Browse Articles

Nanoscale structural alteration of lung collagen in response to strain and bleomycin injury

Nucleosomes as blueprints of genome architecture

De novo design of D-peptide ligands: Application to influenza virus hemagglutinin

D-peptides hold great promise as therapeutics by alleviating the challenges of metabolic stability and immunogenicity in L-peptides. However, current D-peptide discovery methods are severely limited by specific size, structure, and the chemical synthesizability of their protein targets. Here, we describe a computational method for de novo design of D-peptides that bind to an epitope of interest on the target protein using Rosetta’s hotspot-centric approach. The approach comprises identifying hotspot sidechains in a functional protein–protein interaction and grafting these side chains onto much smaller structured peptide scaffolds of opposite chirality. The approach enables more facile design of D-peptides and its applicability is demonstrated by design of D-peptidic binders of influenza A virus hemagglutinin, resulting in identification of multiple D-peptide lead series. The X-ray structure of one of the leads at 2.38 Å resolution verifies the validity of the approach. This method should be generally applicable to targets with detailed structural information, independent of molecular size, and accelerate development of stable, peptide-based therapeutics.

Direct observation of 3D nitrogen distribution in silicon-based dielectrics using atom probe tomography

Abstract The distribution of nitrogen in semiconductor devices plays a crucial role in tuning their physical and electrical properties. However, direct observation and precise quantification of nitrogen remain challenging because of analytical limitations, particularly at critical interfaces in silicon-based semiconductors. Although atom probe tomography has emerged as a powerful tool, distinguishing nitrogen from silicon without isotope doping is persistently difficult. In this study, we employ advanced atom probe tomography with an extended flight path under optimized conditions to characterize the three-dimensional nitrogen distribution in actual device structures, including 2- and 5-nm-thick silicon dioxide/silicon oxynitride-based gate dielectrics and a fin-structured three-dimensional device. Our analysis reveals that the nitrogen distribution determines the formation of the nitrogen profile in gate dielectrics, which in turn affects the diffusion of impurities, ultimately impacting the electrical properties and reliability. Our work provides insights into atomic-scale nitrogen behavior, paving the way for advancing next-generation semiconductor devices.

The virulence regulator CovR boosts CRISPR-Cas9 immunity in Group B Streptococcus

Abstract CRISPR-Cas9 immune systems protect bacteria from foreign DNA. However, immune efficiency is constrained by Cas9 off-target cleavages and toxicity. How bacteria regulate Cas9 to maximize protection while preventing autoimmunity is not understood. Here, we show that the master regulator of virulence, CovR, regulates CRISPR-Cas9 immunity against mobile genetic elements in Streptococcus agalactiae, a pathobiont responsible for invasive neonatal infections. We show that CovR binds to and represses a distal promoter of the cas operon, integrating immunity within the virulence regulatory network. The CovR-regulated promoter provides a controlled increase in off-target cleavages to counteract mutations in the target DNA, restores the potency of old immune memory, and stimulates the acquisition of new memory in response to recent infections. Regulation of Cas9 by CovR is conserved at the species level, with lineage specificities suggesting different adaptive trajectories. Altogether, we describe the coordinated regulation of immunity and virulence that enhances the bacterial immune repertoire during host-pathogen interaction.

Nucleation-promoting and growth-limiting synthesis of disordered rock-salt Li-ion cathode materials

Abstract Disordered rock-salt oxides and oxyfluorides are promising positive electrode materials for high-performance lithium-ion batteries free of nickel and cobalt. However, conventional synthesis methods rely on post-synthesis pulverization to achieve cycling-appropriate particle sizes, offering limited control over particle microstructure and crystallinity. This accelerates degradation and complicates secondary particle processing. Here we present a synthesis strategy that enhances nucleation while suppressing particle growth and agglomeration across various disordered rock-salt compositions, including lithium–manganese–titanium oxide, lithium–manganese–niobium oxide, and lithium–nickel–titanium oxide systems. Applied to Li 1.2 Mn 0.4 Ti 0.4 O 2 , this method yields highly crystalline, well-dispersed sub-200 nm particles that form homogeneous electrode films with stable cycling behavior. Tested in cells with lithium metal as the counter electrode, these electrodes deliver ~200 mAh/g with 85% capacity retention relative to the first cycle after 100 cycles (20 mA/g, 1.5–4.8 V), and an average discharge voltage loss of 4.8 mV per cycle, compared to 38.6% retention and 7.5 mV loss per cycle for electrodes derived from pulverized solid-state particles. This approach suggests a route to enhance the performance and durability of disordered rock-salt electrodes for sustainable lithium-ion batteries.

Comparative analysis of lumbar cerebrospinal fluid drainage versus lumbar puncture effectiveness in patients with aneurysmal subarachnoid hemorrhage

Simulation study of the influence of circular arc vortex generator size on the heat transfer characteristics of fin-and-tube heat exchanger

Whole grain and refined grain consumption and the risk of hypertension: a systematic review and meta-analysis of prospective studies

Abstract A high intake of whole grains has been associated with a reduced risk of hypertension, however, studies have not been entirely consistent. Findings regarding refined grains and hypertension have also been inconsistent. We conducted a systematic review and meta-analysis of prospective cohort studies on whole grain and refined grain consumption and hypertension risk. PubMed and Embase databases were searched up to 25th of July 2024. Random effects models were used to estimate summary relative risks (RRs) and 95% confidence intervals (CIs) for the association between whole grain and refined grain intake and hypertension. Restricted cubic splines were used to investigate potential nonlinear associations. Nine cohort studies were included in the meta-analysis. The summary RR (95% CI) for high vs. low whole grain intake was 0.74 (0.59–0.93, I2 = 97%, pheterogeneity<0.001, n = 9) and per 90 g/d was 0.86 (0.82–0.90, I2 = 63%, pheterogeneity=0.008, n = 8). The summary RR (95% CI) for high vs. low refined grain intake was 0.94 (0.88–1.01, I2 = 7.9%, pheterogeneity=0.36, n = 5) and per 90 g/d was 0.97 (0.93–1.02, I2 = 0%, pheterogeneity=0.42, n = 4). There was no indication of publication bias in either analysis, although the number of studies was low for refined grains. There was no evidence of nonlinearity for whole grains (pnonlinearity=0.31) or refined grains (pnonlinearity=0.21), and for whole grains there was a 22% reduction in risk at 200 vs. 0 g/d. These findings provide further support for a beneficial role of whole grain consumption in relation to hypertension risk and support recommendations to increase whole grain intake in the general population. No clear association was observed between refined grains and risk of hypertension.

Alteration in epigenetic profile in subclinical atherosclerosis and in high uric acid

The association of PTEN/PI3K/Akt pathway gene expression with insulin indices in adipose tissues of non-diabetic female adults: a cross-sectional study

Quantitative modeling of rod outer segment phagocytosis and recycling

Mechanical properties and sealing performance evaluation of packers in high temperature underground gas storage

Deciphering the biosynthesis pathway of gamma terpinene cuminaldehyde and para cymene in the fruit of Bunium persicum

A reliable framework for supply chain management using cluster based blockchain for intelligent industrial automation

Light controls gene functions through alternative splicing in fungi

Light controls important biological processes in fungi by regulating transcriptional gene activation. Here, we found that beyond the regulation of mRNA transcript abundance, light regulates alternative splicing (AS) in the filamentous fungi Aspergillus nidulans , Trichoderma guizhouense, and Neurospora crassa . Blue light-regulated AS was involved in ergothioneine biosynthesis and conidiation in T. guizhouense , which required the blue light receptor BLR1. Blue light activated the MAPK HOG (Sak) pathway which then transmitted the signal via the serine/threonine kinase SRK1 to the AS key regulator SRP1. SRK1 and SRP1 are important for light-induced conidiation. The light-activated HOG pathway led to an increase of the SRK1 protein level and its phosphorylation status. Phosphorylated SRK1 translocated from the cytoplasm to the nucleus to interact with SRP1, thereby regulating AS efficiency. This study unravels another level of complexity of fungal environmental sensing and responses and also first describes the entire cascade from an environmental signal to the splicing machinery.

Characterizing trachoma elimination using serology

Abstract Trachoma is targeted for global elimination as a public health problem by 2030. Measurement of IgG antibodies in children is being considered for surveillance and programmatic decision-making. There are currently no programmatic guidelines based on serology, which represents a generalizable problem in seroepidemiology and disease elimination. Here, we collate Chlamydia trachomatis Pgp3 and CT694 IgG measurements from 48 serosurveys across Africa, Latin America, and the Pacific Islands (41,168 children ages 1–5 years) and propose a novel approach to estimate the probability that population C. trachomatis transmission is below or above levels requiring ongoing programmatic action. We determine that trachoma programs could halt control measures with >90% certainty when seroconversion rates (SCRs) are ≤2.2 per 100 person-years. Conversely, SCRs ≥4.5 per 100 person-years correspond with >90% certainty that further control interventions are needed. More extreme SCR thresholds correspond with higher levels of confidence of elimination (lower SCR) or ongoing action needed (higher SCR). This study demonstrates a robust approach for using trachoma serosurveys to guide elimination program decisions.

The ocean flows downhill near the seafloor and recirculates upward above

Movie-watching evokes ripple-like activity within events and at event boundaries

Natural Sunlight‐Driven Activation of Inert Aryl Halides Using Plasmonic Cu@CdS with Polysulfide Active Sites

Abstract Visible light photoredox catalysis has become a rapidly emerging area owing to its potential of using sunlight to tame previously hard‐to‐harness radicals for organic synthesis. At present, such a blueprint faces a significant challenge, namely how to accomplish thermodynamically demanding reactions with sunlight encompassing a wide range of low‐energy photons. Here, we report a new reaction framework to overcome this bottleneck through decoupling the thermodynamic limits of photoreduction from photoexcitation. This is fulfilled based on the construction of a heterogeneous photocatalyst Cu@CdS possessing in situ‐formed surficial polysulfide species (including S 3 •− and S 4 2− ), which can efficiently harvest solar energy via plasmonic absorption of Cu while manifest sufficient redox potential for activating inert aryl bromides/chlorides enacted by excited polysulfides. We demonstrate that this designed material composes a potent photoredox catalyst for efficient aryl cross‐coupling, borylation, hydrogenation, as well as Birch‐type dearomatization reactions, with good recyclability and stability. In particular, when exclusively using natural sunlight as an energy source, the product yield can still reach up to 90%. Our findings introduce a straightforward yet viable way to progress toward the century‐long dream of leveraging natural sunlight to produce structurally complex organic molecules, just like plants on Earth.