Structure-guided engineering of a mutation-tolerant inhibitor peptide against variable SARS-CoV-2 spikes.

Pathogen mutations present an inevitable and challenging problem for therapeutics and the development of mutation-tolerant anti-infective drugs to strengthen global health and combat evolving pathogens is urgently needed. While spike proteins on viral surfaces are attractive targets for preventing viral entry, they mutate frequently, making it difficult to develop effective therapeutics. Here, we used a structure-guided strategy to engineer an inhibitor peptide against the SARS-CoV-2 spike, called CeSPIACE, with mutation-tolerant and potent binding ability against all variants to enhance affinity for the invariant architecture of the receptor-binding domain (RBD).

Effects of Progesterone on Isoflurane Requirement for Balance Disturbance and Loss of Righting Reflex in Male Mice.

Introduction It has been known that progesterone has central effects, as measured by minimum alveolar concentration in various experimental settings. Previously, we showed that progesterone reduces the sevoflurane requirement for the loss of righting reflex (LORR) using male mice. However, the combination of progesterone and isoflurane has not been studied.

Survival Outcomes Associated With Radiological Progressive Disease Subtypes in Patients With Atezolizumab and Bevacizumab-Treated HCC.

Background And Aim: To assess the relationship between survival outcomes and subtypes of radiological progressive disease (PD) in patients with hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Atezo/Bev).

Methods: A total of 462 patients with Atezo/Bev-treated HCC diagnosed with radiological PD during follow-up were enrolled. PD was classified into three categories: progression or emergence of intrahepatic lesions (PD-IH), macroscopic vascular invasion (PD-MVI), and extrahepatic spread lesions (PD-EHS).

Evaluation of Treatment Outcomes Using dNLR and GNRI in Combination Therapy With Atezolizumab and Bevacizumab for Hepatocellular Carcinoma.

Aim: This study aims to investigate the clinical utility of the derived neutrophil-to-lymphocyte ratio (dNLR) and the Geriatric Nutritional Risk Index (GNRI) in predicting treatment outcomes for patients with unresectable hepatocellular carcinoma (HCC) undergoing combination therapy with atezolizumab and bevacizumab (Atez/Bev).

Methods: A retrospective analysis was conducted on 310 patients. The dNLR, NLR, and GNRI were calculated, and their impact on progression-free survival (PFS) and overall survival (OS) was assessed.

Effect of Proteinuria Before Lenvatinib Administration on Treatment Response After Atezolizumab Bevacizumab Combination Therapy.

Aim: We investigated the impact of proteinuria on the therapeutic effect before lenvatinib administration as second-line treatment after atezolizumab-bevacizumab.

Methods: We examined 64 patients who were administered lenvatinib as second-line treatment after discontinuation of atezolizumab and bevacizumab. Proteinuria assessed before lenvatinib administration was considered severe if the qualitative value test (QV) was 3+ or the urine protein/creatinine ratio (UPCR) was ≥ 2.