Consequences of plateau pika disturbance on plant-soil carbon and nitrogen in alpine meadows.

The presence of burrowing mammals can have extensive effects on plants and soils, creating bare soil patches in alpine meadows and potentially altering plant-soil carbon (C) and nitrogen (N). This study focuses on the plateau pika (Ochotona curzoniae) to examine the responses of plant-soil C and N to a small burrowing mammal from quadrat scale to plot scale. The density of active burrow entrances in disturbed plots was used as an indicator of the disturbance intensity of plateau pikas. The study found that the below-ground biomass (BGB) and its C and N, as well as soil C and N concentrations were significantly lower in bare soil areas than in vegetated areas and undisturbed plots. This shows that the quadrat scale limited the estimation of the C and N sequestration potential. Therefore, further research on the plot scale found that the disturbance by plateau pika significantly reduced plant biomass and BGB carbon stock. However, plateau pika did not affect soil C and N stocks or ecosystem C and N stocks. These findings suggest the bare soil patches formed by plateau pika caused plant and soil heterogeneity but had a trade-off effect on plant-soil C and N stocks at the plot scale. Nevertheless, moderate disturbance intensity increased the C and N sequestration potential in grassland ecosystems. These results provide a possible way to estimate how disturbance by small burrowing mammals affects C and N cycling in grassland ecosystems while accurately assessing the effects of small burrowing mammal densities on C and N in grassland ecosystems.

A 31-year (1990-2020) global gridded population dataset generated by cluster analysis and statistical learning.

Continuously monitoring global population spatial dynamics is crucial for implementing effective policies related to sustainable development, including epidemiology, urban planning, and global inequality. However, existing global gridded population data products lack consistent population estimates, making them unsuitable for time-series analysis. To address this issue, this study designed a data fusion framework based on cluster analysis and statistical learning approaches, which led to the generation of a continuous global gridded population dataset (GlobPOP). The GlobPOP dataset was evaluated through two-tier spatial and temporal validation to demonstrate its accuracy and applicability. The spatial validation results show that the GlobPOP dataset is highly accurate. The temporal validation results also reveal that the GlobPOP dataset performs consistently well across eight representative countries and cities despite their unique population dynamics. With the availability of GlobPOP datasets in both population count and population density formats, researchers and policymakers can leverage the new dataset to conduct time-series analysis of the population and explore the spatial patterns of population development at global, national, and city levels.

Targeting ADAM10 in Renal Diseases.

ADAM10 is part of the ADAM superfamily containing cell surface proteins with special structures and potential adhesion and protease domains. This paper provides a review of the specific effects of ADAM10 in kidney development as well as its relations with renal diseases. ADAM10 plays an important role in developing tissues and organs and the pathogenesis of multiple diseases. The catalytic mechanism of ADAM10 on kidney-related molecules, including Notch, epidermal growth factor receptors, tumor necrosis factor-α, CXCL16, E-cadherin, cell adhesion molecule 1, meprin and klotho. ADAM10 is also closely associated with the progress of glomerular diseases, acute kidney injury and renal fibrosis. It probably is a good therapeutic target for renal diseases.

Correlation between gut microbiota and glucagon-like peptide-1 in patients with gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) places both the mother and offspring at high risk of complications. Increasing evidence suggests that the gut microbiota plays a role in the pathogenesis of GDM. However, it is still unclear whether the gut microbiota is related to blood biochemical traits, particularly glucagon-like peptide-1 (GLP-1), in GDM patients. AIM: To explore the correlation between the gut microbiota and blood biochemical traits, particularly GLP-1, in GDM patients. METHODS: The V4 region of the 16S ribosomal ribonucleic acid (rRNA) gene was sequenced based on the fecal samples of 35 pregnant women with GDM and was compared to that of 25 pregnant women with normal glucose tolerance (NGT). RESULTS: The results showed that Ruminococcaceae_UCG-002, Ruminococcaceae_UCG-005, Clostri-dium_sensu_stricto_1, and Streptococcus were more abundant in the NGT group than in the GDM group. Bacteroides and Lachnoclostridium were more abundant in the GDM group than in the NGT group. Spearman's correlation analysis was performed to identify the relationships between microbiota genera and blood biochemical traits. Paraprevotella, Roseburia, Faecalibacterium, and Ruminococcaceae_UCG-002 were significantly negatively correlated with glucose. Ruminococcaceae_UCG-002 was significantly negatively correlated with hemoglobin A1c. Bacteroides was significantly positively correlated with glucose. Sutterella, Oscillibacter, and Bifidobacterium were significantly positively correlated with GLP-1. A random forest model showed that 20 specific genera plus glucose provided the best discriminatory power, as indicated by the area under the receiver operating characteristic curve (0.94). CONCLUSION: The results of this study reveal novel relationships between the gut microbiome, blood bio-chemical traits, particularly GLP-1, and GDM status. These findings suggest that some genera are crucial for controlling blood glucose-related indices and may be beneficial for GDM treatment. Alteration in the microbial composition of the gut may potentially serve as a marker for identifying individuals at risk of GDM.

A comparative study on ultrasound-guided elite, Mammotome, and core needle biopsy for diagnosing malignant breast masses.

Introduction: The present study aims to clarify the advantages and disadvantages of elite biopsy, to provide a reference for selecting the puncture method. Material and methods: A total of 802 patients with a BI-RADS grade ≥ 4, as evaluated by the molybdenum target, and measurable lesions revealed by colour Doppler ultrasound, who were admitted at our department from January 2017 to January 2018, were enrolled in the present study. These patients were randomly divided into three groups: elite, Mammotome and core needle biopsy groups. The pathological underestimation rate, diagnostic accordance rate, haematoma incidence rate, and costs of these three biopsy methods were compared. Results: The difference in diagnostic accordance rates between the elite biopsy group and core needle biopsy group was statistically significant (98.9% vs. 94.7%, p = 0.003), as well as between the Mammotome biopsy group and core needle biopsy group (99.6% vs. 94.7%, p < 0.001). The difference in pathological underestimation rates between the elite biopsy group and core needle biopsy group was statistically significant (7.2% vs. 37.3%, p < 0.001), as well as between the Mammotome biopsy group and core needle biopsy group (1.6% vs. 7.2%, p < 0.001). The difference between the Mammotome biopsy group and elite biopsy group was not statistically significant. The incidence of haematoma in the Mommotome, elite, and core needle groups was 15.9%, 13%, and 21.7%, respectively (13% vs. 21.7%, p = 0.021). Conclusions: Elite biopsy has a low rate of pathological underestimation and low incidence of haematoma, can improve the breast conserving rate, and has an affordable cost. As a biopsy method with high accuracy, safety, and economy, elite biopsy can be widely used in clinics.

Restriction of iron loading into developing seeds by a YABBY transcription factor safeguards successful reproduction in Arabidopsis.

Iron (Fe) storage in plant seeds is not only necessary for seedling establishment following germination but is also a major source of dietary Fe for humans and other animals. Accumulation of Fe in seeds is known to be low during early seed development. However, the underlying mechanism and biological significance remain elusive. Here, we show that reduced expression of Arabidopsis YABBY transcription factor INNER NO OUTER (INO) increases embryonic Fe accumulation, while transgenic overexpression of INO results in the opposite effect. INO is highly expressed during early seed development, and decreased INO expression increases the expression of NATURAL RESISTANCE-ASSOCIATED MACROPHAGE PROTEIN 1 (NRAMP1), which encodes a transporter that contributes to seed Fe loading. The relatively high embryonic Fe accumulation conferred by decreased INO expression is rescued by the nramp1 loss-of-function mutation. We further demonstrated that INO represses NRAMP1 expression by binding to NRAMP1-specific promoter region. Interestingly, we found that excessive Fe loading into developing seeds of ino mutants results in greater oxidative damage, leading to increased cell death and seed abortion, a phenotype that can be rescued by the nramp1 mutation. Taken together, these results indicate that INO plays an important role in safeguarding reproduction by reducing Fe loading into developing seeds by repressing NRAMP1 expression.

High level of H3K4 tri-methylation modification predicts poor prognosis in esophageal cancer.

Objectives: An increase in the trimethylation of lysine 4 of histone 3 (H3K4me3) has been reported to be involved in the development of several types of tumors. However, the level and role of H3K4me3 in human esophageal cancer (HEC) remain unknown. Here, we assessed the role and clinical significance of H3K4me3 in HEC. Methods: The level of H3K4me3 was determined in 15 pairs of HEC and paracancerous tissues by Western blotting. A tissue microarray including samples from 100 HEC patients was analyzed by immunohistochemistry to determine the relationship between the level of H3K4me3 and the clinicopathological features of HEC patients. Then, the levels of H3K4me3 in HEC cells were elevated via knockdown of inhibitor of growth family member 4(Ing4) expression. Finally, the prognostic significance of H3K4me3 levels in HEC patients was further analyzed. Results: We found that H3K4me3 levels were frequently elevated in HEC tissues compared with adjacent esophageal tissues, and elevated H3K4me3 was significantly associated with poor tumor differentiation (p =1.39×10-5) and advanced tumor stage (p=8.5×10-5). After Ing4 knockdown in HEC cells, we found that the cell proliferation, metastasis, invasion and colony formation abilities were enhanced compared to those in the control cells. Notably, we found that HEC patients with a high level of H3K4me3 exhibited an unfavorable 5-year survival rate compared to those with a low level of H3K4me3 (p=6.8×10-5). The univariate analysis showed that the tumor differentiation, TNM stage, and H3K4me3 level were predictors of the overall survival rate of HEC patients. In the multivariate analysis, tumor stage (p=0.015) and H3K4me3 level (p=0.034) were revealed to be independent parameters for predicting the prognosis of HEC patients. Conclusions: Thus, high levels of H3K4me3 may be used as a meaningful biomarker for HEC prognosis evaluation.

Dgcr8 deletion in the primitive heart uncovered novel microRNA regulating the balance of cardiac-vascular gene program

Primitive mammalian heart transforms from a single tube to a four-chambered muscular organ during a short developmental window. We found that knocking out global microRNA by deleting Dgcr8 microprocessor in Mesp1 cardiovascular progenitor cells lead to the formation of extremely dilated and enlarged heart due to defective cardiomyocyte (CM) differentiation. Transcriptome analysis revealed unusual upregulation of vascular gene expression in Dgcr8 cKO hearts. Single cell RNA sequencing study further confirmed the increase of angiogenesis genes in single Dgcr8 cKO CM. We also performed global microRNA profiling of E9.5 heart for the first time, and identified that miR-541 was transiently highly expressed in E9.5 hearts. Interestingly, introducing miR-541 back into microRNA-free CMs partially rescued their defects, downregulated angiogenesis genes and significantly upregulated cardiac genes. Moreover, miR-541 can target Ctgf and inhibit endothelial function. Our results suggest that microRNAs are required to suppress abnormal angiogenesis gene program to maintain CM differentiation.

Experimental study on the clinical effects of Xiaoru Sanjie Jiaonang on mammary glands hyperplasia and ki-67.

OBJECTIVE: This study aims to observe the effect and mechanism of Xiaoru Sanjie Jiaonang (XRSJ) on the treatment of mammary gland hyperplasia, and provide a theoretical basis and clinical evidence for clinical expansion. METHODS: Japanese white rabbits were randomly divided into three groups: high-, middle- and low-dose groups; Xiaoyao Pill group; model control group; normal control group. The observation points were as follows: before XRSJ administration, three months after XRSJ administration, and three months after XRSJ discontinuance. Changes in breast height, morphological changes of the mammary gland under a light and electron microscope, and the expression of ki-67 were observed. At the same time, patients diagnosed with mammary gland hyperplasia at an Outpatient Clinic were selected and divided into treatment groups. These patients received XRSJ and Xiaoyao Pills, respectively, for one month, while patients in the control group did not receive any drug treatment. Clinical efficacy was observed while rechecking at the Outpatient Clinic after three months. Treatment with a therapeutic dose of XRSJ could significantly reduce breast height, decrease the number of lobules and acini in hyperplastic mammary glands and the layer number of ductal glandular epithelial cells, substantially lower the content of serum estradiol (E2), significantly downregulate the expression of ki-67 protein in mammary tissues, and inhibit mammary gland hyperplasia. CONCLUSION: XRSJ treatment can relieve mammary tissue hyperplastic lesions, reduce E2 levels and downregulate the expression of ki-67. It has a significant therapeutic effect on mammary gland hyperplasia.

shRNA-induced silencing of Ras-related C3 botulinum toxin substrate 1 inhibits the proliferation of colon cancer cells through upregulation of BAD and downregulation of cyclin D1.

Ras-related C3 botulinum toxin substrate 1 (RAC1) is a member of the Rho family of small GTPases. Recent studies have reported that RAC1 serves an important role in colon cancer cell proliferation. The present study aimed to investigate the effects of RAC1 knockdown on cell proliferation, cell cycle progression and apoptosis of colon cancer cells. Lentivirus­mediated short hairpin RNA (shRNA) was used to knockdown RAC1 expression in colon cancer cell lines, and cell proliferation, apoptosis, cell cycle progression were evaluated by MTT assays and flow cytometry. The differences in mRNAs expression were identified between RAC1-knockdown cells and control cells using a mRNA microarray, following which quantitative PCR (qPCR) and western blot were employed to confirm the results of the mRNA microarray. The proliferative ability of colon cancer cells was significantly decreased following RAC1 knockdown, and RAC1 knockdown increased the apoptotic rate and enhanced cell cycle arrest at G1 phase in colon cancer cells. In addition, >1,200 known genes were demonstrated to be involved in RAC1­associated tumorigenic functions in SW620 colon cancer cells, as determined by gene chip analysis; these genes were associated with cell proliferation, cell cycle, apoptosis and metastasis. Furthermore, western blot analysis indicated that cyclin D1 was downregulated, whereas B­cell lymphoma 2­associated agonist of cell death (BAD) was upregulated following RAC1 knockdown in colon cancer cells. In conclusion, RAC1 silencing may suppress the proliferation of colon cancer cells by inducing apoptosis and cell cycle arrest. In addition, a large number of genes were revealed to be involved in the process, including BAD, which was upregulated and cyclin D1, which was downregulated. Further studies on these differentially expressed genes may provide a better understanding of the potential roles of RAC1 in colon carcinogenesis.

All-trans retinoic acid enhances cytotoxicity of CIK cells against human lung adenocarcinoma by upregulating MICA and IL-2 secretion.

To determine the growth inhibition capability of all-trans retinoic acid (ATRA) with cytokine-induced killer cells (CIKs), we evaluated their effects, alone and in combination, on human lung carcinoma A549 cells. CIKs treated with ATRA significantly inhibited cell growth. Additionally, CIK with ATRA synergistically inhibited migration and invasiveness, colony formation of A549 and NCI-H520 cells. Furthermore, analysis of apoptosis markers Bcl-2, Bax, Survivin and cleaved Caspase-3 showed that Bcl-2 and Survivin mRNA levels significantly decreased, and that Bax mRNA significantly increased, in the CIK + ATRA-treated cells, with corresponding effects on their respective proteins. The involved mechanisms may be associated with upregulated expression of MHC class I-Related Chain (MICA) and interleukin (IL)-2. These results suggest that administration of combined CIK and ATRA is a potentially novel treatment for lung carcinoma.

Expression profile of circular RNAs in human gastric cancer tissues.

Circular RNAs (circRNAs) represent a newly identified class of non­coding RNA molecules, which interfere with gene transcription by adsorbing microRNAs (miRNAs). CircRNAs serve important roles in disease development and have the potential to serve as a novel class of biomarkers for clinical diagnosis. However, the role of circRNAs in the occurrence and development of gastric cancer (GC) remains unclear. In the present study, the expression profiles of circRNAs were compared between GC and adjacent normal tissues using a circRNA microarray, following which quantitative polymerase chain reaction (qPCR) was used to confirm the results of the circRNA microarray. Compared with the adjacent, normal mucosal tissues, 16 circRNAs were upregulated and 84 circRNAs were downregulated in GC. A total of 10 circRNAs were selected for validation in three pairs of GC and adjacent noncancerous tissues. The qPCR results were consistent with the findings of the microarray­based expression analysis. Of the circRNAs studied, only circRNA­0026 (hsa_circ_0000026) exhibited significantly different expression in GC (2.8­fold, P=0.001). Furthermore, online Database for Annotation, Visualization and Integrated Discovery annotation was used to predict circRNA­targeted miRNA­gene interactions. The analysis revealed that circRNA­0026 may regulate RNA transcription, RNA metabolism, gene expression, gene silencing and other biological functions in GC. In conclusion, differential expression of circRNAs may be associated with GC tumorigenesis, and circRNA­0026 is a promising biomarker for GC diagnosis and targeted therapy.

An inducible CRISPR-ON system for controllable gene activation in human pluripotent stem cells

Human pluripotent stem cells (hPSCs) are an important system to study early human development, model human diseases, and develop cell replacement therapies. However, genetic manipulation of hPSCs is challenging and a method to simultaneously activate multiple genomic sites in a controllable manner is sorely needed. Here, we constructed a CRISPR-ON system to efficiently upregulate endogenous genes in hPSCs. A doxycycline (Dox) inducible dCas9-VP64-p65-Rta (dCas9-VPR) transcription activator and a reverse Tet transactivator (rtTA) expression cassette were knocked into the two alleles of the AAVS1 locus to generate an iVPR hESC line. We showed that the dCas9-VPR level could be precisely and reversibly controlled by the addition and withdrawal of Dox. Upon transfection of multiplexed gRNA plasmid targeting the NANOG promoter and Dox induction, we were able to control NANOG gene expression from its endogenous locus. Interestingly, an elevated NANOG level promoted naïve pluripotent gene expression, enhanced cell survival and clonogenicity, and enabled hESCs to integrate with the inner cell mass (ICM) of mouse blastocysts in vitro. Thus, iVPR cells provide a convenient platform for gene function studies as well as high-throughput screens in hPSCs.

Differential regulation of H3S10 phosphorylation, mitosis progression and cell fate by Aurora Kinase B and C in mouse preimplantation embryos

Coordination of cell division and cell fate is crucial for the successful development of mammalian early embryos. Aurora kinases are evolutionarily conserved serine/threonine kinases and key regulators of mitosis. Aurora kinase B (AurkB) is ubiquitously expressed while Aurora kinase C (AurkC) is specifically expressed in gametes and preimplantation embryos. We found that increasing AurkC level in one blastomere of the 2-cell embryo accelerated cell division and decreasing AurkC level slowed down mitosis. Changing AurkB level had the opposite effect. The kinase domains of AurkB and AurkC were responsible for their different ability to phosphorylate Histone H3 Serine 10 (H3S10P) and regulate metaphase timing. Using an Oct4-photoactivatable GFP fusion protein (Oct4-paGFP) and fluorescence decay after photoactivation assay, we found that AurkB overexpression reduced Oct4 retention in the nucleus. Finally, we show that blastomeres with higher AurkC level elevated pluripotency gene expression, which were inclined to enter the inner cell mass lineage and subsequently contributed to the embryo proper. Collectively, our results are the first demonstration that the activity of mitotic kinases can influence cell fate decisions in mammalian preimplantation embryos and have important implications to assisted reproduction.

Analysis of antibacterials drug for department of respiration in old patients / 药学实践杂志

Objective To investigate the utility of antibiotics in elderly patients of respiratory department in No. 210 Hospital of PLA, and to understand the rational use of antibiotics in respiratory department. Methods A total of 534 patients >60 in respiratory department of our hospital from September to December in 2011 were randomly selected. The usage rate of antibiotics, the types that used, dosing routes and so on were recorded and analyzed. Some rational suggestions were dis‐cussed put forward. Results ① The usage rate of antibiotics was 97%. ② A total of 21 kinds of antibiotics had been used. The types of drugs are Amp C, levofloxacin, β‐lactamase inhibitors, nitromidazoles, aminoglycoside, antifungals, MALS, lincomycin. The percentage rate of the top three antibiotics were 59. 97%, 17. 30% and 7. 58%. ③ There were some problems in the usage of antibiotics, such as no indication of medicine, high use rate of antibiotics, improper variety selection, dosing routes and drug intervals, irrational use of drugs combinations. Conclusion The application rate of antibiotics was 97%, there was some illegiti‐mate phenomenon in the use of antibiotics. Some attentions should be paid to the rational use of antibiotics in elderly patients, and to raise the rational use rate of antibiotics.

Aneuploidy in pluripotent stem cells and implications for cancerous transformation

Owing to a unique set of attributes, human pluripotent stem cells (hPSCs) have emerged as a promising cell source for regenerative medicine, disease modeling and drug discovery. Assurance of genetic stability over long term maintenance of hPSCs is pivotal in this endeavor, but hPSCs can adapt to life in culture by acquiring non-random genetic changes that render them more robust and easier to grow. In separate studies between 12.5% and 34% of hPSC lines were found to acquire chromosome abnormalities over time, with the incidence increasing with passage number. The predominant genetic changes found in hPSC lines involve changes in chromosome number and structure (particularly of chromosomes 1, 12, 17 and 20), reminiscent of the changes observed in cancer cells. In this review, we summarize current knowledge on the causes and consequences of aneuploidy in hPSCs and highlight the potential links with genetic changes observed in human cancers and early embryos. We point to the need for comprehensive characterization of mechanisms underpinning both the acquisition of chromosomal abnormalities and selection pressures, which allow mutations to persist in hPSC cultures. Elucidation of these mechanisms will help to design culture conditions that minimize the appearance of aneuploid hPSCs. Moreover, aneuploidy in hPSCs may provide a unique platform to analyse the driving forces behind the genome evolution that may eventually lead to cancerous transformation.

Phosphorescent chemosensor for Hg2+ and acetonitrile based on iridium(III) complex.

A new phosphorescent chemosensor for Hg(2+) and acetonitrile (MeCN) based on iridium(III) complex Ir(dpp)(2)(dtc) (Ir1, dppH = 4,6-diphenylpyrimidine, dtcH = diethyl dithiocarbamic acid) was realized. Upon addition of a tetrahydrofuran (THF) solution of Hg(2+), the dichloromethane (DCM) solution of Ir1 gave a visual color change and significant fluorescent quenching. When MeCN was added, a new fluorescent emission emerged, which constituted a selective MeCN phosphorescent chemosensor. Complex Ir1 has been developed as an AND logic gate with Hg(2+) and MeCN as inputs.

Efficacy of transvenous embolization of cavernous sinus dural arteriovenous fistula with Onxy or in combination with detachable coils / 中国脑血管病杂志

Objective: To investigate the safety and effectiveness of transvenous embolization of cavernous sinus dural arteriovenous fistula with Onxy or in combination with detachable coils. Methods: Twelve patients with cavernous sinus dural arteriovenous fistula treated by transvenous embolization from February 2007 to December 2010 were analyzed retrospectively. Ten patients were treated via the inferior petrosal sinus approach, 2 were treated via the vein-superior ophthalmic vein approach. Eight patients used Onyx alone, and 4 used Onxy in combination with detachable coils. Results: Circled digit oneAngiography showed complete occlusion in 10 patients immediately after treatment, small amount of residues remained in 2 patients. Six patients were cured with Onyx embolization alone, 2 were improved, 2 were cured with Onyx in combination with detachable coils embolization, and 2 were improved. The total effective rate was 100%, the total cure rate was 66.7%, and none of the patients worsened or died. Circled digit twoTwo patients had intraoperative bradycardia, 3 had postoperative orbital ache. Circled digit threeAll patients received clinical follow-up for 6 to 32 months and no recurrent and worsened were found. Conclusion: The clinical efficacy of transvenous embolization of cavernous sinus dural arteriovenous fistula with Onxy or in combination with detachable coils is effective and safe.

Mechanism and methods to induce pluripotency

Pluripotent stem cells are able to self-renew indefinitely and differentiate into all types of cells in the body. They can thus be an inexhaustible source for future cell transplantation therapy to treat degenerative diseases which currently have no cure. However, non-autologous cells will cause immune rejection. Induced pluripotent stem cell (iPSC) technology can convert somatic cells to the pluripotent state, and therefore offers a solution to this problem. Since the first generation of iPSCs, there has been an explosion of relevant research, from which we have learned much about the genetic networks and epigenetic landscape of pluripotency, as well as how to manipulate genes, epigenetics, and microRNAs to obtain iPSCs. In this review, we focus on the mechanism of cellular reprogramming and current methods to induce pluripotency. We also highlight new problems emerging from iPSCs. Better understanding of the fundamental mechanisms underlying pluripotenty and refining the methodology of iPSC generation will have a significant impact on future development of regenerative medicine.