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Osteoporosis is a prevalent systemic skeletal disorder entailing bone fragility and increased fracture risk, often emerging in post-menopausal life. Emerging evidence implicates the dysregulation of microRNAs (miRNAs or miRs) in the progression of osteoporosis. This study investigated the effect of miR-199a-3p on osteoporosis and its underlying mechanism. We first examplished an ovariectomized (OVX)-induced rat osteoporosis model, and then isolated mesenchymal stem cells (MSCs) from bone marrow of the model rats. The overexpression and knock down of miR-199a-3p were conducted in OVX rats and MSCs to verify the role of miR-199a-3p on MSC differentiation. Calcium nodules were measured using alizarin red S (ARS) staining. RT-qPCR and Western blot assay were performed to measure the expression of miR-199a-3p, Kdm3a and osteogenic differentiation-related markers in rat tissues and cells. The correlation between miR-199a-3p and Kdm3a was confirmed using dual-luciferase reporter assay. The enrichment of Kdm3a at the Erk2 and Klf2 promoter was assessed using chromatin immunoprecipitation (ChIP) assay. Isolated MSCs were positive for CD29, CD44, CD90, and CD45, suggesting successful isolation of MSCs. There was increased expression of miR-199a-3p and inhibited osteogenic differentiation in OVX rats. Kdm3a was negatively targeted by miR-199a-3p. Our results also demonstrated that Kdm3a elevated the expression of Erk2 and Erk2 by promoting Erk2 and Klf2 demethylation, which further contributed to osteogenic differentiation. Overall, our results revealed a regulatory network of miR-199a-3p in osteogenic differentiation, highlighting miR-199a-3p as a potential target for therapeutic interventions in osteoporosis.

Shrubs can induce spatial heterogeneity of soil nutrition and play a crucial role in dune stabilization in arid and semi-arid ecosystems. Soil enzyme activity can be used to investigate soil nutrient cycling, which further indicates soil recovery after sand stabilization. However, information regarding the effects of different shrubs on soil enzyme activity is scarce. To reveal and compare soil enzyme activities of two dominating sand-stabilizing shrubs, namely, Caragana korshinskii Kom. and Artemisia ordosica , we evaluated various hydrolase and oxidase enzymes involved in the carbon cycle (polyphenol oxidase, cellulose, and β-glucosidase) and nitrogen cycle (nitrate reductase and urease) at the shrub base (ASB), beneath the midcanopy (BMC), and in bare intershrub spaces (BIS). The results indicated that the sand-stabilizing shrubs improved soil nutrition and enzyme activity compared with bare soil. The effects varied with shrub type and position. Soil enzyme activities were greater in C. korshinskii than those in A. ordosica , and maximum enzyme activity was found at ASB, followed by BMC and BIS. All enzyme activities, except polyphenol oxidase, were higher at 0–5 cm depth. The enzyme activities exhibited similar seasonal patterns during the growing season, with relatively higher values in the summer rainy season than in the other seasons because of soil moisture and shrub growth. The results of this study suggest that sand-stabilizing shrubs, especially C. korshinskii , can increase soil nutrition and improve soil properties, thus playing a vital role in soil recovery in degraded areas of desert ecosystems.

The aim of this study was to evaluate canopy water storage (CWS) of the co-dominant shrubs in the revegetation of sand dunes in northwest China. Our results indicated that CWS differed among the xerophyte taxa studied. The average CWS increased exponentially with decreased raindrop size. The time course of CWS in terms of leaf area indicated that Artemisia ordosica attains its peak value of 0.48 mm within 170 min. The corresponding values for Caragana korshinskii and Hedysarum scoparium were 0.38 mm and 178 min, and 0.32 mm and 161 min, respectively, implying that A. ordosica had a higher CWS than C. korshinskii and H. scoparium. Dry biomass was a desirable predictor for estimation of CWS for C. korshinskii and H. scoparium, and shrub volume for A. ordosica. Our results show that the dependence of CWS on raindrop size varied in accordance with the shrub canopy structure. Editor Z.W. Kundzewicz

Dysregulation of microRNAs (miRs) can contribute to cancer development and progression. In the present study, the function and underlying molecular mechanisms of miR-320 in breast cancer tumorigenesis and progression were investigated. The results of a reverse transcription-quantitative polymerase chain reaction analysis demonstrated that miR-320 was frequently downregulated in breast cancer tissues compared with adjacent normal tissues. In addition, knockdown of miR-320 in breast cancer cell lines promoted cell proliferation and invasion in vitro, whereas miR-320 overexpression had the opposite effect. Furthermore, a Dual-Luciferase reporter assay indicated that SRY-box 4 (SOX4) is a direct target of miR-320, and the restoration of SOX4 in miR-320-overexpressing cells attenuated the tumor-suppressive effects of miR-320. Collectively, these results indicated that miR-320 acts as a tumor suppressor in breast cancer tumorigenesis and progression.

Pentatricopepetide repeat (PPR) proteins are a large family of RNA-binding proteins involved in RNA metabolism in plant organelles. Although many PPR proteins have been functionally studied, few of them are identified with a function in mitochondrial RNA stability. By using a reverse genetic approach, we characterized the role of the mitochondrion-targeted PPR78 protein in nad5 mature mRNA stability and maize (Zea mays) seed development. Loss of PPR78 function leads to a dramatic reduction in the steady-state level of mitochondrial nad5 mature mRNA, blocks the assembly of complex I in the electron transport chain, and causes an arrest in embryogenesis and endosperm development. Characterization of a second strong allele confirms the function of PPR78 in nad5 mRNA accumulation and maize seed development. The generation of mature nad5 requires the assembly of three distinct precursor RNAs via trans-splicing reactions, and the accumulation of nad5T1 precursor is reduced in the ppr78 mutants. However, it is the instability of mature nad5 rather than nad5T1 causing loss of the full-length nad5 transcript, and degradation of nad5 losing both translation start and stop codons is enriched in the mutant. Our data imply the assembly of mature nad5 mRNA precedes the protection of PPR78.

Stemflow production has been reported to be influenced by a suite of biotic and abiotic factors. Nevertheless, relative contributions of biotic and abiotic factors to stemflow production and funneling efficiency were largely unclear due to complex interactions among those factors. In this study, stemflow of nine xerophytic shrubs of Caragana korshinskii were measured in nearly nine growing seasons from 2010 to 2018 within a desert area of northern China, accompanying with observing on six biotic variables (shrub morphological attributes) and ten abiotic variables (meteorological conditions). We performed boosted regression trees (BRT) model to evaluate the relative contribution (θ) of each biotic and abiotic variable to stemflow volume (SFv), stemflow percentage (SFp), and funneling ratio (FR), associating with partial dependence plots (PDPs) to visualize the effects of individual explanatory variables on SFv, SFp, and FR, respectively. Generally, we observed that larger shrubs generated more SFv, while had lower SFp and FR. BRT analysis demonstrated that biotic variables outweighed abiotic variables by 1.5-fold as to their contribution to SFv, whereas abiotic variables prevailed for SFp and FR, respectively. Differences in θ between variables for SFv (CV = 146%) were much pronounced than for SFp (CV = 57%) and FR (CV = 26%), with the foremost three influential variables for SFv ranking in descending orders of θ by rainfall amount (33.2%), basal area (20.9%), projected canopy area (15.1%), and that for SFp by projected canopy area (13.2%), rainfall amount (13.0%), and air temperature (11.1%), and that for FR by antecedent dry period (9.1%), rainfall amount (8.4%), and wind speed (8.3%). The quantitative and mechanistic explanations regarding the effects of biotic and abiotic variables on three stemflow parameters from the present study are expected to be applicable to other shrub species within arid and semi-arid ecosystems.

Summary RNA editing modifies cytidines (C) to uridines (U) at specific sites in the transcripts of mitochondria and plastids, altering the amino acid specified by the DNA sequence. Here we report the identification of a critical editing factor of mitochondrial nad7 transcript via molecular characterization of a small kernel 1 (smk1) mutant in Zea mays (maize). Mutations in Smk1 arrest both the embryo and endosperm development. Cloning of Smk1 indicates that it encodes an E-subclass pentatricopeptide repeat (PPR) protein that is targeted to mitochondria. Loss of SMK1 function abolishes the C → U editing at the nad7-836 site, leading to the retention of a proline codon that is edited to encode leucine in the wild type. The smk1 mutant showed dramatically reduced complex–I assembly and NADH dehydrogenase activity, and abnormal biogenesis of the mitochondria. Analysis of the ortholog in Oryza sativa (rice) reveals that rice SMK1 has a conserved function in C → U editing of the mitochondrial nad7-836 site. T-DNA knock-out mutants showed abnormal embryo and endosperm development, resulting in embryo or seedling lethality. The leucine at NAD7-279 is highly conserved from bacteria to flowering plants, and analysis of genome sequences from many plants revealed a molecular coevolution between the requirement for C → U editing at this site and the existence of an SMK1 homolog. These results demonstrate that Smk1 encodes a PPR-E protein that is required for nad7-836 editing, and this editing is critical to NAD7 function in complex-I assembly in mitochondria, and hence to embryo and endosperm development in maize and rice.

To characterize the CBFP reaction in the modern era, we analyzed the results of parallel rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TPPA) tests from a total of 63,765 blood samples obtained at Zhongshan Hospital in the Medical College of Xiamen University from May 2008 to February 2013. Among the 63,765 tested blood samples, 206 (0.32%) had the CBFP reaction. In multivariate analysis, an increased likelihood of the CBFP reaction was associated with female subjects, subjects ≥80years old, and subjects between 16 and 35years old (P

Background. Algorithms for the diagnosis of syphilis continue to be a source of great controversy, and numerous test interpretations have perplexed many clinicians. Methods. We conducted a cross-sectional study of 24 124 subjects to analyze 3 syphilis testing algorithms: traditional algorithm, reverse algorithm, and the European Centre for Disease Prevention and Control (ECDC) algorithm. Every serum sample was simultaneously evaluated using the rapid plasma reagin, Treponema pallidum particle agglutination, and chemiluminescence immunoassay tests. With the results of clinical diagnoses of syphilis as a gold standard, we evaluated the diagnostic accuracy of the 3 syphilis testing algorithms. The κ coefficient was used to compare the concordance between the reverse algorithm and the ECDC algorithm. Results. Overall, 2749 patients in our cohort were diagnosed with syphilis. The traditional algorithm had the highest negative likelihood ratio (0.24), a missed diagnosis rate of 24.2%, and only 75.81% sensitivity. However, both the reverse and ECDC algorithms had higher diagnostic efficacy than the traditional algorithm. Their sensitivity, specificity, and accuracy were 99.38%–99.85%, 99.98%–100.00%, and 99.93%–99.96%, respectively. Moreover, the overall percentage of agreement and κ value between the reverse and the ECDC algorithms were 99.9% and 0.996, respectively. Conclusions. Our research supported use of the ECDC algorithm, in which syphilis screening begins with atreponemal immunoassay that is followed by a second, different treponemal assay as a confirmatory test in highprevalence populations. In addition, our results indicated that nontreponemal assay is unnecessary for syphilis diagnosis but can be recommended for determining serological activity and the effect of syphilis treatment.

Introduction: In this study we investigated the gender difference of serum angiotensin-converting enzyme (ACE) activity in a population of Hong Kong-dwelling elderly Chinese. Materials and methods: A total of 1767 (843 male, 924 female) Hong Kong-dwelling elderly Chinese were recruited. ACE I/D genotypes were identified by polymerase chain reaction amplification and serum ACE activity was determined using a commercially available kinetic kit. ACE I/D genotype distribution was compared by chi-square test, the correlation between ACE I/D polymorphism and serum ACE activity was analysed by ANOVA test and gender difference of serum ACE activity of different genotypes was compared by independent sample t -test. Results: No statistically significant difference of genotype distribution between male and female subjects was found. Serum ACE activity was significantly correlated with ACE genotype. Overall, there was no gender difference of serum ACE activity; however, when sub-grouping the subjects by ACE I/D genotype, male subjects with DD genotype had higher serum ACE activity than female subjects with DD genotype. Conclusions: No significant gender difference of genotype distribution was found in elderly Chinese. Serum ACE activity was significantly correlated with ACE I/D polymorphism in elderly Chinese. Male subjects with DD genotype had higher serum ACE activity than female subjects with DD genotype.

Dysregulation of microRNAs has been confirmed to serve an important role in cancer development and progression. However, the role of microRNA (miR)-544 in colorectal cancer progression remains unknown. In the present study, it was observed that the expression level of miR-544 was increased in breast cancer cell lines and tissues using the quantitative polymerase chain reaction. Overexpression of miR-544 promoted cell proliferation and invasion in colorectal cancer, whereas inhibition of miR-544 suppressed colorectal cancer progression as determined using MTT, colony formation and Transwell assays. Furthermore, forkhead box O1 (FOXO1) was a direct target of miR-544. FOXO1 mediated miR-544-regulated colorectal cancer progression and cell cycle distribution. In conclusion, the results of the present study revealed that miR-544 serves an important role in promoting human colorectal cancer cell progression.

In this study we analyzed the independent effect of angiotensin-converting enzyme (ACE) inhibitor use on bone loss in elderly Chinese. The subjects were from two cohort studies which investigated the risk factors of osteoporotic fractures in Hong Kong-dwelling elderly Chinese. A total of 2161 subjects (1280 male, 881 female) were selected for this analysis. The results showed that unadjusted annualized percentage bone loss of male ACE inhibitor users was not different from non-users; however, female ACE inhibitor users had significantly greater bone loss both in total hip and femoral neck than non-users. After adjusting for significant confounders, female continuous ACE inhibitor users had significantly greater bone loss at total hip and femoral neck. In conclusion, continuous use of ACE inhibitors over 4 years was associated with increased bone loss in total hip and femoral neck in older Chinese women.

Robertson’s Mutator (Mu) system has been used in large scale mutagenesis in maize, exploiting its high mutation frequency, controllability, preferential insertion in genes, and independence of donor location. Eight Mutator elements have been fully characterized (Mu1, Mu2 /Mu1.7, Mu3, Mu4, Mu5, Mu6/7, Mu8, MuDR), and three are defined by TIR (Mu10, Mu11 and Mu12). The genome sequencing revealed a complex family of Mu-like-elements (MULEs) in the B73 genome. In this article, we report the identification of a new Mu element, named Mu13. Mu13 showed typical Mu characteristics by having a ∼220 bp TIR, creating a 9 bp target site duplication upon insertion, yet the internal sequence is completely different from previously identified Mu elements. Mu13 is not present in the B73 genome or a Zea mays subsp. parviglumis accession, but in W22 and several inbreds that found the Robertson’s Mutator line. Analysis of mutants isolated from the UniformMu mutagenic population indicated that the Mu13 element is active in transposition. Two novel insertions were found in expressed genes. To test other unknown Mu elements, we selected six new Mu elements from the B73 genome. Southern analysis indicated that most of these elements were present in the UniformMu lines. From these results, we conclude that Mu13 is a new and active Mu element that significantly contributed to the mutagenesis in the UniformMu population. The Robertson’s Mutator line may harbor other unknown active Mu elements.

miR-410-3p acts as an oncogene or tumor-suppressor gene in various types of cancer. However, its role in breast cancer remains unknown. In the present study, expression of miR-410-3p in 30 breast cancer and paired adjacent normal tissues was detected by RT-qPCR. The expression of miR-410-3p was downregulated in 76.7% of the breast cancer samples. To further validate the expression of miR-410-3p in breast cancer, we analyzed miR-410-3p expression profiling data set from The Cancer Genome Atlas (TCGA) including 683 breast cancer and 87 normal breast tissues. We observed that the expression of miR-410-3p was downregulated in breast cancer tissues. Next, we investigated the influence of miR-410-3p on cell proliferation by transiently transfecting the miR-410-3p mimic or inhibitor, as well as their corresponding controls in the MDA-MB-231 and MCF7 cell lines. miR-410-3p overexpression reduced cell growth, colony formation and the number of EdU-positive cells in the MDA-MB-231 cells. In contrast, inhibition of miR-410-3p in the MCF7 cells resulted in a higher proliferation rate as assessed by MTT assay, plate colony formation and EdU assays. Furthermore, miR-410-3p inhibited epithelial-mesenchymal transition. In addition, Snail was found to be a direct target of miR-410-3p based on a luciferase assay. Overexpression of Snail was able to rescue the effect of miR-410-3p in breast cancer cells. Moreover, miR‑410-3p was inversely expressed with Snail in breast cancer samples. Our data provide new knowledge regarding the role of miR-410-3p in breast cancer progression.

Neurosyphilis (NS) caused by Treponema pallidum (T. pallidum) subspecies pallidum, can affect the central nervous system during any stage of the disease. To assess several laboratory parameters for NS diagnosis, we performed a case control study on 42 hospitalized NS patients negative for human immunodeficiency virus (HIV) and 40 syphilis/non-NS patients, excluding NS patients at Xiamen Zhongshan Hospital from June 2010 to June 2011. Multivariate logistic regression model showed that the cerebrospinal fluid white blood cell (CSF-WBC, P = 0.009) levels, the CSF-LDH (P = 0.006) levels, the albumin quotient (P = 0.009) and the IgA index (P = 0.042) were independently associated with high risk of NS. The receiver operator characteristic (ROC) curve analysis revealed that the optimal cut-offs were 10 × 106 cells/L for the CSF-WBC concentration, 19.3 U/L for the CSF lactate dehydrogenase (LDH) concentration, 7.08 for the albumin quotient, and 0.14 for the IgA index. Combining the CSF-WBC level, the CSF-LDH level, the albumin quotient and the IgA index increased the NS diagnosis sensitivity to 97.6%. T. pallidum particle agglutination (TPPA) index significantly correlated with the CSF-WBC (r = 0.453, P = 0.000), the IgA index (r = 0.446, P = 0.000), the albumin quotient (r = 0.262, P = 0.017), and the CSF-LDH (r = − 0.278, P = 0.012), respectively. In addition, there were correlations between the CSF-WBC and the IgA index (r = 0.329, P = 0.003), and between the CSF-WBC and the albumin quotient (r = 0.306, P = 0.005). Our results indicated that simultaneous testing of CSF-WBC levels, albumin quotient, IgA index and CSF-LDH can help predict the likelihood of NS in HIV-negative patients.

Objective:In this study, we set out to investigate the relationship between angiotensin-converting enzyme ( ACE) I/D polymorphism, serum ACE activity and bone mineral density (BMD) in older Chinese.Methods:A standardized, structured, face-to-face interview was performed to collect demographic information. BMD was measured using dual-energy X-ray absorptiometry (DXA). I/D genotypes of ACE were determined by polymerase chain reaction (PCR) amplification. Serum ACE activity was determined photometrically by a commercially available kinetic kit. Multiple linear regression analysis was used to examine the relationship between ACE I/D polymorphism, serum ACE activity and BMD.Results:A total of 1567 males and 1760 females were selected for analyzing the relationship between ACE I/D polymorphism and BMD. There was no significant difference in spine BMD, total hip BMD and femur neck BMD among different ACE I/D genotypes both in males and females. A total of 1699 males and 1739 females were selected for analyzing the relationship between serum ACE activity and BMD. There was also no significant difference in spine BMD, total hip BMD and femur neck BMD among different serum ACE activity groups both in males and females.Conclusion:There was no relationship between ACE I/D polymorphism, serum ACE activity and BMD in older Chinese.

Lead (Pb) has great toxicity to human beings and other livings. Although there are varied ways to rehabilitate the Pb contaminated area, phytoremediation of Pb pollution in arid lands is still a difficult task, it is therefore urgent to find and identify Pb tolerant plants in arid areas. The physiological responses and tolerance mechanisms to Pb stress (expressed as the Pb concentration, e.g., 0, 50, 150, 300, 600, 800, 1000 mg/L) were investigated for the xerophils Salsola passerina Bunge and Chenopodium album L. Results indicated that S. passerina exhibited higher Pb tolerance than Ch. album in terms of the seed germination rate, bio-activities of SOD and POD, and lower MDA production. There were two ways for S. passerina to reduce Pb toxicity in organism level, e.g., cell wall precipitation and state transfer of free Pb into anchorage. These findings demonstrate that S. passerina is a Pb tolerant species and may have potential application in phytoremediation of Pb contaminated arid lands.

Plastid gene expression is essential to embryogenesis in higher plants, but the underlying mechanism is obscure. Through molecular characterization of an embryo defective 16 (emb16) locus, here we report that the requirement of plastid translation for embryogenesis is dependent on the genetic background in maize (Zea mays). The emb16 mutation arrests embryogenesis at transition stage and allows the endosperm to develop largely normally. Molecular cloning reveals that Emb16 encodes WHIRLY1 (WHY1), a DNA/RNA binding protein that is required for genome stability and ribosome formation in plastids. Interestingly, the previous why1 mutant alleles (why1-1 and why1-2) do not affect embryogenesis, only conditions albino seedlings. The emb16 allele of why1 mutation is in the W22 genetic background. Crosses between emb16 and why1-1 heterozygotes resulted in both defective embryos and albino seedlings in the F1 progeny. Introgression of the emb16 allele from W22 into A188, B73, Mo17, Oh51a and the why1-1 genetic backgrounds yielded both defective embryos and albino seedlings. Similar results were obtained with two other emb mutants (emb12 and emb14) that are impaired in plastid protein translation process. These results indicate that the requirement of plastid translation for embryogenesis is dependent on genetic backgrounds, implying a mechanism of embryo lethality suppression in maize.