Pan-Cancer Analysis of Prognostic and Immune Infiltrates for the TMEM65, Especially for the Breast Cancer.

Introduction: Transmembrane protein 65 (TMEM65) is an inner mitochondrial membrane protein, which played important role in mediating autophagy, smooth muscle contraction, protein glycosylation, and immune response. In recent years, the interest had risen for exploring the function of the TMEM genes in the cancer fields. As a consequence, in our pan-cancer research of the TMEM65, we explored the function of the gene in kinds of database and tried to apply the finding in the clinical practice. Methods: In this research, we provide a comprehensive investigation of TMEM65 expression in a pan-cancer manner containing 33 cancer types. We evaluated the association of TMEM65 with the prognosis, immune infiltration, drug sensitivity analysis, GSVA enrichment analysis, TMB, MSI, NEO, and hotspot mechanisms. Results: TMEM65 was abnormally expressed in 24 types of cancers and showed correlation with the OS for 6 cancers and PFI for 9 cancers and kpI for 3 types. Moreover, the TME score, CD8 T effector, and immune checkpoint scoring systems showed a close correlation with the TMEM65. Moreover, TMEM65 was strongly correlated with some of the most common tumor-related genes and certain pathways (TGF beta signaling, TNFA signaling, hypoxia, pyroptosis, DNA repairing, autophagy, ferroptosis, and other related genes). Additionally, the TMEM65 showed correlations with the tumor mutational burden (TMB), microsatellite instability (MSI), NEO, and drug sensitivity. Finally, we confirmed several pathways by the GSEA and GSVA for the TMEM65 at the breast cancer aspects. Nomogram prediction model was also established for the breast tumors based on the TMEM65 level and other variables. Conclusion: Above all, the TMEM65 played important roles in predicting the prognosis of the cancers and correlated with the tumor immunity in the pan-cancer analysis.

Assessment of echinocandin regimens by pharmacokinetic/pharmacodynamic analysis against Candida spp. in paediatric patients.

This study aimed to investigate the cumulative fraction of response of various echinocandin (caspofungin, micafungin and anidulafungin) dosing regimens against Candida spp. in paediatric patients with invasive fungal infections (IFIs). Monte Carlo simulations were performed using previously published pharmacokinetic parameters and pharmacodynamic data to evaluate the ability of each echinocandin regimen in terms of fAUC/MIC (free drug area under the concentration-time curve/minimum inhibition concentration ratio) targets of caspofungin, micafungin and anidulafungin. Pharmacodynamic targets were attained in paediatric patients by both caspofungin regimens as well as by a high micafungin dosing regimens against Candida albicans and Candida glabrata. However, the results for anidulafungin suggested that the dosing regimens recommended were not optimal for paediatric patients. In addition, the predicted efficacy of all of the echinocandins against Candida parapsilosis was low. This is the first study to assess caspofungin, micafungin and anidulafungin therapy using Monte Carlo simulation. These results rationalise and optimise the dosage regimens of caspofungin, micafungin and anidulafungin against C. albicans, C. glabrata and C. parapsilosis for paediatric patients with IFIs.

High-order photonic differentiator employing on-chip cascaded microring resonators.

We propose and experimentally demonstrate a high-order photonic differentiator using on-chip complementary metal oxide semiconductor-compatible cascaded microring resonators, including first-, second-, and third-order differentiators. All the microring resonator units have a radius of 150 µm and a free spectral range of 80 GHz. The microring resonator can implement the first-order derivative of the optical field near its critical coupling region. Hence higher-order differentiation can be obtained by cascading more microring units on a single chip. For the periodical Gaussian optical pulse injection, the average deviations of all differentiators are less than 6.2%. The differentiation of pseudo-random bit sequence signals at 5 Gbit/s is also demonstrated. Our scheme is a compact and low-power-consumption solution since the cascaded microring units are fabricated with compact size on the silicon-on-insulator substrate.