Intestinal Flora Modulates Blood Pressure by Regulating the Synthesis of Intestinal-Derived Corticosterone in High Salt-Induced Hypertension.

RATIONALE: High-salt diet is one of the most important risk factors for hypertension. Intestinal flora has been reported to be associated with high salt-induced hypertension (hSIH). However, the detailed roles of intestinal flora in hSIH pathogenesis have not yet been fully elucidated. OBJECTIVE: To reveal the roles and mechanisms of intestinal flora in hSIH development. METHODS AND RESULTS: The abovementioned issues were investigated using various techniques including 16S rRNA gene sequencing, untargeted metabolomics, selective bacterial culture, and fecal microbiota transplantation. We found that high-salt diet induced hypertension in Wistar rats. The fecal microbiota of healthy rats could dramatically lower blood pressure (BP) of hypertensive rats, whereas the fecal microbiota of hSIH rats had opposite effects. The composition, metabolism, and interrelationship of intestinal flora in hSIH rats were considerably reshaped, including the increased corticosterone level and reduced Bacteroides and arachidonic acid levels, which tightly correlated with BP. The serum corticosterone level was also significantly increased in rats with hSIH. Furthermore, the above abnormalities were confirmed in patients with hypertension. The intestinal Bacteroides fragilis could inhibit the production of intestinal-derived corticosterone induced by high-salt diet through its metabolite arachidonic acid. CONCLUSIONS: hSIH could be transferred by fecal microbiota transplantation, indicating the pivotal roles of intestinal flora in hSIH development. High-salt diet reduced the levels of B fragilis and arachidonic acid in the intestine, which increased intestinal-derived corticosterone production and corticosterone levels in serum and intestine, thereby promoting BP elevation. This study revealed a novel mechanism different from inflammation/immunity by which intestinal flora regulated BP, namely intestinal flora could modulate BP by affecting steroid hormone levels. These findings enriched the understanding of the function of intestinal flora and its effects on hypertension.

Pleiotropic effect analysis and marker development for grain zinc and iron concentrations in spring wheat.

Wheat (Triticum aestivum L.) is one of the main food crops in the world and a primary source of zinc (Zn) and iron (Fe) in the human body. The genetic mechanisms underlying related traits have been clarified, thereby providing a molecular theoretical foundation for the development of germplasm resources. In this study, a total of 23,536 high-quality DArT markers was used to map quantitative trait loci (QTL) of grain Zn (GZn) and grain Fe (GFe) concentrations in recombinant inbred lines crossed by Avocet/Chilero. A total of 17 QTLs was located on chromosomes 1BL, 2BL, 3BL, 4AL, 4BS, 5AL, 5DL, 6AS, 6BS, 6DS, and 7AS accounting for 0.38-16.62% of the phenotypic variance. QGZn.haust-4AL, QGZn.haust-7AS.1, and QGFe.haust-6BS were detected on chromosomes 4AL, 6BS, and 7AS, accounting for 10.63-16.62% of the phenotypic variance. Four stable QTLs, QGZn.haust-4AL, QGFe.haust-1BL, QGFe.haust-4AL, and QGFe.haust-5DL, were located on chromosomes 1BL, 4AL, and 5DL. Three pleiotropic effects loci for GZn and GFe concentrations were located on chromosomes 1BL, 4AL, and 5DL. Two high-throughput Kompetitive Allele Specific PCR markers were developed by closely linking single-nucleotide polymorphisms on chromosomes 4AL and 5DL, which were validated by a germplasm panel. Therefore, it is the most important that quantitative trait loci and KASP marker for grain zinc and iron concentrations were developed for utilizing in marker-assisted breeding and biofortification of wheat grain in breeding programs.

Identification and genetic analysis of EMS-mutagenized wheat mutants conferring lesion-mimic premature aging.

BACKGROUND: Lesion-mimic and premature aging (lmpa) mutant lmpa1 was identified from the ethyl methane sulfonate (EMS) mutant library in the bread wheat variety Keda 527 (KD527) background. To reveal the genetic basis of lmpa1 mutant, phenotypic observations and analyses of chlorophyll content and photosynthesis were carried out in lmpa1, KD527 and their F1 and F2 derivatives. Further, bulked segregation analysis (BSA) in combination with a 660 K SNP array were conducted on the F2 segregation population of lmpa1/Chinese spring (CS) to locate the lmpa1 gene. RESULTS: Most agronomic traits of lmpa1 were similar to those of KD527 before lesion-like spots appeared. Genetic analysis indicated that the F1 plants from the crossing of lmpa1 and KD527 exhibited the lmpa phenotype and the F2 progenies showed a segregation of normal (wild type, WT) and lmpa, with the ratios of lmpa: WT = 124:36(χ2 = 1.008 < =3.841), indicating that lmpa is a dominant mutation. The combination of BSA and the SNP array analysis of CS, lmpa1 and lmpa1/CS F2 WT pool (50 plants) and lmpa pool (50 plants) showed that polymorphic SNPs were enriched on chromosome 5A, within a region of 30-40 Mb, indicating that the wheat premature aging gene Lmpa1 was probably located on the short arm of chromosome 5A. CONCLUSIONS: EMS-mutagenized mutant lmpa1 deriving from elite wheat line KD527 conferred lmpa. Lmpa phenotype of lmpa1 mutant is controlled by a single dominant allele designated as Lmpa1, which affected wheat growth and development and reduced the thousand grain weight (tgw) of single plant in wheat. The gene Lmpa1 was tentatively located within the region of 30-40 Mb near to the short arm of chromosome 5A.

Genome-wide association study of heading and flowering dates and construction of its prediction equation in Chinese common wheat.

Heading date is one of the most important traits in wheat breeding as it affects adaptation and yield potential. A genome-wide association study (GWAS) using the 90 K iSelect SNP genotyping assay indicated that a total of 306 loci were significantly associated with heading and flowering dates in 13 environments in Chinese common wheat from the Yellow and Huai wheat region. Of these, 105 loci were significantly correlated with both heading and flowering dates and were found in clusters on chromosomes 2, 5, 6, and 7. Based on differences in distribution of the vernalization and photoperiod genes among chromosomes, arms, or block regions, 13 novel, environmentally stable genetic loci were associated with heading and flowering dates, including RAC875_c41145_189 on 1DS, RAC875_c50422_299 on 2BL, and RAC875_c48703_148 on 2DS, that accounted for more than 20% phenotypic variance explained (PVE) of the heading/flowering date in at least four environments. GWAS and t test of a combination of SNPs and vernalization and photoperiod alleles indicated that the Vrn-B1, Vrn-D1, and Ppd-D1 genes significantly affect heading and flowering dates in Chinese common wheat. Based on the association of heading and flowering dates with the vernalization and photoperiod alleles at seven loci and three significant SNPs, optimal linear regression equations were established, which show that of the seven loci, the Ppd-D1 gene plays the most important role in modulating heading and flowering dates in Chinese wheat, followed by Vrn-B1 and Vrn-D1. Additionally, three novel genetic loci (RAC875_c41145_189, Excalibur_c60164_137, and RAC875_c50422_299) also show important effect on heading and flowering dates. Therefore, Ppd-D1, Vrn-B1, Vrn-D1, and the novel genetic loci should be further investigated in terms of improving heading and flowering dates in Chinese wheat. Further quantitative analysis of an F10 recombinant inbred lines population identified a major QTL that controls heading and flowering dates within the Ppd-D1 locus with PVEs of 28.4% and 34.0%, respectively; this QTL was also significantly associated with spike length, peduncle length, fertile spikelets number, cold resistance, and tiller number.

Genome-wide association study for 13 agronomic traits reveals distribution of superior alleles in bread wheat from the Yellow and Huai Valley of China.

Bread wheat is a leading cereal crop worldwide. Limited amount of superior allele loci restricted the progress of molecular improvement in wheat breeding. Here, we revealed new allelic variation distribution for 13 yield-related traits in series of genome-wide association studies (GWAS) using the wheat 90K genotyping assay, characterized in 163 bread wheat cultivars. Agronomic traits were investigated in 14 environments at three locations over 3 years. After filtering SNP data sets, GWAS using 20 689 high-quality SNPs associated 1769 significant loci that explained, on average, ~20% of the phenotypic variation, both detected already reported loci and new promising genomic regions. Of these, repetitive and pleiotropic SNPs on chromosomes 6AS, 6AL, 6BS, 5BL and 7AS were significantly linked to thousand kernel weight, for example BS00021705_51 on 6BS and wsnp_Ex_c32624_41252144 on 6AS, with phenotypic variation explained (PVE) of ~24%, consistently identified in 12 and 13 of the 14 environments, respectively. Kernel length-related SNPs were mainly identified on chromosomes 7BS, 6AS, 5AL and 5BL. Plant height-related SNPs on chromosomes 4DS, 6DL, 2DS and 1BL were, respectively, identified in more than 11 environments, with averaged PVE of ~55%. Four SNPs were confirmed to be important genetic loci in two RIL populations. Based on repetivity and PVE, a total of 41 SNP loci possibly played the key role in modulating yield-related traits of the cultivars surveyed. Distribution of superior alleles at the 41 SNP loci indicated that superior alleles were getting popular with time and modern cultivars had integrated many superior alleles, especially for peduncle length- and plant height-related superior alleles. However, there were still 19 SNP loci showing less than percentages of 50% in modern cultivars, suggesting they should be paid more attention to improve yield-related traits of cultivars in the Yellow and Huai wheat region. This study could provide useful information for dissection of yield-related traits and valuable genetic loci for marker-assisted selection in Chinese wheat breeding programme.

Integrated genome-wide association study and QTL mapping reveals qSa-3A associated with English grain aphid, Sitobion avenae (Fabricius) resistance in wheat.

BACKGROUND: The English grain aphid, Sitobion avenae (Fabricius), is a devastating pest impacts yield and quality in wheat (Triticum aestivum L.). Breeding resistant wheat varieties and detecting resistance genes are important strategies to control aphid. RESULTS: In this study, we evaluated the number of aphids per spike, the rate of thousand kernel weight decrease and aphid index based on three classic resistance mechanisms (antibiosis, tolerance and antixenosis), and detected SNPs/QTLs for resistance to S. avenae in a natural population of 163 varieties with 20 689 high-quality single-nucleotide polymorphism (SNP) markers and recombinant inbred line (RIL) population of 164 lines with 3627 diversity arrays technology (DArT) markers. Results showed that 83 loci significantly associated with S. avenae antibiosis and 182 loci significantly associated with S. avenae tolerance were detected by genome-wide association study (GWAS), explaining 6.47-15.82% and 8.36-35.61% of the phenotypic variances, respectively. The wsnp_Ku_c4568_8243646 detected in two periods was localized at 34.52 Mb on chromosome 3AS. Then, we confirmed a stable QSa.haust-3A.2 explained 11.19-20.10% of the phenotypic variances in two periods with S. avenae antixenosis in the physical interval of 37.49-37.50 Mb on chromosome 3A in the RIL population. Therefore, a narrow region in the physical interval of 34.52-37.50 Mb on chromosome 3AS was named as qSa-3A, which was a new locus between wsnp_Ku_c4568_8243646 and QSa.haust-3A.2 associated with S. avenae resistance. CONCLUSION: We found qSa-3A was a new locus associated with S. avenae resistance. The results could be applied in gene cloning and genetic improvement of S. avenae resistance in wheat. © 2023 Society of Chemical Industry.

QTL cluster analysis and marker development for kernel traits based on DArT markers in spring bread wheat (Triticum aestivum L.).

Genetic dissection of yield component traits including kernel characteristics is essential for the continuous improvement in wheat yield. In the present study, one recombinant inbred line (RIL) F6 population derived from a cross between Avocet and Chilero was used to evaluate the phenotypes of kernel traits of thousand-kernel weight (TKW), kernel length (KL), and kernel width (KW) in four environments at three experimental stations during the 2018-2020 wheat growing seasons. The high-density genetic linkage map was constructed with the diversity arrays technology (DArT) markers and the inclusive composite interval mapping (ICIM) method to identify the quantitative trait loci (QTLs) for TKW, KL, and KW. A total of 48 QTLs for three traits were identified in the RIL population on the 21 chromosomes besides 2A, 4D, and 5B, accounting for 3.00%-33.85% of the phenotypic variances. Based on the physical positions of each QTL, nine stable QTL clusters were identified in the RILs, and among these QTL clusters, TaTKW-1A was tightly linked to the DArT marker interval 3950546-1213099, explaining 10.31%-33.85% of the phenotypic variances. A total of 347 high-confidence genes were identified in a 34.74-Mb physical interval. TraesCS1A02G045300 and TraesCS1A02G058400 were among the putative candidate genes associated with kernel traits, and they were expressed during grain development. Moreover, we also developed high-throughput kompetitive allele-specific PCR (KASP) markers of TaTKW-1A, validated in a natural population of 114 wheat varieties. The study provides a basis for cloning the functional genes underlying the QTL for kernel traits and a practical and accurate marker for molecular breeding.

Removal of Fe(III)/Al(III)/Mg(II) by phosphonic group functionalized resin in wet-process phosphoric acid: Mechanism and intrinsic selectivity.

The removal of iron ions (Fe(III)), aluminum ions (Al(III)), and magnesium ions (Mg(II)) in phosphoric acid (H3PO4) solution is vital for the production of H3PO4 and supply of phosphate fertilizer. However, the mechanism and intrinsic selectivity for removal of Fe(III), Al(III), and Mg(II) from wet-process phosphoric acid (WPA) by phosphonic group (-PO3H2) functionalized MTS9500 are still unclear. In this work, the removal mechanisms were determined via combined analysis of FT-IR, XPS, molecular dynamics (MD), and quantum chemistry (QC) simulations based on density functional theory (DFT). The metal-removal kinetics and isotherms were further studied to confirm the removal mechanisms. The results indicate that Fe(III), Al(III), and Mg(II) interact with the -PO3H2 functional groups in MTS9500 resin with sorption energies of -126.22 kJ·mol-1, -42.82 kJ·mol-1, and -12.94 kJ·mol-1, respectively. Moreover, the intrinsic selectivities of the resin for Fe(III), Al(III), and Mg(II) removal were quantified by the selectivity coefficient (Si/j). The SFe(III)/Al(III), SFe(III)/Mg(II) and SAl(III)/Mg(II) are 18.2, 55.1 and 3.02, respectively. This work replenishes sorption theory that can be used in the recycling of electronic waste treatment acid, sewage treatments, hydrometallurgy, and purification of WPA in industry.

QTL mapping and KASP marker development for seed vigor related traits in common wheat.

Seed vigor is an important parameter of seed quality, and identification of seed vigor related genes can provide an important basis for highly efficient molecular breeding in wheat. In the present study, a doubled haploid (DH) population with 174 lines derived from a cross between Yangmai16 and Zhongmai 895 was used to evaluate 10 seed vigor related traits in Luoyang during the 2018-2019 cropping season and in Mengjin and Luoning Counties during 2019-2020 cropping season for three environments. Quantitative trait locus (QTL) mapping of 10 seed vigor related traits in the DH population resulted in the discovery/identification of 28 QTLs on chromosomes 2B, 3D, 4B, 4D, 5A, 5B, 6A, 6B, 6D, 7A and 7D, explaining 3.6-23.7% of the phenotypic variances. Among them, one QTL cluster for shoot length, root length and vigor index was mapped between AX-89421921 and Rht-D1_SNP on chromosome 4D in the physical intervals of 18.78-19.29 Mb (0.51 Mb), explaining 9.2-20.5% of the phenotypic variances. Another QTL for these traits was identified at the physical position 185.74 Mb on chromosome 5B, which was flanked by AX-111465230 and AX-109519938 and accounted for 8.0-13.3% of the phenotypic variances. Two QTLs for shoot length, shoot fresh weight and shoot dry weight were identified in the marker intervals of AX-109384026-AX-111120402 and AX-111651800-AX-94443918 on chromosomes 6A and 6B, explaining 8.2-11.7% and 3.6-10.3% of the phenotypic variance, respectively; both alleles for increasing phenotypic values were derived from Yangmai 16. We also developed the KASP markers for the QTL cluster QVI.haust-4D.1/QSL.haust-4D/QRL.haust-4D, and validated in an international panel of 135 wheat accessions. The germplasm, genes and KASP markers were developed for breeders to improve wheat varieties with seed vigor related traits.

SS31 Alleviates Pressure Overload-Induced Heart Failure Caused by Sirt3-Mediated Mitochondrial Fusion.

Heart failure caused by pressure overload is one of the leading causes of heart failure worldwide, but its pathological origin remains poorly understood. It remains critical to discover and find new improvements and treatments for pressure overload-induced heart failure. According to previous studies, mitochondrial dysfunction and myocardial interstitial fibrosis are important mechanisms for the development of heart failure. The oligopeptide Szeto-Schiller Compound 31 (SS31) can specifically interact with the inner mitochondrial membrane and affect the integrity of the inner mitochondrial membrane. Whether SS31 alleviates pressure overload-induced heart failure through the regulation of mitochondrial fusion has not yet been confirmed. We established a pressure-overloaded heart failure mouse model through TAC surgery and found that SS31 can significantly improve cardiac function, reduce myocardial interstitial fibrosis, and increase the expression of optic atrophy-associated protein 1 (OPA1), a key protein in mitochondrial fusion. Interestingly, the role of SS31 in improving heart failure and reducing fibrosis is inseparable from the presence of sirtuin3 (Sirt3). We found that in Sirt3KO mice and fibroblasts, the effects of SS31 on improving heart failure and improving fibroblast transdifferentiation were disappeared. Likewise, Sirt3 has direct interactions with proteins critical for mitochondrial fission and fusion. We found that SS31 failed to increase OPA1 expression in both Sirt3KO mice and fibroblasts. Thus, SS31 can alleviate pressure overload-induced heart failure through Sirt3-mediated mitochondrial fusion. This study provides new directions and drug options for the clinical treatment of heart failure caused by pressure overload.

Tongxinluo May Alleviate Inflammation and Improve the Stability of Atherosclerotic Plaques by Changing the Intestinal Flora.

Intestinal flora plays an important role in atherosclerosis. Tongxinluo, as a multi-target Chinese medicine to improve atherosclerosis, whether it can improve atherosclerosis by affecting the intestinal flora is worth exploring. We established a vulnerable plaque model of atherosclerosis in New Zealand white rabbits by high cholesterol diet and balloon injury (HCB), and performed Tongxinluo intervention. We detected the level of inflammation by immunohistochemistry, Western Blot, and ELISA, analyzed plaque characteristics by calculating the vulnerability index, and analyzed the changes of gut microbiota and metabolites by 16S rRNA gene sequencing and untargeted metabolomic sequencing. The results showed that Tongxinluo intervention improved plaque stability, reduced inflammatory response, inhibited NLRP3 inflammatory pathway, increased the relative abundance of beneficial bacteria such as Alistipes which reduced by HCB, and increased the content of beneficial metabolites such as trans-ferulic acid in feces. Through correlation analysis, we found that some metabolites were significantly correlated with some bacteria and some inflammatory factors. In particular, the metabolite trans-ferulic acid was also significantly positively correlated with plaque stability. Our further studies showed that trans-ferulic acid could also inhibit the NLRP3 inflammatory pathway. In conclusion, Tongxinluo can improve plaque stability and reduce inflammation in atherosclerotic rabbits, which may be achieved by modulating intestinal flora and intestinal metabolism. Our study provides new views for the role of Tongxinluo in improving atherosclerotic vulnerable plaque, which has important clinical significance.

A Case Report: An Elderly Male Patient With Takayasu Arteritis After Coronary Artery Bypass Grafting.

Background: Takayasu arteritis is a rare chronic granulomatous inflammation involving the aorta and its main branches. In this report, we describe an extremely rare elderly male patient with Takayasu arteritis (TA) after coronary artery bypass grafting (CABG). Case Summary: A 61-year-old male patient with persistent precordial pain underwent angiography. Vascular murmurs could be heard in carotid artery and bilateral renal artery by auscultation. Laboratory parameters showed high Erythrocyte Sedimentation Rate (ESR) and C-reactive protein (CRP). CT coronary angiography showed multiple stenoses of aorta and its main branches, such as carotid and renal artery involvement. Coronary angiography showed that the coronary artery had multiple branch stenoses, the left anterior descending artery (LAD) had severe stenosis, the distal end of which was reversed to the right coronary artery (RCA), and the RCA was completely occluded. Because of the high level of markers of inflammatory activity, the patient began to take glucocorticoid. Although the patient still had multibranch stenosis of coronary artery, considering the previous CABG operation history, surgery, and interventional therapy of the patient were not feasible, the patient was given conservative drug for further treatment. After treatment, the inflammatory index was significantly descended, and N terminal-pro Brain natriuretic peptide (NT-pro BNP) was decreased. Discussion: A rare case of an elderly male patient with Takayasu arteritis after coronary artery bypass grafting was reported. In addition to hypertension, hyperlipidemia, and other risk factors, coronary artery involvement caused by TA may be a major cause of aggravation of symptoms in patients with acute myocardial infarction (AMI), especially after CABG.

Gut Dysbiosis Contributes to the Imbalance of Treg and Th17 Cells in Graves' Disease Patients by Propionic Acid.

BACKGROUND: Graves' disease (GD) is a typical organ-specific autoimmune disease. Intestinal flora plays a pivotal role in immune homeostasis and autoimmune disease development. However, the association and mechanism between intestinal flora and GD remain elusive. OBJECTIVE: To investigate the association and mechanism between intestinal flora and GD. METHODS: We recruited 58 initially untreated GD patients and 63 healthy individuals in the study. The composition and metabolic characteristics of the intestinal flora in GD patients and the causal relationship between intestinal flora and GD pathogenesis were assessed using 16S rRNA gene sequencing, targeted/untargeted metabolomics, and fecal microbiota transplantation. RESULTS: The composition, metabolism, and inter-relationships of the intestinal flora were also changed, particularly the significantly reduced short-chain fatty acid (SCFA)-producing bacteria and SCFAs. The YCH46 strain of Bacteroides fragilis could produce propionic acid and increase Treg cell numbers while decreasing Th17 cell numbers. Transplanting the intestinal flora of GD patients significantly increased GD incidence in the GD mouse model. Additionally, there were 3 intestinal bacteria genera (Bacteroides, Alistipes, Prevotella) could distinguish GD patients from healthy individuals with 85% accuracy. CONCLUSIONS: Gut dysbiosis contributes to a Treg/Th17 imbalance through the pathway regulated by propionic acid and promotes the occurrence of GD, together with other pathogenic factors. Bacteroides, Alistipes, and Prevotella have great potential to serve as adjunct markers for GD diagnosis. This study provided valuable clues for improving immune dysfunction of GD patients using B. fragilis and illuminated the prospects of microecological therapy for GD as an adjunct treatment.

Genome-wide association study revealed that the TaGW8 gene was associated with kernel size in Chinese bread wheat.

Using Wheat 90 K SNP assay, kernel-related traits of Chinese bread wheat were used to perform association mapping in 14 environments by GWAS. Results indicated that 996 and 953 of 4417 and 3172 significant SNPs for kernel length and thousand-kernel weight were located on the chromosome 7B. Haplotype analysis of these SNPs on 7B generated the block containing the predicted TaGW8-B1 gene. TaGW8-B1 gene was further cloned by sequencing in bread wheat and a 276-bp InDel was found in the first intron. TaGW8-B1 without and with the 276-bp InDel were designated as TaGW8-B1a and TaGW8-B1b, respectively. Analysis of agronomic traits indicated that cultivars with TaGW8-B1a possessed significantly wider kernel width, significantly more kernel number per spike, longer kernel length, higher thousand-kernel weight and more spikelet number per spike than cultivars with TaGW8-B1b. Furthermore, cultivars with TaGW8-B1a possessed significantly higher yield than cultivars with TaGW8-B1b. Therefore, TaGW8-B1a was considered as a potentially superior allele. Meanwhile, TaGW8-B1a possessed a significantly higher expression level than TaGW8-B1b in mature seeds by qRT-PCR. It possibly suggested that the high expression of TaGW8-B1 was positively associated with kernel size in bread wheat. Distribution of TaGW8-B1 allele indicated that TaGW8-B1a has been positively selected in Chinese wheat.

SIRT3 inhibits Ang II-induced transdifferentiation of cardiac fibroblasts through ß-catenin/PPAR-γ signaling.

AIMS: Cardiac fibrosis is an inevitable process of numerous cardiovascular diseases in which the transdifferentiation of cardiac fibroblasts plays a pivotal role. Sirtuin3 (SIRT3) has been believed to protect against cardiac fibrosis. However, the mechanism underlying this beneficial effect has not yet been elucidated. In this study, we investigated the potential mechanism of SIRT3 on the inhibition of fibroblast-to-myoblast transdifferentiation. MAIN METHODS: Cells were stimulated by angiotension II (Ang II) with SIRT3 overexpression or knockdown. Also, PPARγ agonist (Pioglitazone PIO) and inhibitor (GW9662) were used to confirm the antifibrotic effect of PPARγ. Western blot, qRT-PCR, CCK-8 and immunofluorescence staining analysis were used for investigation. KEY FINDINGS: Our data demonstrated that overexpression of SIRT3 prevented the transdifferentiation of CFs while SIRT3 knockdown promoted the process. Simultaneously, SIRT3 overexpression increased total PPARγ expression and suppressed the acetylated PPARγ. Besides, pretreatment with PPARγ agonist, pioglitazone protected CFs from transdifferentiation while PPARγ inhibitor prevented the protective effect of SIRT3. In addition, we have found that SIRT3 upregulated the expression of PPARγ by degeration of ß-catenin. SIGNIFICANCE: Our findings indicate that this newly identified SIRT3/ß-catenin/PPAR-γ axis will provide novel insight into the understanding of the mechanism of transdifferentiation of CFs to myofibroblasts.

SIRT3-KLF15 signaling ameliorates kidney injury induced by hypertension.

Renal fibrosis participates in the progression of hypertension-induced kidney injury. The effect of SIRT3, a member of the NAD+-dependent deacetylase family, in hypertensive nephropathy remains unclear. In this study, we found that SIRT3 was reduced after angiotensin II (AngII) treatment both in vivo and in vitro. Furthermore, SIRT3-knockout mice aggravated hypertension-induced renal dysfunction and renal fibrosis via chronic AngII infusion (2000 ng/kg per minute for 42 days). On the contrary, SIRT3-overexpression mice attenuated AngII-induced kidney injury compared with wild-type mice. Remarkably, a co-localization of SIRT3 and KLF15, a kidney-enriched nuclear transcription factor, led to SIRT3 directly deacetylating KLF15, followed by decreased expression of fibronectin and collagen type IV in cultured MPC-5 podocytes. In addition, honokiol (HKL), a major bioactive compound isolated from Magnolia officinalis (Houpo), suppressed AngII-induced renal fibrosis through activating SIRT3-KLF15 signaling. Taken together, our findings implicate that a novel SIRT3-KLF15 signaling may prevent kidney injury from hypertension and HKL can act as a SIRT3-KLF15 signaling activator to protect against hypertensive nephropathy.

Haplotypes of the TaGS5-A1 Gene Are Associated with Thousand-Kernel Weight in Chinese Bread Wheat.

In previous work, we cloned TaGS5 gene and found the association of TaGS5-A1 alleles with agronomic traits. In this study, the promoter sequence of the TaGS5-A1 gene was isolated from bread wheat. Sequencing results revealed that a G insertion was found in position -1925 bp of the TaGS5-A1 gene (Reference to ATG), which occurred in the Sp1 domain of the promoter sequence. Combined with previous single nucleotide polymorphism (SNP) in the TaGS5-A1 exon sequence, four genotypes were formed at the TaGS5-A1 locus and were designated as TaGS5-A1a-a, TaGS5-A1a-b, TaGS5-A1b-a, and TaGS5-A1b-b, respectively. Analysis of the association of TaGS5-A1 alleles with agronomic traits indicated that cultivars with the TaGS5-A1a-b allele possessed significantly higher thousand-kernel weight (TKW) and lower plant height than cultivars with the TaGS5-A1a-a allele, and cultivars with the TaGS5-A1b-b allele showed higher TKW than cultivars with the TaGS5-A1b-a allele. The differences of these traits between the TaGS5-A1a-a and TaGS5-A1a-b alleles were larger than those of the TaGS5-A1b-a and TaGS5-A1b-b alleles, suggesting that the -1925G insertion plays the more important role in TaGS5-A1a genotypes than in TaGS5-A1b genotypes. qRT-PCR indicated that TaGS5-A1b-b possessed the significantly highest expression level among four TaGS5-A1 haplotypes in mature seeds and further showed a significantly higher expression level than TaGS5-A1b-a at five different developmental stages of the seeds, suggesting that high expression of TaGS5-A1 was positively associated with high TKW in bread wheat. This study could provide a relatively superior genotype in view of TKW in wheat breeding programs and could also provide important information for dissection of the regulatory mechanism of the yield-related traits.