Karonudib is a promising anticancer therapy in hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is the most common form of liver cancer and is generally caused by viral infections or consumption of mutagens, such as alcohol. While liver transplantation and hepatectomy is curative for some patients, many relapse into disease with few treatment options such as tyrosine kinase inhibitors, for example, sorafenib or lenvatinib. The need for novel systemic treatment approaches is urgent. Methods: MTH1 expression profile was first analyzed in a HCC database and MTH1 mRNA/protein level was determined in resected HCC and paired paracancerous tissues with polymerase chain reaction (PCR) and immunohistochemistry. HCC cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA. 8-oxoG was measured by the modified comet assay. The effect of MTH1 inhibition on tumor growth was explored in HCC xenograft in vivo models. Results: MTH1 protein level is elevated in HCC tissue compared with paracancerous liver tissue and indicates poor prognosis. The MTH1 inhibitor Karonudib (TH1579) and siRNA effectively introduce toxic oxidized nucleotides into DNA, 8-oxoG, and kill HCC cell lines in vitro. Furthermore, we demonstrate that HCC growth in a xenograft mouse model in vivo is efficiently suppressed by Karonudib. Conclusion: Altogether, these data suggest HCC relies on MTH1 for survival, which can be targeted and may open up a novel treatment option for HCC in the future

Traditional Chinese Medicine JianPiHuaTan formula improving quality of life and survival in patients with colorectal cancer through RAS/RAF downstream signaling pathways

ObjectiveJianPiHuaTan Formula (JPHTF), a traditional Chinese medicine (TCM), has been utilized as an adjunctive therapy for colorectal cancer (CRC). The study aims to evaluate the potential clinical benefits of JPHTF and its effectiveness in inhibiting tumor growth.Methods300 stage II/III CRC patients and 412 advanced CRC patients were enrolled to verify the clinical value of JPHTF in CRC treatment. Furthermore, CRC patient-derived xenograft (PDX) mice were utilized to investigate the regulatory mechanisms of JPHTF.ResultsJPHTF significantly improved abdominal distension, shortness of breath, drowsiness, loss of appetite, sleep, and tiredness in stage II/III CRC patients, thereby improving their quality of life. Simultaneously, JPHTF served as a supportive therapy in extending the overall survival (OS) of stage IV CRC patients with RAS/RAF mutations undergoing chemotherapy. Additionally, JPHTF effectively impeded tumor progression in CRC PDX models with RAS mutation, accompanied by a reduction in tumor cell content in the JPHTF group. Transcriptomic analysis revealed the involvement of the Hippo and Hedgehog signaling pathways in JPHTF-mediated CRC inhibition. Furthermore, mice in the JPHTF group exhibited increased immune cell infiltration.ConclusionThese findings suggested that JPHTF may inhibits tumor growth in CRC with RAS mutation by modulating RAS/RAF downstream signaling pathways, specifically the Hippo and Hedgehog signaling, leading to increased immune cell infiltration

The Effect of Geometric Parameters on Flow and Heat Transfer Characteristics of a Double-Layer Microchannel Heat Sink for High-Power Diode Laser

The effect of the geometric parameters on the flow and heat transfer characteristics of a double-layer U-shape microchannel heat sink (DL-MCHS) for a high-power diode laser was investigated in this work. FLUENT 19.2 based on the finite volume method was employed to analyze the flow and heat transfer performance of DL-MCHS. A single variable approach was used to fully research the impact of different parameters (the number of channels, the channel cross-sectional shape, and the aspect ratio) on the temperature distribution, pressure drop, and thermal resistance of the DL-MCHS. The rectangular DL-MCHS heat transfer performance and pressure drop significantly increased with the rise in the channel’s aspect ratio due to there being a larger wet perimeter and convective heat transfer area. By comparing the thermal resistance of the DL-MCHS at the same power consumption, it was found that the rectangular DL-MCHS with an aspect ratio in the range of 5.1180–6.389 had the best overall performance. With the same cross-sectional area and hydraulic diameter (AC = 0.36 mm, Dh = 0.417 mm), the thermal resistance of the trapezoidal microchannel heat sink was 32.14% and 42.42% lower than that of the triangular and rectangular ones, respectively, under the condition that the pumping power (Wpp) was 0.2 W. Additionally, the thermal resistance was reduced with the increment of the number of channels inside the DL-MCHS, but this would induce an increased pressure drop. Thus, the channel number has an optimal range, which is between 50 and 80 for the heat sinks in this study. Our study served as a simulation foundation for the semiconductor laser double-layer U-shaped MCHS optimization method using geometric parameters

Plasmonically Enhanced Colloidal Quantum Dot/Graphene Doped Polymer Random Lasers

An improvement in random lasers based on a colloidal quantum dot (QD)/graphene-doped polymer was observed and attributed to multiple light-scattering and graphene surface plasmon resonance. The emission characteristics of quantum dots doped with graphene oxide and reduced graphene oxide were compared. The QD/reduced graphene oxide hybrid exhibited a lower laser emission threshold (~460 μJ/cm2). The emission modes and thresholds were strongly dependent on both the graphene doping concentration and the external temperature. Decreased plasmon coupling was the primary reason for lower QD/graphene laser emission with increasing temperature. The optimum reduced graphene oxide concentration was 0.2 wt.%. This work provides a practical approach to optimizing the threshold and stability of random laser devices, with potential applications in displays, sensors, and anti-counterfeiting labels