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Objective: The predictive value of microalbuminuria (MAU) for kidney damage is limited in type 2 diabetes (T2D). We studied whether a urine proteome specific for sight-threatening proliferative diabetic retinopathy (PDR) is an indicator to predict chronic renal insufficiency (CRI) in patients with T2D.Research Design and Methods: A shotgun urine proteomic analysis was performed in patients with MAU and PDR (case subjects) and in patients with MAU and a duration of T2D for >10 years but without any degree of retinopathy (control subjects). In the cohort study, 210 patients with T2D with an estimated glomerular filtration rate (eGFR) ≥80 mL/min/1.73 m2 were followed for a median of 5.3 years. Urine proteins specific for PDR were used for predicting CRI (eGFR <60 mL/min/1.73 m2).Results: The top two urine proteins with the highest difference in ratio of case subjects to control subjects were haptoglobin (8.7 times; P < 0.0001) and α-2-macroglobulin (5.7 times; P < 0.0001). In the cohort study, patients with baseline urinary haptoglobin ≥20 ng/min (haptoglobinuria) had a higher incidence of CRI than those without (hazard ratio [95% CI] 3.27 [1.41-7.58]; P = 0.006). The overall CRI rate was 3.2% for patients without haptoglobinuria or MAU, 9.5% for those with MAU, and 13.3% for those with haptoglobinuria. The highest rate for CRI (22.4%) was in patients with both MAU and haptoglobinuria (P < 0.001).Conclusions: Urine haptoglobin, which is specific for PDR, is a novel biomarker and complement to urine albumin for predicting kidney damage in patients with T2D. [ABSTRACT FROM AUTHOR]

Findings on the association between television (TV) viewing and all-cause mortality in epidemiologic studies have been inconsistent. Therefore, we conducted a meta-analysis of data from prospective cohort studies to quantify this association. Relevant articles were identified by searching MEDLINE (PubMed; National Library of Medicine, Bethesda, Maryland) and EMBASE (Elsevier B.V., Amsterdam, the Netherlands) from inception to March 1, 2015, and reviewing the reference lists of retrieved articles. Study-specific results were pooled using a random-effects model. Of 2,578 citations identified by the search strategy, 10 cohort studies (61,494 deaths among 647,475 individuals) met the inclusion criteria. The summary relative risk of all-cause mortality for the highest category of TV viewing time versus the lowest was 1.33 (95% confidence interval: 1.20, 1.47), with heterogeneity among studies (I² = 66.7%, Pheterogeneity = 0.001). In dose-response meta-analysis, TV viewing time was statistically significantly associated with all-cause mortality risk in a J-shaped fashion (Pnonlinearity = 0.001 ). These results indicate that prolonged TV viewing time might increase the risk of all-cause mortality. Given the high prevalence of excessive TV viewing, public health recommendations or interventions aimed at decreasing the amount of TV viewing time in modern societies are warranted. [ABSTRACT FROM AUTHOR]

The identification difficulties for a dual-rate Hammerstein system lie in two aspects. First, the identification model of the system contains the products of the parameters of the nonlinear block and the linear block, and a standard least squares method cannot be directly applied to the model; second, the traditional single-rate discrete-time Hammerstein model cannot be used as the identification model for the dual-rate sampled system. In order to solve these problems, by combining the polynomial transformation technique with the key variable separation technique, this paper converts the Hammerstein system into a dual-rate linear regression model about all parameters (linear-in-parameter model) and proposes a recursive least squares algorithm to estimate the parameters of the dual-rate system. The simulation results verify the effectiveness of the proposed algorithm. [ABSTRACT FROM AUTHOR]

A series of developed ammonium oxidative-thermoregulated bifunctional ionic liquids (ILs) catalysts have been synthesized. The structures of these task-specific ionic liquids (TSILs) are characterized by FT-IR and ¹H NMR. The thermoregulated properties of ILs in aqueous and common organic solvent are investigated. The prepared ionic liquid has the cloud point (CP) in aqueous, and has the minimum solubility in toluene. The ionic liquid has the corresponding critical solution temperature (CST) in toluene/n-octane or n-dodecane mixed solvents, which makes the system with the thermoregulated feature of "homogeneous at high temperature, heterogeneous at low temperature". The developed thermoregulated system has been used for catalytic H2O2 oxidative desulfurization of model fuels to achieve an integration of homogeneous catalysis and heterogeneous separation. The recycle of the ionic liquid catalyst is easily achieved. The desulfurization rate only keeps a gradually slight drop during the recycles of the catalyst. [ABSTRACT FROM AUTHOR]

Grass carp reovirus (GCRV) is the causative agent of grass carp hemorrhage and causes significant loss of fingerlings. However, little is known about how the virus is distributed in organs and tissues. The aim of the present study was to investigate the distribution of different GCRV stains in tissues and organs of grass carp. The pathogenicity and tissue distribution of GCRV were monitored after intraperitoneal administration. The study showed a distribution of GCRV in different tissues and organs, particularly in the liver, spleen, kidney, intestine, and muscle, which had a higher number of viral RNA copies during the sixth to ninth days. The kidney had the highest numbers of viral RNA copies, as high as 24000 copies. Until the fourteenth day, nearly no viral RNA copies could be detected. This study defined the virus distribution in different tissues of grass carp inoculated by i.p. and supplied clues for the pathogenesis of GCRV. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to investigate the reversal effects of 5,5'-dimethoxylariciresinol-4'-O-β-D-glucoside (DMAG) extracted from traditional Chinese medicines Mahonia on multidrug resistance (MDR) of human leukemia cells to chemotherapeutic agents. Materials and Methods: MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed to determine the effect of DMAG on doxorubicin sensitivity to K562/DOX cells. Propidium iodide /Hoechst 33342 double staining assay was used to investigate the effect of DMAG on doxorubicin-induced cellular apoptosis. Intracellular accumulation of doxorubicin and rhodamine 123 assay were performed to evaluate the effect of DMAG on drugs efflux activity of P-glycoprotein. Results: DMAG significantly enhanced the doxorubicin cytotoxicity to K562/DOX cells. In the presence of 1.0 μM of DMAG, the IC50 of doxorubicin decreased from 34.93 ± 1.37 μM to 12.51 ± 1.28 μM. DMAG of 1.0 μM significantly enhanced doxorubicininduced cell apoptosis in K562/DOX cells and the enhancement was time-dependent. A significant increase in accumulation of doxorubicin in the presence of DMAG was observed. After treatment of the K562/DOX cells for 1 h with 15.0 μM doxorubicin alone, the fluorescence intensity was 33093.12. With the addition of 1.0 μM of DMAG, the fluorescence intensity of doxorubicin was 2.3-fold higher. A significant increase of accumulation of rhodamine 123 in the presence of DMAG was also observed. With the addition of 1.0 μM of DMAG, the fluorescence intensity was increased by 49.11% compared with rhodamine 123 alone. Conclusion: DMAG was shown to effectively enhance chemosensitivity of resistant cells, which makes it might be a suitable candidate for potential MDR-reversing agents. [ABSTRACT FROM AUTHOR]

By monitoring the time evolution of the optical absorption spectrum corresponding to dy- namic information of aspect ratio (AR) and volume, we succeeded in following the growth kinetics of gold nanorods. The results indicate that the rods growth consists of two stages: seeds develop into rods with a fast AR increase and the rods grow big with constant AR. Here, a charge transfer model, involving positive charge transfer from Au(I) to seed and neu- tralization by electron from ascorbic acid, has been introduced to explain the autocatalysis mechanism of rod growth. The good agreement between the numerical simulation based on this moldel and experimental results supports the proposed mechanism. [ABSTRACT FROM AUTHOR]

MicroRNAs are a class of small noncoding RNAs that function as critical gene regulators through targeting mRNAs for translational repression or degradation. In this study, we showed that miR-128 expression levels were decreased in glioma, and identified p70S6K1 as a novel direct target of miR-128. Overexpression of miR-128 suppressed p70S6K1 and its downstream signaling molecules such as HIF-1 and VEGF expression, and attenuated cell proliferation, tumor growth and angiogenesis. Forced expression of p70S6K1 can partly rescue the inhibitory effect of miR-128 in the cells. Taken together, these findings will shed light to the role and mechanism of miR-128 in regulating glioma tumor angiogenesis via miR-128/ p70S6K1 axis, and miR-128 may serve as a potential therapeutic target in glioma in the future. [ABSTRACT FROM AUTHOR]

Objective.We aim to study the therapeutic effects of scraping by investigating the changes of temperature and local blood perfusion volume in healthy subjects after scraping stimulation, and to explore the mechanism of scraping stimulation from the points of microcirculation and energymetabolism. Methods. Twenty-three health subjects were included in this study. Local blood perfusion volume and body surface temperature was detected at 5min before scraping stimulation, 0, 15, 30, 60 and 90min after scraping using Laser Doppler imager and infrared thermograph. Results. Significant increase was noted in the blood perfusion volume in the scraping area within 90 minutes compared to the baseline level and non-scraping area (P < 0.001). Compared with non-scraping area, an increase of body temperature with an average of 1°C was observed after scraping stimulation (P < 0.01). Conclusion. Scraping can significantly improve the blood perfusion volume and increase the temperature in the scraping area, promoting the local blood circulation and energy metabolism. [ABSTRACT FROM AUTHOR]

Protective mucus coatings typically trap and rapidly remove foreign particles from the eyes, gastrointestinal tract, airways. nasopharynx, and female reproductive tract, thereby strongly limiting opportunities for controlled drug delivery at mucosal surfaces. No synthetic drug delivery system composed of biodegradable polymers has been shown to penetrate highly viscoelastic human mucus, such as non-ovulatory cervicovagirial mucus, at a significant rate. We prepared nanoparticles composed of a biodegradable diblock copolymer of poly(sebacic acid) and poly(ethylene glycol) (PSA-PEG), both of which are routinely used in humans. In fresh undiluted human cervicovaginal mucus (CVM), which has a bulk viscosity approximately 1.800-fold higher than water at low shear. PSA-PEG nanoparticles diffused at an average speed only 12-fold lower than the same particles in pure water. In contrast, similarly sized biodegradable nanoparticles composed of PSA or poly(lacticco-glycolic acid) (PLGA) diffused at least 3.300-fold slower in CVM than in water. PSA-PEG particles also rapidly penetrated sputum expectorated from the lungs of patients with cystic fibrosis, a disease characterized by hyperviscoelastic mucus secretions. Rapid nanoparticle transport in mucus is made possible by the efficient partitioning of PEG to the particle surface during formulation. Biodegradable polymeric nanoparticles capable of overcoming human mucus barriers and providing sustained drug release open significant opportunities for improved drug and gene delivery at mucosal surfaces. [ABSTRACT FROM AUTHOR]

The ability of mucus to function as a protective barrier at mucosal surfaces rests on its viscous and elastic properties, which are not well understood at length scales relevant to pathogens and ultrafine environmental particles. Here we report that fresh, undiluted human cervicovaginal mucus (CVM) transitions from an impermeable elastic barrier to non-adhesive objects sized 1 μm and larger to a highly permeable viscoelastic liquid to non-adhesive objects smaller than 500 nm in diameter. Addition of a nonionic detergent, present in vaginal gels, lubricants and condoms, caused CVM to behave as an impermeable elastic barrier to 200 and 500 nm particles, suggesting that the dissociation of hydrophobically-bundled mucin fibers created a finer elastic mucin mesh. Surprisingly, the macroscopic viscoelasticity, which is critical to proper mucus function, was unchanged. These findings provide important insight into the nanoscale structural and barrier properties of mucus, and how the penetration of foreign particles across mucus might be inhibited. [ABSTRACT FROM AUTHOR]

The present studies examined the relationship between fasting blood glucose and Hb A1c in C57BL/6J, DBA/2J, and KK/HlJ mice with and without diabetes mellitus. Daily averaged blood glucose levels based on continuous glucose monitoring and effects of 6-h vs. overnight fasting on blood glucose were determined. Daily averaged blood glucose levels were highly correlated with Hb A1c, as determined with a hand-held automated device using an immunodetection method. R² values were 0.90, 0.95, and 0.99 in KK/HIJ, C57BL/6J, and DBA/2J, respectively. Six-hour fasting blood glucose correlated more closely with the level of daily averaged blood glucose and with Hb A1c than did blood glucose following an overnight fast. To validate the immunoassay-determined Hb A1c, we also measured total glycosylated hemoglobin using boronate HPLC. Hb A1c values correlated well with total glycosylated hemoglobin in all three strains but were relatively lower than total glycosylated hemoglobin in diabetic DBA/2J mice. These results show that 6-h fasting glucose provides a superior index of glycemic control and correlates more closely with Hb A1c than overnight-fasted blood glucose in these strains of mice. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to study the phenotypic and molecular characterization of 5 novel CTX-M-β-1actamases carried by 5 Klebsiella pneumoniae isolates and 3 Escherichia coli isolates collected from 4 hospitals in Hefei, China. Methods: The purified PCR products were ligated with pGEM-Teasy vectors, expressed, and sequenced. The complete genes of the CTX-M-β-lactamases were ligated with the pHSG398 vector to express prokaryotic recombinant proteins. Plasmids were extracted by rapid alkaline lysis protocol, and the PCR method was performed to determine whether the prokaryotic expression was successful or not. Antimicrobial susceptibility was tested and the phenotypes of transformants were determined according to criteria recommended by the Clinical and Laboratory Standards Institute. The kinetic parameters of enzymes were confirmed. The isoelectric points (pI) were determined by isoelectric focusing assay. Pulsed-field gel electrophoresis and plasmid profiling were performed. Results: The PCR products had 1101 nucleotides and were determined as CTX-M-46, CTX-M-47, CTX-M-48, CTX-M-49, and CTX-M-50. All strains were resistant to cefotaxime, but most of them were susceptible or intermediate to ceftazidime. The phenotypes of novel enzymes were determined as extended-spectrum β-lactamases (ESBL). Penicillin G, cephalothin, cefuroxime, and cefotaxime were determined to good substrates, whereas ceftazidime hydrolysis was not detected. The pI of the 5 novel CTX-M-β-lactamases were 8.0. CTX-M-derivatives could be the multiplex genesis in our area. Conclusion: This is the first report of these 5 novel plasmid-mediated CTX-M ESBL produced from China in the world. Molecular typing reveals notably different origin in genes encoding different CTX-M variants of 8 strains. [ABSTRACT FROM AUTHOR]

Nanoparticles larger than the reported mesh-pore size range (10- 200 nm) in mucus have been thought to be much too large to undergo rapid diffusional transport through mucus barriers. However, large nanoparticles are preferred for higher drug encapsulation efficiency and the ability to provide sustained delivery of a wider array of drugs. We used high-speed multiple-particle tracking to quantify transport rates of individual polymeric particles of various sizes and surface chemistries in samples of fresh human cervicovaginal mucus. Both the mucin concentration and viscoelastic properties of these cervicovaginal samples are similar to those in many other human mucus secretions. Unexpectedly, we found that large nanoparticles, 500 and 200 nm in diameter, if coated with polyethylene glycol, diffused through mucus with an effective diffusion coefficient (Deff) only 4-and 6-fold lower than that for the same particles in water (at time scale τ = 1 s). In contrast, for smaller but otherwise identical 100-nm coated particles, Deeff was 200-fold lower in mucus than in water. For uncoated particles 100-500 nm in diameter, Deff was 2,400- to 40,000-fold lower in mucus than in water. Much larger fractions of the 100-nm particles were immobilized or otherwise hindered by mucus than the large 200- to 500-nm particles. Thus, in contrast to the prevailing belief, these results demonstrate that large nanoparticles, if properly coated, can rapidly penetrate physiological human mucus, and they offer the prospect that large nanoparticles can be used for mucosal drug delivery. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The routine teaching mode of diabetes mellitus (DM) is divided into various sub-majors of medical laboratory, which is not conducive to clinical laboratory physicians quickly mastering relevant knowledge. A novel DM laboratory testing pathway is established to improve teaching efficiency and enhance the effects of talent cultivation in laboratory medicine. METHODS: The guidelines and expert consensuses of DM were gathered from professional websites and databases. The clinical laboratory diagnostic pathway was formulated, and the questionnaire and mutual evaluation were used to evaluate the teaching effectiveness of 8-year undergraduate students enrolled in 2018 and enrolled in 2019, respectively. RESULTS: Clinical laboratory physicians developed and approved the DM clinical laboratory diagnostic pathway, which included the entire process of DM diagnosis and differential diagnosis, drug selection, treatment impact monitoring, prognosis evaluation, etc. The results of the questionnaires showed that, in comparison to the teaching mode used with the students enrolled in 2018 and enrolled in 2019, the percentages of more improvement and significant improvement were significantly increased (P< 0.01) and the percentages of no improvement and slight improvement were significantly decreased (P <0.01). Following the instruction of the DM clinical laboratory diagnostic route, the results were greatly improved, including points emphasized and the accuracy of responding to questions, among other things, according to the teachers' and students' mutual evaluation (P< 0.05). CONCLUSIONS: To enhance the teaching quality in laboratory medicine, it is required to build the disease clinical laboratory diagnostic pathway for a novel teaching method. This may boost teachers' and students' confidence and broaden their knowledge. [ABSTRACT FROM AUTHOR]

An advanced hierarchically porous nanosheets-constructed three-dimensional (3D) carbon material (HPNSC) is prepared by using low-cost agricultural waste-nelumbium seed-pods as the precursor, and potassium hydroxide (KOH) as the activator. The as-prepared HPNSC material has a hierarchically porous nanosheets-constructed structure with 3D carbon nanosheet network morphology, which can enable fast and efficient transfer of Li+/Na+/H+ during charge–discharge process. The assembled HPNSC//HPNSC symmetric supercapacitors exhibit an improved energy density of 41.3 W h kg−1 with a power density of 180 W kg−1 in 1 mol l−1 Na2SO4 electrolyte. The energy density can still be maintained at 16.3 W h kg−1 even if the power density is increased to 9000 W kg−1. When acting as the reversible electrode for lithium ion batteries, this HPNSC material can achieve a high specific capacity of 1246 mA h g−1 at 0.1 A g−1. Moreover, sodium ion battery with HPNSC electrode exhibits excellent cycling performance of 161.8 mA h g−1 maintained even after being cycled 3350 times. The electrochemical performances clearly indicate that the HPNSC developed in this work is a very promising energy storage electrode material, and can further provide new insights for designing and developing highly porous materials for energy storage in other fields. [ABSTRACT FROM AUTHOR]

Text classification is a common task in natural language processing,in which there are a lot of research and progress based on machine learning and deep learning.However,these traditional methods can only process Euclidean spatial data,and cannot express the semantic information of the document effectively.To break the traditional learning mode,many recent studies start to use graphs to represent complicated relationships among entities in the document,and explore graph convolutional neural network for text representation.This paper reviews the text classification methods based on graph convolutional network.Firstly,the background and principle of graph convolutional network are summarized.Then,text classification methods based on graph convolutional network are described in detail according to different types of graph-based networks.Meanwhile,it analyzes the limi-tation of graph convolutional network in the depth of networks,and introduces the latest developments of deep networks in text classification.Finally,the classification performance of models involved in this paper is compared through some experiments,and the challenges and future research direction in this field are discussed.

Objective To analyze the differential expressions of miRNA in monocyte derived dendritic cells (moDCs) from systemic lupus erythematosus (SLE) patients and healthy people by bioinformatic analysis. Methods The GSE79240 dataset was downloaded from the gene expression omnibus (GEO) database, differential miRNAs were screened by R language. Funrich software was used to analyze the gene ontology (GO) enrichment, Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment and transcription factors. MiRTarBase database was used to predict target genes. Results A total of 19 differential miRNAs were screened out,of which 11 were up-regulated and 8 were down-regulated.Biological process of GO enrichment was enriched in signal transduction and cell communication; cellular component of GO enrichment was enriched in nucleus and cytoplasm; molecular function of GO enrichment was expressed in transcription factor activity, ubiquitin-specific protease activity and receptor signalling complex scaffold activity. KEGG pathway was shown mainly in glypican signalling pathway, TRAIL signalling pathway and S1P signalling pathway. The transcription factors related to miRNA mainly included: SP1, SP4, EGR1 and POU2F1. Forteen miRNAs have been experimentally verified to have target genes. Conclusions The differential miRNAs in moDCs of SLE patients may play an important role in the pathogenesis of SLE and provide new clue for the diagnosis of SLE.

BACKGROUND:To reach WHO End tuberculosis (TB) targets, countries need a quality-assured laboratory network equipped with rapid diagnostics for tuberculosis diagnosis and drug susceptibility testing. Diagnostic network analysis aims to inform instrument placement, sample referral, staffing, geographical prioritization, integration of testing enabling targeted investments and programming to meet priority needs. METHODS:Supply chain modelling and optimization software was used to map Lesotho's TB diagnostic network using available data sources, including laboratory and programme reports and health and demographic surveys. Various scenarios were analysed, including current network configuration and inclusion of additional GeneXpert and/or point of care instruments. Different levels of estimated demand for testing services were modelled (current [30,000 tests/year], intermediate [41,000 tests/year] and total demand needed to find all TB cases [88,000 tests/year]). RESULTS:Lesotho's GeneXpert capacity is largely well-located but under-utilized (19/24 sites use under 50% capacity). The network has sufficient capacity to meet current and near-future demand and 70% of estimated total demand. Relocation of 13 existing instruments would deliver equivalent access to services, maintain turnaround time and reduce costs compared with planned procurement of 7 more instruments. Gaps exist in linking people with positive symptom screens to testing; closing this gap would require extra 11,000 tests per year and result in 1000 additional TB patients being treated. Closing the gap in linking diagnosed patients to treatment would result in a further 629 patients being treated. Scale up of capacity to meet total demand will be best achieved using a point-of-care platform in addition to the existing GeneXpert footprint. CONCLUSIONS:Analysis of TB diagnostic networks highlighted key gaps and opportunities to optimize services. Network mapping and optimization should be considered an integral part of strategic planning. By building efficient and patient-centred diagnostic networks, countries will be better equipped to meet End TB targets.

BackgroundThe pluripotent state of embryonic stem (ES) cells is controlled by a network of specific transcription factors. Recent studies also suggested the significant contribution of mitochondria on the regulation of pluripotent stem cells. However, the molecules involved in these regulations are still unknown.Methodology/principal findingsIn this study, we found that prohibitin 2 (PHB2), a pleiotrophic factor mainly localized in mitochondria, is a crucial regulatory factor for the homeostasis and differentiation of ES cells. PHB2 was highly expressed in undifferentiated mouse ES cells, and the expression was decreased during the differentiation of ES cells. Knockdown of PHB2 induced significant apoptosis in pluripotent ES cells, whereas enhanced expression of PHB2 contributed to the proliferation of ES cells. However, enhanced expression of PHB2 strongly inhibited ES cell differentiation into neuronal and endodermal cells. Interestingly, only PHB2 with intact mitochondrial targeting signal showed these specific effects on ES cells. Moreover, overexpression of PHB2 enhanced the processing of a dynamin-like GTPase (OPA1) that regulates mitochondrial fusion and cristae remodeling, which could induce partial dysfunction of mitochondria.Conclusions/significanceOur results suggest that PHB2 is a crucial mitochondrial regulator for homeostasis and lineage-specific differentiation of ES cells.

The present studies examined the relationship between fasting blood glucose and Hb A1c in C57BL/6J, DBA/2J, and KK/HlJ mice with and without diabetes mellitus. Daily averaged blood glucose levels based on continuous glucose monitoring and effects of 6-h vs. overnight fasting on blood glucose were determined. Daily averaged blood glucose levels were highly correlated with Hb A1c, as determined with a hand-held automated device using an immunodetection method. R² values were 0.90, 0.95, and 0.99 in KK/HIJ, C57BL/6J, and DBA/2J, respectively. Six-hour fasting blood glucose correlated more closely with the level of daily averaged blood glucose and with Hb A1c than did blood glucose following an overnight fast. To validate the immunoassay-determined Hb A1c, we also measured total glycosylated hemoglobin using boronate HPLC. Hb A1c values correlated well with total glycosylated hemoglobin in all three strains but were relatively lower than total glycosylated hemoglobin in diabetic DBA/2J mice. These results show that 6-h fasting glucose provides a superior index of glycemic control and correlates more closely with Hb A1c than overnight-fasted blood glucose in these strains of mice. [ABSTRACT FROM AUTHOR]

To reliably infect a primate model for human immunodeficiency virus (HIV), ~10,000-fold more virus must be delivered vaginally than intravenously. However, the vaginal mechanisms that help protect against HIV are poorly understood. Here, we report that human cervicovaginal mucus (CVM), obtained from donors with normal lactobacillus-dominated vaginal flora, efficiently traps HIV, causing it to diffuse more than 1,000-fold more slowly than it does in water. Lactobacilli acidify CVM to pH ~4 by continuously producing lactic acid. At this acidic pH, we found that lactic acid, but not HCl, abolished the negative surface charge on HIV without lysing the virus membrane. In contrast, in CVM neutralized to pH 6 to 7, as occurs when semen temporarily neutralizes the vagina, HIV maintained its native surface charge and diffused only 15-fold more slowly than it would in water. Thus, methods that can maintain both a high lactic acid content and acidity for CVM during coitus may contribute to both vaginal and penile protection by trapping HIV before it can reach target cells. Our results reveal that CVM likely plays an important but currently unappreciated role in decreasing the rate of HIV sexual transmission. [ABSTRACT FROM AUTHOR]