Differential oral and gut microbial structure related to systemic metabolism in kidney stone patients.

OBJECTIVES: To investigate the role of the oral and gut microbiome related to systemic metabolism and clinical parameters in various types of kidney stone disease. PATIENTS AND METHODS: We conducted a case-control study by analyzing 16S rRNA and untargeted metabolomics profiling of 76 fecal, 68 saliva, 73 urine, and 43 serum samples from 76 participants aged 18-75 years old. The participants included 15 patients with uric acid stones, 41 patients with calcium oxalate stones, and 20 healthy controls. Correlations among microbiome, metabolism, and clinical parameters were identified through Spearman's correlation analysis. (Clinical trial No. ChiCTR2200055316). RESULTS: Patients with uric acid stones exhibited reduced richness and diversity in their microbiome, as well as altered composition in both oral and gut microbiome. Furthermore, their fecal samples showed lower relative abundances of Bacteroides and Lachnospiraceae, while their saliva samples showed higher relative abundances of Porphyromonas and Neisseria. Predicted KEGG metabolism pathways, including amino acid and fatty acid metabolisms, were significantly altered in subjects with uric acid stones. Oral, gut microbiota, and metabolism were also associated with low water intake and urine pH. The area under the curve (AUC) of the specific microbiota and metabolite prediction models was over 0.85. CONCLUSION: The structure and composition of the oral and gut microbiome in different types of kidney stone disease, the correlations between oral and gut microbiome, and the associations among oral and gut microbiota, systemic metabolism and clinical parameters imply an important role that the oral and gut microbiome may play in kidney stone disease.

QTL-seq and transcriptomic integrative analyses reveal two positively regulated genes that control the low-temperature germination ability of MTP-maize introgression lines.

KEY MESSAGE: Two candidate genes (ZmbZIP113 and ZmTSAH1) controlling low-temperature germination ability were identified by QTL-seq and integrative transcriptomic analyses. The functional verification results showed that two candidate genes positively regulated the low-temperature germination ability of IB030. Low-temperature conditions cause slow maize (Zea mays L.) seed metabolism, resulting in slow seedling emergence and irregular seedling emergence, which can cause serious yield loss. Thus, improving a maize cultivar's low-temperature germination ability (LTGA) is vital for increasing yield production. Wild relatives of maize, such as Z. perennis and Tripsacum dactyloides, are strongly tolerant of cold stress and can thus be used to improve the LTGA of maize. In a previous study, the genetic bridge MTP was constructed (from maize, T. dactyloides, and Z. perennis) and used to obtain a highly LTGA maize introgression line (IB030) by backcross breeding. In this study, IB030 (Strong-LTGA) and Mo17 (Weak-LTGA) were selected as parents to construct an F2 offspring. Additionally, two major QTLs (qCS1-1 and qCS10-1) were mapped. Then, RNA-seq was performed using seeds of IB030 and the recurrent parent B73 treated at 10 °C for 27 days and 25 °C for 7 days, respectively, and two candidate genes (ZmbZIP113 and ZmTSAH1) controlling LTGA were located using QTL-seq and integrative transcriptomic analyses. The functional verification results showed that the two candidate genes positively regulated LTGA of IB030. Notably, homologous cloning showed that the source of variation in both candidate genes was the stable inheritance of introgressed alleles from Z. perennis. This study was thus able to analyze the LTGA mechanism of IB030 and identify resistance genes for genetic improvement in maize, and it proved that using MTP genetic bridge confers desirable traits or phenotypes of Z. perennis and tripsacum essential to maize breeding systems.

QTL Mapping and a Transcriptome Integrative Analysis Uncover the Candidate Genes That Control the Cold Tolerance of Maize Introgression Lines at the Seedling Stage.

Chilling injury owing to low temperatures severely affects the growth and development of maize (Zea mays.L) seedlings during the early and late spring seasons. The existing maize germplasm is deficient in the resources required to improve maize's ability to tolerate cold injury. Therefore, it is crucial to introduce and identify excellent gene/QTLs that confer cold tolerance to maize for sustainable crop production. Wild relatives of maize, such as Z. perennis and Tripsacum dactyloides, are strongly tolerant to cold and can be used to improve the cold tolerance of maize. In a previous study, a genetic bridge among maize that utilized Z. perennis and T. dactyloides was created and used to obtain a highly cold-tolerant maize introgression line (MIL)-IB030 by backcross breeding. In this study, two candidate genes that control relative electrical conductivity were located on MIL-IB030 by forward genetics combined with a weighted gene co-expression network analysis. The results of the phenotypic, genotypic, gene expression, and functional verification suggest that two candidate genes positively regulate cold tolerance in MIL-IB030 and could be used to improve the cold tolerance of cultivated maize. This study provides a workable route to introduce and mine excellent genes/QTLs to improve the cold tolerance of maize and also lays a theoretical and practical foundation to improve cultivated maize against low-temperature stress.

Ureteroscopic and flexible ureteroscopic lithotripsy: continuation or discontinuation of anticoagulant or antiplatelet drugs? A Chinese survey among urologists.

PURPOSE: To evaluate the management of antithrombotic drugs made by different urologists before ureteroscopic lithotripsy and flexible ureteroscopy in stone patients undergoing active anticoagulant or antiplatelet therapy. METHODS: A survey was distributed to 613 urologists in China, which included personal work information and views on the management of anticoagulants (AC) or antiplatelet (AP) drugs during the perioperative period of ureteroscopic lithotripsy (URL) and flexible ureteroscopy (fURS). RESULTS: 20.5% of urologists believed that AP drugs could be continued and 14.7% believed that AC drugs could be continued. 26.1% of the urologists who participated in more than 100 ureteroscopic lithotripsy or flexible ureteroscopy surgeries each year believed that AP drugs could be continued and 19.1% believed that AC drugs could be continued, compared with 13.6% (P < 0.01) and 9.2% (P < 0.01) of the urologists who performed less than 100 surgeries. Among the urologists with more than 20 cases undergoing active AC or AP therapy per year, 25.9% thought that AP drugs could be continued and 19.7% thought that AC drugs could be continued, compared with 17.1% (P = 0.008) and 11.5% (P = 0.005) of the urologists with less than 20 cases. CONCLUSION: The decision on the continuation of AC or AP drugs before ureteroscopic and flexible ureteroscopic lithotripsy should be individualized. The experience in URL and fURS surgeries and in dealing with patients under AC or AP therapy is the influencing factor.

Upregulation of KLF14 expression attenuates kidney fibrosis by inducing PPARα-mediated fatty acid oxidation.

Tubulointerstitial fibrosis (TIF) is essential during the development of end-stage kidney disease (ESKD) and is associated with the impairment of fatty acid oxidation (FAO). Kruppel-like factor 14 (KLF14) is an important gene in lipid metabolism, but its role in TIF remains unknown. TGF-ß-stimulated HK-2 cells and mouse unilateral ureteral obstruction (UUO) were used as renal fibrosis models. The role of KLF14 in the process of renal fibrosis was verified by gene knockout mice, genetic or pharmacological interference in animal model and cell model respectively. In the current study, we found that KLF14 expression increased after activation of the TGF-ß signaling pathway during TIF. In KLF14-/- mice, more severe fibrosis was observed after unilateral ureteral obstruction (UUO) was induced. In human HK2 cells, knockdown of KLF14 led to more severe fibrosis induced by TGF-ß1, while overexpression of KLF14 partially attenuated this process. Specifically, KLF14 deficiency decreased mitochondrial FAO activity, resulting in lipid accumulation. Thus, the energy supply to the cells was insufficient, finally resulting in TIF. We further proved that KLF14 could target peroxisome proliferator activated receptor alpha (PPARα) as a transcriptional activator. This study identified the upregulation of KLF14 expression in response to kidney stress during the process of fibrosis. Upon TIF, the activated TGF-ß signaling pathway can enhance KLF14 expression, while the upregulation of KLF14 expression can decrease the degree of TIF by improving FAO activity in tubular epithelial cells and recovering the energy supply mediated by PPARα.

[Spatial Distribution and Pollution Assessment of As at a Small Scale in Agricultural Soils of the Karst Region].

The karst landforms in Guizhou are widely distributed, and the problem of soil arsenic (As) pollution is prominent in these areas because of the high environmental background levels. In order to study the distribution characteristics of As contents in agricultural soils with high background values of As, representative As polluted regions (typical karst region, semi-karst region) in southwestern Xingyi City of Guizhou Province were selected as the research objects, and the non-karst region served as the control group. Geostatistical analyses were then combined with GIS data to study the spatial variability and pollution conditions of As in agricultural soils. Furthermore, Moran's I statistic was used to analyze the spatial autocorrelation and directional characteristics of As at a small scale in the soil. The results showed that As contents in soils from different geomorphological regions were ranked as follows:typical karst region > semi-karst region > non-karst region. The arithmetic mean value and geometric mean value of As in agricultural soils in the typical karst region were 47.9 mg·kg-1 and 43.3 mg·kg-1, respectively. Meanwhile, the arithmetic mean value and geometric mean value of As in agricultural soils in the semi-karst region were 36.8 mg·kg-1 and 30.1 mg·kg-1, respectively. The As content in agricultural soils from these two regions was significantly higher than the background values of As in Guizhou. In addition, the standard exceedance rates of As in those two regions were 98.5% and 96.7%, respectively, thus demonstrating a high degree of As accumulation. In contrast, the standard exceedance rate of As in the non-karst region was only 6.7%. Among these three afore-mentioned landform types, the results of independent sample T tests showed that there were no significant differences in the content of As between agricultural soil and (natural) soil (P>0.05). The Moran's I coefficient of the As content in agricultural soil was 0.45, and the Z value was 11.61, thus suggesting that there was a significant positive spatial autocorrelation at the small scale (P<0.05), especially in the northeast-southwest direction, and the structural variation was dominant. The As polluted agricultural soils were generally at the slight pollution and mild pollution levels, which accounted for 27.10% and 29.02% of the samples, respectively. However, some regions were at the level of moderate pollution. The non-polluted samples accounted for 41.94% of the samples.

[Cd Accumulation and Risk Assessment for Arable Soils in the Karst Region of Northern Luodian, Guizhou].

Background levels of cadmium (Cd) in carbonate rock areas of Guizhou Province are high. In order to understand the characteristics of Cd in arable soils in these karst areas, the soils in the northern county of Luodian were selected as the study object. By comparing soils in non-karst areas, the distribution characteristics of soil Cd were studied by combining geostatistical analysis and GIS, and the potential ecological risk index and health risk were used to evaluate the potential level of risk to adults and children. The results show that the arable soil Cd content in this karst area is significantly higher than that in non-karst areas (P<0.05), with a geometric mean of 1.33mg·kg-1 and 0.27 mg·kg-1, respectively. In comparison, the geometric mean of soil Cd content in forested land in the same areas is 1.57mg·kg-1 and 0.22 mg·kg-1, respectively. Based on "soil pollution risk control standards", the Cd content of 90% and 22% of arable soil samples was higher than the risk screening value and the risk control value for karst and non-karst areas, respectively. The areas with medium and high Cd values were mainly distributed in the karst areas, presenting medium to strong ecological risks and extremely strong ecological risks, respectively. In contrast, the areas with the lowest Cd concentrations were distributed in the non-karst areas of Jiaoyan, presenting low potential ecological risk. The health risk assessment showed that the non-carcinogenic risk and carcinogenic risk of the three exposure pathways for adults and children in the karst areas are significantly higher than those in the non-karst areas, but the Cd content in the soil does not present non-carcinogenic and carcinogenic risks to local residents. Overall, the problem of Cd pollution in arable soils in the karst area of northern Luodian, Guizhou, is prominent. Therefore, the study of the risks posed by Cd pollution to the soil-plant-human system should be strengthened, and appropriate measures should be taken to prevent and control Cd pollution in the areas at risk.

Mysterious meiotic behavior of autopolyploid and allopolyploid maize.

This study was aimed to investigate the stability of chromosomes during meiosis in autopolyploid and allopolyploid maize, as well as to determine an association of chromosomes between maize (Zea mays ssp. mays Linnaeus, 1753) and Z. perennis (Hitchcock, 1922) Reeves & Mangelsdor, 1942, by producing a series of autopolyploid and allopolyploid maize hybrids. The intra-genomic and inter-genomic meiotic pairings in these polyploids were quantified and compared using dual-color genomic in-situ hybridization. The results demonstrated higher level of chromosome stability in allopolyploid maize during meiosis as compared to autopolyploid maize. In addition, the meiotic behavior of Z. perennis was relatively more stable as compared to the allopolyploid maize. Moreover, ten chromosomes of "A" subgenome in maize were homologous to twenty chromosomes of Z. perennis genome with a higher pairing frequency and little evolutionary differentiation. At the same time, little evolutionary differentiation has been shown by chromosomes of "A" subgenome in maize, while chromosomes of "B" subgenome, had a lower pairing frequency and higher evolutionary differentiation. Furthermore, 5IM + 5IIPP + 5IIIMPP and 5IIMM + 5IIPP + 5IVMMPP were observed in allotriploids and allotetraploids respectively, whereas homoeologous chromosomes were found between the "A" and "B" genome of maize and Z. perennis.

Mild Hypothermia Promotes Pericontusion Neuronal Sprouting via Suppressing Suppressor of Cytokine Signaling 3 Expression after Moderate Traumatic Brain Injury.

Mild therapeutic hypothermia is a candidate for the treatment of traumatic brain injury (TBI). However, the role of mild hypothermia in neuronal sprouting after TBI remains obscure. We used a fluid percussion injury (FPI) model to assess the effect of mild hypothermia on pericontusion neuronal sprouting after TBI in rats. Male Sprague-Dawley rats underwent FPI or sham surgery, followed by mild hypothermia treatment (33°C) or normothermia treatment (37°C) for 3 h. All the rats were euthanized at 7 days after FPI. Neuronal sprouting that was confirmed by an increase in growth associated protein-43 (GAP-43) expression was evaluated using immunofluorescence and Western blot assays. The expression levels of several intrinsic and extrinsic sprouting-associated genes such as neurite outgrowth inhibitor A (NogoA), phosphatase and tensin homolog (PTEN), and suppressor of cytokine signaling 3 (SOCS3) were analyzed by quantitative real-time polymerase chain reaction (RT-PCR). Our results revealed that mild hypothermia significantly increased the expression level of GAP-43 and dramatically suppressed the expression level of interleukin-6 (IL-6) and SOCS3 at 7 days after FPI in the ipsilateral cortex compared with that of the normothermia TBI group. These data suggest that post-traumatic mild hypothermia promotes pericontusion neuronal sprouting after TBI. Moreover, the mechanism of hypothermia-induced neuronal sprouting might be partially associated with decreased levels of SOCS3.

Alteration of microRNA expression in cerebrospinal fluid of unconscious patients after traumatic brain injury and a bioinformatic analysis of related single nucleotide polymorphisms.

PURPOSE: It is becoming increasingly clear that genetic factors play a role in traumatic brain injury (TBI), whether in modifying clinical outcome after TBI or determining susceptibility to it. MicroRNAs are small RNA molecules involved in various pathophysiological processes by repressing target genes at the post- transcriptional level, and TBI alters microRNA expression levels in the hippocampus and cortex. This study was designed to detect differentially expressed microRNAs in the cerebrospinal fluid (CSF) of TBI patients remaining unconscious two weeks after initial injury and to explore related single nucleotide polymorphisms (SNPs). METHODS: We used a microarray platform to detect differential microRNA expression levels in CSF samples from patients with post-traumatic coma compared with samples from controls. A bioinformatic scan was performed covering microRNA gene promoter regions to identify potential functional SNPs. RESULTS: Totally 26 coma patients and 21 controls were included in this study, with similar distribution of age and gender between the two groups. Microarray showed that fourteen microRNAs were differentially expressed, ten at higher and four at lower expression levels in CSF of traumatic coma patients compared with controls (p<0.05). One SNP (rs11851174 allele: C/T) was identified in the motif area of the microRNA hsa-miR-431-3P gene promoter region. CONCLUSION: The altered microRNA expression levels in CSF after brain injury together with SNP identified within the microRNA gene promoter area provide a new perspective on the mechanism of impaired consciousness after TBI. Further studies are needed to explore the association between the specific microRNAs and their related SNPs with post-traumatic unconsciousness.

A replication study for association of 53 single nucleotide polymorphisms in ScoliScore test with adolescent idiopathic scoliosis in French-Canadian population.

STUDY DESIGN: A replication association study that used genomic data generated from French-Canadian case and control cohorts. OBJECTIVES: To determine whether the 53 single nucleotide polymorphisms (SNPs) that were previously associated with spinal deformity progression in an American Caucasian cohort are similarly associated in French-Canadian population. SUMMARY OF BACKGROUND DATA: It is widely accepted that genetic factors contribute to adolescent idiopathic scoliosis. The identification of genetic variants associated with the predisposition or progression of curvature could facilitate diagnostic/prognostic tool development. Although 53 SNPs have been associated with spinal curve progression in Caucasian cohorts in the United States, these associations were not replicated in a large Japanese population study, arguing that such a discrepancy could be explained by ethnicity, thus raising the importance of a replication study in an independent Caucasian population of European descent. METHODS: Genomic data were collected from the French-Canadian population, using the Illumina HumanOmni 2.5M BeadChip. Fifty-two SNPs, tested in ScoliScore or in high linkage disequilibrium with SNPs in the test, were selected to assess their association with scoliosis generally, and with spinal curve progression. One SNP in ScoliScore, rs16909285, could not be evaluated in our Genome-Wide association study. RESULTS: None of the SNPs used in ScoliScore were associated with adolescent idiopathic scoliosis curve progression or curve occurrence in French-Canadian population. We evaluated 52 SNPs in severe patients by comparing risk allele frequencies with those in nonsevere patients and with those in control individuals. There was no significant difference between the severe group and the nonsevere group or between the severe group and the control group. CONCLUSION: Although the 52 SNPs studied here were previously associated with curve progression in an American population of European descent, we found no association in French-Canadian patients with adolescent idiopathic scoliosis. This second replication cohort suggests that the lack of association of these SNPs in a Japanese cohort is not due to ethnicity. LEVEL OF EVIDENCE: 4.

[Cytological observation on pollen abortion of genetic male sterile mutant induced by space flight in maize].

In order to understand the cytological mechanism of pollen abortion of genetic male sterile mutant induced by space flight in maize, the sister cross population were used for sterility analysis and cytological observation. Intact anther observation, isolated cells observation and paraffin section were adopted in this research. The results showed that pollen abortion occured mostly in dyad stage of meiosis in genetic male sterile mutant. The dyad were degenerated with abnormal shape. In late anther developing stage, the tapetal cells were giant vacuolated and delayed degeneration. The pollen mother cells (PMC) began to dissolve and degenerate in a few anther before meiosis.

[The production and multi-color genomic in situ hybridization identification of maize-Z. perennis substituted material].

Genus Zea. L was composed of two sections: sect. Luxuriantes Doebley & Iltis including Z. dipperennis, Z. luxurians and Z. perennis, and sect. Zea. mays consisting only one species, annual Z. mays. To improve the biodiversity of germ-plasm in maize breeding, the study of transferring maize relatives gene into common maize were performed. Firstly, interspecific hybrids between maize (Zea. L) (2n = 20) and Z. perennis (2n = 40) were produced with the aim of transferring desirable horticultural traits from Z. perennis to maize. The F1 of maize x Z. perennis (2n = 30) plant had the most frequent configuration of 5 III + 5 II + 5 I, which were sterile and difficult to produce progeny because of genomic affinities. However,few F2 individuals of maize x Z. perennis could be obtained by some specially treatments, and one maize-like F2 plant were obtained, which were used as a female parent in backcrossing with maize parent. Twelve F2 x P1 ( BC1 F2 ) plants were obtained and then self-crossed to produce self-crossing generation of F2 x P1 (2n = 20) ( BC1 F3). The phenotypic characters of parents, F1 (2n = 30) hybrids, F2 and F2 x P1 were investigated, such as plant height, flowering, leaf shape and tillers. To further verify the genomic organization of maize-Z. perennis material, maize (inbred line 48-2) and BC1 F3 chromosomes, the root tip cells were analyzed by Multi-color GISH. We probed maize and BC1 F3 chromosomes with the probe mixture containing biotin-labeled Z. perennis genomic DNA and digoxigenin-labeled maize genomic DNA, the maize spread exhibited 10 chromosomes with yellow signals and the other 10 chromosomes carried green fluorescing bands. However, although the BC1 F3 was 2n = 20 in all cases. Multi-color GISH images revealed that 17 chromosomes had uniform signals similar to maize chromosomes, but dispersed red signals over the remaining three chromosomes were observed, which indicated that the 3 chromosomes originated from Z. perennis, and they were smaller than maize chromosomes. Data obtained from multi-color GISH images indicated that BC1 F3 was probably a substituted material from maize-Z. perennis.