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Xiaomei Wu - Top 30 Publications

Chemical constituents of the fermentative extracts of marine fungi Phoma sp. CZD-F11 and Aspergillus sp. CZD-F18 from Zhoushan Archipelago, China.

A new diphenyl ether (1) as well as 20 other compounds were identified from the fermentative extracts of marine-derived fungi Phoma sp. CZD-F11 (Compounds 1-8) and Aspergillus sp. CZD-F18(Compounds 9-21). Their structures were elucidated on the basis of extensive spectroscopic analysis. The broth extracts of the fungi exhibited very good anticancer activity against H1975 cells with 5.62 and 25.8% viability at concentration of 10 μg/mL for Phoma sp. CZD-F11 and Aspergillus sp. CZD-F18, respectively. The inhibitory activity of all compounds against PC-3 cell lines, BRD4 and aromatase were evaluated. The results showed compound 7 exhibited moderate anticancer activity with 66.1% inhibition against PC-3 cell lines at the concentration of 10 μg/mL. Compound 7 and 8 exhibited favourable BRD4 inhibitory activity with 78.5 and 76.4% inhibition at the concentration of 10 μg/mL.

Dihydromyricetin prevents monocrotaline-induced pulmonary arterial hypertension in rats.

Pulmonary artery hypertension (PAH) is a chronic and deadly disease, for which effective medical treatments are lacking. Here, we investigated whether 2R,3R-dihydromyricetin (DHM) could prevent monocrotaline (MCT)-induced PAH in rats. The MCT-injected rats were treated with normal saline or DHM (100mg/kg body weight/d) for 4 weeks, followed by measurements of right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), pulmonary arterial remodeling (PAR), and expression levels of IL-6, TNF-α, and IL-10. In vitro, we assessed the role of DHM on IL-6-induced migration of primary human pulmonary arterial smooth muscle cells (HPASMCs). We found that DHM treatment attenuated changes in RVSP, RVHI, and PAR in MCT-injected PAH rats. The observed increase of IL-6 levels in PAH rats was inhibited by DHM treatment. In vitro, DHM pretreatment reduced IL-6-induced HPASMC migration. Furthermore, MCT- and IL-6-mediated increases in MMP9 and P-STAT3 (tyr705) PY-STAT3 levels were suppressed by DHM treatment in vivo and in vitro. These results suggest that DHM could prevent MCT-induced rat PAH and IL-6-induced HPASMC migration through a mechanism involving inhibiting of the STAT3/MMP9 axis.

Effects of electrophysiological heterogeneity on vulnerability to re-entry in human ventricular tissue: A simulation study.

In this study, we constructed a two-dimensional ventricular tissue sheet with cellular electrophysiology modified from the Ten Tusscher 2006 Model. Heterogeneity was created by dividing the tissue into endocardium, midmyocardium and epicardium, further enhanced by a central ischemic zone. Subsequently, we investigated how electrophysiological heterogeneity affects re-entry initiation and maintenance in this tissue. Furthermore, we analyzed the vulnerable window (VW) under several conditions and concluded that heterogeneity across various myocardia expands the VW further than the monolayer myocardium model does.

Knowledge and Awareness of Cervical Cancer, Human Papillomavirus (HPV), and HPV Vaccine Among HPV-Infected Chinese Women.

BACKGROUND It is important to understand the knowledge that various groups of a population have about cervical cancer and human papillomavirus (HPV) and their attitudes toward HPV vaccination, as it will ultimately influence their decision-making for or against the acceptability of vaccines and other preventive methods. This study was designed to determine the level of knowledge and awareness about cervical cancer, HPV, and the HPV vaccine among Chinese women in Yunnan province. MATERIAL AND METHODS A survey was conducted in Yunnan province by the Laboratory of Molecular Virology in collaboration with the Yunnan First People's Hospital in Feb 2015. A total of 388 women were recruited and asked to participate in a questionnaire-based interview that collected information related to their awareness and knowledge about: (1) cervical cancer, (2) HPV and HPV vaccine and willingness to have their children receive vaccination, and (3) demographic characteristics. RESULTS A total of 388 HPV-positive women were included; 300/388 (73.3%) were Han, and 88/388 (22.7%) were other ethnicities. Overall, 204/388 (52.6%) of the women were aware of cervical cancer, with a significant difference between Han women and women of other ethnic groups (168/388, 56.0% and 36/88, 40.9%; P=0.015). Overall, 26.5% of the women were aware of the role of HPV in cervical cancer; 29.0% of the Han women and 18.2% of women of other ethnic groups were aware of this role of HPV (P=0.05). The knowledge that HPV infection leads to cervical cancer was higher among Han women (29.0%) compared to women of other ethnicities (18.2%). Knowledge about the HPV vaccine was very low in all ethnic groups, but the Han women were more willing to allow their children to be vaccinated before they become sexually active. A similar difference has also been found in women from various regions. CONCLUSIONS Although level of awareness and knowledge about cervical cancer was moderate, knowledge and awareness of HPV and the HPV vaccine was very low. Targeted communication is very important among populations in which knowledge gaps exist in order to promote dialogue about the vaccine among patients and their healthcare providers.

Therapeutic Mechanism of Glucocorticoids on Cellular Crescent Formation in Patients With Antiglomerular Basement Membrane Disease.

This study aimed to explore the therapeutic mechanism of glucocorticoids (GCs) in antiglomerular basement membrane disease.

A hyperspectral X-ray computed tomography system for enhanced material identification.

X-ray computed tomography (CT) can distinguish different materials according to their absorption characteristics. The hyperspectral X-ray CT (HXCT) system proposed in the present work reconstructs each voxel according to its X-ray absorption spectral characteristics. In contrast to a dual-energy or multi-energy CT system, HXCT employs cadmium telluride (CdTe) as the x-ray detector, which provides higher spectral resolution and separate spectral lines according to the material's photon-counter working principle. In this paper, a specimen containing ten different polymer materials randomly arranged was adopted for material identification by HXCT. The filtered back-projection algorithm was applied for image and spectral reconstruction. The first step was to sort the individual material components of the specimen according to their cross-sectional image intensity. The second step was to classify materials with similar intensities according to their reconstructed spectral characteristics. The results demonstrated the feasibility of the proposed material identification process and indicated that the proposed HXCT system has good prospects for a wide range of biomedical and industrial nondestructive testing applications.

Increased expression of Siglec-9 in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common inflammatory lung disease. Sialic acid-binding immunoglobulin-type lectins 9 (Siglec-9) is predominantly expressed on innate immune cells and has been shown to exert regulatory effect on immune cells through glycan recognition. Soluble Siglec-9 (sSiglec-9), the extracellular region of Siglec-9, might fulfill its function partly by competitive inhibiting siglec-9 binding to its ligands; however, the role of Siglec-9 and sSiglec-9 in the pathogenesis COPD remain largely unknown. In this study, we showed that Siglec-9 expression in alveolar and peripheral blood neutrophil were increased in COPD patients by immunofluorescence and flow cytometry, respectively. Plasma levels of sSiglelc-9 were elevated in COPD patients by ELISA. In vitro, Siglec-9 expression and/or sSiglelc-9 levels were up-regulated by cigarette smoke extract (CSE), lipopolysaccharide (LPS), some cytokines, and dexamethasone (DEX). Recombinant sSiglce-9 increased oxidative burst in neutrophil and enhanced neutrophil chemotaxis toward IL-8 independent on CXCR1 and CXCR2 expression, but it did not affect neutrophil apoptosis or secretions of inflammatory cytokines. In conclusion, Siglec-9 was complementarily increased to induce a negative feedback loop to limit neutrophil activation in COPD, sSiglce-9 enhanced neutrophil ROS and chemotaxis toward IL-8 likely via competitively inhibiting ligands binding to Siglec-9.

Strongly singular integrals along curves on α-modulation spaces.

In this paper, we study the strongly singular integrals [Formula: see text] along homogeneous curves [Formula: see text]. We prove that [Formula: see text] is bounded on the α-modulation spaces, including the inhomogeneous Besov spaces and the classical modulation spaces.

Low post-traumatic stress disorder rate in Chinese in Beijing, China.

There have been significantly fewer community-based, epidemiological studies focusing on PTSD and its socio-demographic correlates among the Chinese than Western populations.

Phylogenetic and Molecular Evolutionary Analysis of Mitophagy Receptors under Hypoxic Conditions.

As animals evolved to use oxygen as the main strategy to produce ATP through the process of mitochondrial oxidative phosphorylation, the ability to adapt to fluctuating oxygen concentrations is a crucial component of evolutionary pressure. Three mitophagy receptors, FUNDC1, BNIP3 and NIX, induce the removal of dysfunctional mitochondria (mitophagy) under prolonged hypoxic conditions in mammalian cells, to maintain oxygen homeostasis and prevent cell death. However, the evolutionary origins and structure-function relationships of these receptors remain poorly understood. Here, we found that FUN14 domain-containing proteins are present in archaeal, bacterial and eukaryotic genomes, while the family of BNIP3 domain-containing proteins evolved from early animals. We investigated conservation patterns of the critical amino acid residues of the human mitophagy receptors. These residues are involved in receptor regulation, mainly through phosphorylation, and in interaction with LC3 on the phagophore. Whereas FUNDC1 may be able to bind to LC3 under the control of post-translational regulations during the early evolution of vertebrates, BINP3 and NIX had already gained the ability for LC3 binding in early invertebrates. Moreover, FUNDC1 and BNIP3 each lack a layer of phosphorylation regulation in fishes that is conserved in land vertebrates. Molecular evolutionary analysis revealed that BNIP3 and NIX, as the targets of oxygen sensing HIF-1α, showed higher rates of substitution in fishes than in mammals. Conversely, FUNDC1 and its regulator MARCH5 showed higher rates of substitution in mammals. Thus, we postulate that the structural traces of mitophagy receptors in land vertebrates and fishes may reflect the process of vertebrate transition from water onto land, during which the changes in atmospheric oxygen concentrations acted as a selection force in vertebrate evolution. In conclusion, our study, combined with previous experimental results, shows that hypoxia-induced mitophagy regulated by FUDNC1/MARCH5 might use a different mechanism from the HIF-1α-dependent mitophagy regulated by BNIP3/NIX.

The distribution of human papillomavirus genotypes in cervical cancer and intraepithelial neoplasia lesions among Chinese women in Yunnan Province.

This study was designed to explore baseline data about the prevalence and distribution of human papillomavirus (HPV) genotypes among Chinese women who had cervical intraepithelial lesions and cervical cancer. A total of 511 patients were recruited, and biopsy samples were collected from these patients. Polymerase chain reaction was used to detect HPV-positive samples, and the HPV GenoArray kit was used for genotyping. A total of 23 genotypes were detected, including 13 that were high risk-HPV (HR-HPV), 3 that were potential high risk-HPV (PHR-HPV) and 7 that were low risk-HPV (LR-HPV). The prevalence rates of HPV infection in Han women diagnosed with cervical intraepithelial lesions (CIN) 1, 2, and 3 and squamous cell carcinoma (SCC) were 98.30%, 97.56, 100% and 90%, respectively. The HPV-positive cases in women of other ethnicities diagnosed with CIN1, CIN2, and CIN3 and SCC were 95%, 90.91%, 88.23% and 83.33%, respectively. The most frequent genotypes in both ethnic groups were HPV-16, 52, and 58. LR-HPV was detected in SCC lesions in the non-Han ethnic group. In the Han ethnic group, the LR-HPV genotype was mostly restricted to CIN1 lesions. Furthermore, we found a high prevalence of PHR-HPV-81 in SCC lesions among Han women. Ethnic background, smoking, sex at an early age, unprotected sex, use of contraceptives, and the withdrawal method were found to be significantly associated with HPV infection. In conclusion, this study explores epidemiological data regarding the prevalence of HPV and the genotype distribution in patients with SCC and CIN lesions in Yunnan Province, China.

Smoking status and gene susceptibility play important roles in the development of chronic obstructive pulmonary disease and lung function decline: A population-based prospective study.

We conducted this study to identify the influences and synergistic effects of smoking status and polymorphisms in hedgehog interacting protein (HHIP) on chronic obstructive pulmonary disease (COPD) and lung function decline.

Plastic Classification with X-ray Absorption Spectroscopy Based on Back Propagation Neural Network.

Currently, spectral analysis methods used in the classification of plastics have limitations that do not apply to opaque plastics or the stability of experimental results is not strong. In this paper, X-ray absorption spectroscopy (XAS) has been applied to classify plastics due to its strong penetrability and stability. Fifteen kinds of plastics are selected as specimens. X-ray, which is excited by a voltage of 60 kV, penetrated these specimens. The spectral data acquired by CdTe X-ray detector are processed by principal component analysis (PCA) and other data analysis methods. Then the back propagation neural networks (BPNN) algorithm is used to classify the processed data. The average recognition rate reached 96.95% and classification results of all types of plastic results were analyzed in detail. It indicates that XAS has the potential to classify plastics and that XAS can be used in some fields such as plastic waste sorting and recycling. At the same time, the technology of XAS, in the future, can also be used to classify more substances.

The relationship between diabetes and colorectal cancer prognosis: A meta-analysis based on the cohort studies.

Though a meta-analysis reported the effect of diabetes on colorectal prognosis in 2013, a series of large-scale long-term cohort studies has comprehensively reported the outcome effect estimates on the relationship between diabetes and colorectal prognosis, and their results were still consistent.

Tumor necrosis factor-alpha gene polymorphisms and susceptibility to ischemic heart disease: A systematic review and meta-analysis.

A number of studies had reported the association between tumor necrosis factor-alpha (TNF-α) gene polymorphisms and ischemic heart disease (IHD) risk. However, the results remained controversial. Therefore, we performed a systematic review with multiple meta-analyses to provide the more precise estimations of the relationship.

Sleep duration and risk of stroke: a dose-response meta-analysis of prospective cohort studies.

Suboptimal sleep duration has been considered to increase the risk of stroke incidence. Thus we aimed to conduct a dose-response meta-analysis to examine the association between sleep duration and stroke incidence.

Prevalence and risk factors for human papillomavirus infection among Chinese ethnic women in southern of Yunnan, China.

Dai is a major Chinese ethnic minority group residing in rural areas of the southern part of Yunnan. However, no data exist on the Human Papillomavirus (HPV) prevalence and genotype distribution among Dai women.

Low-energy defibrillation research using a rabbit ventricular model: optimizing the potential gradient distribution using multiple epicardial electrodes.

Cardiac potential gradient distribution directly affects defibrillation efficacy, and the electrode configuration that ensures optimal distribution is yet to be determined. In this study, a rabbit ventricular finite element conductor model containing blood perfusion in ventricular cavities was developed. The electric field was solved on the model by using 95% myocardial volume potential gradient higher than 5 V/cm as the successful defibrillation threshold (DFT). Multiple epicardial electrodes (MEE) protocols and a SCAN protocol were used to identify the optimum defibrillation method. Results showed that when using the SCAN protocol, DFT energy reduced to 4.3% that of the control group which had the traditional implantable cardioverter defibrillator current path. Rapidly switching scanning stimuli generated using MEE pairs is a promising low-energy defibrillation method. For multiple electrodes defibrillation, the distribution of the electrode pairs determine the defibrillation efficacy, and the counteraction effect has negative effect on defibrillation. These findings can provide suggestions for clinical applications.

GLCCI1 rs37973: a potential genetic predictor of therapeutic response to inhaled corticosteroids in Chinese chronic obstructive pulmonary disease patients.

Inhaled corticosteroids (ICSs) are widely prescribed in chronic obstructive pulmonary disease (COPD). However, little is known about predictors of ICSs therapeutic response. To investigate whether the variation in glucocorticoid-induced transcript 1 (GLCCI1) rs37973 is associated with ICS efficacy. A total of 204 clinically stable COPD patients were recruited and administered to inhaled fluticasone propionate/salmeterol combination (500/50 ug, twice daily) for 24 weeks. We genotyped the functional rs37973 and mainly assessed its effects on changes in lung function. In vitro, neutrophils isolated from parts of patients were incubated with various concentrations of dexamethasone (0, 10(-6) M and 10(-4) M) in the presence or absence of cigarette smoke extract, apoptosis was then assessed by flow cytometry. Patients with the homozygous GG genotype (increases of 15.3 ± 33.2 mL) had significantly poorer improvement in FEV1 than those with the AA (92.7 ± 29.6 mL; p < 0.001) or AG (59.4 ± 26.9 mL; p < 0.001) genotypes after 24-week treatment. In vitro, dexamethasone had less inhibitory effect of neutrophil apoptosis on GG genotype, which further validated the presence of mutant allele 'G' might negatively affect glucocorticoid responsiveness irrespective of smoking status. The GG genotype of rs37973 may associated with decreased ICSs efficacy in Chinese COPD patients.

Effect of bilirubin concentration on the risk of diabetic complications: A meta-analysis of epidemiologic studies.

Diabetes can affect many parts of the body and is associated with serious complications. Oxidative stress is a major contributor in the pathogenesis of diabetic complications and bilirubin has been shown to have antioxidant effects. The number of studies on the effect of bilirubin on the risk of diabetic complications has increased, but the results are inconsistent. Thus, we performed a meta-analysis to determine the relationship between bilirubin concentration and the risk of diabetic complications, and to investigate if there was a dose-response relationship. We carried out an extensive search in multiple databases. A fixed or random-effects model was used to calculate the pooled estimates. We conducted a dose-response meta-analysis to analyze the association between these estimates. A total of 132,240 subjects from 27 included studies were analyzed in our meta-analysis. A negative nonlinear association between bilirubin concentration and the risk of diabetic complications was identified (OR: 0.77, 95% CI: 0.73-0.81), with a nonlinear association. We also found that there was a negative association between bilirubin concentration and the risk of diabetic nephropathy, diabetic retinopathy and diabetic neuropathy. The results of our meta-analysis indicate that bilirubin may play a protective role in the occurrence of diabetic complications.

Prognostic role of copeptin with all-cause mortality after heart failure: a systematic review and meta-analysis.

As the C-terminal section of vasopressin precursor, copeptin has been recently suggested as a new prognostic biomarker after heart failure (HF). Thus, the aim of this study was to evaluate the prognostic value of plasma copeptin level with all-cause mortality in patients with HF.

Theoretical and experimental analysis of amplitude control ablation and bipolar ablation in creating linear lesion and discrete lesions for treating atrial fibrillation.

Radiofrequency (RF) energy is often used to create a linear lesion or discrete lesions for blocking the accessory conduction pathways for treating atrial fibrillation. By using finite element analysis, we study the ablation effect of amplitude control ablation mode (AcM) and bipolar ablation mode (BiM) in creating a linear lesion and discrete lesions in a 5-mm-thick atrial wall; particularly, the characteristic of lesion shape has been investigated in amplitude control ablation.

Sex-determining region Y-box3 (SOX3) functions as an oncogene in promoting epithelial ovarian cancer by targeting Src kinase.

Ovarian cancer is one of the most common cancers which cause female mortality. The knowledge of ovarian cancer initiation and progression is critical to develop new therapeutic strategies to treat and prevent it. Recently, SOX3 has been reported to play a pivotal role in tumor progression. However, the clinical significance of SOX3 in human ovarian cancer remains elusive, and the identity of SOX3 in ovarian cancer initiation, progression, and the related underlying mechanism is unknown. In this study, we showed that SOX3 expression increased from benign and borderline to malignant ovarian tumors. Subsequently, we found that overexpression of SOX3 in EOC cells promoted proliferation, migration, and invasion, while restrained apoptosis and adhesion of ovarian cancer cells. In contrast, silencing of SOX3 gained the opposite results. Finally, we discovered SOX3 targeted Src kinase in EOC cells. These data imply that SOX3, acting as an oncogene in EOC, is not only a crucial factor in the carcinogenesis but also a promising therapeutic target for EOC.

Compensatory variances of drug-induced hepatitis B virus YMDD mutations.

Although the drug-induced mutations of HBV have been ever documented, the evolutionary mechanism is still obscure. To deeply reveal molecular characters of HBV evolution under the special condition, here we made a comprehensive investigation of the molecular variation of the 3432 wild-type sequences and 439 YMDD variants from HBV genotype A, B, C and D, and evaluated the co-variant patterns and the frequency distribution in the different YMDD mutation types and genotypes, by using the naïve Bayes classification algorithm and the complete induction method based on the comparative sequence analysis. The data showed different compensatory changes followed by the rtM204I/V. Although occurrence of the YMDD mutation itself was not related to the HBV genotypes, the subsequence co-variant patterns were related to the YMDD variant types and HBV genotypes. From the hierarchy view, we clarified that historical mutations, drug-induced mutation and compensatory variances, and displayed an inter-conditioned relationship of amino acid variances during multiple evolutionary processes. This study extends the understanding of the polymorphism and fitness of viral protein.

The Negative Relationship between Bilirubin Level and Diabetic Retinopathy: A Meta-Analysis.

Findings on the relationship between total bilirubin level (TBL) and diabetic retinopathy (DR) are inconsistent. Thus, we carried out a meta-analysis to investigate the relationship between TBL and the risk of DR.

Association of vascular endothelial growth factor gene polymorphisms with ectopic pregnancy among Chinese women.

To assess the association of vascular endothelial growth factor (VEGF) gene polymorphisms with ectopic pregnancy (EP) among Chinese women.

Incidence of antimicrobial-resistance genes and integrons in antibiotic-resistant bacteria isolated from eels and aquaculture ponds.

The overuse of antimicrobials in aquaculture has promoted the selection of antimicrobial-resistant bacteria. Here we investigated the abundance of antimicrobial-resistance genes and integrons in 108 strains of antibiotic-resistant bacteria isolated from eels and aquaculture ponds in China. Conventional PCR was implemented to examine common antibiotic-resistance genes, integrons, and their gene cassette arrays. The results showed that the antibiotic-resistance genes blaTEM, tetC, sulI, aadA, floR, and qnrB were detected at high percentages, as were a number of other resistance genes. Class I integrons were present in 79.63% of the strains, and 10 out of 108 isolates carried class II integrons. Class III integrons were not detected. Three strains carried both class I and class II integrons, and 73.26% of the class I integron-positive isolates contained the qacEΔ1/sul1 gene. Fourteen types of integron cassette arrays were found among class I integron-positive isolates. A new array, dfrB4-catB3-blaOXA-10-aadA1, was discovered in this study. The gene cassette array dfrA12-orfF-aadA2 was the most widely distributed. In summary, 23 different gene cassettes encoding resistance to 8 classes of antibiotics were identified in the class I integrons, and the main cassettes contained genes encoding resistance to aminoglycosides (aad) and trimethoprim (dfr). All class II integron-positive strains had only a single gene cassette array, viz. dfrA1-catB2-sat2-aadA1. High levels of antimicrobial-resistance genes and integrons in eels and auqauculture ponds suggest that the overuse of antimicrobials should be strictly controlled and that the levels of bacterial antimicrobial-resistance genes in aquaculture should be monitored.

Epidemiologic characterization of human papillomavirus (HPV) infection in various regions of Yunnan Province of China.

This study was designed to determine the Human papillomavirus (HPV) prevalence and its distribution of genotypes in various regions of Yunnan Province, China.

Study on Accurately Controlling Discharge Energy Method Used in External Defibrillator.

This paper introduces a new method which controls discharge energy accurately. It is achieved by calculating target voltage based on transthoracic impedance and accurately controlling charging voltage and discharge pulse width. A new defibrillator is designed and programmed using this method. The test results show that this method is valid and applicable to all kinds of external defibrillators.

Myosin light chain kinase facilitates endocytosis of synaptic vesicles at hippocampal boutons.

At nerve terminals, endocytosis efficiently recycles vesicle membrane to maintain synaptic transmission under different levels of neuronal activity. Ca(2+) and its downstream signal pathways are critical for the activity-dependent regulation of endocytosis. An activity- and Ca(2+) -dependent kinase, myosin light chain kinase (MLCK) has been reported to regulate vesicle mobilization, vesicle cycling, and motility in different synapses, but whether it has a general contribution to regulation of endocytosis at nerve terminals remains unknown. We investigated this issue at rat hippocampal boutons by imaging vesicle endocytosis as the real-time retrieval of vesicular synaptophysin tagged with a pH-sensitive green fluorescence protein. We found that endocytosis induced by 200 action potentials (5-40 Hz) was slowed by acute inhibition of MLCK and down-regulation of MLCK with RNA interference, while the total amount of vesicle exocytosis and somatic Ca(2+) channel current did not change with MLCK down-regulation. Acute inhibition of myosin II similarly impaired endocytosis. Furthermore, down-regulation of MLCK prevented depolarization-induced phosphorylation of myosin light chain, an effect shared by blockers of Ca(2+) channels and calmodulin. These results suggest that MLCK facilitates vesicle endocytosis through activity-dependent phosphorylation of myosin downstream of Ca(2+) /calmodulin, probably as a widely existing mechanism among synapses. Our study suggests that MLCK is an important activity-dependent regulator of vesicle recycling in hippocampal neurons, which are critical for learning and memory. The kinetics of vesicle membrane endocytosis at nerve terminals has long been known to depend on activity and Ca(2+) . This study provides evidence suggesting that myosin light chain kinase increases endocytosis efficiency at hippocampal neurons by mediating Ca(2+) /calmodulin-dependent phosphorylation of myosin. The authors propose that this signal cascade may serve as a common pathway contributing to the activity-dependent regulation of vesicle endocytosis at synapses.