Assembly and architecture of endogenous NMDA receptors in adult cerebral cortex and hippocampus.

The cerebral cortex and hippocampus are crucial brain regions for learning and memory, which depend on activity-induced synaptic plasticity involving N-methyl-ᴅ-aspartate receptors (NMDARs). However, subunit assembly and molecular architecture of endogenous NMDARs (eNMDARs) in the brain remain elusive. Using conformation- and subunit-dependent antibodies, we purified eNMDARs from adult rat cerebral cortex and hippocampus.

Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer.

Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0.

Vat Photopolymerization Additive Manufacturing of WC-Co Hardmetals Enabled by In Situ Polymerization-Induced Microencapsulation.

The additive manufacturing of hardmetals has attracted great attention recently but faces significant challenges in low printing resolution and low mechanical strength. Herein, the fabrication of hardmetal parts with complex structures and high surface quality by vat photopolymerization assisted with a sintering process has been achieved. This was enabled by in situ polymerization-induced microencapsulation of WC powder, which simultaneously enhances the photocuring ability and sedimentation stability of the WC-Co slurry.

CD137 agonism enhances anti-PD1 induced activation of expanded CD8 T cell clones in a neoadjuvant pancreatic cancer clinical trial.

Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy requires therapeutic combinations that induce quality T cells. Tumor microenvironment (TME) analysis following therapeutic interventions can identify response mechanisms, informing design of effective combinations. We provide a reference single-cell dataset from tumor-infiltrating leukocytes (TILs) from a human neoadjuvant clinical trial comparing the granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic PDAC vaccine GVAX alone, in combination with anti-PD1 or with both anti-PD1 and CD137 agonist.

Deciphering the endogenous SUMO-1 landscape: a novel combinatorial peptide enrichment strategy for global profiling and disease association.

Small ubiquitin-like modifier (SUMO) plays a pivotal role in diverse cellular processes and is implicated in diseases such as cancer and neurodegenerative disorders. However, large-scale identification of endogenous SUMO-1 faces challenges due to limited enrichment methods and its lower abundance compared to SUMO-2/3. Here we propose a novel combinatorial peptide strategy, combined with anti-adhesive polymer development, to enrich endogenous SUMO-1 modified peptides, revealing a comprehensive SUMOylation landscape.

How to Put Survival After Cardiothoracic Interventions in the General Population Context: A Case-Based Practical Guideline to Calculate Cumulative Matched-General-Population Survival.

Background: Observed patient survival after cardiothoracic interventions should ideally be placed in the context of matched-general-population survival. This study outlines several methodologies of matching general population mortality to the study sample, subsequently calculating cumulative matched-general-population survival, highlighting their respective advantages, disadvantages, and limitations.

Methods: A multicenter data set containing survival data after the Ross procedure was used for methodological illustration.

Highly Humidity-Resistant Oxynitride Phosphor BaSiNO:Ce for pc-LEDs.

Many phosphor hosts, for example, nitrides and sulfides, often face challenges such as hydrolysis and oxidation, limiting their application in phosphor-converted white light-emitting diodes (pc-LEDs). In this study, we developed a highly humidity-resistant yellow-green-emitting phosphor BaSiNO:Ce (BSNO:Ce). The DFT calculations revealed a high Debye temperature (Θ = 1159 K), indicating a rigid crystal structure that contributes to the photoluminescence thermal quenching resistance of BSNO.

Safety and Efficacy of Remote Ischemic Conditioning in Patients With Intravenous Thrombolysis: The SERIC-IVT Trial.

Background: Approximately half of the patients with acute ischemic stroke who receive intravenous thrombolysis (IVT) do not achieve an excellent outcome. Remote ischemic conditioning (RIC) as a promising neuroprotective treatment may improve clinical outcomes in this population. This study aimed to assess the efficacy and safety of RIC in patients with IVT.

A new class of penicillin-binding protein inhibitors to address drug-resistant .

β-Lactams are the most widely used antibiotics for the treatment of bacterial infections because of their proven track record of safety and efficacy. However, susceptibility to β-lactam antibiotics is continually eroded by resistance mechanisms. Emerging multidrug-resistant (MDR) strains possessing altered alleles (encoding PBP2) pose a global health emergency as they threaten the utility of ceftriaxone, the last remaining outpatient antibiotic.

A narrow band blue phosphor NaBaAlBOCl:Eu for white light emitting diodes.

Exploring new photoexcited phosphors has attracted attention for improving the performance of white LEDs. Here, an NaBaAlBOCl:Eu phosphor with high color purity (94.11%) has been synthesized.

Performance and stability analysis of all-perovskite tandem photovoltaics in light-driven electrochemical water splitting.

All-perovskite tandem photovoltaics are a potentially cost-effective technology to power chemical fuel production, such as green hydrogen. However, their application is limited by deficits in open-circuit voltage and, more challengingly, poor operational stability of the photovoltaic cell. Here we report a laboratory-scale solar-assisted water-splitting system using an electrochemical flow cell and an all-perovskite tandem solar cell.

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

Assembling MOF on CNTs into 0D-1D heterostructures for enhanced volatile organic compounds detection.

The rapid advancement of the Internet of Things has created a substantial demand for portable gas sensors. Nevertheless, the development of gas sensors that can fulfill the demanding criteria of high sensitivity and rapid response time continues to pose a considerable challenge. Herein, an in-situ anchoring strategy is proposed to construct CNTs@MOF heterostructure to establish strong electronic coupling and charge relocation for enhancing the monitoring capabilities of isopropanol (freshness markers for fruits) at room temperature.

Ferrocene-decorated graphene nanosheets built by edge-to-face π-π interaction for room temperature ppb-level NO sensing.

The development of materials toward ppb-level nitric oxide (NO) sensing at room temperature remains in high demand for the monitoring of respiratory inflammatory diseases. In order to find an iron-containing molecule without steric hindrance to combine with graphene for room temperature NO gas sensing, here a supramolecular assembly of ferrocene (Fc) and reduced graphene oxide (rGO) was designed and prepared for NO sensing. The assembly of Fc/rGO was characterized using FT-IR, TEM, and XPS measurements.

Heteroaryl Glutarimides and Dihydrouracils as Cereblon Ligand Scaffolds for Molecular Glue Degrader Discovery.

Stabilization of cereblon (CRBN)/neosubstrate complexes with molecular glues followed by degradation of those neosubstrates is an emerging strategy in drug discovery with compelling potential to target certain proteins that were previously considered to be undruggable. In this context, the discovery of novel CRBN ligands is an important area of ongoing research that holds promise to expand the scope of proteins that can be targeted through this mode of action. Herein, we describe the synthesis and evaluation of CRBN ligands featuring heteroaryl glutarimide and dihydrouracil scaffolds.

Enhanced Reader Confidence and Differentiation of Calcification from Cerebral Microbleed Diagnosis Using QSM Relative to SWI.

Purpose: Accurate detection of cerebral microbleeds (CMBs) is important for detection of multiple conditions. However, CMBs can be challenging to identify on MR images, especially for distinguishing CMBs from the mimic of calcification. We performed a comparative reader study to assess the diagnostic performance of two primary MR sequences for differentiating CMBs from calcification.

A robust benchmark for detecting low-frequency variants in the HG002 Genome In A Bottle NIST reference material.

Somatic mosaicism is an important cause of disease, but mosaic and somatic variants are often challenging to detect because they exist in only a fraction of cells. To address the need for benchmarking subclonal variants in normal cell populations, we developed a benchmark containing mosaic variants in the Genome in a Bottle Consortium (GIAB) HG002 reference material DNA from a large batch of a normal lymphoblastoid cell line. First, we used a somatic variant caller with high coverage (300x) Illumina whole genome sequencing data from the Ashkenazi Jewish trio to detect variants in HG002 not detected in at least 5% of cells from the combined parental data.

π-HuB: the proteomic navigator of the human body.

The human body contains trillions of cells, classified into specific cell types, with diverse morphologies and functions. In addition, cells of the same type can assume different states within an individual's body during their lifetime. Understanding the complexities of the proteome in the context of a human organism and its many potential states is a necessary requirement to understanding human biology, but these complexities can neither be predicted from the genome, nor have they been systematically measurable with available technologies.

Intestinal mucosal barrier repair and immune regulation with an AI-developed gut-restricted PHD inhibitor.

Hypoxia-inducible factor prolyl hydroxylase (PHD) inhibitors have been approved for treating renal anemia yet have failed clinical testing for inflammatory bowel disease because of a lack of efficacy. Here we used a multimodel multimodal generative artificial intelligence platform to design an orally gut-restricted selective PHD1 and PHD2 inhibitor that exhibits favorable safety and pharmacokinetic profiles in preclinical studies. ISM012-042 restores intestinal barrier function and alleviates gut inflammation in multiple experimental colitis models.

A peptide-centric local stability assay enables proteome-scale identification of the protein targets and binding regions of diverse ligands.

By using a limited-proteolysis strategy that employs a large amount of trypsin to generate peptides directly from native proteins, we found that ligand-induced protein local stability shifts can be sensitively detected on a proteome-wide scale. This enabled us to develop the peptide-centric local stability assay, a modification-free approach that achieves unprecedented sensitivity in proteome-wide target identification and binding-region determination. We demonstrate the broad applications of the peptide-centric local stability assay by investigating interactions across various biological contexts.

Serum GFAP and UCH-L1 Levels for the Assessment of the Absence of Hemorrhagic Transformation: A Multicenter Prospective Cohort Study.

Background: Currently, validated biomarkers for assessing hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) are lacking. We aimed to validate a test combining GFAP (glial fibrillary acidic protein) and UCH-L1 (ubiquitin C-terminal hydrolase-L1) to indicate the absence of HT after IVT.

Methods: We prospectively enrolled consecutive patients with stroke treated with IVT from 16 hospitals.

Microparticle-assisted protein capture method facilitates proteomic and glycoproteomic analysis of urine samples.

Serum tests have become a partial alternative to renal biopsy for diagnosing primary membranous nephropathy (pMN). However, urine tests, due to their non-invasive nature and ability to more accurately reflect glomerular diseases, hold great promise for the detection of pMN. However, the low protein concentration and the time-consuming sample preparation procedure of urine samples challenges the proteomic and glycoproteomic analysis to find urine-derived signatures associated with pMN.

Multi-Functional Descriptor Design of V-Based Double Atomic Catalysts for Room Temperature Sodium-Sulfur Batteries.

Double atomic catalysts (DACs) have emerged as a promising approach for addressing the shuttle effect and sluggish kinetics in room temperature sodium-sulfur batteries (RT-SSBs). However, identifying optimal metal combinations to meet the multiple requirements for RT-SSBs is challenging. Herein, a method for designing V-based DACs catalysts (DAC-VX, X = metal atoms) is presented by distilling descriptors through first-principle calculations and Multi-Task Learning-Sure Independence Screening and Sparsifying Operator.

Discovery of potential female-specific biomarkers for major depressive disorder by LC-MS-based metabolomics.

The prevalence of major depressive disorder (MDD) is higher in females than males, emphasizing the need to identify gender-specific biomarkers to improve diagnosis accuracy. In this study, a cross-sectional investigation with 258 samples was conducted to evaluate the discriminative power of potential gender-specific biomarkers for MDD. Eighteen MDD-related differential metabolites have been identified, involving pathways of phospholipids, glycerolipids, fatty acids, sphingolipids, cholesterol, vitamin E, and heme.