The first-in-human study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of the factor XI monoclonal antibody SHR-2004 in healthy subjects.

BACKGROUND: Inhibiting the coagulation factor XI (FXI) is a novel strategy for prevention and treatment of thromboembolism without affecting extrinsic coagulation pathways. SHR-2004 is a humanized monoclonal antibody that selectively binds to FXI and factor XIa (FXIa). RESEARCH DESIGN & METHODS: This randomized, double-blind, dose-escalation, placebo-controlled study evaluated SHR-2004 administered either intravenously (i.v.; Part A) or subcutaneously (s.c.; Part B). In Part A, 24 subjects received a single i.v. dose of SHR-2004 (0.1, 0.3, or 1.0 mg/kg) or placebo. In Part B, 40 subjects received a single s.c. dose of SHR-2004 (0.5, 1.0, 3.0, or 4.5 mg/kg) or placebo. RESULTS: SHR-2004 was well tolerated. Plasma exposure to SHR-2004 increased in a dose-dependent manner. The geometric mean half-time ranged from 11.6 to 13.0 days. FXI activity decreased, and the activated partial thromboplastin time (APTT) was prolonged after i.v. and s.c. administration in a dose- and time-dependent manner. FXI activity was nearly completely abolished immediately after administering the highest i.v. dose, with the average APTT prolonged to nearly three times of baseline. CONCLUSION: SHR-2004 is a promising candidate for further development as an anticoagulant drug that exerts effective anticoagulation with minimal risk of bleeding. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT05369767.

Nondestructive detection of Pleurotus geesteranus strain degradation based on micro-hyperspectral imaging and machine learning.

In the production of edible fungi, the use of degraded strains in cultivation incurs significant economic losses. Based on micro-hyperspectral imaging and machine learning, this study proposes an early, nondestructive method for detecting different degradation degrees of Pleurotus geesteranus strains. In this study, an undegraded strain and three different degradation-level strains were used. During the mycelium growth, 600 micro-hyperspectral images were obtained. Based on the average transmittance spectra of the region of interest (ROI) in the range of 400-1000 nm and images at feature bands, feature spectra and images were extracted using the successive projections algorithm (SPA) and the deep residual network (ResNet50), respectively. Different feature input combinations were utilized to establish support vector machine (SVM) classification models. Based on the results, the spectra-input-based model performed better than the image-input-based model, and feature extraction improved the classification results for both models. The feature-fusion-based SPA+ResNet50-SVM model was the best; the accuracy rate of the test set was up to 90.8%, which was better than the accuracy rates of SPA-SVM (83.3%) and ResNet50-SVM (80.8%). This study proposes a nondestructive method to detect the degradation of Pleurotus geesteranus strains, which could further inspire new methods for the phenotypic identification of edible fungi.

Association of IGF-I gene polymorphisms with milk yield and body size in Chinese dairy goats

The association of IGF-I gene polymorphisms with certain traits in 708 individuals of two Chinese dairy-goat breeds (Guanzhong and Xinong Saanen) was investigated. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing methods were employed in screening for genetic variation. Two novel mutations were detected in the 5'-flanking region and in intron 4 of IGF-I gene, viz., g.1617 G > A and g.5752 G > C (accession D26119.2), respectively. The associations of the g.1617 G > A mutation with milk yield and the body size were not significant (p > 0.05). However, in the case of g.5752 G > C, Xinong Saanen dairy goats with the CG genotype presented longer bodies (p < 0.05). Chest circumference (p < 0.05) was larger in Guanzhong goats with the GG genotype. In Xinong Saanen dairy goats with the CC genotype, milk yields were significantly higher during the first and second lactations (p < 0.05). Hence, the g.5752 G > C mutation could facilitate association analysis and serve as a genetic marker for Chinese dairy-goat breeding and genetics.