Pancreatic cancer (PanCa) is a lethal disease. Conventional chemotherapies for PanCa offer severe systemic toxicities. Thus, the development of a successful nanomedicine-based therapeutic regimen with augmented therapeutic efficacy is highly sought. Naturally occurring pectin and modified pectin-based drug delivery systems exhibit remarkable self-targeting ability via galactose residues to various cancer cells. Herein, we developed and used an innovative approach of highly stable nanocomplexes based on modified pectin and tannic acid (MPT-NCs). The nanocomplex formation was enabled by strong intermolecular interactions between pectin and tannic acid under very mild conditions. These nanocomplexes were characterized by particle size and morphology (DLS, TEM, and SEM), FT-IR spectroscopy, and zeta potential measurements. Additionally, MPT-NCs were capable of encapsulating anticancer drugs (5-fluorouracil, gemcitabine, and irinotecan) through tannic acid binding. The in vitro bioactivity of these drug MPT-NCs were evaluated in pancreatic cancer adenocarcinoma (PDAC) cell lines (HPAF-II and PANC-1). A dose-dependent internalization of nanocomplexes was evident from microscopy and flow cytometry analysis. Both proliferation and colony formation assays indicated the anticancer potential of pectin drug nanocomplexes against PDAC cells compared to that of free drug treatments. Together, the pectin-based nanocomplexes could be a reliable and efficient drug delivery strategy for cancer therapy.Staphylococcus aureus is an important bacterial pathogen. This study utilized known staphylococcal epidemiology to track S. aureus between patients, surfaces, staff hands and air in a ten-bed intensive care unit (ICU). METHODS Patients, air and surfaces were screened for total colony counts and S. aureus using dipslides, settle plates and an MAS-100 slit-sampler once a month for 10 months. Data were modelled against proposed standards for air and surfaces, and ICU-acquired staphylococcal infection. Whole-cell genomic typing (WGS) demonstrated possible transmission pathways between reservoirs. RESULTS Frequently touched sites were more likely to be contaminated (>12 cfu/cm2; p = 0.08). Overall, 235 of 500 (47%) sites failed the surface standard (≤2.5 cfu/cm2); 20 of 40 (50%) passive air samples failed the "Index of Microbial Air" standard (2 cfu/9 cm plate/h), and 15/40 (37.5%) air samples failed the air standard ( less then 10 cfu/m3). Settle plate data were closer to surface counts than automated air data; the surface count most likely to reflect pass/fail rates for air was 5 cfu/cm2. Surface counts/bed were associated with staphylococcal infection rates (p = 0.012). Of 34 pairs of indistinguishable S. aureus, 20 (59%) showed autogenous transmission, with another four (12%) occurring between patients. Four (12%) pairs linked patients with hand-touch sites and six (18%) linked airborne S. aureus, staff hands and hand-touch sites. CONCLUSION Most ICU-acquired S. aureus infection is autogenous, while staff hands and air were rarely implicated in onward transmission. Settle plates could potentially be used for routine environmental screening. ICU staphylococcal infection is best served by admission screening, systematic cleaning and hand hygiene.Most flaviviruses are arthropod-borne viruses, transmitted by either ticks or mosquitoes, and cause morbidity and mortality worldwide. They are endemic in many countries and have recently emerged in new regions, such as the Zika virus (ZIKV) in South-and Central America, the West Nile virus (WNV) in North America, and the Yellow fever virus (YFV) in Brazil and many African countries, highlighting the need for preparedness. Currently, there are no antiviral drugs available to treat flavivirus infections. We have previously discovered a broad-spectrum antiviral compound, benzavir-2, with potent antiviral activity against both DNA- and RNA-viruses. Our purpose was to investigate the inhibitory activity of benzavir-2 against flaviviruses. We used a ZIKV ZsGreen-expressing vector, two lineages of wild-type ZIKV, and other medically important flaviviruses. Benzavir-2 inhibited ZIKV derived reporter gene expression with an EC50 value of 0.8 ± 0.1 µM. Furthermore, ZIKV plaque formation, progeny virus production, and viral RNA expression were strongly inhibited. In addition, 2.5 µM of benzavir-2 reduced infection in vitro in three to five orders of magnitude for five other flaviviruses WNV, YFV, the tick-borne encephalitis virus, Japanese encephalitis virus, and dengue virus. In conclusion, benzavir-2 was a potent inhibitor of flavivirus infection, which supported the broad-spectrum antiviral activity of benzavir-2.The high density, large capacity, and long-term stability of DNA molecules make them an emerging storage medium that is especially suitable for the long-term storage of large datasets. The DNA sequences used in storage need to consider relevant constraints to avoid nonspecific hybridization reactions, such as the No-runlength constraint, GC-content, and the Hamming distance. In this work, a new nonlinear control parameter strategy and a random opposition-based learning strategy were used to improve the Harris hawks optimization algorithm (for the improved algorithm NOL-HHO) in order to prevent it from falling into local optima. Experimental testing was performed on 23 widely used benchmark functions, and the proposed algorithm was used to obtain better coding lower bounds for DNA storage. The results show that our algorithm can better maintain a smooth transition between exploration and exploitation and has stronger global exploration capabilities as compared with other algorithms. https://www.selleckchem.com/products/erastin.html At the same time, the improvement of the lower bound directly affects the storage capacity and code rate, which promotes the further development of DNA storage technology.An air-backed diaphragm is the key structure of most dynamic pressure sensors and plays a critical role in determining the sensor performance. Our previous analytical model investigated the influence of air cavity length on the sensitivity and bandwidth. The model found that as the cavity length decreases, the static sensitivity monotonically decreases, and the fundamental natural frequency shows a three-stage trend increasing in the long-cavity-length range, reaching a plateau value in the medium-cavity-length range, and decreasing in the short-cavity-length range, which cannot be captured by the widely used lumped model. In this study, we conducted the first experimental measurements to validate these findings. Pressure sensors with a circular polyimide diaphragm and a backing air cavity with an adjustable length were designed, fabricated, and characterized, from which the static sensitivities and fundamental natural frequencies were obtained as a function of the cavity length. A further parametric study was conducted by changing the in-plane tension in the diaphragm.
Pancreatic cancer (PanCa) is a lethal disease. Conventional chemotherapies for PanCa offer severe systemic toxicities. Thus, the development of a successful nanomedicine-based therapeutic regimen with augmented therapeutic efficacy is highly sought. Naturally occurring pectin and modified pectin-based drug delivery systems exhibit remarkable self-targeting ability via galactose residues to various cancer cells. Herein, we developed and used an innovative approach of highly stable nanocomplexes based on modified pectin and tannic acid (MPT-NCs). The nanocomplex formation was enabled by strong intermolecular interactions between pectin and tannic acid under very mild conditions. These nanocomplexes were characterized by particle size and morphology (DLS, TEM, and SEM), FT-IR spectroscopy, and zeta potential measurements. Additionally, MPT-NCs were capable of encapsulating anticancer drugs (5-fluorouracil, gemcitabine, and irinotecan) through tannic acid binding. The in vitro bioactivity of these drug MPT-NCs were evaluated in pancreatic cancer adenocarcinoma (PDAC) cell lines (HPAF-II and PANC-1). A dose-dependent internalization of nanocomplexes was evident from microscopy and flow cytometry analysis. Both proliferation and colony formation assays indicated the anticancer potential of pectin drug nanocomplexes against PDAC cells compared to that of free drug treatments. Together, the pectin-based nanocomplexes could be a reliable and efficient drug delivery strategy for cancer therapy.Staphylococcus aureus is an important bacterial pathogen. This study utilized known staphylococcal epidemiology to track S. aureus between patients, surfaces, staff hands and air in a ten-bed intensive care unit (ICU). METHODS Patients, air and surfaces were screened for total colony counts and S. aureus using dipslides, settle plates and an MAS-100 slit-sampler once a month for 10 months. Data were modelled against proposed standards for air and surfaces, and ICU-acquired staphylococcal infection. Whole-cell genomic typing (WGS) demonstrated possible transmission pathways between reservoirs. RESULTS Frequently touched sites were more likely to be contaminated (>12 cfu/cm2; p = 0.08). Overall, 235 of 500 (47%) sites failed the surface standard (≤2.5 cfu/cm2); 20 of 40 (50%) passive air samples failed the "Index of Microbial Air" standard (2 cfu/9 cm plate/h), and 15/40 (37.5%) air samples failed the air standard ( less then 10 cfu/m3). Settle plate data were closer to surface counts than automated air data; the surface count most likely to reflect pass/fail rates for air was 5 cfu/cm2. Surface counts/bed were associated with staphylococcal infection rates (p = 0.012). Of 34 pairs of indistinguishable S. aureus, 20 (59%) showed autogenous transmission, with another four (12%) occurring between patients. Four (12%) pairs linked patients with hand-touch sites and six (18%) linked airborne S. aureus, staff hands and hand-touch sites. CONCLUSION Most ICU-acquired S. aureus infection is autogenous, while staff hands and air were rarely implicated in onward transmission. Settle plates could potentially be used for routine environmental screening. ICU staphylococcal infection is best served by admission screening, systematic cleaning and hand hygiene.Most flaviviruses are arthropod-borne viruses, transmitted by either ticks or mosquitoes, and cause morbidity and mortality worldwide. They are endemic in many countries and have recently emerged in new regions, such as the Zika virus (ZIKV) in South-and Central America, the West Nile virus (WNV) in North America, and the Yellow fever virus (YFV) in Brazil and many African countries, highlighting the need for preparedness. Currently, there are no antiviral drugs available to treat flavivirus infections. We have previously discovered a broad-spectrum antiviral compound, benzavir-2, with potent antiviral activity against both DNA- and RNA-viruses. Our purpose was to investigate the inhibitory activity of benzavir-2 against flaviviruses. We used a ZIKV ZsGreen-expressing vector, two lineages of wild-type ZIKV, and other medically important flaviviruses. Benzavir-2 inhibited ZIKV derived reporter gene expression with an EC50 value of 0.8 ± 0.1 µM. Furthermore, ZIKV plaque formation, progeny virus production, and viral RNA expression were strongly inhibited. In addition, 2.5 µM of benzavir-2 reduced infection in vitro in three to five orders of magnitude for five other flaviviruses WNV, YFV, the tick-borne encephalitis virus, Japanese encephalitis virus, and dengue virus. In conclusion, benzavir-2 was a potent inhibitor of flavivirus infection, which supported the broad-spectrum antiviral activity of benzavir-2.The high density, large capacity, and long-term stability of DNA molecules make them an emerging storage medium that is especially suitable for the long-term storage of large datasets. The DNA sequences used in storage need to consider relevant constraints to avoid nonspecific hybridization reactions, such as the No-runlength constraint, GC-content, and the Hamming distance. In this work, a new nonlinear control parameter strategy and a random opposition-based learning strategy were used to improve the Harris hawks optimization algorithm (for the improved algorithm NOL-HHO) in order to prevent it from falling into local optima. Experimental testing was performed on 23 widely used benchmark functions, and the proposed algorithm was used to obtain better coding lower bounds for DNA storage. The results show that our algorithm can better maintain a smooth transition between exploration and exploitation and has stronger global exploration capabilities as compared with other algorithms. https://www.selleckchem.com/products/erastin.html At the same time, the improvement of the lower bound directly affects the storage capacity and code rate, which promotes the further development of DNA storage technology.An air-backed diaphragm is the key structure of most dynamic pressure sensors and plays a critical role in determining the sensor performance. Our previous analytical model investigated the influence of air cavity length on the sensitivity and bandwidth. The model found that as the cavity length decreases, the static sensitivity monotonically decreases, and the fundamental natural frequency shows a three-stage trend increasing in the long-cavity-length range, reaching a plateau value in the medium-cavity-length range, and decreasing in the short-cavity-length range, which cannot be captured by the widely used lumped model. In this study, we conducted the first experimental measurements to validate these findings. Pressure sensors with a circular polyimide diaphragm and a backing air cavity with an adjustable length were designed, fabricated, and characterized, from which the static sensitivities and fundamental natural frequencies were obtained as a function of the cavity length. A further parametric study was conducted by changing the in-plane tension in the diaphragm.
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