The treatment of cancer has evolved significantly in recent years with a strong focus on immunotherapy. Encapsulated Cell Therapy (ECT) for immunotherapy-based anti-cancer treatment is a unique niche within this landscape, where molecules such as signaling factors and antibodies produced from cells are encapsulated within a vehicle, with a host amount of benefits in terms of treatment efficacy and reduced side effects. However, traditional ECTs generally lie in two extremes; either a macro scale vehicle is utilized, resulting in a retrievable system but with limited diffusion and surface area, or a micro scale vehicle is utilized, resulting in a system that has excellent diffusion and surface area but is unretrievable in the event of side effects occurring, which greatly compromises the biosafety of patients. In this study we adapted our patented and novel electrospun Polysulfone (PSF) Microtube Array Membranes (MTAMs) as a ‘middle’ approach to the above dilemma, which possess excellent diffusion and surface area while being retrievable. Hybridoma cells were encapsulated within the PSF MTAMs, where they produced CEACAM6 antibodies to be used in the suppression of cancer cell line A549, MDA-MB-468 and PC 3 (control). In vitro and in vivo studies revealed excellent cell viability of hybridoma cells with continuous secretion of CEACAM6 antibodies which suppressed the MDA-MB-468 throughout the entire 21 days of experiment. Such outcome suggested that the PSF MTAMs were not only an excellent three-dimensional (3D) cell culture substrate but potentially also an excellent vehicle for the application in ECT systems. Future research needs to include a long term in vivo >6 months study before it can be used in clinical applications.
Graphene thermoacoustic loudspeakers, composed of a graphene film on a substrate, generate sound with heat. Improving thermoacoustic efficiency of graphene speakers is a goal for optimal design. In this work, we first modified the existing TA model with respect to small thermal wavelengths, and then built an acoustic platform for model validation. Additionally, sensitivity analyses for influential factors on thermoacoustic efficiency were performed, including the thickness of multilayered graphene films, the thermal effusivity of substrates, and the characteristics of inserted gases. The higher sensitivity coefficients result in the stronger effects on thermoacoustic efficiency. We find that the thickness (5 nm–15 nm) of graphene films plays a trivial role in efficiency, resulting in the sensitivity coefficient less than 0.02. The substrate thermal effusivity, however, has significant effects on efficiency, with the sensitivity coefficient around 1.7. Moreover, substrates with a lower thermal effusivity show better acoustic performances. For influences of ambient gases, the sensitivity coefficients of density ρg, thermal conductivity κg, and specific heat cp,g are 2.7, 0.98, and 0.8, respectively. Furthermore, large magnitudes of both ρg and κg lead to a higher efficiency and the sound pressure level generated by graphene films is approximately proportional to the inverse of cp,g. These findings can refer to the optimal design for graphene thermoacoustic speakers.
By December 2020, the COVID-19 pandemic had caused more than 74 million confirmed cases and 1.6 million related deaths around the world. However, only a few drugs have been approved in certain areas and for use in conditional patients, and the vaccine candidates were only recently approved or authorized for emergency use without being fully implemented worldwide, suggesting that we are yet to reach effective control of the current outbreak as its uninhibited transmission continues precariously. Over the past few months, several therapeutic candidates have been proven ineffective in large clinical trials, while some other agents exhibited promising preliminary results. Meanwhile, the investigation of SARS-CoV-2-specific antivirals is underway. Despite still being preclinical, these agents could be beneficial for the long-term control of COVID-19 and deserve more research focus. In this article, we update the current status of therapeutic candidates that have been examined for COVID-19 management, including the virus-targeting inhibitors and host-targeting agents, with their antiviral efficacy in vitro, in vivo, and in clinical studies. Finally, we highlight the current challenges and future prospect of developing potent therapeutic agents against COVID-19.
Cutaneous evaporative heat loss in Bos indicus and Bos taurus has been well documented. Nonetheless, how crossbreds with different fractional genetic proportions respond to such circumstances is of interest. A study to examine the physiological responses to cutaneous evaporative heat loss, also lactation period and milk yield, were conducted in Sahiwal (Bos indicus, n = 10, 444±64.8 kg, 9±2.9 years), Holstein Friesian (Bos taurus, HF100% (n = 10, 488±97.9 kg, 6±2.8 years)) and the following crossbreds: HF50% (n = 10, 355±40.7 kg, 2±0 years) and HF87.5% (n = 10, 489±76.8 kg, 7±1.8 years). They were allocated so as to determine the physiological responses of sweating rate (SR), respiration rate (RR), rectal temperature (RT), and skin temperature (ST) with and without hair from 06:00 h am to 15:00 h pm. And milk yield during 180 days were collected at days from 30 to 180. The ambient temperature-humidity-index (THI) increased from less than 80 in the early morning to more than 90 in the late afternoon. The interaction of THI and breed were highly affected on SR, RR, RT, and ST (p<0.01). The SR was highest in Sahiwal (595 g/m2/h) compared to HF100% (227 g/m2/h), and their crossbreds both HF50% (335 g/m2/h) and HF87.5% (299 g/m2/h). On the other hand, RR was higher in HF87.5% (54 bpm) and both HF100% (48 bpm) and HF50% (42 bpm) than Sahiwal (25 bpm) (p<0.01). The RT showed no significant differences as a result of breed (p>0.05) but did change over time. The ST with and without hair were similar, and was higher in HF100% (37.4°C; 38.0°C) and their crossbred HF50% (35.5°C; 35.5°C) and HF87.5% (37.1°C; 37.9°C) than Sahiwal (34.8°C; 34.8°C) (p<0.01). Moreover, the early lactation were higher at HF100% (25 kg) and 87.5% (25 kg) than HF50% (23 kg) which were higher than Sahiwal (18 kg) while the peak period of lactation was higher at HF100% (35 kg) than crossbreds both HF87.5% and HF50% (32 kg) which was higher than Sahiwal (26 kg) (p<0.05). In conclusion, sweating and respiration were the main vehicle for dissipating excess body heat for Sahiwal, HF and crossbreds, respectively. The THI at 76 to 80 were the critical points where the physiological responses to elevated temperature displayed change.
Sepsis is a deadly disease that is widely attributed to endotoxin released by gram‐negative bacterial infections often plague emergency care facilities. Conventionally antibiotics and vasopressors are used to treat this disease. Recent treatment protocol shifted to a membrane to remove the offending endotoxin monomer. Despite this shift, membrane‐based devices are often extremely costly, hindering accessibility to this life saving medical device. In view of this challenges, we adopted the internally developed polysulfone (PSF) microtube array membrane alternating (MTAM‐A) for use in blood sepsis treatment. PSF MTAM‐A were with polymyxin B (PMB) molecules immobilized were assembled into an internally developed cartridge housing and subjected to endotoxin removal models with water and blood spiked with 100 EU/ml of endotoxin as the feed solution. Samples were derived at 15, 30, 60, and 120 min and endotoxin levels were determined with limulus amebocyte lysate assay and benchmarked against the commercially available Toraymyxin device. The PSF MTAM‐A with 2.3 times the surface area was successfully fabricated and with PMB molecules immobilized, and assembled into a hemoperfusion device. Dynamic endotoxin removal test revealed and overall endotoxin removal capacity of 90% and a superior endotoxin removal efficiency that was significantly higher than that of Toraymyxin (internally conducted and reported). The data suggested that PSF MTAM‐A PMB membranes could potentially be applied in future hemoperfusion devices which would be significantly more efficient, compact, and affordable; potentially making such a life‐saving medical device widely available to the general public.
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