A retrospective multicenter study on the efficacy and safety of disitamab vedotin monotherapy versus combination with anti-PD-1 immunotherapy in advanced gastric cancer.

Novel therapeutic agents including disitamab vedotin (RC48, an antibody-drug conjugate) and immune-checkpoint inhibitors (e.g., PD-1 inhibitors) have provided new hope as an advanced gastric-cancer (GC) treatment.

Selective deficiency of mitochondrial respiratory complex I subunits Ndufs4/6 causes tumor immunogenicity.

Cancer cells frequently rewire their metabolism to support proliferation and evade immune surveillance, but little is known about metabolic targets that could increase immune surveillance. Here we show a specific means of mitochondrial respiratory complex I (CI) inhibition that improves tumor immunogenicity and sensitivity to immune checkpoint blockade (ICB). Targeted genetic deletion of either Ndufs4 or Ndufs6, but not other CI subunits, induces an immune-dependent growth attenuation in melanoma and breast cancer models.

Role of transforming growth factor-β1 in regulating adipocyte progenitors.

Adipose tissue (AT) metabolism involves coordinating various cells and cellular processes to regulate energy storage, release, and overall metabolic homeostasis. Therein, macrophage and its cytokine are important in controlling tissue homeostasis. Among cytokines, the role of transforming growth factor-β1 (Tgf-β1), a cytokine abundantly expressed in CD206 M2-like macrophage and correlated with the expansion of AT and fibrosis, in AT metabolism, remains unknown.

Exploration of linear and interpretable models for quantification of cell parameters via contactless short-wave infrared hyperspectral sensing.

The development of optical sensors for label-free quantification of cell parameters has numerous uses in the biomedical arena. However, using current optical probes requires the laborious collection of sufficiently large datasets that can be used to calibrate optical probe signals to true metabolite concentrations. Further, most practitioners find it difficult to confidently adapt black box chemometric models that are difficult to troubleshoot in high-stakes applications such as biopharmaceutical manufacturing.

Multi-faceted examination of a deepwater seamount reveals ecological patterns among coral and sponge communities in the equatorial Pacific.

Spatial changes in benthic community structure have been observed across natural gradients in deep-sea ecosystems, but these patterns remain under-sampled on seamounts. Here, we identify the spatial composition and distribution of coral and sponge taxa on four sides of a single central Pacific equatorial "model" seamount within the US EEZ surrounding the Howland and Baker unit of the Pacific Islands Heritage Marine National Monument. This seamount rises from 5,000 + m to mesophotic depths of 196 m, and is influenced by the Equatorial Undercurrent.

Cola beverage reduces risk of lead poisoning from accidental ingestion of contaminated soil particles in rat and swine models.

Accidental ingestion of lead (Pb)-contaminated soils represents a major route of Pb exposure for both adults and children, and the development of accessible and cost-effective solutions to reduce Pb poisoning is urgently required. Here, we present an effective and straightforward technique, involving the consumption of cola beverages, for the purpose of lowering blood Pb levels following the ingestion of contaminated soils in animal models. This method facilitated the direct passage of Pb in contaminated soil through the digestive system, enhancing its elimination without absorption into systemic circulation.

Patterns of Klebsiella pneumoniae bacteremic dissemination from the lung.

Bacteremia, a leading cause of death, generally arises after bacteria establish infection in a particular tissue and transit to secondary sites. Studying dissemination from primary sites by solely measuring bacterial burdens does not capture the movement of individual clones. By barcoding Klebsiella pneumoniae, a leading cause of bacteremia, we track pathogen dissemination following pneumonia.

Streptococcus abundance and oral site tropism in humans and non-human primates reflects host and lifestyle differences.

The genus Streptococcus is highly diverse and a core member of the primate oral microbiome. Streptococcus species are grouped into at least eight phylogenetically-supported clades, five of which are found almost exclusively in the oral cavity. We explored the dominant Streptococcus phylogenetic clades in samples from multiple oral sites and from ancient and modern-day humans and non-human primates and found that clade dominance is conserved across human oral sites, with most Streptococcus reads assigned to species falling in the Sanguinis or Mitis clades.

Energy and climate policy implications on the deployment of low-carbon ammonia technologies.

The economic feasibility of low-carbon ammonia production pathways, such as steam methane reforming with carbon capture and storage, biomass gasification, and electrolysis, is assessed under various policy frameworks, including subsidies, carbon pricing, and renewable hydrogen regulations. Here, we show that employing a stochastic techno-economic analysis at the plant level and a net present value approach under the US Inflation Reduction Act reveals that carbon capture and biomass pathways demonstrate strong economic potential due to cost-effectiveness and minimal public support needs. Conversely, the electrolytic pathway faces significant economic challenges due to higher costs and lower efficiency.

Dynamic hydrogen-bonding enables high-performance and mechanically robust organic solar cells processed with non-halogenated solvent.

Developing active-layer systems with both high performance and mechanical robustness is a crucial step towards achieving future commercialization of flexible and stretchable organic solar cells (OSCs). Herein, we design and synthesize a series of acceptors BTA-C6, BTA-E3, BTA-E6, and BTA-E9, featuring the side chains of hexyl, and 3, 6, and 9 carbon-chain with ethyl ester end groups respectively. Benefiting from suitable phase separation and vertical phase distribution, the PM6:BTA-E3-based OSCs processed by o-xylene exhibit lower energy loss and improved charge transport characteristic and achieve a power conversion efficiency of 19.

Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost.

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.

The widely used Ucp1-Cre transgene elicits complex developmental and metabolic phenotypes.

Bacterial artificial chromosome transgenic models, including most Cre-recombinases, enable potent interrogation of gene function in vivo but require rigorous validation as limitations emerge. Due to its high relevance to metabolic studies, we perform comprehensive analysis of the Ucp1-Cre line which is widely used for brown fat research. Hemizygotes exhibit major brown and white fat transcriptomic dysregulation, indicating potential altered tissue function.

Enhanced sampling of protein conformational changes via true reaction coordinates from energy relaxation.

The bottleneck in enhanced sampling lies in finding collective variables that effectively accelerate protein conformational changes; true reaction coordinates that accurately predict the committor are the well-recognized optimal choice. However, identifying them requires unbiased natural reactive trajectories, which, paradoxically, require effective enhanced sampling. Using the generalized work functional method, we uncover that true reaction coordinates control both conformational changes and energy relaxation, enabling us to compute them from energy relaxation simulations.

Interferon-α promotes HLA-B-restricted presentation of conventional and alternative antigens in human pancreatic β-cells.

Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but the effect of IFN-α on the antigen repertoire of HLA Class I (HLA-I) in pancreatic β-cells is unknown. Here we characterize the HLA-I antigen presentation in resting and IFN-α-exposed β-cells and find that IFN-α increases HLA-I expression and expands peptide repertoire to those derived from alternative mRNA splicing, protein cis-splicing and post-translational modifications. While the resting β-cell immunopeptidome is dominated by HLA-A-restricted peptides, IFN-α largely favors HLA-B and only marginally upregulates HLA-A, translating into increased HLA-B-restricted peptide presentation and activation of HLA-B-restricted CD8 T cells.

Tuning Dual Catalytic Active Sites of Pt Single Atoms Paired with High-Entropy Alloy Nanoparticles for Advanced Li-O Batteries.

To achieve a long cycle life and high-capacity performance for Li-O batteries, it is critical to rationally modulate the formation and decomposition pathway of the discharge product LiO. Herein, we designed a highly efficient catalyst containing dual catalytic active sites of Pt single atoms (Pt) paired with high-entropy alloy (HEA) nanoparticles for oxygen reduction reaction (ORR) in Li-O batteries. HEA is designed with a moderate d-band center to enhance the surface adsorbed LiO intermediate (LiO(ads)), while Pt active sites exhibit weak adsorption energy and promote the soluble LiO pathway (LiO(sol)).

Enhancing Catalytic Removal of Autoexhaust Soot Particles via the Modulation of Interfacial Oxygen Vacancies in Cu/CeO Catalysts.

The purification efficiency of autoexhaust carbon strongly depends on the heterogeneous interface structure between active metal and oxide, which can modulate the local electronic structure of defect sites to promote the activation of reactant molecules. Herein, the high-dispersion CuO clusters supported on the well-defined CeO nanorods were prepared using the complex deposition slow method. The formation of heteroatomic Cu-O-Ce interfacial structural units as active sites can capture electrons to achieve activation of the NO and O molecules.

How Pediatric Readiness can Impact Pediatric Trauma From Every Day to Mass Events.

Disaster events such as weather events and mass casualty events are increasing in frequency and severity. Caring for children during a surge requires a regional approach given limited pediatric inpatient capacity and expertise. During the 2024 American Academy of Pediatrics National Convention and Exhibition, the Section on Surgery and Council on Children and Disasters (COCD) partnered to present a joint symposium emphasizing importance of pediatric readiness and disaster preparedness and role of pediatric trauma surgeons in disaster preparedness and response in all communities.

Comprehensive Review of Multilingual Patient-Reported Outcome Measures for Dysphonia.

Introduction: Patient-reported outcome measures (PROMs) represent an important part of a comprehensive voice assessment for clinical care and research. Access to multilingual PROMs enables inclusion of information from diverse patient populations. This review compares available translated and validated PROMs for adult dysphonia.

Topographic Axes of Wiring Space Converge to Genetic Topography in Shaping Human Cortical Layout.

Genetic information is involved in the gradual emergence of cortical areas since the neural tube begins to form, shaping the heterogeneous functions of neural circuits in the human brain. Informed by invasive tract-tracing measurements, the cortex exhibits marked interareal variation in connectivity profiles, revealing the heterogeneity across cortical areas. However, it remains unclear about the organizing principles possibly shared by genetics and cortical wiring to manifest the spatial heterogeneity across cortex.

Differential impacts of strabismic and anisometropic amblyopia on the mesoscale functional organization of the human visual cortex.

We employed high-resolution fMRI to distinguish the impacts of anisometropia and strabismus amblyopia on the evoked ocular dominance (OD) response. Sixteen amblyopic participants (8 females) plus 8 individuals with normal vision (1 female), participated in this study for whom, we measured the difference between the response to stimulation of the two eyes, across areas V1-V4.In controls, the evoked OD response formed the expected striped pattern within V1.

T follicular helper cell expansion and hyperimmunoglobulinemia with spontaneous IgE production to dietary antigens in IgA-deficient mice.

Immunoglobulin A (IgA), the most abundantly produced antibody at mucosal surfaces, is thought to play key roles in immune responses to respiratory and enteric pathogens and in the regulation of commensal colonization. Low IgA levels have been associated with recurrent infections and immune dysregulation, including inflammatory bowel disease and autoimmunity. Levels of IgA in maternal breast milk and infant stool are both inversely associated with the emergence of immune responses to food antigens in infants and, in naturally resolving food sensitivity and immunotherapy protocols, the induction of IgA antibodies to dietary antigens has been associated with the acquisition of food tolerance.

Merestinib inhibits cuproptosis by targeting NRF2 to alleviate acute liver injury.

The emergence of cuproptosis, a novel form of regulated cell death, is induced by an excess of copper ions and has been associated with the progression of multiple diseases, including liver injury, cardiovascular disease, and neurodegenerative disorders. However, there are currently no inhibitors available for targeting specific cuproptosis-related pathways in therapy. Here, the compound merestinib (MTB) has been identified as a strong inhibitor of cuproptosis through screening of a kinase inhibitor library.

Biosorption of rhodamine B and sunset yellow dyes on cross-linked chitosan-alginate biocomposite beads: Experimental and theoretical studies.

This research explores the biosorption of Rhodamine B (Rd-B) and Sunset Yellow (SY) dyes using cross-linked chitosan-alginate (Ch-A) biocomposite beads, combining experimental investigations with theoretical studies to elucidate the biosorption mechanisms. The biocomposite beads were synthesized through an eco-friendly cross-linking method, and their structural properties were characterized using various characterization techniques. Complementary theoretical studies using Monte Carlo (MC) simulations and molecular dynamics (MD) calculations provided insights into the molecular interactions between the dyes and the biocomposite beads.

The investigation of the interaction of warangalone with transferrin as a therapeutic biological macromolecule and the formation of a protein-ligand nanocomplex with superior anticancer activity against lung cancer cells.

Though warangalone has shown anticancer properties against breast cancer cells, its colloidal stability and therapeutic index ought to be improved using a potential strategy, especially via protein-based (nano)carriers. In this research, transferrin was used as a plasma protein for the development of the warangalone-transferrin NPs. To investigate the mechanism underlying the formation of this complex, the interaction between warangalone and transferrin, as well as transferrin NPs, was analyzed using spectroscopic methods.