Browse Articles
Discover research articles across all indexed journals
Cryo-EM structures of NHEJ assemblies with nucleosomes
Abstract DNA double-strand breaks (DSBs) are highly deleterious lesions that can trigger cell death or carcinogenesis if unrepaired or misrepaired. In mammals, most DSBs are repaired by non-homologous end joining (NHEJ), which begins when Ku70/80 binds DNA ends and recruits DNA-PKcs to form the DNA-PK holoenzyme. Although recent cryo-EM studies have resolved several NHEJ assemblies, how these factors access DSBs within nucleosomes remains unclear. Here, we present cryo-EM structures of human Ku70/80 and DNA-PK bound to nucleosomes. Ku70/80 binds the DNA end and bends it away from the nucleosome core, while the Ku70 C-terminal SAP domain makes an additional, specific DNA contact. Our DNA-PK–nucleosome structure further reveals the opening of the Ku80 vWA domain, and we show that non-hydrolysable ATP promotes synapsis by stabilising the Ku80-mediated DNA-PK dimer. These structures reveal a model for DSB recognition on nucleosomal DNA and provide insights relevant to targeting NHEJ in cancer therapy.
Assessment of gait speed in older adults using a short–distance walking test with smartphone motion sensors and machine learning
GBP2 condensates promote ferroptosis to sensitize anti-PD-L1 immunotherapy in melanoma
Research on multi-source data fusion and high-precision mapping method for complex landforms based on computer vision
Sustainable polyolefin upcycling using liquid organic hydrogen carrier based hydrogen delivery and hydrocracking
Influence of ApoE genotype on doxorubicin-induced cognitive impairment in juvenile rats
Zishen Yutai Pill increased live births in advanced maternal age women: a randomized clinical trial
Abstract Advanced maternal age (AMA, ≥35 years) women undergoing assisted reproductive technology (ART) face reduced live birth rates (LBR) and remain a major clinical challenge. In a large randomized trial, Zishen Yutai Pill (ZYP) improved LBR in the general population, and a subsequent post hoc analysis suggested efficacy in AMA women, though it was underpowered to draw firm conclusions. To address the issue, we conducted a multicenter, prospective, double-blind, placebo-controlled, randomized trial (NCT03703700) to evaluate whether ZYP increases LBR in AMA women. Women aged 35-42 years with BMI < 28 kg/m 2 at 12 tertiary-level hospitals in China were randomly assigned to receive ZYP or placebo orally (5 g once, three times daily) from day 19-23 of the preceding menstrual cycle until 2 weeks after embryo transfer, continuing to 5 weeks post transfer if biochemical pregnancy was confirmed. The primary outcome was fresh-cycle LBR. A total of 1467 participants (734 ZYP, 733 placebo) were enrolled. In the intention-to-treat analysis, live birth occurred in 23.3% (171/734) with ZYP vs. 19.0% (139/733) with placebo (relative ratio 1.23 [95% CI, 1.01-1.50]; absolute difference 4.3% [95% CI, 0.2-8.5]; P = 0.042). This study showed that Zishen Yutai Pill increased live birth rates in women aged 35–42 undergoing IVF, without elevating the risk of maternal or neonatal adverse events. (NCT03703700, https://clinicaltrials.gov/study/NCT03703700 )
Treatment effect based on antimicrobial resistance in Staphylococcus aureus infections related to orthopedics
Abstract Staphylococcus aureus is a prevalent pathogen in infections related to orthopedics. Here, we report on the antimicrobial resistance and treatment with emphasis on both clinical and microbiological perspectives. We recruited 196 patients with S. aureus isolates. Antimicrobial resistance was described by resistance rates, and multidrug resistance (MDR) was classified according to international standards. Antimicrobial agents were classified as active, untested, or inactive according to the antimicrobial susceptibility tests. The treatment stage was divided into empirical and targeted stages, and effects were classified as first-, second-, or third-grade healing. Resistance rates ranged from 0.0 to 89.2%, and no resistance to vancomycin or linezolid was found. As the signal of methicillin resistance, the incidence of oxacillin resistance was 21.0%. MDR was identified in 84 (42.9%) isolates, not related to gender ( p = 0.505) or age ( p = 0.459). Cefuroxime and cefazolin were common untested agents, whereas clindamycin and levofloxacin were common active agents used in treatment. Out of the participants, 173 had first-grade healing, 16 had second-grade healing, and 7 had third-grade healing. Of the patients who received active and untested agents, the numbers of patients who had first-, second-, and third-grade healing were 74, 6, and 4 vs. 99, 10, and 3 ( p = 0.709), respectively. Among the patients who received untested agents during empirical treatment, 20.9% (28/134) switched to active agents for treatment success. Antimicrobial resistance is a prevalent concern, especially methicillin resistance. Active agents represented by clindamycin and levofloxacin are valuable according to antimicrobial susceptibility tests and clinical practice.
Cavity-QED-controlled two-dimensional Moiré excitons without twisting
Abstract We propose an all-optical Moiré-like exciton confinement by means of spatially periodic optical cavities. Such periodic photonic structures can control the material properties by coupling the matter excitations to the confined photons and their quantum fluctuations. We develop a low energy non-perturbative quantum electro-dynamical description of strongly coupled excitons and photons at finite momentum transfer. We find that in the classical limit of a laser driven cavity the induced optical confinement directly emulates Moiré physics. In a dark cavity instead, the sole presence of quantum fluctuations of light generates a sizable renormalization of the excitonic bands and effective mass. We attribute these effects to long-range cavity-mediated exciton-exciton interactions which can only be captured in a non-perturbative treatment. With these findings we propose spatially structured cavities as a promising avenue for cavity material engineering.