A global systematic review and meta-analysis of prevalence of repeat induced abortion and correlated risk factors.

As a significant public health problem, repeat-induced abortion is a challenge to women's sexual and reproductive health. Despite many studies in this area, they lack consensus regarding risk factors for repeat-induced abortion. A global systematic review was conducted to analyze prevalence of repeat-induced abortion among women worldwide and determine correlated risk factors. Three electronic databases were systematically searched. Data on prevalence of repeat-induced abortion and related factors were extracted and pooled using a meta-analysis and narrative approach. Sixty-five (which were published between 1972 and 2021) of 3,706 articles were included, consisting of a total of 535,308 participants from 25 countries. The overall pooled prevalence of repeat-induced abortion was 31.3 percent (95 percent CI 25.7 percent, 36.9 percent). Of 57 exposures extracted, 33 factors were significantly correlated with repeat induced abortion, comprising 14 individual demographic factors (i.e. age, education, marriage, etc.), three reproductive history-related factors (i.e. parity, age at sexual debut, and time since sexual debut), five contraception-related factors (i.e. contraceptive use at sexual debut, attitude toward contraceptive use, etc.), four abortion-related factors (i.e. age at the index abortion, previous abortion at the index abortion, etc.), and seven sexual partner-related factors (i.e. multiple sexual partners, sexual partner's age, etc.). The study findings highlight the problem of repeat-induced abortion worldwide and suggest the need for government and civil society in each country to increase efforts to reduce the alarming risk of repeat-induced abortion among women and improve their sexual and reproductive health.

An explainable integrated optimization methodology for source apportionment of ambient particulate matter components.

Source apportionment of fine particulate matter (PM2.5) components is crucial for air pollution control. Prediction accuracies by the chemical transport model (CTM) significantly affect source apportionment results. Many efforts have been made to improve source apportionment results based on the CTM using mathematical algorithms, but the reasons for uncertainties in source apportionment results are less concerned. Here, an integrated optimization methodology is developed to quantify deviations from emission inventory and chemical mechanism in the model for improving prediction and source apportionment accuracies. Emission deviations of primary aerosols and gaseous pollutants are firstly calculated by an optimization algorithm with observation and receptor model constraints. Emission inventory is then adjusted for a new CTM simulation. Deviations from chemical mechanism for secondary conversions are evaluated by biases between observations and new predictions. Source apportionment results are adjusted according to both emission and chemical mechanism deviations. A winter month in 2016 at the Qingpu supersite in eastern China is selected as a case study. Results show that our integrated optimization methodology can successfully adjust emissions to pull original predictions towards observations. Total deviations of emissions for elemental carbon, organic carbon, primary sulfate, primary nitrate, primary ammonium, sulfur dioxide (SO2), nitrogen oxides (NOx) and ammonia (NH3) are estimated +59.6%, +95.9%, +72.9%, +82.2%, +75.9%, -6.4%, +67.6% and -17.6%, respectively. Also, major directions of deviations from chemical mechanisms can be captured. Deviations from SO2 to secondary sulfate, nitrogen dioxide (NO2) to secondary nitrate and NH3 to secondary ammonium conversions are estimated -77.3%, +27.1% and -38.8%, respectively. Consequently, source apportionment results are significantly improved. This developed methodology provides an efficient way to quantify deviations from emissions and chemical mechanisms to improve source apportionment for air pollution management.

Contamination characteristics, source analysis and health risk assessment of heavy metals in the soil in Shi River Basin in China based on high density sampling.

To explore the contamination of heavy metals in the Shi River Basin soil in China, a high density sampling of surface soil was conducted. In this study, an absolute principal component scores multiple linear regression model (APCS-MLR) was used to identify the sources of heavy metals in the soil and quantify their amounts. The methods to assess the heavy metals included a fuzzy synthetic evaluation, index and health risk assessment. The results show that heavy metals are relatively rich southwest of the study area. Their levels may be affected by natural sources, such as parent materials. The pollution caused by human factors cannot be ignored, and it is primarily influenced by traffic emissions and processing sources, which contribute 62.6%, followed by agricultural sources, such as pesticides and fertilizers, that contribute 21.1%. The risk assessment indicated that the study area was slightly to moderately polluted. All heavy metals pose higher carcinogenic and other health risks to children than adults, and ingestion is the main way that these pollutants enter the body. The carcinogenic risk of children owing to Cr from natural sources merits further study, while the carcinogenic risk to adults and the non-carcinogenic risk to both adults and children are at acceptable levels. Transportation and industrial processing sources are the main cause of the non-carcinogenic risk. The results could provide reference for reducing heavy metal pollution in the soil.

Prevalence and risk factors for repeat induced abortion among Chinese women: a systematic review and meta-analysis.

OBJECTIVES: Repeat induced abortion is a significant public health problem in China. International knowledge about repeat induced abortion and its associated risk factors in Chinese women is scarce, and existing studies are hard to access for international scholars because most are published in Chinese. A systematic review was conducted to analyse the prevalence of repeat induced abortion among Chinese women and determine correlated risk factors. METHODS: Seven electronic databases were systematically searched. Data on the prevalence of repeat induced abortion and related factors were extracted and pooled using a meta-analysis and narrative approach. RESULTS: Of 2458 articles retrieved from seven databases, 21 were included in the study. The overall pooled prevalence of repeat induced abortion was 43.1% (95% confidence interval 36.7%, 49.5%). Of 25 exposures extracted, 15 factors were significantly correlated with repeat induced abortion, comprising seven individual demographic factors (i.e., age, education, employment, migrant status, parity, unhealthy lifestyle habits and region of residence), four reproductive health- and contraception-related factors (i.e., age at sexual debut, history of sexual activity, contraceptive knowledge and having a regular sexual life) and four sexual partner-related factors (i.e., multiple sexual partners, age of sexual partner, educational level of sexual partner and cohabitation with sexual partner). CONCLUSION: The study findings highlight the problem of repeat induced abortion in China and suggest the need for government and civil society to increase efforts to reduce the alarming risks of repeat induced abortion in Chinese women and make them and their sexual partners more aware and protective of their sexual and reproductive health.

SMA1, a homolog of the splicing factor Prp28, has a multifaceted role in miRNA biogenesis in Arabidopsis.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that repress gene expression. In plants, the RNase III enzyme Dicer-like (DCL1) processes primary miRNAs (pri-miRNAs) into miRNAs. Here, we show that SMALL1 (SMA1), a homolog of the DEAD-box pre-mRNA splicing factor Prp28, plays essential roles in miRNA biogenesis in Arabidopsis. A hypomorphic sma1-1 mutation causes growth defects and reduces miRNA accumulation correlated with increased target transcript levels. SMA1 interacts with the DCL1 complex and positively influences pri-miRNA processing. Moreover, SMA1 binds the promoter region of genes encoding pri-miRNAs (MIRs) and is required for MIR transcription. Furthermore, SMA1 also enhances the abundance of the DCL1 protein levels through promoting the splicing of the DCL1 pre-mRNAs. Collectively, our data provide new insights into the function of SMA1/Prp28 in regulating miRNA abundance in plants.

The Stabilizing Excipients in Dry State Therapeutic Phage Formulations.

Phage therapy has gained prominence due to the increasing pathogenicity of "super bugs" and the rise of their multidrug resistance to conventional antibiotics. Dry state formulation of therapeutic phage is attractive to improve their "druggability" by increasing their shelf life, improving their ease of handling, and ultimately retaining their long-term potency. The use and selection of excipients are critical to stabilize phage in solid formulations and protect their viability from stresses encountered during the solidification process and long-term storage prior to use. Here, this review focuses on the current classes of excipients used to manufacture dry state phage formulations and their ability to stabilize and protect phage throughout the process, as discussed in the literature. We provide perspective of outstanding challenges involved in the formulation of dry state phage. We suggest strategies to improve excipient identification and selection, optimize the potential excipient combinations to improve phage viability during formulation, and evaluate new methodologies that can provide greater insight into phage-excipient interactions to improve design criteria to improve formulation of dry state phage therapeutics. Addressing these challenges opens up new opportunities to re-design and re-imagine phage formulations for improved efficacy as a pharmaceutical product.

PEGylation of Tobramycin Improves Mucus Penetration and Antimicrobial Activity against Pseudomonas aeruginosa Biofilms in Vitro.

Pseudomonas aeruginosa is the predominant pathogen in the persistent lung infections of cystic fibrosis (CF) patients among other diseases. One of the mechanisms of resistance of P. aeruginosa infections is the formation and presence of biofilms. Previously, we demonstrated that PEGylated-tobramycin (Tob-PEG) had superior antimicrobial activity against P. aeruginosa biofilms compared to tobramycin (Tob). The goal of this study was to optimize the method of PEGylation of Tob and assess its activity in an in vitro CF-like mucus barrier biofilm model. Tob was PEGylated using three separate chemical conjugation methods and analyzed by 1H NMR. A comparison of the Tob-PEG products from the different conjugation methods showed significant differences in the reduction of biofilm proliferation after 24 h of treatment. In the CF-like mucus barrier model, Tob-PEG was significantly better than Tob in reducing P. aeruginosa proliferation after only 5 h of treatment ( p < 0.01). Finally, Tob-PEG caused a reduction in the number of surviving P. aeruginosa biofilm colonies higher than that of Tob ( p < 0.0001). We demonstrate the significantly improved antimicrobial activity of Tob-PEG against P. aeruginosa biofilms compared to Tob using two PEGylation methods. Tob-PEG had better in vitro activity compared to that of Tob against P. aeruginosa biofilms growing in a CF-like mucus barrier model.

PEGylated Chitosan for Nonviral Aerosol and Mucosal Delivery of the CRISPR/Cas9 System in Vitro.

Chitosan has been widely employed to deliver nucleic acids such as siRNA and plasmids. However, chitosan-mediated delivery of a gene-editing system has not been reported yet. In this study, poly(ethylene glycol) monomethyl ether (mPEG) was conjugated to chitosan with different molecular weights (low molecular weight and medium molecular weight chitosan) achieving a high degree of substitution as identified by Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H NMR) spectra. PEGylated chitosan/pSpCas9-2A-GFP nanocomplexes were formed at different N/ P (amine group to phosphate group) ratios and characterized in terms of size and zeta potential. The nanocomplexes developed showed the capability to protect loaded nucleic acids from DNase I digestion and from the stresses of nebulization. In addition, we demonstrated that the PEG conjugation of chitosan improved the mucus-penetration capability of the formed nanocomplexes at N/ P ratios of 5, 10, 20, and 30. Finally, PEGylated low molecular weight chitosan nanocomplexes showed optimal transfection efficiency at an N/ P ratio of 20, while PEGylated medium molecular weight chitosan nanocomplexes showed an optimal transfection efficiency at an N/ P ratio of 5 at pH 6.5 and 6.8. This study established the basis for the delivery of a gene-editing system by PEGylated chitosan nanocomplexes.

CIAPIN1 targets Na⁺/H⁺ exchanger 1 to mediate MDA-MB-231 cells' metastasis through regulation of MMPs via ERK1/2 signaling pathway.

Cytokine-induced antiapoptotic inhibitor 1 (CIAPIN1) was recently identified as an essential downstream effector of the Ras signaling pathway and has been confirmed to be closely associated with various malignant tumors. However, its potential role in regulating breast cancer metastasis remains unclear. Matrix metalloproteinases (MMPs) are a broad family of zinc-biding endopeptidases that participate in the extracellular matrix (ECM) degradation that accompanies cancer cell invasion, metastasis and angiogenesis. In this study, we found up-regulation of CIAPIN1 by lentiviral expression vector inhibited the migration, invasion and MMPs expression of MDA-MB-231 cells. Further, CIAPIN1 over-expression decreased NHE1 (Na(+)/H(+) exchanger 1) expression and ERK1/2 phosphorylation. Importantly, treating CIAPIN1 over-expressed MDA-MB-231 cells with the NHE1 specific inhibitor, Cariporide, further inhibited the metastatic capacity, MMPs expression and phosphorylated ERK1/2. Treatment with the MEK1 specific inhibitor, PD98059, induced nearly the same suppression of CIAPIN1 over-expression-dependent migration, invasion and MMPs expression as was observed with Cariporide. Further, Cariporide and PD98059 synergistically suppressed migration, invasion and MMPs expression of CIAPIN1 over-expressed MDA-MB-231 cells. Thus, our results revealed the mechanism by which CIAPIN1 targeted NHE1 to mediate migration and invasion of MDA-MB-231 cells through regulation of MMPs via ERK1/2 signaling pathway.

Down-regulation of lipocalin 2 suppresses the growth of human lung adenocarcinoma through oxidative stress involving Nrf2/HO-1 signaling.

Lipocalin 2 (LCN2), a multifunctional secretory protein known as neutrophil gelatinase-associated lipocalin (NGAL), is expressed in a variety of cancers. However, little is known about the biological functions of NGAL in the development of lung adenocarcinoma. In the present study, we primarily found that NGAL expression was up-regulated in human lung adenocarcinoma tissues. Additionally, depletion of NGAL expression decreased the ability of cell proliferation and induced cell apoptosis. Furthermore, with the addition of N-acetylcysteine, a scavenger of reactive oxygen species (ROS), it was found that NGAL depletion was sufficient to cause apoptosis of lung adenocarcinoma cells by generating ROS through the inhibition of the nuclear factor E2-related factor 2/heme oxygenase-1 anti-oxidant pathway. Finally, the effect of NGAL down-regulation on the growth of human lung adenocarcinoma was determined in BALB/c nude mice. These findings demonstrate that NGAL may be a potential therapy target for patients with lung adenocarcinoma.

Phase interrogation used for a wireless passive pressure sensor in an 800 °C high-temperature environment.

A wireless passive pressure measurement system for an 800 °C high-temperature environment is proposed and the impedance variation caused by the mutual coupling between a read antenna and a LC resonant sensor is analyzed. The system consists of a ceramic-based LC resonant sensor, a readout device for impedance phase interrogation, heat insulating material, and a composite temperature-pressure test platform. Performances of the pressure sensor are measured by the measurement system sufficiently, including pressure sensitivity at room temperature, zero drift from room temperature to 800 °C, and the pressure sensitivity under the 800 °C high temperature environment. The results show that the linearity of sensor is 0.93%, the repeatability is 6.6%, the hysteretic error is 1.67%, and the sensor sensitivity is 374 KHz/bar. The proposed measurement system, with high engineering value, demonstrates good pressure sensing performance in a high temperature environment.

Decreased intracellular pH induced by cariporide differentially contributes to human umbilical cord-derived mesenchymal stem cells differentiation.

BACKGROUND/AIMS: Na+/H+ exchanger 1 (NHE1) is an important regulator of intracellular pH (pHi). High pHi is required for cell proliferation and differentiation. Our previous study has proven that the pHi of mesenchymal stem cells is higher than that of normal differentiated cells and similar to tumor cells. NHE1 is highly expressed in both mesenchymal stem cells and tumor cells. Targeted inhibition of NHE1 could induce differentiation of K562 leukemia cells. In the present paper we explored whether inhibition of NHE1 could induce differentiation of mesenchymal stem cells. METHODS: MSCs were obtained from human umbilical cord and both the surface phenotype and functional characteristics were analyzed. Selective NHE1 inhibitor cariporide was used to treat human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). The pHi and the differentiation of hUC-MSCs were compared upon cariporide treatment. The putative signaling pathway involved was also explored. RESULTS: The pHi of hUC-MSCs was decreased upon cariporide treatment. Cariporide up-regulated the osteogenic differentiation of hUC-MSCs while the adipogenic differentiation was not affected. For osteogenic differentiation, ß-catenin expression was up-regulated upon cariporide treatment. CONCLUSION: Decreased pHi induced by cariporide differentially contributes to hUC-MSCs differentiation.

[Application of European five-dimensional health questionnaire for the quality of life among the population over 60 years old in Dalian city].

OBJECTIVE: Using European five-dimensional health questionnaire (EQ-5D) to study the quality of life among the population over 60 years old in Dalian city and analyze the influence factors. METHOD: In 2013, multi-stage stratified cluster random sampling method and EQ-5D questionnaire were used to investigate the status of 4 081 participants over the age of 60 in Dalian. The questionnaire contained EQ-5D health describing system and the VAS. The EQ-5D index and EQ-VAS score of the study objects were calculated and the participants' quality of life and impact factors were analyzed. RESULT: Women's percentage of "having difficulty" in 5 dimensionalities was 18.1% (373/2 059), 12.6% (264/2 059), 16.2% (334/2 059), 32.0% (659/2 059), 17.5% (371/2 059) respectively, men' percentage of "having difficulty" in 5 dimensionalities was 13.3% (269/2 022), 10.2% (218/2 022), 12.5% (253/2 022), 23.1% (467/2 022), 13.7% (77/2 022) respectively, and the difference was significant (P < 0.05). The EQ-5D index and VAS score of men was (0.82 ± 0.30), (72.75 ± 16.26), higher than those of women ( (0.79 ± 0.33), (70.79 ± 16.64 )) and the difference was significant (P < 0.05). The score of quality of life who were married was (0.82 ± 0.28) and (73.27 ± 16.60).With age increasing, the elders' quality of life score decreased, and with education level increasing, the elders' quality of life score increased (P < 0.05). CONCLUSION: The quality of life of the elders in Dalian city was kind of good, and it could be impacted by genders, marital status, education levels and the chronic diseases.

A rare case of Baker's cysts with hematoma of the lower calf treated with arthroscopic internal drainage combined with intramuscular dissection.

Popliteal cysts, also termed Baker's cysts, are clinically common cystic lesions in the popliteal fossa. Typically, the contents of a ruptured cyst tend to spread into the myofascial interfaces in any direction, most commonly inferomedially or into a palpable superficial position. However, to our knowledge, reports of Baker's cysts dissecting into the deep intermuscular septum of the lower calf are extremely rare. We present here the details of the successful treatment through arthroscopy combined with lower calf incision of a patient who sustained hematoma of the knee and lower calf secondary to Baker's cyst rupture. Given the rarity of this disease in China, we present this case report to improve our understanding of the disease and avoid misdiagnosis and provide evidence for its clinical treatment, management, and prognosis.

[Progress on study of factors influencing the prognosis and complications of surgery for discoid meniscus injury in children].

The discoid meniscus is a common congenital meniscal malformation that is prevalent mainly in Asians and often occurs in the lateral discoid meniscus. Patients with asymptomatic discoid meniscus are usually treated by conservative methods such as observation and injury avoidance, while patients with symptoms and tears need to be treated surgically. Arthroscopic saucerization combined with partial meniscectomy and meniscus repair is the most common surgical approach., and early to mid-term reports are good. The prognostic factors are the patient's age at surgery、follow-up time and type of surgery. Some patients experience complications such as prolonged postoperative knee pain, early osteoarthritis, retears and Osteochondritis dissecans. The incidence of prolonged postoperative knee pain was higher and the incidence of Osteochondritis dissecans was the lowest. Retears of the lateral meniscus is the main reason for reoperation.

Tibial tubercle avulsion fracture following preexisting Osgood-Schlatter disease in an adolescent: a case report.

Tibial tubercle avulsion fractures (TTAFs) are rare but typical in children and adolescents and Osgood-Schlatter disease (OSD) may be involved in their pathogenesis. However, few publications have reported the relationship between OSD and TTAF. A 16-year-old healthy male adolescent presented with pain, swelling and limited range of motion of the right knee following sudden acceleration while running. Based on the radiographic evidence, the patient was diagnosed with an avulsion fracture of the right tibial tubercle and OSD. Open reduction and internal fixation were performed using two cannulated screws and two Kirschner wires. The patient returned to preinjury activity levels at the 12-month follow-up postoperatively. This case report aimed to highlight this unique injury pattern. For patients with TTAFs, not only should the fracture be treated, but the cause of the fracture, such as OSD, should also be given appropriate treatment.

Senolytic Therapy Enabled by Senescent Cell-Sensitive Biomimetic Melanin Nano-Senolytics.

Cellular senescence is a significant risk factor for aging and age-related diseases (ARD). The canonical senolytics Dasatinib and Quercetin (DQ) have shown promise in clearing senescent cells (SnCs); however, the lack of selectivity poses a challenge in achieving optimal outcomes. Despite the recent occurrence of nanomaterial-based approaches targeting SnCs, limited therapeutic effects, and potential toxicity still remain a major concern. Herein, a "double locks-like" nanoplatform is developed that integrated Galactan coating and mesoporous polydopamine to encase the senolytic drug DQ. By this way, DQ is only released in SnCs that are featured with higher levels of ß-galactosidase (ß-gal) and low PH. Additionally, the nanoparticles are equipped with 2,2,6,6-Tetramethylpiperidine-1-oxyl (Tempo) to gain enhanced photothermal converting potential. Consequently, the synthesized nanosenolytics demonstrate remarkable specificity and efficacy in eradicating SnCs, and accordingly reverse pulmonary fibrosis in mice without affecting normal tissues. Upon exposure of near-infrared (NIR) light, the nanoparticles demonstrate to efficiently remove senescent tumor cells inducted by chemotherapy, thereby hindering the outgrowth and metastasis or breast cancer. Collectively, the present study develops an "On/Off" switchable nanoplatform in response to SnCs, and produces a more safe, efficient, and feasible way to delay aging or alleviate age-associated diseases.

Study on the quality of Corydalis Rhizoma in Zhejiang based on multidimensional evaluation method.

ETHNOPHARMACOLOGICAL RELEVANCE: The quality requirements of Corydalis Rhizoma (CR) in different producing areas are uniform, resulting in uneven efficacy. As a genuine producing area, the effective quality control of CR in Zhejiang Province (ZJ) could provide a theoretical basis for the rational application of medicinal materials. AIM OF THE STUDY: The purpose of this study was to effectively distinguish the CR inside and outside ZJ, and provided a theoretical basis for the quality control and material basis research of ZJ CR. MATERIALS AND METHODS: The core components of ZJ CR could be identified by HPLC combined with chemometrics screening, and the quality of CR from different producing areas was evaluated by a genetic algorithm-back propagation (GA-BP) neural network. Chromaticity and near-infrared (NIR) spectroscopy were used to identify CR inside and outside ZJ, and rapid content prediction was realized. The analgesic effect of CR in different regions was compared by a zebrafish analgesic experiment. Analgesic experiments in rats and analysis of the research status of quality components were used to screen the quality control components of ZJ CR. RESULTS: The contents of palmatine hydrochloride (YSBMT), dehydrocorydaline (TQZJJ), tetrahydropalmatine (YHSYS), tetrahydroberberine (SQXBJ), corydaline (YHSJS), stylopine (SQHLJ), and isoimperatorin (YOQHS) in ZJ CR were higher than those in CR from outside ZJ, but the content of protopine (YAPJ) and berberine hydrochloride (YSXBJ) was lower than that in CR from outside ZJ. YHSJS and SQHLJ could be used as the core components to identify ZJ CR. The GA-BP neural network showed that the relative importance of ZJ CR was the strongest. Chroma-content correlation analysis and the NIR qualitative model could effectively distinguish CR from inside and outside of ZJ, and the NIR quantitative model could quickly predict the content of CR from inside and outside of ZJ. Zebrafish experiments showed that ZJ, Shaanxi (SX), Henan (HN), and Sichuan (SC) CR had significant analgesic effects, while Hebei (HB) CR had no significant analgesic effect. Overall comparison, the analgesic effect of ZJ CR was better than that of CR outside ZJ. The comprehensive score of the grey correlation degree between YAPJ, YSBMT, YSXBJ, TQZJJ, YHSYS, YHSJS, SQXBJ, and SQHLJ were higher than 0.9, and the research frequency were extremely high. CONCLUSIONS: The relative importance of the content and origin of most components of ZJ CR was higher than that of CR outside ZJ. The holistic analgesic effect of ZJ CR was better than that of CR outside ZJ, but slightly lower than that of SX CR. YHSJS and SQHLJ could be used as the core components to identify ZJ CR. YAPJ, YSBMT, YSXBJ, TQZJJ, YHSYS, SQXBJ, YHSJS, and SQHLJ could be used as the quality control components of ZJ CR. The multidimensional evaluation method used in this study provided a reference for the quality control and material basis research of ZJ CR.

CD44 targets Wnt/ß-catenin pathway to mediate the proliferation of K562 cells.

BACKGROUND: Chronic myeloid leukemia is a clonal myeloproliferative disorder disease in which BCR/ABL plays an important role as an oncoprotein and molecular target. Despite the success of targeted therapy using tyrosine kinase inhibitors, CML remains largely incurable, most likely due to the treatment resistance after firstly chemical therapy. So know well the unique molecular pathway of CML is very important. METHODS: The expressions of CD44 in different leukemia patients and cell lines were detected by real-time PCR and western blotting. The effects of CD44 on proliferation of K562 cells were determined using the MTT and colony formation assays, and even in a nude mouse transplantation model. Then, the cell cycle changes were detected by flow cytometric analysis and the early apoptosis of cells was detected by the annexin V/propidium iodide double-staining assay. The expressions of the cycles and apoptosis-related proteins p21, Cyclin D1 and Bcl-2 were analyzed by western blot and real-time PCR assay. Finally, the decreased nuclear accumulation of ß-catenin was detected by western blotting and immunefluorescence. RESULTS: Firstly, we showed that CD44 expression was increased in several kinds of leukemia patients and K562 cells. By contrast, the down-regulation of CD44 resulted in decreased proliferation with a G0/G1 arrest of cell cycle in K562 cells according to the MTT assay and the flow cytometric analysis. And no significant induction of both the early and late phases of apoptosis was shown by the annexin V-FITC and PI staining. During this process, p21 and cyclin D1 are the major causes for cell cycle arrest. In addition, we found CD44 down-regulation decreased the expression of ß-catenin and increased the expression of phosphorylated ß-catenin. The instability of Wnt/ß-catenin pathway induced by increased expression of p-ß-catenin resulted in a decreased nuclear accumulation in CD44 silenced K562 cells. In the nude mouse transplantation model, we also found the same results. CONCLUSIONS: These results show that K562 cells depend to a greater extent on CD44 for proliferation, and CD44 down-regulation may induce a cell cycle arrest through Wnt/ß-catenin pathway. CD44 blockade may be beneficial in therapy of CML.

[Control of organ shape and size by YUAN1 in Arabidopsis thaliana].

Control of organ shape and size by cell proliferationandcell expansion is a fundamental process in plant development. However, little is known about the molecular mechanisms that set the shape and size of determinate organs in plants. We have previously demonstrated that the Arabidopsis gene DA1 controls the final size of organs by restricting cell proliferation. Through an activation tagging screen for modifiers of da1-1, we have identified a semi-dominant mutant (yuan1-1D) with altered leaf shape and size. The yuan1-1D mutation results in reduced plant height, short and round leaves and short petioles due to defects in cell elongation. YUAN1 encodes a PHD zinc finger domain-containing protein. The GFP-YUAN1 fusion protein is localized to the nucleus. Overexpression of YUAN1 leads to round leaves and short petioles. Genetic analyses show that YUAN1 acts independently of DA1, ROTUNDIFOLIA 3 (ROT3) and ROTUNDIFOLIA4 (ROT4) to influence leaf shape and size. Collectively, our findings show that Arabidopsis YUAN1, a PHD zinc finger domain-containing protein, controls organ shape and size by restricting cell elongation, and give insight into how plants control their organ shape and size.