Modeling and analysis of a human papilloma virus transmission model with impact of media.

The human papillomavirus (HPV) is threatening human health as it spreads globally in varying degrees. On the other hand, the speed and scope of information transmission continues to increase, as well as the significant increase in the number of HPV-related news reports, it has never been more important to explore the role of media news coverage in the spread and control of the virus. Using a decreasing factor that captures the impact of media on the actions of people, this paper develops a model that characterizes the dynamics of HPV transmission with media impact, vaccination and recovery. We obtain global stability of equilibrium points employing geometric method, and further yield effective methods to contain the HPV pandemic by sensitivity analysis. With the center manifold theory, we show that there is a forward bifurcation when R0=1. Our study suggested that, besides controlling contact between infected and susceptible populations and improving effective vaccine coverage, a better intervention would be to strengthen media coverage. In addition, we demonstrated that contact rate and the effect of media coverage result in multiple epidemics of infection when certain conditions are met, implying that interventions need to be tailored to specific situations.

Integrated RPA-CRISPR/Cas12a system towards Point-of-Care H. pylori detection.

The rapidly advanced CRISPR/Cas biosensing technology provides unprecedent potential for the development of novel biosensing systems. It provides a new approach for realizing rapid, sensitivity and highly specific pathogen nucleic acid detection, with the capability to combine other technologies, including Polymerase Chain Reaction or isothermal amplifications. The detection of Helicobacter pylori (H. pylori), one of the most common human pathogens to cause various gastroduodenal diseases, has also been explored with the assistance of CRISPR/Cas systems. However, gaps still remain for the development of end-user friendly sensing systems.In this study, a combined RPA-CRISPR/Cas12a biosensing system has been established. It shown the capability to quantitively detect the presence of H. pylori genome DNA with 4 orders of magnitude linear range, and sensitivity of 1.4 copies/µL. The overall reaction can be done within 45 mins at room temperature, which eliminates the needs for heating instrumentation. In addition, with the addition of pullulan as a protective reagent, the potential of storing CRISPR/Cas12a system reagents by using a freeze-dry approach has also been demonstrated.Clinical Relevance - This study represents a novel exploration to applying CRISPR/Cas12a-based biosensing technology to the detection of pathogen DNA with improved potential for the development of Point-of-Care diagnostics. This critical aspect of our technology will contribute to address the newly emerged pathogenic threats and support public health systems.

Impact of vaccine measures on the transmission dynamics of COVID-19.

In many nations, efforts to prevent and control COVID-19 have been significantly impeded by the SARS-CoV-2 virus ongoing mutation. The Omicron strain, a more recent and prevalent strain, has had more significant detrimental effects in countries worldwide. To investigate the impact of the Omicron BA.2 strain on vaccine efficacy, we proposed a model with vaccination and immunological decline in this research. Then, we fitted our model based on the number of daily new instances reported by the government in Jilin and Shanghai, China. We estimated the effective reproduction number Re = 4.71 for the Jilin and Re = 3.32 for Shanghai. Additionally, we do sensitivity analysis to identify the critical factors affecting the effective reproduction number Re. It was found that vaccination rate, effectiveness rate, and declining rate had a significant effect on Re. Further, we investigate the relevant parameter thresholds that make Re lower than unity. Finally, rich numerical experiments were then carried out. We observed that even when vaccine efficiency was not high, increasing vaccination rates had a significant effect on early disease transmission, that limiting social distance was the most economical and rational measure to control the spread of disease, and that for a short period, reducing immune decline was not significant in curbing disease transmission.

Stability and Hopf bifurcation of an SIR epidemic model with density-dependent transmission and Allee effect.

In this paper, an SIR model with a strong Allee effect and density-dependent transmission is proposed, and its characteristic dynamics are investigated. The elementary mathematical characteristic of the model is studied, including positivity, boundedness and the existence of equilibrium. The local asymptotic stability of the equilibrium points is analyzed using linear stability analysis. Our results indicate that the asymptotic dynamics of the model are not only determined using the basic reproduction number ${R_0}$. If ${R_0} < 1$, there are three disease-free equilibrium points, and a disease-free equilibrium is always stable. At the same time, the conditions for other disease-free equilibrium points to be bistable were determined. If ${R_0} > 1$ and in certain conditions, either an endemic equilibrium emerges and is locally asymptotically stable, or the endemic equilibrium becomes unstable. What must be emphasized is that there is a locally asymptotically stable limit cycle when the latter happens. The Hopf bifurcation of the model is also discussed using topological normal forms. The stable limit cycle can be interpreted in a biological significance as a recurrence of the disease. Numerical simulations are used to verify the theoretical analysis. Taking into account both density-dependent transmission of infectious diseases and the Allee effect, the dynamic behavior becomes more interesting than when considering only one of them in the model. The Allee effect makes the SIR epidemic model bistable, which also makes the disappearance of diseases possible, since the disease-free equilibrium in the model is locally asymptotically stable. At the same time, persistent oscillations due to the synergistic effect of density-dependent transmission and the Allee effect may explain the recurrence and disappearance of disease.

Effect of continuous positive airway pressure on albuminuria in patients with obstructive sleep apnea: a meta-analysis.

PURPOSE: A relationship between albuminuria and obstructive sleep apnea (OSA) has been documented in previous studies. Nevertheless, the impact of continuous positive airway pressure (CPAP) treatment on albuminuria in subjects with OSA is debated. This meta-analysis was carried out to investigate whether or not CPAP treatment affected urinary albumin-to-creatinine ratio (UACR) in subjects with OSA. METHODS: A comprehensive literature search was conducted on Web of Science, Embase, and PubMed from January 1990 to December 2020. Information on patients' characteristics, features of the studies, and UACR of pre- and post-CPAP treatment was collected. For estimation of the pooled effects, standardized mean difference (SMD) was applied. RESULTS: This meta-analysis included 6 articles and 211 subjects. The pooled analysis suggested that CPAP therapy exerted a favorable effect on the decrease of UACR in subjects with OSA (SMD = 0.415, 95% CI = 0.026 to 0.804, z = 2.09, p = 0.037). Subgroup analyses revealed that the CPAP treatment effect was not influenced by sample size, BMI, age, or AHI. CONCLUSION: The present meta-analysis indicated that UACR was significantly reduced by CPAP therapy in subjects with OSA. Further well-designed randomized controlled trials with large sample size are required to confirm the benefits.

Validation of fatty liver index and hepatic steatosis index for screening of non-alcoholic fatty liver disease in adults with obstructive sleep apnea hypopnea syndrome.

BACKGROUND: Obstructive sleep apnea hypopnea syndrome (OSAHS) is a contributing factor for non-alcoholic fatty liver disease (NAFLD). Non-invasive algorithms including fatty liver index (FLI) and hepatic steatosis index (HSI) have been used as a screening test for NAFLD in epidemiologic studies. The aim of this study is to compare the diagnostic accuracy of FLI and HSI for NAFLD detection in adults with OSAHS. METHODS: We enrolled consecutive adult subjects who were newly diagnosed with OSAHS from March 2016 to January 2018. NAFLD was diagnosed by ultrasonography. The accuracy and cut-off point of the FLI and HSI to detect NAFLD were assessed by analyzing the area under the receiver operating characteristic (AUROC) curve and the maximum Youden index analysis, respectively. RESULTS: The 326 subjects were diagnosed as NAFLD according to ultrasound findings, while 105 subjects who had normal abdominal ultrasonography were grouped as controls. Both FLI and HSI values were significantly higher in patients with NAFLD compared with controls. The AUROC of FLI and HSI for predicting NAFLD was 0.802 (95% confidence interval [CI] 0.762-0.839) and 0.753 (95% CI 0.710-0.793), respectively. The AUROC of FLI was significantly higher than that of HSI (P = 0.0383). The optimal cut-off value of FLI and HSI was 60 (sensitivity 66% and specificity 80%) and 35 (sensitivity 81% and specificity 60%), respectively. CONCLUSIONS: Both FLI and HSI can serve as screening tools for NAFLD in OSAHS adults. The FLI shows better performance in diagnosing NAFLD than HSI. TRIAL REGISTRATION: Chinese Clinical Trial Registry (No. ChiCTR-OOB-15007253), http://www.chictr.org.cn/showproj.aspx?proj=11606.

Supercritical Fluid-Assisted Porous Microspheres for Efficient Delivery of Insulin and Inhalation Therapy of Diabetes.

Pulmonary delivery of drugs has attracted increasing attention in healthcare, as the lungs are an easily accessible site for noninvasive systemic delivery of drugs. Although pulmonary inhalation of porous microparticles has been shown to sustain drug delivery, there are limited reports on efficient delivery of insulin and inhalation therapy of diabetes based on supercritical carbon dioxide (SC-CO2 ) technology. Herein, this study reports the fabrication of insulin-loaded poly-l-lactide porous microspheres (INS-PLLA PMs) by using the SC-CO2 technology, and their use as an inhalation delivery system potentially for diabetes therapy. Biocompatibility and delivery efficiency of the PLLA PMs in the lungs are investigated. The PLLA PMs show negligible toxicity to lung-derived cells, resulting in no significant reduction in cell viability, as well as levels of various inflammatory mediators such as interleukin (IL)-6, IL-8, and tumor necrosis factor-α, compared with the negative control group. INS-PLLA PMs are further efficiently deposited in the trachea and the bronchi of superior lobes of the lungs, which exhibit pronounced hypoglycemic activity in induced diabetic rats. Together, the results demonstrate that the INS-PLLA PMs have a strong potential as an effective strategy for inhalation treatment of diabetes.

Supercritical Fluid-Assisted Decoration of Nanoparticles on Porous Microcontainers for Codelivery of Therapeutics and Inhalation Therapy of Diabetes.

The impact of nanotechnology and its advancements have allowed us to explore new therapeutic modalities. To this end, we designed nanoparticles-inlaid porous microparticles (NIPMs) coloaded with small interfering RNA (siRNA) and glucagon-like peptide-1 (GLP-1) using the supercritical carbon dioxide (SC-CO2) technology as an inhalation delivery system for diabetes therapy. siRNA-encapsulating chitosan (CS) nanoparticles were first synthesized by an ionic gelation method, which resulted in particles with small sizes (100-150 nm), high encapsulation efficiency (∼94.8%), and sustained release performance (∼60% in 32 h). These CS nanoparticles were then loaded with GLP-1-dispersed poly-l-lactide (PLLA) porous microparticles (PMs) by SC-CO2-assisted precipitation with the compressed antisolvent (PCA) process. The hypoglycemic efficacy of NIPMs administered via pulmonary route in mice persisted longer due to sustained release of siRNA from CS nanoparticles and the synergistic effects of GLP-1 in PMs, which significantly inhibited the expression of dipeptidyl peptidase-4 mRNA (DPP-4-mRNA). This ecofriendly technology provides a convenient way to fabricate nanoparticle-microparticle composites for codelivery of a gene and a therapeutic peptide, which will potentially find widespread applications in the field of pharmaceutics.

Composite Membranes of Recombinant Silkworm Antimicrobial Peptide and Poly (L-lactic Acid) (PLLA) for biomedical application.

Antimicrobial peptides, produced by innate immune system of hosts in response to invading pathogens, are capable of fighting against a spectrum of bacteria, viruses, fungi, parasites and cancer cells. Here, a recombinant silkworm AMP Bmattacin2 from heterologous expression is studied, indicating a broad spectrum of antibacterial activity and showing selective killing ability towards skin and colon cancer cells over their normal cell counterparts. For the purpose of biomedical application, the electrospinning fabrication technique is employed to load Bmattacin2 into PLLA nanofibrous membrane. In addition to a good compatibility with the normal cells, Bmattacin2 loaded nanofibrous membranes demonstrate instant antibacterial effects and sustained anticancer effects. The cancer cell and bacteria targeting dynamics of recombinant Bmattacin2 are investigated. With these characteristics, PLLA/Bmattacin2 composite membranes have a great potential for developing novel biomedical applications such as cancer therapies and wound healing treatments.

Temperature induced modulation of lipid oxidation and lipid accumulation in palmitate-mediated 3T3-L1 adipocytes and 3T3-L1 adipocytes.

Human skin temperature can vary widely depending on anatomical location and ambient temperature. It is also known that local changes in skin and subcutaneous temperature can affect fat metabolism. This study aimed to explore the potential effects of surrounding thermal environment on fat by investigating cell viability, lipid oxidation, and lipid accumulation in 3T3-L1 adipocytes and palmitate-treated adipocytes after 4h incubation. No significant differences of viability in 3T3-L1 adipocytes were detected under different temperature conditions. Despite no significant increase being observed under warm temperature (39°C) conditions, a similarly significant suppression of intracellular reactive oxygen species (ROS) and lipid peroxidation were found in 3T3-L1 adipocytes and palmitate-treated adipocytes under 4h exposure to cooler temperatures of 31-33°C (P<0.01). ROS, chemically reactive molecules containing oxygen, are currently understood to be a major contributor to oxidantive stress in obesity. Additionally, cooler temperatures (31-33°C) could improve the size of lipid droplets in 3T3-L1 adipocytes (P<0.01), but no significant effect was generated by temperature change on lipid droplets in palmitate-treated adipocytes. In the palmitate-induced adiposity model, although excessive ROS and lipid peroxidation has been attenuated by temperature decrease (P<0.01), it still does not positively modulate lipid droplet size (P>0.05) and remedy the palmitate damage induced cell death (P<0.01). These findings provide preliminary support for potential interventions based on temperature manipulation for cell metabolism of adipocytes.

Nano-curcumin prepared via supercritical: Improved anti-bacterial, anti-oxidant and anti-cancer efficacy.

Curcumin (CM) possesses multiple biological activities. However, poor water solubility and low bioavailability limit its application in biomedical fields. CM nanoparticles (NPs) (230-240nm) were prepared by solution-enhanced dispersion via supercritical CO2 (SEDS) (22-22.5MPa pressure, 31-32.5°C temperature) and its biological functions were evaluated in this study. The Minimum inhibitory concentration of CM NPs against S. aureus (∼250µg/mL) was lower than CM-DMSO (∼500µg/mL). Meanwhile, CM NPs showed effective anti-oxidant ability at a concentration raging from 125 to 2000µg/mL. CM NPs showed time-dependent intracellular internalization ability, resulting in an enhanced anti-cancer effect on colorectal cancer cells (HCT116), and the mechanism could be explained by cell cycle arrest in G2/M phase associated with inducing apoptotic cells. Moreover, CM NPs exhibited reduced cytotoxicity on normal cells (NCM460) compared to CM-DMSO and 5-Fu. In conclusion, CM NPs prepared via SEDS showed potentials in biomedical applications.

Silencing of Livin inhibits tumorigenesis and metastasis via VEGF and MMPs pathway in lung cancer.

Livin, an inhibitor of apoptosis protein (IAP), is overexpressed in various cancers and decreases tumor sensitivity to chemotherapy and radiotherapy. However, the effect of Livin on lung adenocarcinoma metastasis and the specific mechanism involved remain unclear. RNAi technology was used to stably silence Livin in A549 cells in the present study. The effect of Livin on tumor growth and invasion was investigated in lung cancer cells in vitro and animal models were established to determine the anti-metastasis ability of Livin silencing in vivo. The results indicated that Livin knock-down suppressed cell proliferation and inhibited cell invasion, accompanied by downregulation of VEGF and MMP-2/-9. Silencing of Livin resulted in the prevention of xenograft tumor formation. Seventy-five immunodeficient male BALB/C nude mice were randomly divided into three groups, the relative ratio of the areas with pulmonary nodules in the experimental group decreased from 46.71±7.27% to 11.07±2.94% compared with the negative control group (P<0.001), indicating the interaction between Livin, VEGF and MMPs. The xenograft tumor model of intravenous injection of tumor cells were successfully established and applied for the analysis of lung cancer tumorigenesis and metastasis in a time-dependent manner for the first time. Based on the reliable and reproducible animal model, our findings indicate that knock-down of Livin inhibits cell growth and invasion through blockade of the VEGF and MMPs pathways in lung cancer cells in vitro, and inhibits tumorigenesis and metastasis of lung cancer in vivo, suggesting that Livin is a promising antitumor target.

Biological evaluation of Fe3O4-poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide) magnetic microspheres prepared in supercritical CO2.

The biocompatibility of Fe3O4-poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide) magnetic microspheres (Fe3O4-PLLA-PEG-PLLA MMPs) prepared in a process of suspension-enhanced dispersion by supercritical CO2 (SpEDS) was evaluated at various levels: cellular, molecular, and integrated. At the cellular level, the investigations of cytotoxicity and intracellular reactive oxygen species (ROS) generation indicate that the polymer-coated MMPs (2.0 mg/mL) had a higher toxicity than uncoated Fe3O4 nanoparticles, which led to about 20% loss of cell viability and an increase (0.2 fold) in ROS generation; the differences were not statistically significant (p > 0.05). However, an opposite phenomenon was observed in tests of hemolysis, which showed that the MMPs displayed the weakest hemolytic activity, namely only about 6% at the highest concentration (20 mg/mL). This phenomenon reveals that polymer-coated MMPs created less toxicity in red blood cells than uncoated Fe3O4 nanoparticles. At the molecular level, the MMPs were shown to be less genotoxic than Fe3O4 nanoparticles by measuring the micronucleus (MN) frequency in CHO-K1 cells. Furthermore, the mRNA expression of pro-inflammatory cytokines demonstrates that polymer-coated MMPs elicited a less intense secretion of pro-inflammatory cytokines than uncoated Fe3O4 nanoparticles. Acute toxicity tests of MMPs show quite a low toxicity, with an LD50 > 1575.00 mg/kg. The evidence of low toxicity presented in the results indicates that the Fe3O4-PLLA-PEG-PLLA MMPs from the SpEDS process have great potential for use in biomedical applications.

[Clinical trials of antiphlogistic agent series in treating chronic nonbacterial prostatitis].

OBJECTIVE: To investigate the curative effect of antiphlogistic agent series on treating chronic nonbacterial prostatitis (CNP). METHODS: One hundred and sixty patients were randomized into 4 groups for an 8-week clinical observation: group A (oral antiphlogistic medicinal granules only), group B (oral antiphlogistic medicinal granules + retention enema), group C (oral antiphlogistic medicinal granules + rectal), and group D (antiphlogistic medicinal granules + rectally + hip bath). Single blind trials were employed. RESULTS: The curative rates of the 4 groups were 37.5%, 57.5%, 52.5% and 82.5% respectively, while the total efficacy rates were 42.5%, 82.5%, 77.5% and 92.5% respectively. Compared with groups A, B and C, the curative rate of group D was significantly higher (P < 0.05). The difference in efficacy rates was slight between groups B and D (P < 0.05), but significant between groups A and C (P < 0.05). CONCLUSIONS: Combined treatment therapy can improve the effect of CNP treatment and clear away heat and toxic material. The antiphlogistic agent series, with the effect of motivating blood circulation and removing blood stasis, turned out to be an effective traditional Chinese medicine in treating CNP.