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Layered silicate materials were often used for bitumen modification, but their improvement effect on bitumen performance was limited due to their poor compatibility with bitumen. Introducing long-chain organic compounds on the surface of inorganic materials can make them exhibit solvent-free fluid characteristics, which can significantly enhance the compatibility between inorganic and organic materials. In this study, 3-(trimethoxysilyl propyl) dimethyl octadecyl ammonium chloride (DC5700) and nonylphenol polyoxyethylene ether sodium sulfate (NPES) were used to organically treat bentonite (Ben) to prepare solvent-free bentonite fluid (Ben-fluid) so as to effectively improve the overall performance of styrene-butadiene-styrene copolymer (SBS) modified bitumen (SMB). Ben and DC5700 organically treated bentonite (DC5700-Ben) were used as comparative samples. The microstructure, ultraviolet reflectance and lipophilicity of Ben, DC5700-Ben and Ben-fluid as well as fluidization characteristics of Ben-fluid were tested and characterized. The results of X-ray diffraction spectrometer and Fourier transform infrared spectrometer (FTIR) demonstrated that DC5700 intercalated into the layers of the Ben and chemically grafted on the Ben surface, and the NPES was anchored on DC5700 molecules through ionic bonds. Compared with Ben and DC5700-Ben, Ben-fluid had the highest ultraviolet reflectance and the best lipophilicity. As the temperature exceeded 82.3 ℃, the fluidization characteristics of Ben-fluid began to appear. Meanwhile, the effects of Ben-fluid on physical, rheological and aging properties of SMB were investigated. Ben-fluid was more conducive to enhance the high-temperature stability of SMB than Ben and DC5700-Ben, and has less adverse effects on the low-temperature physical and rheological properties. The aging results of different SMBs revealed that the change in physical properties of SMB containing Ben-fluid after thermal and ultraviolet aging was significantly lower than that of SMB containing Ben and DC5700-Ben. In addition, FTIR showed that compared with Ben and DC5700-Ben, the Ben-fluid could inhibit the increase of carbonyl index and the decrease of butadiene index of SMB after aging. Comprehensive analysis suggested that Ben-fluid was more conducive to improve the physical, rheological and anti-aging properties of SMB.

Abstract Aspergillus genus is a key component in fermentation and food processing. However, sterigmatocystin (STE)—a mycotoxin produced by several species of Aspergillus—limits the use of some Aspergillus species (such as Aspergillus versicolor, Aspergillus inflatus, and Aspergillus parasiticus) because of its toxicity and carcinogenicity. Here, we engineered an STE‐free Aspergillus versicolor strain based on genome mining techniques. We sequenced and assembled the Aspergillus versicolor D5 genome (34.52 Mb), in which we identified 16 scaffolds and 54 biosynthetic gene clusters (BGCs). We silenced cytochrome P450 coding genes STC17 and STC27 by insertional inactivation. The production of STE in the Δstc17 mutant strain was increased by 282% but no STE was detected in the Δstc27 mutant. Metabolites of Δstc27 mutant exhibited growth‐promoting effect on plants. Our study makes significant progress in improving the application of some Aspergillus strains by restricting their production of toxic and carcinogenic compounds.

Exploring the effective recycling of waste styrene-butadiene-styrene block copolymer (SBS) modified asphalt mixture is the difficulty and hotspot in the field of road materials research. Common rejuvenation method and reactive rejuvenation method were used to recover the road performances of aged SBS modified asphalt mixture (ASMBM) in this paper. The recovery effect of high- and low-temperature performance, fatigue resistance and water stability for ASMBM after rejuvenation was studied, and the road performance development of ASMBM after reactive rejuvenation in the early stage was also investigated. The results show that reactive rejuvenation method could significantly enhance the Marshall stability and rutting resistance of rejuvenated ASMBM, and further improve its low-temperature cracking resistance as compared with common rejuvenation method, which attributes to the reconstruction of aged SBS cross-linking structure and its improvement on the interface stability of rejuvenated mixture. Meanwhile, the fatigue life of reactive rejuvenated ASMBM under strain level of 400 με is 26.6 % higher than that of common rejuvenated mixture. Water stability test results show that reactive rejuvenation is more beneficial to restore the water-immersed Marshall stability and Hamburger rutting resistance of ASMBM. Furthermore, the road performances of reactive rejuvenated ASMBM have a further improvement with the extension of time in the early stage after rejuvenation, its Marshall stability, the freeze-thaw splitting strength ratio and water-immersed Marshall stability could restore to the initial level of fresh mixture. Thus, reactive rejuvenation method is more conducive to realizing the high-performance recycling of waste SBS modified asphalt mixture and enhance its recycling value.

Tobacco bacterial wilt caused by Ralstonia solanacearum is one of the most devastating diseases. Microbial keystone taxa were proposed as promising targets in plant disease control. In this study, we obtained an antagonistic Bacillus isolate EM-1 from bacterial wilt-suppressive soil, and it was considered rhizosphere-resident bacteria based on high (100%) 16S rRNA gene similarity to sequences derived from high-throughput amplicon sequencing. According to 16S rRNA gene sequencing and MLSA, strain EM-1 was identified as Bacillus velezensis. This strain could inhibit the growth of R. solanacearum, reduce the colonization of R. solanacearum in tobacco roots, and decrease the incidence of bacterial wilt disease. In addition, strain EM-1 also showed a strong inhibitory effect on other phytopathogens, such as Alternaria alternata and Phytophthora nicotianae, indicating a wide antagonistic spectrum. The antimicrobial ability of EM-1 can be attributed to its volatile, lipopeptide and polyketide metabolites. Iturin A (C14, C15, and C16) was the main lipopeptide, and macrolactin A and macrolactin W were the main polyketides in the fermentation broth of EM-1, while heptanone and its derivatives were dominant among the volatile organic compounds. Among them, heptanones and macrolactins, but not iturins, might be the main potential antibacterial substances. Complete genome sequencing was performed, and the biosynthetic gene clusters responsible for iturin A and macrolactin were identified. Moreover, strain EM-1 can also induce plant resistance by increasing the activity of CAT and PPO in tobacco. These results indicated that EM-1 can serve as a biocontrol Bacillus strain for tobacco bacterial wilt control. This study provides a better insight into the strategy of exploring biocontrol agent based on rhizosphere microbiome.

Abstract Generation of kidney organoids using autologous kidney stem cells represents an attractive strategy for treating and potentially replacing the failing kidneys. However, whether adult mammalian kidney stem cells have regenerative capacity remains unknown. Here, previously unidentified adult kidney Sca1+ Oct4+ stem/progenitor cells are isolated. Interestingly, culturing these cells leads to generation of kidney‐like structures. First, the assembly of self‐organizing 3D kidney‐like structures is observed. These kidney organoids contain podocytes, proximal tubules, and endothelial cells that form networks of capillary loop‐like structures. Second, the differentiation of kidney stem cells into functionally mature tubules and self‐organizing kidney‐shaped structures in monolayer culture that selectively endocytoses dextran, is shown. Finally, the de novo generation of an entire self‐organizing nephron from monolayer cultures is observed. Mechanistically, it is demonstrated that Sirt2‐mediated canonical Wnt/β‐catenin signaling is critical for the development of kidney organoids. Thus, the first evidence is provided that the adult mouse kidney stem cells are capable of de novo generating kidney organoids.

Bacterial communities in the rhizosphere play an important role in sustaining plant growth and the health of diverse soils. Recent studies have demonstrated that microbial keystone taxa in the rhizosphere microbial community are extremely critical for the suppression of diseases. However, the mechanisms involved in disease suppression by keystone species remain unclear. The present study assessed the effects of three Pseudomonas strains, which were identified as keystone species in our previous study, on the growth performance and root-associated bacterial community of tobacco plants. A high relative abundance of Ralstonia was found in the non-inoculated group, while a large Azospira population was observed in all groups inoculated with the three Pseudomonas strains. Correspondingly, the activities of the defense-related enzymes and the expression levels of the defense signaling marker genes of the plant were increased after inoculation with the Pseudomonas strains. Moreover, the correlation analyses showed that the relative abundance of Azospira, the activity of superoxide dismutase, catalase, and polyphenol oxidase, and the expression of H1N1, ACC Oxidase, and PR1 a/c had a significantly negative (p

Recent studies have observed differing microbiomes between disease-suppressive and disease-conducive soils. However, it remains unclear whether the microbial keystone taxa in suppressive soil are critical for the suppression of diseases. Bacterial wilt is a common soil-borne disease caused by Ralstonia solanacearum that affects tobacco plants. In this study, two contrasting tobacco fields with bacterial wilt disease incidences of 0% (disease suppressive) and 100% (disease conducive) were observed. Through amplicon sequencing, as expected, a high abundance of Ralstonia was found in the disease-conducive soil, while large amounts of potential beneficial bacteria were found in the disease-suppressive soil. In the fungal community, an abundance of the Fusarium genus, which contains species that cause Fusarium wilt, showed a positive correlation (p < 0.001) with the abundance of Ralstonia. Network analysis revealed that the healthy plants had more complex bacterial networks than the diseased plants. A total of 9 and 13 bacterial keystone taxa were identified from the disease-suppressive soil and healthy root, respectively. Accumulated abundance of these bacterial keystones showed a negative correlation (p < 0.001) with the abundance of Ralstonia. To complement network analysis, culturable strains were isolated, and three species belonging to Pseudomonas showed high 16S rRNA gene similarity (98.4–100%) with keystone taxa. These strains displayed strong inhibition on pathogens and reduced the incidence of bacterial wilt disease in greenhouse condition. This study highlighted the importance of keystone species in the protection of crops against pathogen infection and proposed an approach to obtain beneficial bacteria through identifying keystone species, avoiding large-scale bacterial isolation and cultivation.

Paenibacillus polymyxa is an important member of the plant growth-promoting rhizobacteria. P. polymyxa YC0136 inoculation had beneficial effect on growth promotion and biological control of tobacco (Nicotiana tabacum L.) under field conditions. This study aimed to reveal the growth-promoting mechanisms of strain YC0136. In growth-promotion assays, tobacco plant height was increased by 8.42% and 8.25% at 60 and 90 days, respectively, after inoculation with strain YC0136. Strain YC0136 also promoted the accumulation of tobacco biomass in varying degrees. Following inoculation with strain YC0136, 3,525 and 4,368 tobacco genes were up-regulated and down-regulated, respectively. Strain YC0136 induced the expression of plant hormone-related genes in tobacco, including auxin, cytokinin, and gibberellin, as well as transcription factors related to stress resistance such as WRKY and MYB. In addition, strain YC0136 induced the up-regulation of genes in the phenylpropanoid biosynthesis pathway by 1.51–4.59 times. Interaction with tobacco also induced gene expression changes in strain YC0136, with 286 and 223 genes up-regulated and down-regulated, respectively. Tobacco interaction induced up-regulation of the ilvB gene related to auxin biosynthesis in strain YC0136 by 1.72 times and induced expression of some nutrient transport genes. This study contributes to our understanding of the growth-promoting mechanisms of strain YC0136 on tobacco and provides a theoretical basis for the application of P. polymyxa YC0136 as a biological fertilizer.

Chub mackerel (Scomber japonicus) is a pelagic fish widely distributed in temperate and subtropical zones throughout the Indian and Pacific Oceans and is commercially exploited, particularly in the North Pacific. Although highly targeted in this region, little is known about their life history aspects. The objectives of this study are to evaluate the growth heterogeneities and ageing analysis of this species. We describe the length-at-age, weight-at-length, relative condition factor relationships, spatiotemporal heterogeneity and compare estimated growth parameter values to those reported from other regions. This study used data obtained from Chinese fishing vessels collected from 2016–2020 in the northwest Pacific Ocean. Length-weight data from 2686 specimens (40–294 mm, fork length; 0.8–311.8 g body weight) were analyzed, and the Length-weight relationship was W = (1.41 × 10−6) × FL3.37. Seven linear mixed-effects models (LMEM) were used to analyze the heterogeneity of length-weight relationships of Chub mackerel. The Length-weight relationships for Chub mackerel were best described by a model with random effects with both year and season (spring, summer, autumn) with the scalar parameter a. Age estimates were obtained from 175 specimens, and the length-at-estimated ages relationship was described using three non-linear candidate growth models. The von Bertalanffy growth model fit the data best for Chub mackerel in the northwest Pacific Ocean. Comparing the results to that of previous studies, we observed that individual Chub mackerel exhibited a slower growth rate than that observed in previous studies. In addition, relative condition factors varied among years, seasons, and regions. Information presented in this study provides an effective scientific basis for stock assessment and fishery management of Chub mackerel in the northwest Pacific Ocean.

A novel bio-fertilizer, produced from prickly ash seeds (PAS), Bacillus subtilis and biochar, was evaluated for its disease-preventing potential on tobacco black shank caused by Phytophthora nicotianae. The results showed that biochar promoted the growth of Tpb55 in PAS and increased the pH of the organic fertilizer. The final concentration of B. subtilis could reach 1.7 × 1010 cfu g−1 in the biological organic fertilizer (PBB) under the optimal medium under conditions of solid-state fermentation. PBB exhibited a strong fumigation effect on P. nicotianae, including inhibiting mycelium growth, reducing the disease severity and decreasing the pathogen population in rhizospheric soil. PBB treatment also could significantly increase the pH of acidified soil and improve soil nutrition content such as available K, alkali hydrolysable N and organic carbon. High-throughput pyrosequencing of 16S and 18S rRNA genes revealed that 4% PBB addition in soil had significant effects on the diversity and richness of fungi but not on that of bacteria. The microbial community structure was also shifted after PBB treatment. Some potentially beneficial microbes such as Bacillus, Mucor, Cunninghamella, Chitinophaga and Phenylobacterium were enriched, while potential pathogen Fusarium was significantly decreased. In conclusion, the agricultural waste PAS combined with biochar can replace soybean as a source for the production of biocontrol B. subtilis Tpb55, and the novel bio-fertilizer could effectively control tobacco black shank by pathogen inhibition, soil nutrient improvement and shifting the rhizomicrobial community.

Two novel 3-decalinoyltetramic acid (3DTA) derivatives, namely fusarisetins C and D (1 and 2), and four known derivatives (3–6) were isolated from the marine-derived fungus Fusarium equiseti D39. Their structures were determined by spectroscopic data, vibrational circular dichroism (VCD) calculations, and X-ray crystallography. Compound 2 was identified as the first fusarisetin to possess an unprecedented carbon skeleton with a tetracyclic ring system comprised of a decalin moiety (6/6) and a tetramic acid moiety. A plausible biosynthetic pathway for the isolated compounds was proposed. All 3DTAs derivatives exhibited a potent phytotoxicity, and 5 also displayed a remarkable anti-phytopathogenic activity superior to the positive control resulting in damage of the cell membrane of Pseudomonas syringae and ensuing leakage of the intracellular components. Here, the phytotoxicity of fusarisetins has been reported for the first time. The OSMAC fermentation optimization approach to give 5 was performed by varying the culture media and salinities. The results showed that potato liquid medium with 1% salinity is the most favorable condition for the production of 5.

The present study evaluated the fumigant effect and potential mechanisms of Chinese prickly ash seed kernel (PSK) against tobacco black shank caused by Phytophthora nicotianae Breda de Haan. The results showed that PSK fumigant increased the soil organic matter, hydrolysable nitrogen, available potassium, and total phosphorus significantly, while the pH was decreased. Application of 2% PSK promoted plant growth, with higher plant height, root length, and dry weight compared to those in the treatment with no PSK. Both in vitro and in vivo tests indicated that PSK fumigant effectively inhibited mycelial growth of P. nicotianae, and significantly reduced the severity of tobacco black shank. Based on the analysis of volatiles in PSK by headspace solid-phase microextraction (HS-SPME) gas chromatography-mass spectrometry (GC-MS), 28 components were identified, among which monoterpenes were the major components (accounting for 79.46% of peak area). Among the six top components, linalool, piperitone, sabinene, and limonene exhibited strong mycelial inhibition of P. nicotianae. Linalool was the most effective with an IC50 value of 18.03 μL/L. Results of GC-MS revealed that the main components of PSK extract were cis-Vaccenic acid (40.81%), n-Hexadecanoic acid (15.67%), 9,12-Octadecadienoic acid (Z,Z)- (15.25%), Ethanone-1-(2-hydroxy-4,6-dimethoxyphenyl)- (10.32%), cis-9-Hexadecenoic acid (6.21%), and Psilocin (11.75%). Among them, Ethanone-1-(2-hydroxy-4,6-dimethoxyphenyl)- and 9,12-Octadecadienoic acid (Z,Z)- have an obvious inhibitory effect on P. nicotianae. Additionally, changes in soil bacterial and fungal communities were observed. The relative abundance of some microbes, such as Pseudomonas, Azospirillum, Thermomonas, Glutamicibacter, Dyella, and Trichoderma, increased, which have many beneficial microbes in these genera, indicating that microbial community shift could be one of the important outcomes of the PSK fumigant effect. In conclusion, PSK could be a new bio-fumigation material against plant soilborne pathogens, which can function as both a fungicide and fertilizer.

High-purity solanesol can be used for pharmaceutical applications, but the current method for purifying solanesol has high cost and difficult continuous operation, and the use of molecular imprinting to purify natural products is a hot research topic of current research. Solanesol molecularly imprinted polymers were synthesized via emulsion polymerization for the first time. The morphology of the SSO-MIPs was observed with a scanning electron microscope, and the effects of the synthesis time, initiator dosage, functional monomer dosage, and cross-linking agent dosage on the adsorption effects under high-temperature and rapid synthesis conditions were discussed. The results demonstrate that the optimum synthesis conditions were a ratio of the template molecules to the functional monomers to the cross-linking agents of 1:8:30 (mol:mol:mol), 10 mg of the initiator, and a synthesis temperature of 70 °C. The imprinting factor of SSO-MIPs synthesized under the optimized process was found to reach 2.51, and the SSO-MIPs synthesized by this method exhibited a good adsorption effect, emitted less pollution during the synthesis process, and are convenient for demulsification. This research reports a reliable method for the synthesis of solanesol molecularly imprinted polymers.

Fibroblast growth factor-23 (FGF-23) is a bone-derived hormone that activates FGFR/α-Klotho binary complexes in the kidney renal tubules to regulate phosphate reabsorption and vitamin D metabolism. The objective of this review is to discuss the emerging data that show that FGF-23 has functions beyond regulation of mineral metabolism, including roles in innate immune and hemodynamic responses. Excess FGF-23 is associated with inflammation and adverse infectious outcomes, as well as increased morbidity and mortality, particularly in patients with chronic kidney disease. Enhancer elements in the FGF-23 promoter have been identified that mediate the effects of inflammatory cytokines to stimulate FGF-23 gene transcription in bone. In addition, inflammation induces ectopic expression of FGF-23 and α-Klotho in macrophages that do not normally express FGF-23 or its binary receptor complexes. These observations suggest that FGF-23 may play an important role in regulating innate immunity through multiple potential mechanisms. Circulating FGF-23 acts as a counter-regulatory hormone to suppress 1,25D production in the proximal tubule of the kidney. Since vitamin D deficiency may predispose infectious and cardiovascular diseases, FGF-23 effects on innate immune responses may be due to suppression of 1,25D production. Alternatively, systemic and locally produced FGF-23 may modulate immune functions through direct interactions with myeloid cells, including macrophages and polymorphonuclear leukocytes to impair immune cell functions. Short-acting small molecules that reversibly inhibit FGF-23 offer the potential to block pro-inflammatory and cardiotoxic effects of FGF-23 with less side effects compared with FGF-23 blocking antibodies that have the potential to cause hyperphosphatemia and soft tissue calcifications in animal models. In conclusion, there are several mechanisms by which FGF-23 impacts the innate immune system and further investigation is critical for the development of therapies to treat diseases associated with elevated FGF-23.

This study explored the chemical compositions of garlic essential oil, the inhibitory activity of garlic essential oil and diallyl disulfide (DADS) against Phytophthora nicotianae, and the effects on mycelial plasma membrane permeability and P. nicotianae inhibition. In total, 29 compounds were detected in garlic essential oil, of which 26 were detected by gas chromatography‒mass spectrometry (GC-MS) and 21 by headspace solid-phase microextraction (HS-SPME) GC-MS. DADS (60.12% and 19.09%) and trisulfide di-2-propenyl (14.18% and 17.98%) were the major components identified by HS-SPME GC-MS and GC-MS analysis, respectively. Half-inhibitory concentration (Ec50, antagonism) and minimum inhibitory concentration (MIC, fumigation) of DADS against P. nicotianae were 150.83 μL/L and 20 μL/L, respectively, while Ec50 of garlic essential oil was 1108.25 μL/L. Mycelial membrane permeability gradually increased in a concentration-dependent manner, and cell death increased at 450 μL/L DADS. Furthermore, DADS treatment significantly reduced the incidence of tobacco black shank and the number of P. nicotianae pathogens in rhizosphere soil. DADS also promoted root development of tobacco seedlings at low concentrations, which was inhibited at high concentrations. Therefore, DADS may play an important role in the antifungal effect against P. nicotianae by destroying mycelial cell membrane integrity, causing an increase in cell membrane permeability, and leading to cell death.

Erosion effect of chloride ions from the marine, deicing salt, saline-alkali land and some industrial environments will cause the corrosion of rebar in concrete, which is one of the most harmful factors affecting the durability of concrete structure. It had been proved that the incorporation of rubber aggregates increase the capillary saturation of cement concrete and reduce the corrosion degree of rebar. This paper investigated the rebar corrosion behavior in rubber aggregate concrete under the chloride electro-accelerated corrosion condition and such an investigation has not been seen in any public literature. Two water-cement ratios (0.45 and 0.55) and four rubber contents (0, 50, 100, and 150 kg/m3) were selected for experiment. Four-point bending tests of concrete beam were conducted before and after chloride ion erosion in order to determine effect of rubber aggregate on the durability of rebar. Results showed that rebar corrosion degree decreased with the increase of rubber aggregate in concrete. Besides, the more the dosage of rubber is, the better the anti-crack performance of cement concrete. This will postpone the crack development and reduce the peak of rebar corrosion.

A postnatal role of fibroblast growth factor receptor-1 (FGFR1) in the kidney is suggested by its binding to α-Klotho to form an obligate receptor for the hormone fibroblast growth factor-23 (FGF-23). FGFR1 is expressed in both the proximal and distal renal tubular segments, but its tubular specific functions are unclear. In this study, we crossed Fgfr1flox/flox mice with either gamma-glutamyltransferase-Cre (γGT-Cre) or kidney specific-Cre (Ksp-Cre) mice to selectively create proximal tubule (PT) and distal tubule (DT) Fgfr1 conditional knockout mice (designated Fgfr1PT-cKO and Fgfr1DT-cKO, respectively). Fgfr1PT-cKO mice exhibited an increase in sodium-dependent phosphate co-transporter expression, hyperphosphatemia, and refractoriness to the phosphaturic actions of FGF-23, consistent with a direct role of FGFR1 in mediating the proximal tubular phosphate responses to FGF-23. In contrast, Fgfr1DT-cKO mice unexpectedly developed hypercalciuria, secondary elevations of parathyroid hormone (PTH), hypophosphatemia and enhanced urinary phosphate excretion. Fgfr1PT-cKO mice also developed a curly tail/spina bifida-like skeletal phenotype, whereas Fgfr1DT-cKO mice developed renal tubular micro-calcifications and reductions in cortical bone thickness. Thus, FGFR1 has dual functions to directly regulate proximal and distal tubule phosphate and calcium reabsorption, indicating a physiological role of FGFR1 signaling in both phosphate and calcium homeostasis.

Diabetic nephropathy is the leading cause of end stage renal disease in the world. Although tremendous efforts have been made, scientists have yet to identify an ideal animal model that can reproduce the characteristics of human diabetic nephropathy. In this study, we hypothesize that taurine insufficiency is a critical risk factor for development of diabetic nephropathy associated with diabetes mellitus. This hypothesis was tested in vivo in TauT heterozygous (TauT+/-) and homozygous (TauT-/-) knockout in C57BL/6 background mice. We have shown that alteration of the TauT gene (also known as SLC6A6) has a substantial effect on the susceptibility to development of extensive diabetic kidney disease in both TauT+/- and TauT-/-mouse models of diabetes. These animals developed histological changes characteristic of human diabetic nephropathy that included glomerulosclerosis, nodular lesions, arteriosclerosis, arteriolar dilation, and tubulointerstitial fibrosis. Immunohistochemical staining of molecular markers of smooth muscle actin, CD34, Ki67 and collagen IV further confirmed these observations. Our results demonstrated that both homozygous and heterozygous TauT gene deletion predispose C57BL/6 mice to develop end-stage diabetic kidney disease, which closely replicates the pathological features of diabetic nephropathy in human diabetic patients.

Increases in fibroblastic growth factor 23 (FGF23 or Fgf23) production by osteocytes result in hypophosphatemia and rickets in the Hyp mouse homologue of X-linked hypophosphatemia (XLH). Fibroblastic growth factor (FGF) signaling has been implicated in the pathogenesis of Hyp. Here, we conditionally deleted FGF receptor 1 (FGFR1 or Fgfr1) in osteocytes of Hyp mice to investigate the role of autocrine/paracrine FGFR signaling in regulating FGF23 production by osteocytes. Crossing dentin matrix protein 1 (Dmp1)-Cre;Fgfr1null/+ mice with female Hyp;Fgfr1flox/flox mice created Hyp and Fgfr1 (Fgfr1Dmp1-cKO)-null mice (Hyp;Fgfr1Dmp1-cKO) with a 70% decrease in bone Fgfr1 transcripts. Fgfr1Dmp1-cKO-null mice exhibited a 50% reduction in FGF23 expression in bone and 3-fold reduction in serum FGF23 concentrations, as well as reductions in sclerostin (Sost), phosphate regulating endopeptidase on X chromosome (PHEX or Phex), matrix extracellular phosphoglycoprotein (Mepe), and Dmp1 transcripts, but had no demonstrable alterations in phosphate or vitamin D homeostasis or skeletal morphology. Hyp mice had hypophosphatemia, reductions in 1,25(OH)2D levels, rickets/osteomalacia and elevated FGF2 expression in bone. Compared to Hyp mice, compound Hyp;Fgfr1Dmp1-cKO-null mice had significant improvement in rickets and osteomalacia in association with a decrease in serum FGF23 (3607 to 1099 pg/ml), an increase in serum phosphate (6.0 mg/dl to 9.3 mg/dl) and 1,25(OH)2D (121±23 to 192±34 pg/ml) levels, but only a 30% reduction in bone FGF23 mRNA expression. FGF23 promoter activity in osteoblasts was stimulated by FGFR1 activation and inhibited by overexpression of a dominant negative FGFR1(TK-), PLCγ and MAPK inhibitors. FGF2 also stimulated the translation of an FGF23 cDNA transfected into osteoblasts via a FGFR1 and PI3K/Akt-dependent mechanism. Thus, activation of autocrine/paracrine FGF pathways is involved in the pathogenesis of Hyp through FGFR1-dependent regulation of FGF23 by both transcriptional and post-transcriptional mechanisms. This may serve to link local bone metabolism with systemic phosphate and vitamin D homeostasis.

Background Imbalanced gut flora caused by changes in gut microecological structure and diversity plays an important role in the interaction between diabetes and chronic kidney disease. Rational application of probiotics, prebiotics and other microbiota-modulating agents is contributive to the improvement of gut microbial flora environment and chronic inflammation, as well as the delay of deterioration of renal function in patients with diabetic nephropathy (DN) . Objective To understand the effect of probiotics, a microbiota-modulating agent, administered based on gut flora status in patients with DN. Methods Participants were selected from Shanghai Yinhang Community Health Center by use of stratified random sampling in 2019, including 115 patients with DN were randomly divided into control group (57 with usual treatment) and treatment group (58 with treatment with microbiota-modulating agents) . Laboratory test indices and intestinal bacterial culture results were compared between the two groups after eight weeks of treatment to assess the effect of microbiota-modulating agents on improving gut flora in DN. Results Among 115 patients with DN, there were 28 males and 87 females, the mean age was (62.9±10.0) years, and the duration of diabetic nephropathy was (14.3±7.1) years. There were no significant differences in the proportion of males, mean age, body mass index, proportion of early DN, and duration of DN between DN patients with usual treatment and those with microbiota-modulating agents treatment (P>0.05) . Compared with DN patients with usual treatment, DN patients with microbiota-modulating agents treatment had decreased levels of glucose, triglyceride, blood urea nitrogen, serum creatinine, albumin to creatinine ratio, Cystatin C, C-reactive protein, interleukin-1β, and tumor necrosis factor-α, and increased levels of high-density lipoprotein and estimated glomerular filtration rate after treatment (P

In this article, the correlation between components and molecular structures of base bitumen and properties of high-dosage styrene-butadiene-styrene-modified bitumen (HSMB) for waterproof membrane was investigated. Saturates, aromatics, resins, and asphaltenes (SARA components) of eight base bitumens from different crude oils used to prepare HSMB were analyzed by column chromatography, and the molecular structures of these base bitumens were obtained by proton nuclear magnetic resonance, gel permeation chromatography, elemental analysis, and an improved Brown-Ladner calculation method. Softening point and low-temperature flexibility tests were used to estimate the high- and low-temperature performance of HSMBs. The results showed that the highest softening point of the HSMBs was 119.2°C, whereas the lowest was 102.5°C. The best flexibility of HSMB was -24°C, and the worst was -10°C. The softening point of HSMB raised with the increase of the content of saturates and aromatics, aromatic carbon ratio (fA), and condensation index (CI) while decreasing with the increase of H/C. The flexibility of HSMBs was most significantly influenced by the content of saturates, and when the saturate content was 17 %, the flexibility was optimal. However, the flexibility of HSMB was poor when the number average molecular weight (Mn) of bitumen was large. To prepare HSMB with excellent performance, it is recommended that the content of saturates should be between 12 and 17 %, aromatics content should be between 45 and 55 %, resins and asphaltenes content should not be excessive, and fA > 0.25, CI > 0.17, H/C = 1.55. [ABSTRACT FROM AUTHOR]

This research aims to investigate the aging resistance of asphalts from different crude oils based on molecular structure and rheological properties. The average molecular structure of five types of asphalt from different crude oils were analyzed with the element analyzer, nuclear magnetic resonance, gel permeation chromatograph, and the improved Brown-Ladner method. The rheological properties of the asphalts were tested by the dynamic shear rheometer before and after laboratory aging. The antiaging properties of the asphalts were evaluated by the rheological aging index (RAI). The findings indicate that there were significant differences in the molecular structures among the five types of asphalt. The asphalt with the least hydrogen-carbon ratio (H/C), the largest aromatic carbon ratio (fA), and the largest condensation index (CI) had the lowest rate of decline in rheological properties and therefore, the best antiaging performance. The H/C, fA, and CI had good correlations with RAI, which indicated that it was feasible to use these molecular structure parameters to evaluate the differences in the aging resistance of various asphalts. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor-23 (FGF-23) is a bone-derived hormone that activates FGFR/α-Klotho binary complexes in the kidney renal tubules to regulate phosphate reabsorption and vitamin D metabolism. The objective of this review is to discuss the emerging data that show that FGF-23 has functions beyond regulation of mineral metabolism, including roles in innate immune and hemodynamic responses. Excess FGF-23 is associated with inflammation and adverse infectious outcomes, as well as increased morbidity and mortality, particularly in patients with chronic kidney disease. Enhancer elements in the FGF-23 promoter have been identified that mediate the effects of inflammatory cytokines to stimulate FGF-23 gene transcription in bone. In addition, inflammation induces ectopic expression of FGF-23 and α-Klotho in macrophages that do not normally express FGF-23 or its binary receptor complexes. These observations suggest that FGF-23 may play an important role in regulating innate immunity through multiple potential mechanisms. Circulating FGF-23 acts as a counter-regulatory hormone to suppress 1,25D production in the proximal tubule of the kidney. Since vitamin D deficiency may predispose infectious and cardiovascular diseases, FGF-23 effects on innate immune responses may be due to suppression of 1,25D production. Alternatively, systemic and locally produced FGF-23 may modulate immune functions through direct interactions with myeloid cells, including macrophages and polymorphonuclear leukocytes to impair immune cell functions. Short-acting small molecules that reversibly inhibit FGF-23 offer the potential to block pro-inflammatory and cardiotoxic effects of FGF-23 with less side effects compared with FGF-23 blocking antibodies that have the potential to cause hyperphosphatemia and soft tissue calcifications in animal models. In conclusion, there are several mechanisms by which FGF-23 impacts the innate immune system and further investigation is critical for the development of therapies to treat diseases associated with elevated FGF-23. [ABSTRACT FROM AUTHOR]

Fibroblastic growth factor receptor 1 (FGFR1) signaling pathways are implicated in the regulation of FGF-23 gene transcription, but the molecular pathways remain poorly defined. We used low molecular weight (LMW, 18 kDa) FGF-2 and high molecular weight (HMW) FGF-2 isoforms, which, respectively, activate cell surface FGF receptors and intranuclear FGFR1, to determine the roles of membrane FGFRs and integrative nuclear FGFR1 signaling (INFS) in the regulation of FGF-23 gene transcription in osteoblasts. We found that LMW-FGF-2 induced NFAT and Ets1 binding to conserved cis-elements in the proximal FGF-23 promoter and stimulated FGF-23 promoter activity through PLCγ/calcineurin/NFAT and MAPK pathways in SaOS-2 and MC3T3-E1 osteoblasts. In contrast, HMW-FGF-2 stimulated FGF-23 promoter activity in osteoblasts through a cAMP-dependent binding of FGFR1 and cAMP-response element-binding protein (CREB) to a conserved cAMP response element (CRE) contiguous with the NFAT binding site in the FGF-23 promoter. Mutagenesis of the NFAT and CRE binding sites, respectively, inhibited the effects of LMW-FGF-2 and HMW-FGF-23 to stimulate FGF-23 promoter activity. FGF-2 activation of both membrane FGFRs and INFS-dependent FGFR1 pathways may provide a means to integrate systemic and local regulation of FGF-23 transcription under diverse physiological and pathological conditions. [ABSTRACT FROM AUTHOR]

Taurine participates in a number of different physiologic and biologic processes in the kidney, often reflected by urinary excretion patterns. The kidney is key to aspects of taurine body pool size and homeostasis. This review will examine the renal-taurine interactions relative to ion reabsorption; renal blood flow and renal vascular endothelial function; antioxidant properties, especially in the glomerulus; and the role of taurine in ischemia and reperfusion injury. In addition, taurine plays a role in the renal cell cycle and apoptosis, and functions as an osmolyte during the stress response. The role of the kidney in adaptation to variations in dietary taurine intake and the regulation of taurine body pool size are described. Finally, the protective function of taurine against several kidney diseases is reviewed. [ABSTRACT FROM AUTHOR]

Background: Cisplatin is a commonly used chemotherapeutic agent that has a major limitation because of its nephrotoxicity. We have demonstrated that cisplatin down-regulates the expression of the taurine transporter gene (TauT) in renal cells and that forced overexpression of TauT protects against cisplatin-induced apoptosis in renal cells in vitro and in vivo. In the present study, we have investigated how TauT is regulated by p53 and c-Jun and its role during acute kidney injury (AKI). Methods: Regulation of TauT by p53 and c-Jun was determined by reporter gene assay, DNA binding, Western blot analysis, and immunohistochemistry. Results: TauT was down-regulated by p53 and up-regulated by c-Jun. Two potential binding sites for c-Jun were identified in the promoter region of TauT. Inhibition of c-Jun N-terminal kinase (JNK) enhanced TauT promoter activity. Overexpression of TauT protects against cisplatin-induced kidney injury in a TauT transgenic mouse model. Conclusions: Our findings suggest that TauT plays a critical role in renal function. Expression of TauT is negatively regulated by p53 and positively regulated by c-Jun, which is mediated by the JNK signaling pathway. The outcome level of TauT may determine the fate of renal cells during stress-induced AKI. [ABSTRACT FROM AUTHOR]

Mammary epithelia produce an isotonic, low-Na+ fluid that is rich in nutrients. Mechanisms that account for the low electrolyte concentration have not been elucidated, although amiloride-sensitive ion transport has been reported in some situations. We hypothesized that corticosteroid exposure modulates epithelial Na+ channel (ENaC) expression and/or activity in bovine mammary epithelial cells. BME-UV cells were grown to confluent monolayers on permeable supports with a standard basolateral medium and apical medium of low-electrolyte, high-lactose composition that resembles the ionic composition of milk. Ion transport was assessed in modified Ussing flux chambers. Exposure to glucocorticoids (dexamethasone, cortisol, or prednisolone), but not aldosterone, increased short-circuit current (Isc), a sensitive measure of net ion transport, whereas apical exposure to amiloride or benzamil reduced corticosteroid-induced Isc close to basal levels. Quantitative RT-PCR indicated a glucocorticoid-induced increase in mRNA for β- and γ-ENaC, whereas α-ENaC mRNA expression was only mildly affected. Exposure to mifepristone (a glucocorticoid receptor antagonist), but not spironolactone (a mineralocorticoid receptor antagonist), precluded both the corticosteroid-induced elevation in amiloride- sensitive Isc and the induced changes in β- and γ-ENaC mRNA. We conclude that Na+ movement across mammary epithelia is modulated by corticosteroids via a glucocorticoid receptor-mediated mechanism that regulates the expression of the β- and β-subunits of ENaC. ENaC expression and activity could account for the low Na+ concentration that is typical of milk. [ABSTRACT FROM AUTHOR]