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A hotly debated lung cancer drug cut the risk of death by 34% in a late-stage trial in China

An experimental lung cancer drug from Akeso and Summit Therapeutics reduced the risk of death by 34% in a closely watched late-stage trial, according to results released Sunday. When combined with chemotherapy, the drug kept people with squamous non-small-cell lung cancer alive for a median of four months longer than the standard combination of immunotherapy and chemotherapy, a result that was statistically significant, according to an abstract released Sunday ahead of a presentation at the...

CNBC 9d ago

Characterization of expression elements for an AAV delivered antibody in nonhuman primates when co-delivered with PD-L1

Successful AAV-expressed antibody therapy for HIV-1 requires broadly neutralizing antibody (bNAbs) concentrations and reduced immune responses to sustain viral suppression without ART. We have previously demonstrated that co-delivery of AAV-expressed PD-L1 reduces immune responses against HIV-1 bNAbs in rhesus macaques. Here we systematically evaluated six AAV9 transgene cassettes encoding 10-1074 with different promoter/intron combinations (CMV, CMV/R, CBA, CASI, CB7, EF1a) across in vitro...

bioRxiv 11d ago

Preserved CD4+ T cell helper function and coordinated antiviral immunity in people with HBV/HIV co-infection on long-term therapy

ABSTRACT Background & Aims: People with HBV/HIV co-infection on antiretroviral therapy achieve higher rates of HBV functional cure than those with HBV mono-infection, yet the immunological basis remains poorly characterised. HBV-specific CD4+ T cell responses are critical for viral control and functional cure but have been scarcely examined in HBV/HIV co-infection. Our previous studies in HBV/HIV co-infection demonstrated preserved stem-like CD8+ T cells and NK cell functional responses, but...

bioRxiv 4d ago

Co-delivered PD-L1 rescues the protective efficacy mediated by an AAV-expressed HIV-1 bNAb

Adeno-associated virus (AAV)-delivered anti-HIV-1 broadly neutralizing antibodies (bNAbs) could prevent and treat HIV-1 infection but are limited by host immune responses, specifically anti-drug antibodies (ADA). We tested whether PD-L1-mediated immune shielding could improve the consistency of AAV-delivered bNAb expression from muscle tissue in rhesus macaques. AAV9.PD-L1 co-delivery with AAV9.3BNC117 reduced the occurrence of ADA and T cell responses and improved the durability of 3BNC117...

bioRxiv 9d ago

Crystallisation kinetics of supercooled liquid palladium

Announce Type: cross Abstract: In this study, we employ classical molecular dynamics (MD) simulations to investigate the crystallisation kinetics of supercooled liquid palladium and relate the results to time-resolved X-ray diffraction measurements on rapidly quenched Pd thin films. Crystal nucleation and growth rates are determined over the temperature range $700$--$1150~\mathrm{K}$ ($0.38$--$0.65 T_{\mathrm{m}}$) by analysing the evolution of the microstructure during the liquid-to-crystal...

arXiv Physics 9d ago

Crystallisation kinetics of supercooled liquid palladium

Announce Type: replace-cross Abstract: In this study, we employ classical molecular dynamics (MD) simulations to investigate the crystallisation kinetics of supercooled liquid palladium and relate the results to time-resolved X-ray diffraction measurements on rapidly quenched Pd thin films. Crystal nucleation and growth rates are determined over the temperature range $700$--$1150~\mathrm{K}$ ($0.38$--$0.65 T_{\mathrm{m}}$) by analysing the evolution of the microstructure during the...

arXiv Physics 6d ago

Netrin-1 drives cell-type-specific plasticity of human dopaminergic neurons during circuit integration in a Parkinsonian model

The survival of transplanted ventral midbrain (vm) dopaminergic neurons (DAn) and their innervation of host striatal tissue are crucial for ameliorating motor symptoms in Parkinson`s disease (PD). However, human pluripotent stem cells (hPSC) show inferior axonal plasticity compared to fetal donor tissue. While modulation of the host environment with trophic cues, such as glial cell-derived neurotrophic factor (GDNF), can improve graft outcomes, these cues lack specificity for DAn, resulting...

bioRxiv 8d ago

Clinical isolates of Mycobacterium avium complex reveal an M. intracellulare-associated IL-17/neutrophilic pulmonary immune program in a murine disease model

Mycobacterium avium complex (MAC) is the leading cause of nontuberculous mycobacterial pulmonary disease (NTM-PD) and mainly comprises M. avium (MAV) and M. intracellulare (MI). Host-pathogen interactions may contribute to the heterogeneous clinical course of MAC pulmonary disease (MAC-PD); however, species- or isolate-associated differences in virulence and host immune responses induced by MAC strains remain poorly understood. Here, we established a panel of MAC clinical isolates exhibiting...

bioRxiv 10d ago

Neutrophil-Derived Oncostatin M Contributes to Endothelial Cell Dysfunction During Treponema denticola interaction

Periodontitis (PD) is a common chronic inflammatory condition and a risk factor for cardiovascular diseases (CVD), yet underlying linking mechanisms remain unclear. The cytokine Oncostain M (OSM) is elevated in both PD and CVD and has emerged as a potential mediator linking oral inflammation to vascular dysfunction. Neutrophils represent a prominent source of OSM during PD and OSM production is elevated by the periodontal pathobiont Treponema denticola (Td).

bioRxiv 8d ago

Chuwi Minibook X: the netbook we deserve

Netbooks are dead, but the Chuwi Minibook X scratches the same itch. The Minibook X is a 10.5″ x86_64 sub-ultrabook with 16GB RAM, a 512GB NVMe drive, and only one majorly annyoing Linux quirk. I needed a knock-around laptop, so I bought myself a Minibook for my birthday last year.

Hacker News 9d ago