Microneedle Patch Delivery of PLCG1-siRNA Efficient Enhanced Temozolomide Therapy for Glioblastoma

The blood–brain barrier (BBB) and drug resistance present challenges for chemotherapy of glioblastoma (GBM). A microneedle (MN) patch with excellent biocompatibility and biodegradability was designed to bypass the BBB and release temozolomide (TMZ) and PLCG1-siRNA directly into the tumor site for synergistic treatment of GBM. The codelivery of TMZ and PLCG1-siRNA enhanced DNA damage and apoptosis. The potential mechanism behind this enhancement is to knockdown of PLCG1 expression, which positively regulates the expression of signal transducer and activator of transcription 3 genes, thereby preventing DNA repair and enhancing the sensitivity of GBM to TMZ. The MN patch enables long-term sustainable drug release through in situ implantation and increases local drug concentrations in diseased areas, significantly extending mouse survival time compared to other drug treatment groups. MN drug delivery provides a platform for the combination treatment of GBM and other central nervous system diseases

Heat loss in constant temperature aquaculture workshop (25°C).

Heat loss in constant temperature aquaculture workshop (25°C).</p

The measured and calculated values of the inner surface of the workshop roof.

The measured and calculated values of the inner surface of the workshop roof.</p

Measured and calculated values of water temperature in the workshop.

Measured and calculated values of water temperature in the workshop.</p

Workshop interior layout.

Note: The red circle ⭕ indicates the location of the indoor temperature and humidity measuring point, and the blue triangle Δ indicates the water body temperature measuring point.</p

Temperature field at different times at 1.5m height on January 5, 2023.

a. Temperature cloud map at 10:00, b. Temperature cloud map at 2:00.</p

Workshop scene.

With the increasing market demand for high-quality aquatic products, the application of industrialized aquaculture facilities may get more attention. In order to improve the poor performance of thermal insulation, the accuracy of the numerical model was verified in this study through actual measured data. The model verification results shown that the average relative errors of the measured and calculated values of indoor air temperature, water temperature and roof inner surface temperature in the industrialized aquaculture workshop is within 2.5%, it suggested that the numerical calculation results are accurate. Furthermore, the thermal environment and thermal insulation performance of industrialized aquaculture facilities in winter were conducted based on the numerical calculations. After optimized the thermophysical parameters of the workshop enclosure structure, we found that the water body temperature could reach 21°C (which was close to the breeding temperature of grouper (Epinephelinae). Therefore, the numerical calculation method was further used to analyze the energy consumption of aquaculture water in January of a typical year in this area by heating to three constant temperatures (22, 25, and 28°C). When the aquaculture water was heated to the three constant temperature states, it needed to consume 8.56×105, 1.02×106 and 1.22×106 MJ of energy respectively, which were equal to the amount of energy released by the complete combustion of 29.3, 35.1 and 41.8 t standard coal. Moreover, it is concluded that the artificial temperature increase in winter maintains the temperature in the range of 22~25°C to provide the highest heating efficiency. This conclusion can provide theoretical basis and application reference for industrialized aquaculture in winter.</div

Physical characteristic parameters.

With the increasing market demand for high-quality aquatic products, the application of industrialized aquaculture facilities may get more attention. In order to improve the poor performance of thermal insulation, the accuracy of the numerical model was verified in this study through actual measured data. The model verification results shown that the average relative errors of the measured and calculated values of indoor air temperature, water temperature and roof inner surface temperature in the industrialized aquaculture workshop is within 2.5%, it suggested that the numerical calculation results are accurate. Furthermore, the thermal environment and thermal insulation performance of industrialized aquaculture facilities in winter were conducted based on the numerical calculations. After optimized the thermophysical parameters of the workshop enclosure structure, we found that the water body temperature could reach 21°C (which was close to the breeding temperature of grouper (Epinephelinae). Therefore, the numerical calculation method was further used to analyze the energy consumption of aquaculture water in January of a typical year in this area by heating to three constant temperatures (22, 25, and 28°C). When the aquaculture water was heated to the three constant temperature states, it needed to consume 8.56×105, 1.02×106 and 1.22×106 MJ of energy respectively, which were equal to the amount of energy released by the complete combustion of 29.3, 35.1 and 41.8 t standard coal. Moreover, it is concluded that the artificial temperature increase in winter maintains the temperature in the range of 22~25°C to provide the highest heating efficiency. This conclusion can provide theoretical basis and application reference for industrialized aquaculture in winter.</div

Supplementary calorie calculation table.

With the increasing market demand for high-quality aquatic products, the application of industrialized aquaculture facilities may get more attention. In order to improve the poor performance of thermal insulation, the accuracy of the numerical model was verified in this study through actual measured data. The model verification results shown that the average relative errors of the measured and calculated values of indoor air temperature, water temperature and roof inner surface temperature in the industrialized aquaculture workshop is within 2.5%, it suggested that the numerical calculation results are accurate. Furthermore, the thermal environment and thermal insulation performance of industrialized aquaculture facilities in winter were conducted based on the numerical calculations. After optimized the thermophysical parameters of the workshop enclosure structure, we found that the water body temperature could reach 21°C (which was close to the breeding temperature of grouper (Epinephelinae). Therefore, the numerical calculation method was further used to analyze the energy consumption of aquaculture water in January of a typical year in this area by heating to three constant temperatures (22, 25, and 28°C). When the aquaculture water was heated to the three constant temperature states, it needed to consume 8.56×105, 1.02×106 and 1.22×106 MJ of energy respectively, which were equal to the amount of energy released by the complete combustion of 29.3, 35.1 and 41.8 t standard coal. Moreover, it is concluded that the artificial temperature increase in winter maintains the temperature in the range of 22~25°C to provide the highest heating efficiency. This conclusion can provide theoretical basis and application reference for industrialized aquaculture in winter.</div

Heat loss in constant temperature aquaculture workshop (28°C).

Heat loss in constant temperature aquaculture workshop (28°C).</p