A stochastic dynamical model for nosocomial infections with co-circulation of sensitive and resistant bacterial strains.

Nosocomial infections (hospital-acquired) has been an important public health problem, which may make those patients with infections or involved visitors and hospital personnel at higher risk of worse clinical outcomes or infection, and then consume more healthcare resources. Taking into account the stochasticity of the death and discharge rate of patients staying in hospitals, in this paper, we propose a stochastic dynamical model describing the transmission of nosocomial pathogens among patients admitted for hospital stays. The stochastic terms of the model are incorporated to capture the randomness arising from death and discharge processes of patients. Firstly, a sufficient condition is established for the stochastic extinction of disease. It shows that introducing randomness in the model will result in lower potential of nosocomial outbreaks. Further, we establish a threshold criterion on the existence of stationary distribution and ergodicity for any positive solution of the model. Particularly, the spectral radius form of stochastic threshold value is calculated in the special case. Moreover, the numerical simulations are conducted to both validate the theoretical results and investigate the effect of prevention and control strategies on the prevalence of nosocomial infection. We show that enhancing hygiene, targeting colonized and infected patients, improving antibiotic treatment accuracy, shortening treatment periods are all crucial factors to contain nosocomial infections.

Estimating asymptomatic, undetected and total cases for the COVID-19 outbreak in Wuhan: a mathematical modeling study.

BACKGROUND: The COVID-19 outbreak in Wuhan started in December 2019 and was under control by the end of March 2020 with a total of 50,006 confirmed cases by the implementation of a series of nonpharmaceutical interventions (NPIs) including unprecedented lockdown of the city. This study analyzes the complete outbreak data from Wuhan, assesses the impact of these public health interventions, and estimates the asymptomatic, undetected and total cases for the COVID-19 outbreak in Wuhan. METHODS: By taking different stages of the outbreak into account, we developed a time-dependent compartmental model to describe the dynamics of disease transmission and case detection and reporting. Model coefficients were parameterized by using the reported cases and following key events and escalated control strategies. Then the model was used to calibrate the complete outbreak data by using the Monte Carlo Markov Chain (MCMC) method. Finally we used the model to estimate asymptomatic and undetected cases and approximate the overall antibody prevalence level. RESULTS: We found that the transmission rate between Jan 24 and Feb 1, 2020, was twice as large as that before the lockdown on Jan 23 and 67.6% (95% CI [0.584,0.759]) of detectable infections occurred during this period. Based on the reported estimates that around 20% of infections were asymptomatic and their transmission ability was about 70% of symptomatic ones, we estimated that there were about 14,448 asymptomatic and undetected cases (95% CI [12,364,23,254]), which yields an estimate of a total of 64,454 infected cases (95% CI [62,370,73,260]), and the overall antibody prevalence level in the population of Wuhan was 0.745% (95% CI [0.693%,0.814%]) by March 31, 2020. CONCLUSIONS: We conclude that the control of the COVID-19 outbreak in Wuhan was achieved via the enforcement of a combination of multiple NPIs: the lockdown on Jan 23, the stay-at-home order on Feb 2, the massive isolation of all symptomatic individuals via newly constructed special shelter hospitals on Feb 6, and the large scale screening process on Feb 18. Our results indicate that the population in Wuhan is far away from establishing herd immunity and provide insights for other affected countries and regions in designing control strategies and planing vaccination programs.

Repression of the long noncoding RNA-LET by histone deacetylase 3 contributes to hypoxia-mediated metastasis.

Recently, long noncoding RNAs (lncRNAs) were found to be dysregulated in a variety of tumors. However, it remains unknown how and through what molecular mechanisms the expression of lncRNAs is controlled. In this study, we found that the lncRNA Low Expression in Tumor (lncRNA-LET) was generally downregulated in hepatocellular carcinomas, colorectal cancers, and squamous-cell lung carcinomas. We demonstrated that hypoxia-induced histone deacetylase 3 repressed lncRNA-LET by reducing the histone acetylation-mediated modulation of the lncRNA-LET promoter region. Interestingly, the downregulation of lncRNA-LET was found to be a key step in the stabilization of nuclear factor 90 protein, which leads to hypoxia-induced cancer cell invasion. Moreover, the relationship among hypoxia, histone acetylation disorder, low lncRNA-LET expression level, and metastasis was found in clinical hepatocellular carcinoma samples. These results advance our understanding of the role of lncRNA-LET as a regulator of hypoxia signaling and offer new avenues for therapeutic intervention against cancer progression.

Modeling Antibiotic Use Strategies in Intensive Care Units: Comparing De-escalation and Continuation.

Antimicrobial de-escalation refers to the treatment mechanism of switching from empiric antibiotics with good coverage to alternatives based on laboratory susceptibility test results, with the aim of avoiding unnecessary use of broad-spectrum antibiotics. In a previous study, we have developed multi-strain and multi-drug models in an intensive care unit setting, to evaluate the benefits and trade-offs of de-escalation in comparison with the conventional strategy called antimicrobial continuation. Our simulation results indicated that for a large portion of credible parameter combinations, de-escalation reduces the use of the empiric antibiotic but increases the probabilities of colonization and infections. In this paper, we first simplify the previous models to compare the long-term dynamical behaviors between de-escalation and continuation systems under a two-strain scenario. The analytical results coincide with our previous findings in the complex models, indicating the benefits and unintended consequences of de-escalation strategy result from the nature of this treatment mechanism, not from the complexity of the high-dimensional systems. By extending the models to three-strain scenarios, we find that de-escalation is superior than continuation in preventing outbreaks of invading strains that are resistant to empiric antibiotics. Thus decisions on antibiotic use strategies should be made specifically according to ICU conditions and intervention objectives.

Preparation of Antioxidant Peptide by Microwave- Assisted Hydrolysis of Collagen and Its Protective Effect Against H2O2-Induced Damage of RAW264.7 Cells.

Antioxidant peptides have elicited interest for the versatility of their use in the food and pharmaceutical industry. In the current study, antioxidant peptides were prepared by microwave-assisted alkaline protease hydrolysis of collagen from sea cucumber (Acaudina molpadioides). The results showed that microwave irradiation significantly improved the degree of hydrolysis of collagen and the hydroxyl radical (OH⋅) scavenging activity of hydrolysate. The content and OH⋅ scavenging activity of collagen peptides with molecular weight ≤ 1 kDa (CPS) in the hydrolysate obtained at 250 W increased significantly compared with the non-microwave-assisted control. CPS could scavenge OH⋅ and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical in a dose-dependent manner. The scavenging activity of OH⋅ and DPPH radical was 93.1% and 41.2%, respectively, at CPS concentration of 1 mg/mL. CPS could significantly promote RAW264.7 cell proliferation and reduce the Reactive Oxygen Species (ROS) level of H2O2-induced damage in RAW264.7 cells in a dose-dependent manner. Furthermore, all CPS-treated groups exhibited an increase in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and a decrease in malondialdehyde (MDA) level compared with the control. These results showed that CPS could effectively protect RAW264.7 cells from H2O2-induced damage, implying the potential utilization of CPS as a natural antioxidant for food and pharmaceutical applications.

Preparation and Evaluation of Peptides with Potential Antioxidant Activity by Microwave Assisted Enzymatic Hydrolysis of Collagen from Sea Cucumber Acaudina Molpadioides Obtained from Zhejiang Province in China.

The present study was focused on the preparation and characterization of the antioxidant peptides by microwave-assisted enzymatic hydrolysis of collagen from sea cucumber Acaudina molpadioides (ASC-Am) obtained from Zhejiang Province in China. The results exhibited the effects of microwave irradiation on hydrolysis of ASC-Am with different protease. Neutrase was selected from the four common proteases (papain, pepsin, trypsin, and neutrase) based on the highest content and DPPH scavenging activity of hydrolysate Fa (Molecular weight < 1 kDa). The content and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity of Fa obtained by hydrolysis of neutrase increased by 100% and 109% respectively at a microwave power of 300 W compared with no microwave irradiation. Five subfractions were obtained after performing the gel filtration chromatography, and the Fa.2 exhibited the highest DPPH scavenging activity. The amino acid analysis showed that the contents of Glutamic acid, Alanine, Tyrosine, and Phenylalanine in fraction Fa.2 increased significantly, but an obvious decrease in the content of Glycine was observed compared to Fa. Four peptides (Fa.2-A, Fa.2-B, Fa.2-C, and Fa.2-D) were purified from Fa.2 by high performance liquid chromatography, and Fa.2-C showed the highest DPPH scavenging activity. The sequence of Fa.2-C was identified as Phenylalanine-Leucine- Alanine-Proline with a half elimination ratio (EC50) of 0.385 mg/mL. The antioxidant activity of Fa.2-C was probably attributed to the small molecular sizes and the presence of hydrophobic amino acid residues in its sequence. This report provided a promising method for the preparation of antioxidant peptides from collagen for food and medicinal purposes.

A conceptual model for optimizing vaccine coverage to reduce vector-borne infections in the presence of antibody-dependent enhancement.

BACKGROUND: Many vector-borne diseases co-circulate, as the viruses from the same family are also transmitted by the same vector species. For example, Zika and dengue viruses belong to the same Flavivirus family and are primarily transmitted by a common mosquito species Aedes aegypti. Zika outbreaks have also commonly occurred in dengue-endemic areas, and co-circulation and co-infection of both viruses have been reported. As recent immunological cross-reactivity studies have confirmed that convalescent plasma following dengue infection can enhance Zika infection, and as global efforts of developing dengue and Zika vaccines are intensified, it is important to examine whether and how vaccination against one disease in a large population may affect infection dynamics of another disease due to antibody-dependent enhancement. METHODS: Through a conceptual co-infection dynamics model parametrized by reported dengue and Zika epidemic and immunological cross-reactivity characteristics, we evaluate impact of a hypothetical dengue vaccination program on Zika infection dynamics in a single season when only one particular dengue serotype is involved. RESULTS: We show that an appropriately designed and optimized dengue vaccination program can not only help control the dengue spread but also, counter-intuitively, reduce Zika infections. We identify optimal dengue vaccination coverages for controlling dengue and simultaneously reducing Zika infections, as well as the critical coverages exceeding which dengue vaccination will increase Zika infections. CONCLUSION: This study based on a conceptual model shows the promise of an integrative vector-borne disease control strategy involving optimal vaccination programs, in regions where different viruses or different serotypes of the same virus co-circulate, and convalescent plasma following infection from one virus (serotype) can enhance infection against another virus (serotype). The conceptual model provides a first step towards well-designed regional and global vector-borne disease immunization programs.

Enhancement of epoxide hydrolase production by 60 Co gamma and UV irradiation mutagenesis of Aspergillus niger ZJB-09103.

An effective epoxide hydrolase (EH) production strain was mutagenized using 60 Co gamma and UV irradiation. Among positive mutant strains, the EH activity of C2-44 reached 33.7 U/g, which was 267% as much as that of the original Aspergillus niger ZJB-09103. Compared with the wild type, there were significant changes in morphology for C2-44, including the color of mycelia on the slants and the shape of conidial head. In addition, glucose and soybean cake were the optimal carbon and nitrogen source in terms of EH activity for the mutant C2-44 instead of soluble starch and peptone for the wild-type strain. The reaction time required to reach 99% enantiomeric excesses of (S)-epichlorohydrin from racemic substrate was shortened significantly by the mutant C2-44. This phenomenon was probably explained by the higher Vmax for hydrolysis of racemic epichlorohydrin by C2-44 compared with Aspergillus niger ZJB-09103.

Two Cases of Multi-antibiotic Resistant Cronobacter spp. Infections of Infants in China.

Infections by Cronobacter spp. are hazardous to infants since they can lead to neonatal meningitis, bacteremia, and necrotizing enterocolitis. Cronobacter spp. are frequently resistant to ß-lactam derivatives, macrolides, and aminoglycosides. In addition, multi-resistant strains have also been detected. In China, the isolation rate of Cronobacter spp. from commercial powdered infant formula (PIF) or follow-up formula (FUF) is relatively high. Nevertheless, clinical cases of Cronobacter infection have been ignored to date. Here we describe two cases of Cronobacter infection detected at the Wuhan Women and Children Medical Care Center Hospital (Wuhan City, China). We provide the genomic analysis of the isolates and the antibiotic-resistance profiles of the two strains. The Cronobacter strains identified in this study were not susceptible to third-generation cephalosporins, aminoglycoside, and/or trimethoprim-sulfamethoxazole. Whole genome sequencing revealed various genes known to encode antibiotic resistance. Future studies are needed to determine whether the genes predicted in this study are functional. As with Enterobacter spp., the antibiotic resistance of Cronobacter is a serious issue that requires more attention.

Treatment-donation-stockpile dynamics in ebola convalescent blood transfusion therapy.

The interim guidance issued by the World Health Organization during the West Africa 2014 Ebola outbreak provides guidelines on the use of convalescent blood from Ebola survivors for transfusion therapy. Here we develop a novel mathematical model, based on the interim guidance, to examine the nonlinear transmission-treatment-donation-stockpile dynamics during an Ebola outbreak and with a large scale use of the transfusion therapy in the population. We estimate the reduction of case fatality ratio by introducing convalescent blood transfusion as a therapy, and inform optimal treatment-donation-stockpile strategies to balance the treatment need for case fatality ratio reduction and the strategic need of maintaining a minimal blood bank stockpile for other control priorities.

Analysis of flumequine enantiomers in rat plasma by UFLC-ESI-MS/MS.

In this study the analysis and confirmation of flumequine enantiomers in rat plasma by ultra-fast liquid chromatography coupled with electron spray ionization mass spectrometry (using propranolol as an internal standard [IS]) was developed and validated. Plasma samples were prepared by liquid-liquid extraction using methyl tert-butyl ether as the extraction solvent. Direct resolution of the R- and S-isomers was performed on a CHIRALCEL OJ-RH column (4.6 × 150 mm, 5 µm) using acetonitrile / 0.1% formic acid / 1 mM ammonium acetate as the mobile phase. Detection was operated by electron spray ionization in the selected ion monitoring and positive ion mode. The target ions at m/z 262.1 and m/z 260.1 were selected for the quantification of the enantiomers and IS, respectively. The linear range was 0.5-500 ng/mL. The precisions (coefficient of variation, CV%) and recoveries were 1.43-8.68 and 94.24-106.76%, respectively. The lowest quantitation limit for both enantiomers is 0.5 ng/mL, which is sensitive enough to be applied to sample analysis in other related studies.

Validation of a Chiral Liquid Chromatographic Method for the Degradation Behavior of Flumequine Enantiomers in Mariculture Pond Water.

In this work, flumequine (FLU) enantiomers were separated using a Chiralpak OD-H column, with n-hexane-ethanol (20:80, v/v) as the mobile phase at a flow rate of 0.6 mL/min. Solid phase extraction (SPE) was used for cleanup and enrichment. The limit of detection, limit of quantitation, linearity, precision, and intra/interday variation of the chiral high-performance liquid chromatography (HPLC) method were determined. The developed method was then applied to investigate the degradation behavior of FLU enantiomers in mariculture pond water samples. The results showed that the degradation of FLU enantiomers under natural, sterile, or dark conditions was not enantioselective. Chirality 28:649-655, 2016. © 2016 Wiley Periodicals, Inc.

Synthesis and Characterization of Magnetic Molecularly Imprinted Polymer for the Enrichment of Ofloxacin Enantiomers in Fish Samples.

A new method for the isolation and enrichment of ofloxacin enantiomers from fish samples was developed using magnetic molecularly imprinted polymers (MMIPs). These polymers can be easily collected and rapidly separated using an external magnetic field, and also exhibit a high specific recognition for ofloxacin enantiomers. The preparation of amino-functionalized MMIPs was carried out via suspension polymerization and a ring-opening reaction using rac-ofloxacin as a template, ethylenediamine as an active group, glycidyl methacrylate and methyl methacrylate as functional monomers, divinylbenzene as a cross-linker, and Fe3O4 nanoparticles as magnetic cores. The characteristics of the MMIPs were assessed using transmission electron microscopy (TEM), X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and vibrating sample magnetometer (VSM) measurements. Furthermore, the adsorption properties were determined using Langmuir and Freundlich isotherm models. The conditions for use of these MMIPs as magnetic solid-phase extraction (MSPE) sorbents, including pH, adsorption time, desorption time, and eluent, were investigated in detail. An extraction method using MMIPs coupled with high performance liquid chromatography (HPLC) was developed for the determination of ofloxacin enantiomers in fish samples. The limits of quantitation (LOQ) for the developed method were 0.059 and 0.067 µg∙mL(-1) for levofloxacin and dextrofloxacin, respectively. The recovery of ofloxacin enantiomers ranged from 79.2% ± 5.6% to 84.4% ± 4.6% and ofloxacin enantiomers had good linear relationships within the concentration range of 0.25-5.0 µg∙mL(-1) (R² > 0.999). The obtained results demonstrate that MSPE-HPLC is a promising approach for preconcentration, purification, and simultaneous separation of ofloxacin enantiomers in biomatrix samples.

[Effect of continuous hemofiltration on inflammatory mediators and hemodynamics in children with severe hand, foot and mouth disease].

OBJECTIVE: To investigate the effect of continuous veno-venous hemofiltration (CVVH) on inflammatory mediators in children with severe hand, foot and mouth disease (HFMD), and to investigate its clinical efficacy. METHODS: A total of 36 children with stage IV HFMD were enrolled and randomly divided into conventional treatment group and CVVH group (n=18 each). The children in the CVVH group were given CVVH for 48 hours in addition to the conventional treatment. The levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and lactic acid in peripheral venous blood, heart rate, blood pressure, and left ventricular ejection fraction were measured before treatment and after 24 and 48 hours of treatment. RESULTS: After 24 hours of treatment, the conventional treatment group had a significantly reduced serum IL-2 level (P<0.01), and the CVVH treatment group had significantly reduced serum levels of IL-2, IL-6, IL-10, and TNF-α (P<0.05). After 48 hours of treatment, both groups had significantly reduced serum levels of IL-2, IL-6, IL-10, and TNF-α (P<0.01), and the CVVH group had significantly lower levels of these inflammatory factors than the conventional treatment group (P<0.01). After 48 hours of treatment, heart rate, systolic pressure, and blood lactic acid level were significantly reduced, and left ventricular ejection fraction was significantly increased in both groups, and the CVVH group had significantly greater changes in these indices except systolic pressure than the conventional treatment group (P<0.01). CONCLUSIONS: CVVH can effectively eliminate inflammatory factors, reduce heart rate and venous blood lactic acid, and improve heart function in children with severe HFMD.

An agent-based model on antimicrobial de-escalation in intensive care units: Implications on clinical trial design.

Antimicrobial de-escalation refers to reducing the spectrum of antibiotics used in treating bacterial infections. This strategy is widely recommended in many antimicrobial stewardship programs and is believed to reduce patients' exposure to broad-spectrum antibiotics and prevent resistance. However, the ecological benefits of de-escalation have not been universally observed in clinical studies. This paper conducts computer simulations to assess the ecological effects of de-escalation on the resistance prevalence of Pseudomonas aeruginosa-a frequent pathogen causing nosocomial infections. Synthetic data produced by the models are then used to estimate the sample size and study period needed to observe the predicted effects in clinical trials. Our results show that de-escalation can reduce colonization and infections caused by bacterial strains resistant to the empiric antibiotic, limit the use of broad-spectrum antibiotics, and avoid inappropriate empiric therapies. Further, we show that de-escalation could reduce the overall super-infection incidence, and this benefit becomes more evident under good compliance with hand hygiene protocols among health care workers. Finally, we find that any clinical study aiming to observe the essential effects of de-escalation should involve at least ten arms and last for four years-a size never attained in prior studies. This study explains the controversial findings of de-escalation in previous clinical studies and illustrates how mathematical models can inform outcome expectations and guide the design of clinical studies.

METTL3 Promotes Osteosarcoma Metastasis via an m6A-dependent Epigenetic Activity of CBX4.

BACKGROUND: Osteosarcoma cells are prone to metastasis, and the mechanism of N6-methyladenosine (m6A) methylation modification in this process is still unclear. Methylation modification of m6A plays an important role in the development of osteosarcoma, which is mainly due to abnormal expression of enzymes related to methylation modification of m6A, which in turn leads to changes in the methylation level of downstream target genes messenger RNA (mRNA) leading to tumor development. METHODS: We analyzed the expression levels of m6A methylation modification-related enzyme genes in GSE12865 whole-genome sequencing data. And we used shRNA (short hairpin RNA) lentiviral interference to interfere with METTL3 (Methyltransferase 3) expression in osteosarcoma cells. We studied the cytological function of METTL3 by Cell Counting Kit-8 (CCK8), flow cytometry, migration and other experiments, and the molecular mechanism of METTL3 by RIP (RNA binding protein immunoprecipitation), Western blot and other experiments. RESULTS: We found that METTL3 is abnormally highly expressed in osteosarcoma and interferes with METTL3 expression in osteosarcoma cells to inhibit metastasis, proliferation, and apoptosis of osteosarcoma cells. We subsequently found that METTL3 binds to the mRNA of CBX4 (chromobox homolog 4), a very important regulatory protein in osteosarcoma metastasis, and METTL3 regulates the mRNA and protein expression of CBX4. Further studies revealed that METTL3 inhibited metastasis of osteosarcoma cells by regulating CBX4. METTL3 has been found to be involved in osteosarcoma cells metastasis by CBX4 affecting the protein expression of matrix metalloproteinase 2 (MMP2), MMP9, E-Cadherin and N-Cadherin associated with osteosarcoma cells metastasis. CONCLUSIONS: These results suggest that the combined action of METTL3 and CBX4 plays an important role in the regulation of metastasis of osteosarcoma, and therefore, the METTL3-CBX4 axis pathway may be a new potential therapeutic target for osteosarcoma.

Epigenetic activation of the MiR-200 family contributes to H19-mediated metastasis suppression in hepatocellular carcinoma.

Although numerous long non-coding RNAs (lncRNAs) have been identified in mammals, many of their biological roles remain to be characterized. Early reports suggest that H19 contributes to carcinogenesis, including hepatocellular carcinoma (HCC). Examination of the Oncomine resource showed that most HCC cases express H19 at a level that is comparable with the liver, with a tendency toward lower expression. This is consistent with our previous microarray data and indicates a more complicated role of H19 in HCC that needs to be characterized. In this study, the expression level of H19 was assessed in different regions of HCC patients' liver samples. Loss- and gain-of-function studies on this lncRNA in the HCC cell lines, SMMC7721 and HCCLM3, were used to characterize its effects on gene expression and to assess its effect on HCC metastasis both in vitro and in vivo. In this study, we show that H19 was underexpressed in intratumoral HCC tissues (T), as compared with peritumoral tissues (L). Additionally, low T/L ratio of H19 predicted poor prognosis. H19 suppressed HCC progression metastasis and the expression of markers of epithelial-to-mesenchymal transition. Furthermore, H19 associated with the protein complex hnRNP U/PCAF/RNAPol II, activating miR-200 family by increasing histone acetylation. The results demonstrate that H19 can alter the miR-200 pathway, thus contributing to mesenchymal-to-epithelial transition and to the suppression of tumor metastasis. These data provide an explanation for the hitherto puzzling literature on the relationship between H19 and cancer, and could suggest the development of combination therapies that target H19 and the miR-200 family.

Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients' poor recurrence-free survival after hepatectomy.

UNLABELLED: Survival of patients with hepatocellular carcinoma (HCC) remains poor, which is largely attributed to active angiogenesis. However, the mechanisms underlying angiogenesis in HCC remain to be discovered. In this study, we found that long noncoding RNA associated with microvascular invasion in HCC (lncRNA MVIH) (lncRNA associated with microvascular invasion in HCC) was generally overexpressed in HCC. In a cohort of 215 HCC patients, the overexpression of MVIH was associated with frequent microvascular invasion (P = 0.016) and a higher tumor node metastasis stage (P = 0.009) as well as decreased recurrence-free survival (RFS) (P < 0.001) and overall survival (P = 0.007). Moreover, the up-regulation of MVIH served as an independent risk factor to predict poor RFS. We also found that MVIH could promote tumor growth and intrahepatic metastasis by activating angiogenesis in mouse models. Subsequent investigations indicated that MVIH could activate tumor-inducing angiogenesis by inhibiting the secretion of phosphoglycerate kinase 1 (PGK1). Additionally, in 65 HCC samples, MVIH expression was inversely correlated with the serum level of PGK1 and positively correlated with the microvessel density. CONCLUSION: Deregulation of lncRNA MVIH is a predictor for poor RFS of HCC patients after hepatectomy and could be utilized as a potential target for new adjuvant therapies against active angiogenesis.

Linking mathematical models and trap data to infer the proliferation, abundance, and control of Aedes aegypti.

Aedes aegypti is one of the most dominant mosquito species in the urban areas of Miami-Dade County, Florida, and is responsible for the local arbovirus transmissions. Since August 2016, mosquito traps have been placed throughout the county to improve surveillance and guide mosquito control and arbovirus outbreak response. In this paper, we develop a deterministic mosquito population model, estimate model parameters by using local entomological and temperature data, and use the model to calibrate the mosquito trap data from 2017 to 2019. We further use the model to compare the Ae. aegypti population and evaluate the impact of rainfall intensity in different urban built environments. Our results show that rainfall affects the breeding sites and the abundance of Ae. aegypti more significantly in tourist areas than in residential places. In addition, we apply the model to quantitatively assess the effectiveness of vector control strategies in Miami-Dade County.

The histone deacetylase 4/SP1/microrna-200a regulatory network contributes to aberrant histone acetylation in hepatocellular carcinoma.

UNLABELLED: As an important epigenetic mechanism, histone acetylation modulates the transcription of many genes and plays important roles in hepatocellular carcinoma (HCC). Aberrations in histone acetylation have been observed in HCC, but the factors that contribute to the aberrations have not been fully elucidated. MicroRNAs (miRNAs), which are noncoding RNAs that regulate gene expression, are involved in important epigenetic mechanisms. In this study, we determined that miR-200a and the level of histone H3 acetylation at its promoter were reduced in human HCC tissues in comparison with adjacent noncancerous hepatic tissues. Furthermore, our results suggested that the histone deacetylase 4 (HDAC4) inhibited the expression of miR-200a and its promoter activity and reduced the histone H3 acetylation level at the mir-200a promoter through a Sp1-dependent pathway. Interestingly, we observed that the miR-200a directly targeted the 3'-untranslated region of the HDAC4 messenger RNA and repressed expression of HDAC4. Therefore, miR-200a ultimately induced its own transcription and increased the histone H3 acetylation level at its own promoter. Through targeting HDAC4, miR-200a also induced the up-regulation of total acetyl-histone H3 levels and increased the histone H3 acetylation level at the p21(WAF/Cip1) promoter. Finally, we determined that miR-200a inhibited the proliferation and migration of HCC cells in vivo and in vitro. CONCLUSION: Our findings suggest that the HDAC4/Sp1/miR-200a regulatory network induces the down-regulation of miR-200a and the up-regulation of HDAC4 in HCC. As a result, down-regulation of miR-200a enhances the proliferation and migration of HCC cells and induces aberrant histone acetylation in HCC. These findings highlight a potential therapeutic approach in targeting the HDAC4/Sp1/miR-200a regulatory network for the treatment of HCC.