MeJA-induced hairy roots in Plumbago auriculata L. by RNA-seq profiling and key synthase provided new insights into the sustainable production of plumbagin and saponins.

Naturally synthesized secondary metabolites in plants are considered an important source of drugs, food additives, etc. Among them, research on natural plant medicinal components and their synthesis mechanisms has always been of high concern. We identified a novel medicinal floral crop, Plumbago auriculata L., that can be treated with methyl jasmonate (MeJA) for the rapid or sustainable production of natural bioactives from hairy roots. In the study, we globally analyzed the changes in the accumulation of plumbagin and others in the hairy roots of Plumbago auriculata L. hairy roots (PAHR) 15834 in P. auriculata L. based on 100 µmol/L of MeJA treatment by RNA-seq profiling, and we found that there was a significant increase in the accumulation of plumbagin and saponin before 24 h. To explain the principle of co-accumulation, it showed that MeJA induced JA signaling and the shikimic acid pathway, and the methylvaleric acid (MVA) pathway was activated downstream subsequently by the Mfuzz and weighted gene co-expression analysis. Under the shared metabolic pathway, the high expression of PAL3 and HMGR promoted the activity of the "gateway enzymes" phenylalanine ammonia lyase (PAL) and 3-hydroxy-3-methylglutaryl CoA reductase (HMGR), which respectively induced the high expression of key reaction enzyme genes, including chalcone synthase (CHS), isopentenyl diphosphate (IPP), and farnesyl pyrophosphate synthase (FPS), that led to the synthesis of plumbagin and saponin. We speculated that large amounts of ketones and/or aldehydes were formed under the action of these characteristic enzymes, ultimately achieving their co-accumulation through polyketone and high-level sugar and amino acid metabolism. The study results provided a theoretical basis for carrying out the factory refinement and biosynthesis of plumbagin and saponins and also provided new ideas for fully exploiting multifunctional agricultural crops and plants and developing new agricultural by-products.

Self-assembled protein vesicles as vaccine delivery platform to enhance antigen-specific immune responses.

Self-assembling protein nanoparticles are beneficial platforms for enhancing the often weak and short-lived immune responses elicited by subunit vaccines. Their benefits include multivalency, similar sizes as pathogens and control of antigen orientation. Previously, the design, preparation, and characterization of self-assembling protein vesicles presenting fluorescent proteins and enzymes on the outer vesicle surface have been reported. Here, a full-size model antigen protein, ovalbumin (OVA), was genetically fused to the recombinant vesicle building blocks and incorporated into protein vesicles via self-assembly. Characterization of OVA protein vesicles showed room temperature stability and tunable size. Immunization of mice with OVA protein vesicles induced strong antigen-specific humoral and cellular immune responses. This work demonstrates the potential of protein vesicles as a modular platform for delivering full-size antigen proteins that can be extended to pathogen antigens to induce antigen specific immune responses.

Increasing Ca2+ accumulation in salt glands under salt stress increases stronger selective secretion of Na+ in Plumbago auriculata tetraploids.

Under salt stress, recretohalophyte Plumbago auriculata tetraploids enhance salt tolerance by increasing selective secretion of Na+ compared with that in diploids, although the mechanism is unclear. Using non-invasive micro-test technology, the effect of salt gland Ca2+ content on Na+ and K+ secretion were investigated in diploid and tetraploid P. auriculata under salt stress. Salt gland Ca2+ content and secretion rates of Na+ and K+ were higher in tetraploids than in diploids under salt stress. Addition of exogenous Ca2+ increased the Ca2+ content of the salt gland in diploids and is accompanied by an increase in the rate of Na+ and K+ secretion. With addition of a Ca2+ channel inhibitor, diploid salt glands retained large amounts of Ca2+, leading to higher Ca2+ content and Na+ secretion rate than those of tetraploids. Inhibiting H2O2 generation and H+-ATPase activity altered Na+ and K+ secretion rates in diploids and tetraploids under salt stress, indicating involvement in regulating Na+ and K+ secretion. Our results indicate that the increased Na+ secretion rate of salt gland in tetraploids under salt stress was associated with elevated Ca2+ content in salt gland.

ISSR molecular markers and anatomical structures can assist in rapid and directional screening of cold-tolerant seedling mutants of medicinal and ornamental plant in Plumbago indica L.

Plumbago indica L. is a perennial herb with ornamental and anticancer medicinal functions widely distributed in the tropics. It is affected by temperature and cannot bloom normally in colder subtropical regions, which seriously affects its ornamental value. To create low-temperature resistance mutants and enrich new germplasm resources, this study used tissue culture and chemical reagent (0.5 mmol/L NaN3) and low-temperature stress (0°C, full darkness for 48h) induction to target and screen for cold-resistance mutants. The results showed that the ISSR band polymorphism ratio of the 24 suspected mutant materials was 87.5%. The DNA profiles of the 9 mutants initially identified were altered. The content of plumbagin in the stems and leaves of the mutants was examined, and it was found that the accumulation in the leaves of the mutant SA24 could be as high as 3.84 times that of the control, which was 0.5991%. There were significant differences in the anatomical structures of roots, stems and leaves. The mutants mostly exhibited reduced root diameter (only 0.17-0.69 times that of CK), increased stem diameter (up to 2.19 times that of CK), enlarged mesophyll cells, increased thickness (up to 1.83 times that of CK) and high specificity, which are thought to be important for the different cold resistance obtained by the mutants. In the cold resistance experiment, four cold-tolerant mutants were successfully screened according to their morphological characteristics and physiological indexes, and the mutagenesis efficiency could be as high as 2.22% and did not affect the accumulation of plumbagin in their stems and leaves, even higher than CK. The responses of the screened mutants SA15, SA19, SA23 and SA24 to low temperature showed slower leaf wilting, higher light energy conversion efficiency, less accumulation of MDA content, increased enzymatic activities of antioxidant enzymes (SOD, CAT, POD) and more accumulation of soluble sugars and proline content. These characteristics are consistent with the response of cold-resistance plants to low temperatures. The cold- resistance mutants cultivated in soil were observed of agronomic and ornamental traits for one year, mainly manifested as delayed flowering and delayed entry into the senescence stage. This study provides a more rapid and accurate technique for identifying and screening cold-tolerant mutants, and lays the foundation for future experiments on the creation of new cold-resistant varieties.

Rational design of elastin-like polypeptide fusion proteins to tune self-assembly and properties of protein vesicles.

Protein vesicles made from bioactive proteins have potential value in drug delivery, biocatalysis, and as artificial cells. As the proteins are produced recombinantly, the ability to precisely tune the protein sequence provides control not possible with polymeric vesicles. The tunability and biocompatibility motivated this work to develop protein vesicles using rationally designed protein building blocks to investigate how protein sequence influences vesicle self-assembly and properties. We have reported an elastin-like polypeptide (ELP) fused to an arginine-rich leucine zipper (ZR) and functional, globular proteins fused to a glutamate-rich leucine zipper (ZE) that self-assemble into protein vesicles when warmed from 4 to 25 °C due to the hydrophobic transition of ELP. Previously, we demonstrated the ability to tune vesicle properties by changing protein and salt concentration, ZE : ZR ratio, and warming rate. However, there is a limit to the properties that can be achieved via assembly conditions. In order to access a wider range of vesicle diameter and stability profiles, this work investigated how modifiying the hydrophobicity and length of the ELP sequence influenced self-assembly and the final properties of protein vesicles using mCherry as a model globular protein. The results showed that both transition temperature and diameter of protein vesicles were inversely correlated to the ELP guest residue hydrophobicity and the number of ELP pentapeptide repeats. Additionally, sequence manipulation enabled assembly of vesicles with properties not accessible by changes to assembly conditions. For example, introduction of tyrosine at 5 guest residue positions in ELP enabled formation of nanoscale vesicles stable at physiological salt concentration. This work yields design guidelines for modifying the ELP sequence to manipulate protein vesicle transition temperature, size and stability to achieve desired properties for particular biofunctional applications.

DeepCancerMap: A versatile deep learning platform for target- and cell-based anticancer drug discovery.

Discovering new anticancer drugs has been widely concerned and remains an open challenge. Target- and phenotypic-based experimental screening represent two mainstream anticancer drug discovery methods, which suffer from time-consuming, labor-intensive, and high experimental costs. In this study, we collected 485,900 compounds involving in 3,919,974 bioactivity records against 426 anticancer targets and 346 cancer cell lines from academic literature, as well as 60 tumor cell lines from NCI-60 panel. A total of 832 classification models (426 target- and 406 cell-based predictive models) were then constructed to predict the inhibitory activity of compounds against targets and tumor cell lines using FP-GNN deep learning method. Compared to the classical machine learning and deep learning methods, the FP-GNN models achieve considerable overall predictive performance, with the highest AUC values of 0.91, 0.88, 0.91 for the test sets of targets, academia-sourced and NCI-60 cancer cell lines, respectively. A user-friendly webserver called DeepCancerMap and its local version were developed based on these high-quality models, enabling users to perform anticancer drug discovery-related tasks including large-scale virtual screening, profiling prediction of anticancer agents, target fishing, and drug repositioning. We anticipate this platform to accelerate the discovery of anticancer drugs in the field. DeepCancerMap is freely available at https://deepcancermap.idruglab.cn.

The reverse function of lignin-degrading enzymes: The polymerization ability to promote the formation of humic substances in domesticated composting.

This study aimed to confirm the ability of lignin peroxidase (LiP) and manganese peroxidase (MnP) in promoting the formation of humic substances (HS) during domesticated composting. Three raw materials with different lignin types were used for composting, including rice straw, tree branches, and pine needles. Results suggested that LiP and MnP activity increased during domesticated composting. But HS formation was only promoted by LiP. The effect of MnP was insignificant, which might be caused by the lack of enzyme cofactors like Mn2+. Meanwhile, bacteria highly associated with LiP and MnP production were identified as core bacteria. Function prediction of 16S-PICRUSt2 showed that the function of core bacteria was consistent with total bacterial functions which mainly promoted compost humification. Therefore, it speculated that LiP and MnP had the ability to promote HS formation during composting. Accordingly, it is a new understanding of the role of biological enzymes in composting.

Enhanced Na+ and Cl- sequestration and secretion selectivity contribute to high salt tolerance in the tetraploid recretohalophyte Plumbago auriculata Lam.

MAIN CONCLUSION: Enhanced secretion of Na+ and Cl- in leaf glands and leaf vacuolar sequestration of Na+ or root retention of Cl-, combined with K+ retention, contribute to the improved salt tolerance of tetraploid recretohalophyte P. auriculata. Salt stress is one of the major abiotic factors threatening plant growth and development, and polyploids generally exhibit higher salt stress resistance than diploids. In recretohalophytes, which secrete ions from the salt gland in leaf epidermal cells, the effects of polyploidization on ion homeostasis and secretion remain unknown. In this study, we compared the morphology, physiology, and ion homeostasis regulation of diploid and autotetraploid accessions of the recretohalophyte Plumbago auriculata Lam. after treatment with 300 mM NaCl for 0, 2, 4, 6, and 8 days. The results showed that salt stress altered the morphology, photosynthetic efficiency, and chloroplast structure of diploid P. auriculata to a greater extent than those of its tetraploid counterpart. Moreover, the contents of organic osmoregulatory substances (proline and soluble sugars) were significantly higher in the tetraploid than in the diploid, while those of H2O2 and malondialdehyde (MDA) were significantly lower. Analysis of ion homeostasis revealed that the tetraploid cytotype accumulated more Na+ in stems and leaves and more Cl- in roots but less K+ loss in roots compared with diploid P. auriculata. Additionally, the rate of Na+ and Cl- secretion from the leaf surface was higher, while that of K+, Mg2+, and Ca2+ secretion was lower in tetraploid plants. X-ray microanalysis of mesophyll cells revealed that Na+ mainly accumulated in different cellular compartments in the tetraploid (vacuole) and diploid (cytoplasm) plants. Our results suggest that polyploid recretohalophytes require the ability to sequester Na+ and Cl-(via accumulation in leaf cell vacuoles or unloading by roots) and selectively secrete these ions (through salt glands) together with the ability to prevent K+ loss (by roots). This mechanism required to maintain K+/Na+ homeostasis in polyploid recretohalophytes under high salinity provides new insights in the improved maintenance of ion homeostasis in polyploids under salt stress.

Design and Fabrication of an Integrated Hollow Concave Cilium MEMS Cardiac Sound Sensor.

In light of a need for low-frequency, high sensitivity and broadband cardiac murmur signal detection, the present work puts forward an integrated MEMS-based heart sound sensor with a hollow concave ciliary micro-structure. The advantages of a hollow MEMS structure, in contrast to planar ciliated micro-structures, are that it reduces the ciliated mass and enhances the operating bandwidth. Meanwhile, the area of acoustic-wave reception is enlarged by the concave architecture, thereby enhancing the sensitivity at low frequencies. By rationally designing the acoustic encapsulation, the loss of heart acoustic distortion and weak cardiac murmurs is reduced. As demonstrated by experimentation, the proposed hollow MEMS structure cardiac sound sensor has a sensitivity of up to -206.9 dB at 200 Hz, showing 6.5 dB and 170 Hz increases in the sensitivity and operating bandwidth, respectively, in contrast to the planar ciliated MEMS sensor. The SNR of the sensor is 26.471 dB, showing good detectability for cardiac sounds.

Self-assembling nanocarriers from engineered proteins: Design, functionalization, and application for drug delivery.

Self-assembling proteins are valuable building blocks for constructing drug nanocarriers due to their self-assembly behavior, monodispersity, biocompatibility, and biodegradability. Genetic and chemical modifications allow for modular design of protein nanocarriers with effective drug encapsulation, targetability, stimuli responsiveness, and in vivo half-life. Protein nanocarriers have been developed to deliver various therapeutic molecules including small molecules, proteins, and nucleic acids with proven in vitro and in vivo efficacy. This article reviews recent advances in protein nanocarriers that are not derived from natural protein nanostructures, such as protein cages or virus like particles. The protein nanocarriers described here are self-assembled from rationally or de novo designed recombinant proteins, as well as recombinant proteins complexed with other biomolecules, presenting properties that are unique from those of natural protein carriers. Design, functionalization, and therapeutic application of protein nanocarriers will be discussed.

Design and Realization of MEMS Heart Sound Sensor with Concave, Racket-Shaped Cilium.

The biomedical acoustic signal plays an important role in clinical non-invasive diagnosis. In view of the deficiencies in early diagnosis of cardiovascular diseases, acoustic properties of S1 and S2 heart sounds are utilized. In this paper, we propose an integrated concave cilium MEMS heart sound sensor. The concave structure enlarges the area for receiving sound waves to improve the low-frequency sensitivity, and realizes the low-frequency and high-sensitivity characteristics of an MEMS heart sound sensor by adopting a reasonable acoustic package design, reducing the loss of heart sound distortion and faint heart murmurs, and improving the auscultation effect. Finally, experimental results show that the integrated concave ciliated MEMS heart sound sensor's sensitivity reaches -180.6 dB@500 Hz, as compared with the traditional bionic ciliated MEMS heart sound sensor; the sensitivity is 8.9 dB higher. The sensor has a signal-to-noise ratio of 27.05 dB, and has good heart sound detection ability, improving the accuracy of clinical detection methods.

Mycotoxin surveillance on wheats in Shandong province, China, reveals non-negligible probabilistic health risk of chronic gastrointestinal diseases posed by deoxynivalenol.

Abnormal climate changes have resulted in over-precipitation in many regions. The occurrence and contamination levels of mycotoxins in crops and cereals have been elevated largely. From 2017 to 2019, we did investigation targeting 15 mycotoxins shown in the wheat samples collected from Shandong, a region suffering over-precipitation in China. We found that deoxynivalenol (DON) was the dominant mycotoxin contaminating wheats, with detection rates 304/340 in 2017 (89.41%), 303/330 in 2018 (91.82%), and 303/340 in 2019 (89.12%). The ranges of DON levels were < 4 to 580 µg/kg in 2017, < 4 to 3070 µg/kg in 2018, and < 4 to 1540 µg/kg in 2019. The exposure levels were highly correlated with local precipitation. Male exposure levels were generally higher than female's, with significant difference found in 2017 (1.89-fold, p = 0.023). Rural exposure levels were higher than that of cities but not statistically significant (1.41-fold, p = 0.13). Estimated daily intake (EDI) and margin of exposure (MoE) approaches revealed that 8 prefecture cities have probabilistically extra adverse health effects (vomiting or diarrhea) cases > 100 patients in 100,000 residents attributable to DON exposure. As a prominent wheat-growing area, Dezhou city reached ~ 300/100,000 extra cases while being considered as a major regional contributor to DON contamination. Our study suggests that more effort should be given to the prevention and control of DON contamination in major wheat-growing areas, particularly during heavy precipitation year. The mechanistic association between DON and chronic intestinal disorder/diseases should be further investigated.

Growth and survival of aerobic and Gram-negative bacteria on fresh spinach in a Chinese supply chain from harvest through distribution and refrigerated storage.

Spinach is a highly perishable product that degrades over time, including due to bacteria contaminating the product prior to packaging, yet the dynamics of bacterial spoilage and factors that affect it are not well understood. Notably, while China is the top producer of spinach globally, there is limited available microbiological data in the literature for spinach supply chains in China. The overall goal of this foundational study was to establish a baseline understanding of bacterial population dynamics on spinach from harvest to 10 days postprocessing for a Chinese supply chain that includes distribution via traditional grocery (a local physical store) and eCommerce (an online store). To this end, organic spinach samples were collected at different stages in a Chinese supply chain by following the same 3 lots, starting at point-of-harvest through processing and distribution via a local grocery store and eCommerce. After distribution, the same 3 lots were stored at 4 °C with microbiological testing performed on multiple days up to day 10 postprocessing, simulating storage at the point-of-consumer. Results showed aerobic plate counts and total Gram-negative counts did not significantly differ across stages in the supply chain from harvest through processing. However, packaged spinach from the same processing facility and lots, exhibited different patterns in bacterial levels across 0 to 10 days postprocessing, depending on whether it was distributed via the local grocery store or eCommerce. Evaluation of bacterial populations performed on a subset of the packaged spinach samples indicated Gram-negative bacteria, in particular Pseudomonas, were predominant across all days of testing (days 0, 3, and 10 postprocessing), with populations differing at the genus level by day. Overall, this study improves our understanding of the dynamics of bacterial populations on spinach and provides baseline data needed for future studies.

Biological effects of gamma-ray radiation on tulip (Tulipa gesneriana L.).

Tulip, being an important ornamental plant, generally requires lengthy and laborious procedures to develop new varieties using traditional breeding methods requires. But ionizing radiation potentially accelerates the breeding process of ornamental plant species. The biological effects of γ-ray irradiation on tulip, therefore, were investigated through establishing an irradiation-mediated mutation breeding protocol to accelerate its breeding process. ISSR-PCR molecular marker technique was further used to identify the mutants of phenotypic variation plants. This study showed that low irradiation doses (5 Gy) stimulated bulb germination to improve the survival rate of tulip, while high irradiation doses (20 to 100 Gy) significantly (P < 0.05) inhibited its seed germination and growth, and decreased the flowering rate, petal number, flower stem length and flower diameter. More than 40 Gy significantly (P < 0.05) decreased the total chlorophyll content and increased the malondialdehyde (MDA) content in tulips. Interestingly, three types of both stigma variations and flower pattern variations, and four types of flower colour variations were observed. With increasing the irradiation dose from 5 to 100 Gy, the anthocyanin and flavonoid contents continuously decreased. Scanning electron microscopy (SEM) analysis evidenced that high irradiation doses altered the micromorphology of leaf stomata. Microscopic observations of tulip root apical mitosis further showed the abnormal chromosomal division behaviour occurring at different mitotic phases under irradiation treatment (80 Gy). Increasing the irradiation dose from 20 to 100 Gy enhanced the micronucleus rate. Moreover, the suspected genetic variation in tulips was evaluated by inter-simple sequence repeat (ISSR) analysis, and the percentage of polymorphic bands was 68%. Finally, this study concludes that that 80 Gy may be an appropriate radiation does to better enhance the efficiency of mutagenic breeds in tulip plants. Using γ-ray irradiation, therefore, is expected to offer a theoretical basis for mutation breeding in tulips.

A Review on Cement Asphalt Emulsion Mortar Composites, Structural Development, and Performance.

The use of cement emulsified asphalt mortar (CA mortar) in the track structure of high-speed speed railways has been gaining considerations by many researchers due to its coupled merits of the strength of cement as well as the flexibility of asphalt material. The asphalt to cement ratio (A/C) and the compatibility among constituent materials are crucial to the properties of CA mortar. To improve the performance properties and application of CA mortar, it is imperative to have a broad understanding of the composition mechanisms and compatibility between constituent materials. This paper summarizes interesting research outcomes related to the composition and properties of CA mortar. The consumption of water by cement promotes the breakdown of emulsified asphalt, likewise, the adsorption of asphalt droplets on the surface of cement grains retards the hydration process of cement. An appropriate A/C is required for the cement hydration rate to match the speed of demulsification of asphalt emulsion. Depending on the type and properties for which the CA mortar is designed to possess, the A/C ranges from 0.2 to 0.6 for type 1 (CAM I), and 0.6 to 1.2 for type 2 (CAM II). This paper also discusses measures taken to improve performance properties, compatibility, the interaction between constituent materials of CA mortar, and the use of additives as a partial replacement of cement in CA mortar production. The current review also suggests areas of interest for future research studies. This paper is useful to those who aim to understand or study the composition mechanisms and performance properties of CA mortar.

Biological effects of electron beam to target turning X-ray (EBTTX) on two freesia (Freesia hybrida) cultivars.

Electron beam to target turning X-ray (EBTTX) is an emerging irradiation technology that can potentially accelerate the breeding process of plants. The biological effects of EBTTX irradiation on the two freesia cultivars (the red freesia and the purple freesia) were investigated by establishing an irradiation-mediated mutation breeding protocol. The germination rate, survival rate, plant height, leaf number and area, root number and length of the two freesia cultivars decreased following different irradiation doses (25, 50, 75, and 100-Gy). A high irradiation dose exhibited stronger inhibition effects on these plant growth parameters, and the survival rate of the two freesia cultivars was 0.00% following the 100-Gy irradiation treatment. The median lethal dose (LD50) based on survival rates was 54.28-Gy for the red freesia and 60.11-Gy for the purple freesia. The flowering rate, flower number, and pollen vigor were significantly decreased by irradiation treatment. At 75-Gy irradiation, the flowering rate, flower number and pollen viability of the two varieties reached the minimum, exhibiting strong inhibitory effects. Meanwhile, 75-Gy irradiation significantly decreased the chlorophyll content and increased the malondialdehyde (MDA) content of the two freesia cultivars. Furthermore, as the irradiation dose increased, the changes in the micro-morphology of the leaf epidermis and pollen gradually increased according to a scanning electron microscope (SEM) analysis. These results are expected to provide useful information for the mutation breeding of different freesia cultivars and other flowering plants.

Photocrosslinked, Tunable Protein Vesicles for Drug Delivery Applications.

Recombinant proteins have emerged as promising building blocks for vesicle self-assembly because of their versatility through genetic manipulation and biocompatibility. Vesicles composed of thermally responsive elastin-like polypeptide (ELP) fusion proteins encapsulate cargo during assembly. However, vesicle stability in physiological environments remains a significant challenge for biofunctional applications. Here, incorporation of an unnatural amino acid, para-azido phenylalanine, into the ELP domain is reported to enable photocrosslinking of protein vesicles and tuning of vesicle size and swelling. The size of the vesicles can be tuned by changing ELP hydrophobicity and ionic strength. Protein vesicles are assessed for their ability to encapsulate doxorubicin and dually deliver doxorubicin and fluorescent protein in vitro as a proof of concept. The resulting photocrosslinkable vesicles made from full-sized, functional proteins show high potential in drug delivery applications, especially for small molecule/protein combination therapies or targeted therapies.

Synthesis of ZnIn2S4@Co3S4 particles derived from ZIF-67 for photocatalytic hydrogen production.

In this work, ZIF-67 derivative Co3S4 with diamond dodecahedron structure was firstly synthesized via a series of reactions, and ZnIn2S4@Co3S4 heterostructures with adjustable band gaps were successfully obtained through a simple hydrothermal method. Consequently, ZnIn2S4@Co3S4 heterostructures have significantly enhanced visible light absorption and improved photocatalytic efficiency, among which the ZC-5 composite exhibits the highest photocatalytic hydrogen production rate up to 4261 µmol g-1 h-1 under simulated sunlight, to be approximately 4.8 times higher than that of pure ZnIn2S4. The enhanced photocatalytic activity can be attributed to faster electron transfer and more efficient electron-hole pairs separation derived from the heterostructures which form at the interface between Co3S4 and ZnIn2S4. Thus, this study provides a good strategy for photocatalytic hydrogen production without precious metals using heterostructures.

A G-quadruplex nanoswitch in the SGK1 promoter regulates isoform expression by K+/Na+ balance and resveratrol binding.

BACKGROUND: High sodium intake can up-regulate the level of renal serum- and glucocorticoid-inducible kinase-1 (SGK1), which plays a pivotal role in controlling blood pressure via activation of the epithelial sodium channel (ENaC), which can lead to salt-sensitive hypertension. Increased potassium intake, or a vegetarian diet, counteracts salt-sensitive hypertension, but the underlying mechanisms are not fully understood. METHODS: Bioinformatics and molecular modeling were used to identify G-quadruplex (G4) and their conformations in the SGK1 promoter. CD spectra and UV melting dynamics were measured to study the stability of G4 as influenced by potassium/sodium balance and resveratrol. RT-PCR and Western blot were employed to study the effects of potassium and resveratrol on the SGK1 isoform expression. RESULTS: The SGK1 gene encodes a G4 structure in the proximal upstream of promoter-2; the G4 structure is stabilized by potassium or resveratrol, but destabilized by sodium. Super-physiological levels of sodium stimulate the transcription of all SGK1 isoforms, whereas resveratrol or potassium supplementation inhibits the transcription of iso-2 and iso-3, but not iso-1. CONCLUSIONS: Stabilizing the G4 by potassium or resveratrol induces alternative promoter usage and/or pre-mRNA splicing in the transcription of SGK1. GENERAL SIGNIFICANCE: Potassium/sodium ion balance or resveratrol binding can act to regulate G4 molecular switches for controlling SGK1 gene expression, thereby presenting a new avenue for drug development.

Rationally Designed CdS-Based Ternary Heterojunctions: A Case of 1T-MoS2 in CdS/TiO2 Photocatalyst.

As promising heterojunction photocatalysts, the binary CdS-based heterojunctions were investigated extensively. In most of the reported CdS-based heterojunctions, however, electrons come from the semiconductor with wide band gap (e.g., TiO2) would limit the visible-light absorption of CdS and hence lower the performance. In this work, we introduced 1T-MoS2 to form a novel ternary heterojunction, namely CdS/1T-MoS2/TiO2, in which 1T-MoS2 has more positive conduction band than CdS and TiO2. The hydrogen evolution rate of CdS/1T-MoS2/TiO2 reaches 3.15 mmol g-1 h-1, which is approximately 12 and 35 times higher than that of pure CdS and CdS/TiO2 binary heterojunction under the same conditions, respectively. This performance enhancement could be attributed to the presence of 1T-MoS2 and a plausible mechanism is proposed based on photoelectrochemical characterizations. Our results illustrate that the performance of CdS-based heterojunctions for solar hydrogen evolution can be greatly improved by appropriate materials selection.