UDA-seq: universal droplet microfluidics-based combinatorial indexing for massive-scale multimodal single-cell sequencing.

The use of single-cell combinatorial indexing sequencing via droplet microfluidics presents an attractive approach for balancing cost, scalability, robustness and accessibility. However, existing methods often require tailored protocols for individual modalities, limiting their automation potential and clinical applicability. To address this, we introduce UDA-seq, a universal workflow that integrates a post-indexing step to enhance throughput and systematically adapt existing droplet-based single-cell multimodal methods.

An Automatic Deep-Radiomics Framework for Prostate Cancer Diagnosis and Stratification in Patients with Serum Prostate-Specific Antigen of 4.0-10.0 ng/mL: A Multicenter Retrospective Study.

Rationale And Objectives: To develop an automatic deep-radiomics framework that diagnoses and stratifies prostate cancer in patients with prostate-specific antigen (PSA) levels between 4 and 10 ng/mL.

Materials And Methods: A total of 1124 patients with histological results and PSA levels between 4 and 10 ng/mL were enrolled from one public dataset and two local institutions. An nnUNet was trained for prostate masks, and a feature extraction module identified suspicious lesion masks.

Discovery of highly potent and ALK2/ALK1 selective kinase inhibitors using DNA-encoded chemistry technology.

Activin receptor type 1 (ACVR1; ALK2) and activin receptor like type 1 (ACVRL1; ALK1) are transforming growth factor beta family receptors that integrate extracellular signals of bone morphogenic proteins (BMPs) and activins into Mothers Against Decapentaplegic homolog 1/5 (SMAD1/SMAD5) signaling complexes. Several activating mutations in ALK2 are implicated in fibrodysplasia ossificans progressiva (FOP), diffuse intrinsic pontine gliomas, and ependymomas. The ALK2 R206H mutation is also present in a subset of endometrial tumors, melanomas, non-small lung cancers, and colorectal cancers, and ALK2 expression is elevated in pancreatic cancer.

FLAIR: A Phase II, Open Label, Randomized Study of Osimertinib Plus Bevacizumab Versus Osimertinib in Recurrent or Metastatic Treatment-Naïve NSCLC Patients Harboring EGFR 21L858R Mutation.

Introduction: Osimertinib, the 3rd generation EGFR-TKI, has emerged as standard first-line treatment for patients with advanced EGFR mutated nonsmall cell lung cancer (NSCLC). Patients with exon 21 L858R mutation showed lower efficacy with EGFR-TKIs than those with 19Del mutation, even with osimertinib, it remains an unmet medical need to further improve the efficacy in L858R population. We present the rationale and design for FLAIR (NCT04988607), which will investigate the efficacy and safety of osimertinib plus bevacizumab versus osimertinib monotherapy in treatment-naïve recurrent or metastatic NSCLC patients harboring EGFR exon 21 L858R mutation.

Disrupting stroke-induced GAT-1-syntaxin1A interaction promotes functional recovery after stroke.

Although stroke is a frequent cause of permanent disability, our ability to promote stroke recovery is limited. Here, we design a small-molecule stroke recovery promoting agent that works by dissociating γ-aminobutyric acid (GABA) transporter 1 (GAT-1) from syntaxin1A (Synt1A), a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein. Stroke induces an increase in GAT-1-Synt1A interaction in the subacute phase, a critical period for functional recovery.

Vaccine Potency and Structure of Yeast-Produced Polio Type 2 Stabilized Virus-like Particles.

Poliovirus (PV) is on the brink of eradication due to global vaccination programs utilizing live-attenuated oral and inactivated polio vaccines. Recombinant PV virus-like particles (VLPs) are emerging as a safe next-generation vaccine candidate for the impending polio-free era. In this study, we investigate the production, antigenicity, thermostability, immunogenicity, and structures of VLPs derived from PV serotype 2 (PV2) wildtype strain and thermally stabilized mutant (wtVLP and sVLP, respectively).

Divergent and gram-scale syntheses of (-)-veratramine and (-)-cyclopamine.

Veratramine and cyclopamine, two of the most representative members of the isosteroidal alkaloids, are valuable molecules in agricultural and medicinal chemistry. While plant extraction of these compounds suffers from uncertain supply, efficient chemical synthesis approaches are in high demand. Here, we present concise, divergent, and scalable syntheses of veratramine and cyclopamine with 11% and 6.

US-guided Percutaneous Radiofrequency Ablation for Secondary Hyperparathyroidism: Long-term Outcomes and Prognostic Factors.

Background Although favorable outcomes have been reported with radiofrequency ablation (RFA) for secondary hyperparathyroidism (SHPT), the long-term efficacy remains insufficiently investigated. Purpose To evaluate the long-term efficacy and safety of US-guided percutaneous RFA in patients with SHPT undergoing dialysis and to identify possible predictors associated with treatment failure. Materials and Methods This retrospective study included consecutive patients with SHPT with at least one enlarged parathyroid gland accessible for RFA who were undergoing dialysis at seven tertiary centers from May 2013 to July 2022.

A single-agent fusion of human IL-2 and anti-IL-2 antibody that selectively expands regulatory T cells.

The occurrence of many autoimmune diseases takes root on the disrupted balance among Treg cells, Teff cells, etc. Low-dose interleukin-2 (IL-2) cytokine demonstrates promising clinical efficacy in the expansion of Treg cells and the treatment of autoimmune diseases. However, its clinical application is hindered by the small therapeutic index and short half-life.

Gsα Regulates Macrophage Foam Cell Formation During Atherosclerosis.

Background: Many cardiovascular pathologies are induced by signaling through G-protein-coupled receptors via Gsα (G protein stimulatory α subunit) proteins. However, the specific cellular mechanisms that are driven by Gsα and contribute to the development of atherosclerosis remain unclear.

Methods: High-throughput screening involving data from single-cell and bulk sequencing were used to explore the expression of Gsα in atherosclerosis.

-Mediated Antigen-Independent Activation of CD8 T Cells Promotes Salt-Sensitive Hypertension.

Background: CD8 T cells (CD8Ts) have been implicated in hypertension. However, the specific mechanisms are not fully understood. In this study, we explore the contribution of the P2X7 (purinergic receptor P2X7) receptor to CD8T activation and subsequent promotion of sodium retention in the kidney.

CD24+ decidual stromal cells: a novel heterogeneous population with impaired regulatory T cell induction and potential association with recurrent miscarriage.

Objective: To explore the heterogeneity of CD24+ decidual stromal cells (DSCs) in patients with recurrent miscarriages (RMs).

Design: We have discerned that the expression of CD24 serves to differentiate two stable and functionally distinct lineages of DSCs. The heterogeneity of CD24+ DSCs has been scrutinized, encompassing variances in stromal markers, transcriptional profiles, metabolic activity, and immune regulation.

Negative capacitors and inductors enabling wideband waveguide metatronics.

Waveguide metatronics, known as an advanced platform of metamaterial-inspired circuits, provides a promising paradigm for millimeter-wave and terahertz integrated circuits in future fifth/sixth generation (5/6G) communication systems. By exploiting the structural dispersion properties of waveguides, a lumped type of waveguide integrated elements and circuits could be developed in deep subwavelength scales with intrinsic low loss and low crosstalk. In this study, we focus on constructing negative capacitors and inductors for waveguide metatronics, effectively expanding the operating frequency range of waveguide integrated circuits.

Spatial downregulation of CD74 signatures may drive invasive component development in part-solid lung adenocarcinoma.

Pulmonary nodules with part-solid imaging features manifest during the progression from preinvasive to invasive lung adenocarcinoma. To define the spatial composition and evolutionary trajectories of early-stage lung adenocarcinoma, we combined spatial transcriptomics (ST) and pathological annotations from 20 part-solid nodules (PSNs), four of which were matched with single-cell RNA sequencing. Two malignant cell populations (MC1 and MC2) were identified, and a linear evolutionary relationship was observed.

Endothelial FIS1 DeSUMOylation Protects Against Hypoxic Pulmonary Hypertension.

Background: Hypoxia is a major cause and promoter of pulmonary hypertension (PH), a representative vascular remodeling disease with poor prognosis and high mortality. However, the mechanism underlying how pulmonary arterial system responds to hypoxic stress during PH remains unclear. Endothelial mitochondria are considered signaling organelles on oxygen tension.

Rapid prototyping of high-resolution large format microfluidic device through maskless image guided in-situ photopolymerization.

Microfluidic devices have found extensive applications in mechanical, biomedical, chemical, and materials research. However, the high initial cost, low resolution, inferior feature fidelity, poor repeatability, rough surface finish, and long turn-around time of traditional prototyping methods limit their wider adoption. In this study, a strategic approach to a deterministic fabrication process based on in-situ image analysis and intermittent flow control called image-guided in-situ maskless lithography (IGIs-ML), has been proposed to overcome these challenges.

Three-dimensional High-Resolution Dark-Blood Late Gadolinium Enhancement Imaging for Improved Atrial Scar Evaluation.

Background Radiofrequency ablation (RFA) is a widely used treatment for atrial fibrillation, reducing the risk of cardiac arrhythmia. Detailed visualization and quantification of atrial scarring has the potential to improve preprocedural decision-making and postprocedural prognosis. Conventional bright-blood late gadolinium enhancement (LGE) MRI can help detect atrial scars; however, its suboptimal myocardium to blood contrast inhibits accurate scar estimation.

Rhodium nanoparticles supported on silanol-rich zeolites beyond the homogeneous Wilkinson's catalyst for hydroformylation of olefins.

Hydroformylation is one of the largest industrially homogeneous processes that strongly relies on catalysts with phosphine ligands such as the Wilkinson's catalyst (triphenylphosphine coordinated Rh). Heterogeneous catalysts for olefin hydroformylation are highly desired but suffer from poor activity compared with homogeneous catalysts. Herein, we demonstrate that rhodium nanoparticles supported on siliceous MFI zeolite with abundant silanol nests are very active for hydroformylation, giving a turnover frequency as high as ~50,000 h that even outperforms the classical Wilkinson's catalyst.

High-plex protein and whole transcriptome co-mapping at cellular resolution with spatial CITE-seq.

In this study, we extended co-indexing of transcriptomes and epitopes (CITE) to the spatial dimension and demonstrated high-plex protein and whole transcriptome co-mapping. We profiled 189 proteins and whole transcriptome in multiple mouse tissue types with spatial CITE sequencing and then further applied the method to measure 273 proteins and transcriptome in human tissues, revealing spatially distinct germinal center reactions in tonsil and early immune activation in skin at the Coronavirus Disease 2019 mRNA vaccine injection site.

Inhibition of Fap Promotes Cardiac Repair by Stabilizing BNP.

Background: Myocardial infarction (MI) elicits cardiac fibroblast activation and extracellular matrix (ECM) deposition to maintain the structural integrity of the heart. Recent studies demonstrate that Fap (fibroblast activation protein)-a prolyl-specific serine protease-is an important marker of activated cardiac fibroblasts after MI.

Methods: Left ventricle and plasma samples from patients and healthy donors were used to analyze the expression level of FAP and its prognostic value.