Efficacy and safety of zanubrutinib plus R-CHOP in treatment of non-GCB DLBCL with extranodal involvement

IntroductionTreatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) shows poor response rates in non–germinal center B cell–like (non-GCB) diffuse large B-cell lymphoma (DLBCL) patients with multiple extranodal involvement. This study aims to evaluate anti-tumor activity and safety of zanubrutinib with R-CHOP (ZR-CHOP) in treatment naïve non-GCB DLBCL with extranodal involvement.MethodsIn this single-arm, phase 2, prospective, single-center study, patients with newly diagnosed non-GCB DLBCL with extranodal involvement enrolled between October 2020 to March 2022 received ZR-CHOP for 6 cycles followed by 2 cycles of maintenance treatment with rituximab and zanubrutinib. The primary endpoint included progression-free survival (PFS) in the intent-to-treat (ITT) population whereas the secondary endpoints included overall response rate (ORR), complete response (CR), and duration of response. Further, next-generation sequencing (NGS) was used for detection of different oncogenic mutations closely related to DLBCL pathogenesis.ResultsFrom October 2020 to March 2022, 26 patients were enrolled, and 23 of them were evaluated for efficacy after receiving 3 cycles of ZR-CHOP treatment. 1-year PFS and OS were 80.8% and 88.5% respectively while expected PFS and OS for 2-years are 74.0% and 88.5% respectively with median follow-up of 16.7 months and ORR was 91.3% (CR: 82.61%; PR: 8.70%). Oncogenic mutations closely related to DLBCL pathogenesis were assessed in 20 patients using NGS. B-cell receptor and NF-κB pathway gene mutations were detected in 10 patients, which occurred in MYD88 (7/19), CD79B (4/19), CARD11 (5/19), and TNFAIP3 (2/19). Hematological adverse events (AEs) ≥ grade 3 included neutropenia (50%), thrombocytopenia (23.1%), and anemia (7.7%) whereas non-hematological AEs ≥ grade 3 included pulmonary infection (19.2%).ConclusionZR-CHOP is safe and effective for treating treatment naïve non-GCB DLBCL patients with extranodal involvement.Clinical Trial RegistrationClinicaltrials.gov, NCT0483587

Synthesis and biological evaluation of nitric oxide-releasing derivatives of oleanolic acid as inhibitors of HepG2 cell apoptosis

A total of 106 nitric oxide-releasing derivatives of oleanolic acid were synthesized and their effects on the inhibition of anti-Fas-mediated HepG2 cell apoptosis were evaluated in vitro. Several compounds inhibited anti-Fas-mediated HepG2 cell apoptosis in a dose-dependent manner. Within this series of compounds, 8b is the most potent inhibitor. The development of new NO-releasing derivatives of oleanolic acid may aid in the design of NO-based medicines for the intervention of human liver inflammatory diseases. (C) 2007 Elsevier Ltd. All rights reserved

Nanocomposites of Polyhydroxyurethane with POSS Microdomains: Synthesis via Non-Isocyanate Approach, Morphologies and Reprocessing Properties

In this contribution, we reported the synthesis of a novel trifunctional POSS cyclic carbonate [POSS-3(5CC)]. With a difunctional five-member cyclic carbonate and a trifunctional polyetheramine as the precursor, the nanocomposites of polyhydroxyurethane (PHU) with POSS were synthesized. Transmission electron microscopy (TEM) showed that the nanocomposites of PHUs with POSS were microphase-separated; the spherical POSS microdomains via POSS-POSS interactions were generated with the size of 20~40 nm in diameter. After the introduction of POSS microdomains, the nanocomposites displayed improved thermal and mechanical properties. More importantly, the nanocomposites still displayed the reprocessing properties of vitrimers

New insights into the phylogeny of Stephanidae (Hymenoptera: Apocrita), with a revision of the fossil species

The family Stephanidae (Hymenoptera) constitutes a unique group within the Apocrita, playing a pivotal role in the evolution of parasitoid wasps. Although the phylogeny of Stephanidae has been previously inferred, it remains at a low resolution when considering both extinct and extant genera, as well as the enigmatic extinct genus †Electrostephanus. Here, we undertake a revision of Stephanidae extinct, presenting descriptions of new specimens from late Cretaceous Burmese amber and early Eocene Baltic amber. Combining all extant and extinct genera, the phylogeny of Stephanidae was analyzed, incorporating 57 species within 21 genera based on 64 morphological characters. We apply both under maximum parsimony with equal weighting and implied weighting methods, with four species representing early Apocrita as outgroups. Divergence times are estimated by utilizing extinct taxa as calibration points. A new basal subfamily of stephanid wasp, †Lagenostephaninae subf. nov. was established, encompassing †Lagenostephanus and the newly described genera †Tumidistephanus gen. nov and †Neurastephanus gen. nov. The genus †Electrostephanus is redefined, with two species assigned under distinct genera, †Neurastephanus gen. nov. and †Aphanostephanus gen. nov.. We discuss some of the putative morphological synapomorphies of evolutionary significance within the phylogenetic framework. Our results complement several characteristics of great taxonomic importance for Stephanidae and provide new insights into the early evolution of the family

Spatiotemporal Changes of Coastline over the Yellow River Delta in the Previous 40 Years with Optical and SAR Remote Sensing

The integration of multi-source, multi-temporal, multi-band optical, and radar remote sensing images to accurately detect, extract, and monitor the long-term dynamic change of coastline is critical for a better understanding of how the coastal environment responds to climate change and human activities. In this study, we present a combination method to produce the spatiotemporal changes of the coastline in the Yellow River Delta (YRD) in 1980–2020 with both optical and Synthetic Aperture Radar (SAR) satellite remote sensing images. According to the measurement results of GPS RTK, this method can obtain a high accuracy of shoreline extraction, with an observation error of 71.4% within one pixel of the image. Then, the influence of annual water discharge and sediment load on the changes of the coastline is investigated. The results show that there are two significant accretion areas in the Qing 8 and Qingshuigou course. The relative high correlation illustrates that the sediment discharge has a great contribution to the change of estuary area. Human activities, climate change, and sea level rise that affect waves and storm surges are also important drivers of coastal morphology to be investigated in the future, in addition to the sediment transport