Preclinical Pharmacokinetics and Pharmacology Study of RC98: A Programmed Cell Death Ligand 1 Monoclonal Antibody in Cynomolgus Monkeys.

Introduction: RC98 is the monoclonal antibody against Programmed Cell Death Ligand 1 (PD-L1). Relevant reports have confirmed that the influence of PD-L1 expressed by tumor cells on antitumor CD8+ T cell responses is well characterized, but the impact of PD-L1 expressed by immune cells has not been well defined.

Objective: This study aimed to design a Pharmacokinetics/Pharmacology (PK/PD) study of RC98 in normal cynomolgus monkeys to research the effect on the immune system.

Development and validation of bioanalytical methods to support clinical study of disitamab vedotin.

Disitamab vedotin (RC48), a humanized anti-HER2 antibody conjugated with monomethyl auristatin E (MMAE), is the first antibody-drug conjugate in China with an approved biological license application. A bioanalytical method was established for three analytes (total antibody, conjugate antibody and free payload) to help characterize their pharmacokinetic behavior in clinical settings. The bioanalytical methods were validated according to M10 guidance.

Translation of the efficacy of antibody-drug conjugates from preclinical to clinical using a semimechanistic PK/PD model: A case study with RC88.

Three semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) models, Simeoni, Jumbe, and Hybrid, were used for the efficacy translation of RC88 from preclinical to clinical. RC88 is a mesothelin-targeting antibody-drug conjugate for malignant solid tumor. In the preclinical study, the relationship between PKs and PDs was determined using the xenograft mouse model derived from ovarian cancer and lung cancer cell lines.

A High-Sensitivity Vacuum Diode Temperature Sensor Based on Barrier-Lowering Effect.

A new kind of temperature sensor based on a vacuum diode was proposed and numerically studied in this paper. This device operated under different electron emission mechanisms according to the electron density in the vacuum channel. The temperature determination ability of this device was only empowered when working in the electric-field-assisted thermionic emission regime (barrier-lowering effect).

Nanoscale Vacuum Diode Based on Thermionic Emission for High Temperature Operation.

Vacuum diodes, based on field emission mechanisms, demonstrate a superior performance in high-temperature operations compared to solid-state devices. However, when considering low operating voltage and continuous miniaturization, the cathode is usually made into a tip structure and the gap between cathode and anode is reduced to a nanoscale. This greatly increases the difficulty of preparation and makes it difficult to ensure fabrication consistency.

Apoptosis in response to heat stress is positively associated with heat-shock protein 90 expression in chicken myocardial cells .

To determine heat-shock protein (Hsp)90 expression is connected with cellular apoptotic response to heat stress and its mechanism, chicken () primary myocardial cells were treated with the Hsp90 promoter, aspirin, and its inhibitor, geldanamycin (GA), before heat stress. Cellular viability, heat-stressed apoptosis and reactive oxygen species level under different treatments were measured, and the expression of key proteins of the signaling pathway related to Hsp90 and their colocalization with Hsp90 were detected. The results showed that aspirin treatment increased the expression of protein kinase B (Akt), the signal transducer and activator of transcription (STAT)-3 and p-IKKα/β and the colocalization of Akt and STAT-3 with Hsp90 during heat stress, which was accompanied by improved viability and low apoptosis.