. Furthermore, the polymer TPP-SH had a good recycling performance after adsorption-desorption at least five times. Therefore, the TPP-SH exhibited a high adsorption capacity, fast adsorption kinetics, and easy-recycling behavior, providing a new avenue for the preparation of green functionalized adsorbents with good performance for water decontamination.

Efficient adsorption of methyl orange and methyl blue dyes by a novel triptycene-based hyper-crosslinked porous polymer.

It is still a great challenge to develop new materials for the highly efficient entrapment of organic dyes from aqueous solution. Herein, a novel triptycene-based hyper-crosslinked porous polymer (TPP-PP) was designed and synthesized by a simple Friedel-Crafts reaction. The obtained polymer TPP-PP has a high surface area, abundant pore structure and stable thermal performance. Due to the above characteristics, TPP-PP has good adsorption performance for anionic methyl orange solution (MO) and cationic methyl blue solution (MB). Under the optimal experiment conditions, the TPP-PP showed an excellent adsorption capacity for MO (220.82 mg g-1) and MB (159.80 mg g-1), respectively. The adsorption kinetics fitted the pseudo-second-order model. The adsorption of MO by TPP-PP reaches equilibrium within 180 minutes, and the adsorption of MB reaches equilibrium within 150 minutes. The adsorption behavior was not only spontaneous but also endothermic in reality. At the same time, TPP-PP also has good reusability. After 5 cycles of experiments, the removal rate of MO and MB by TPP-PP can still reach more than 80%. Thus, the Friedel-Crafts reaction crosslinked method might be a promising approach for the synthesis of novel material for the highly efficient extraction of dye wastewater.

Characteristics of soil salt crust formed by mixing calcium chloride with sodium sulfate and the possibility of inhibiting wind-sand flow.

Soil salt crust can change the structure of aeolian soil and improve its resistance to wind erosion. Four ions (Na+, Ca2+, Cl-, and SO42-) with high contents in aeolian soil were selected for a salt crust experiment. The experiment set a variety of gradients of soil salt contents and salt mixing ratios of Na2SO4 and CaCl2. The physical properties of the salt crust were tested, and the wind erosion resistance of the salt crust was discussed. The results showed that the soil salt contents and salt mixing ratio influenced the resistance of the salt crust, especially in terms of its compressive strength and toughness. The former affected the compressive strength of the salt crust by changing the amount of cemented soil salt. The latter affected the kinds of crystals by changing the ion ratio, thus changing the structure of the salt crust and affecting its wind erosion resistance. The wind erosion resistance of the salt crust is complicated by the interaction between the soil salt content and salt mixing ratio. A multilayer crust can be formed in mixed salt, which has a strong wind erosion resistance. This result provides new findings on flowing sand soil and a new method for the treatment of flowing sand soil.

Crystal structure and catalytic activity of the PPM1K N94K mutant.

Protein Phosphatase Mg2+ /Mn2+ -Dependent 1K (PPM1K),also named as PP2Cm or branched-chain α-ketoacid dehydrogenase complex phosphatase, is a member of the metal-dependent phosphatase family and an important metabolic regulator. Single nucleotide polymorphisms (SNPs) in PPM1K contributing to protein functional defects have been found to be associated with numerous human diseases, such as cardiovascular disease, maple syrup urine disease, type 2 diabetes, and neurological disease. PPM1K N94K is an identified missense mutant produced by one of the SNPs in the human PPM1K coding sequence. However, the effects of the N94K mutant on its activity and structural property have not been defined. Here, we performed a detailed enzymological study using steady-state kinetics in the presence of pNPP or phospho-peptide substrates and crystallographic analyses of the wild-type and N94K PPM1K. The PPM1K-N94K significantly impaired its Mg2+ -dependent catalytic activity and structural analysis demonstrated that the N94K mutation induced a conformational change in the key residue in coordinating the Mg2+ in the active site. Specifically, three Mg2+ were located in the active site of the PPM1K N94K instead of two Mg2+ in the PPM1K wild type. Therefore, our results provide a structure basis for the metal ion-dependent PPM1K-N94K phosphatase activity.

Comparative proteomic analysis of maize (Zea mays L.) seedlings under rice black-streaked dwarf virus infection.

BACKGROUND: Maize rough dwarf disease (MRDD) is a severe disease that has been occurring frequently in southern China and many other Asian countries. MRDD is caused by the infection of Rice black streaked dwarf virus (RBSDV) and leads to significant economic losses in maize production. To well understand the destructive effects of RBSDV infection on maize growth, comparative proteomic analyses of maize seedlings under RBSDV infection was performed using an integrated approach involving LC-MS/MS and Tandem Mass Tag (TMT) labeling. RESULTS: In total, 7615 maize proteins, 6319 of which were quantified. A total of 116 differentially accumulated proteins (DAPs) were identified, including 35 up- and 81 down-regulated proteins under the RBSDV infection. Enrichment analysis showed that the DAPs were most strongly associated with cyanoamino acid metabolism, protein processing in ER, and ribosome-related pathways. Two sulfur metabolism-related proteins were significantly reduced, indicating that sulfur may participate in the resistance against RBSDV infection. Furthermore, 15 DAPs involved in six metabolic pathways were identified in maize under the RBSDV infection. CONCLUSIONS: Our data revealed that the responses of maize to RBSDV infection were controlled by various metabolic pathways.

Allosteric modulation of the catalytic VYD loop in Slingshot by its N-terminal domain underlies both Slingshot auto-inhibition and activation.

Slingshots are phosphatases that modulate cytoskeleton dynamics, and their activities are tightly regulated in different physiological contexts. Recently, abnormally elevated Slingshot activity has been implicated in many human diseases, such as cancer, Alzheimer's disease, and vascular diseases. Therefore, Slingshot-specific inhibitors have therapeutic potential. However, an enzymological understanding of the catalytic mechanism of Slingshots and of their activation by actin is lacking. Here, we report that the N-terminal region of human Slingshot2 auto-inhibits its phosphatase activity in a noncompetitive manner. pH-dependent phosphatase assays and leaving-group dependence studies suggested that the N-terminal domain of Slingshot2 regulates the stability of the leaving group of the product during catalysis by modulating the general acid Asp361 in the catalytic VYD loop. F-actin binding relieved this auto-inhibition and restored the function of the general acid. Limited tryptic digestion and biophysical studies identified large conformational changes in Slingshot2 after the F-actin binding. The dissociation of N-terminal structural elements, including Leu63, and the exposure of the loop between α-helix-2 and ß-sheet-3 of the phosphatase domain served as the structural basis for Slingshot activation via F-actin binding in vitro and via neuregulin stimulation in cells. Moreover, we designed a FlAsH-BRET-based Slingshot2 biosensor whose readout was highly correlated with the in vivo phosphatase activities of Slingshot2. Our results reveal the auto-inhibitory mechanism and allosteric activation mechanisms of a human Slingshot phosphatase. They also contribute to the design of new strategies to study Slingshot regulation in various cellular contexts and to screen for new activators/inhibitors of Slingshot activity.

Transcriptome Analysis of Cadmium-Treated Roots in Maize (Zea mays L.).

Cadmium (Cd) is a heavy metal and is highly toxic to all plant species. However, the underlying molecular mechanism controlling the effects of auxin on the Cd stress response in maize is largely unknown. In this study, the transcriptome produced by maize 'Zheng 58' root responses to Cd stress was sequenced using Illumina sequencing technology. In our study, six RNA-seq libraries yielded a total of 244 million clean short reads and 30.37 Gb of sequence data. A total of 6342 differentially expressed genes (DEGs) were grouped into 908 Gene Ontology (GO) categories and 198 Kyoto Encyclopedia of Genes and Genomes terms. GO term enrichment analysis indicated that various auxin signaling pathway-related GO terms were significantly enriched in DEGs. Comparison of the transcript abundances for auxin biosynthesis, transport, and downstream response genes revealed a universal expression response under Cd treatment. Furthermore, our data showed that free indole-3-acetic acid (IAA) levels were significantly reduced; but IAA oxidase activity was up-regulated after Cd treatment in maize roots. The analysis of Cd activity in maize roots under different Cd and auxin conditions confirmed that auxin affected Cd accumulation in maize seedlings. These results will improve our understanding of the complex molecular mechanisms underlying the response to Cd stress in maize roots.

The second-sphere residue T263 is important for the function and catalytic activity of PTP1B via interaction with the WPD-loop.

Protein tyrosine phosphatases have diverse substrate specificities and intrinsic activities that lay the foundations for the fine-tuning of a phosphorylation network to precisely regulate cellular signal transduction. All classical PTPs share common catalytic mechanisms, and the important catalytic residues in the first sphere of their active sites have been well characterized. However, little attention has been paid to the second-sphere residues that are potentially important in defining the intrinsic activity and substrate specificity of PTPs. Here, we find that a conserved second-sphere residue, Thr263, located in the surface Q-loop is important for both the function and activity of PTPs. Using PTP1B as a study model, we found that mutations of Thr263 impaired the negative regulation role of PTP1B in insulin signaling. A detailed mechanistic study utilizing steady-state kinetics, Brønsted analysis and pH dependence in the presence of pNPP or phosphopeptide substrates revealed that Thr263 is required for the stabilization of the leaving group during catalysis. Further crystallographic studies and structural comparison revealed that Thr263 regulates the general acid function through modulation of the WPD-loop by the T263:F182/Y/H interaction pair, which is conserved in 26 out of 32 classical PTPs. In addition, the hydrophobic interaction between Thr263 and Arg1159 of the insulin receptor contributes to the substrate specificity of PTP1B. Taken together, our findings demonstrate the general role of the second-sphere residue Thr263 in PTP catalysis. Our findings suggest that the second sphere residues of PTP active site may play important roles in PTP-mediated function in both normal and diseased states.

Optical imaging modalities for biomedical applications.

Optical photographic imaging is a well known imaging method that has been successfully translated into biomedical applications such as microscopy and endoscopy. Although several advanced medical imaging modalities are used today to acquire anatomical, physiological, metabolic, and functional information from the human body, optical imaging modalities including optical coherence tomography, confocal microscopy, multiphoton microscopy, multispectral endoscopy, and diffuse reflectance imaging have recently emerged with significant potential for non-invasive, portable, and cost-effective imaging for biomedical applications spanning tissue, cellular, and molecular levels. This paper reviews methods for modeling the propagation of light photons in a biological medium, as well as optical imaging from organ to cellular levels using visible and near-infrared wavelengths for biomedical and clinical applications.

Long-time course of protease-activated receptor-1 expression after intracerebral hemorrhage in rats.

Thrombin plays an important role in brain injuries associated with intracerebral hemorrhage (ICH). The protease-activated receptor (PAR)-1 is responsible for the vast majority of the thrombin's cellular activation functions. We tested the hypothesis that thrombin-induced brain damage after ICH, at least in part, is mediated by PAR-1. We report that there are significant differences between PAR-1 positive cell number and PAR-1 mRNA absorbance ratio between ICH model group (at 6h, 24h, 3 d, 7 d and 14 d) and normal group (P<0.05). These results suggest that the long-time course of PAR-1 expression may be partly involved in the mechanism of thrombin-induced brain damage after ICH.