Thoughts and thinkers: On the complementarity between objects and processes.

We argue that "processes versus objects" is not a useful dichotomy. There is, instead, substantial theoretical utility in viewing "objects" and "processes" as complementary ways of describing persistence through time, and hence the possibility of observation and manipulation. This way of thinking highlights the role of memory as an essential resource for observation, and makes it clear that "memory" and "time" are also mutually inter-defined, complementary concepts.

Cell-Instructive Biomaterials with Native-Like Biochemical Complexity.

Biochemical signals in native tissue microenvironments instruct cell behavior during many biological processes ranging from developmental morphogenesis and tissue regeneration to tumor metastasis and disease progression. The detection and characterization of these signals using spatial and highly resolved quantitative methods have revealed their existence as matricellular proteins in the matrisome, some of which are bound to the extracellular matrix while others are freely diffusing. Including these biochemical signals in engineered biomaterials can impart enhanced functionality and native-like complexity, ultimately benefiting efforts to understand, model, and treat various diseases.

Clinical utility of receptor status prediction in breast cancer and misdiagnosis identification using deep learning on hematoxylin and eosin-stained slides.

Background: Molecular profiling of estrogen receptor (ER), progesterone receptor (PR), and ERBB2 (also known as Her2) is essential for breast cancer diagnosis and treatment planning. Nevertheless, current methods rely on the qualitative interpretation of immunohistochemistry and fluorescence in situ hybridization (FISH), which can be costly, time-consuming, and inconsistent. Here we explore the clinical utility of predicting receptor status from digitized hematoxylin and eosin-stained (H&E) slides using machine learning trained and evaluated on a multi-institutional dataset.

Inflammatory Bowel Disease Drivers Revealed in Human Organ Chips.

Inflammatory bowel disease (IBD) patients exhibit compromised intestinal barrier function and decreased mucus accumulation, as well as increased inflammation, fibrosis, and cancer risk, with symptoms often being exacerbated in women during pregnancy. Here, we show that these IBD hallmarks can be replicated using human Organ Chips lined by IBD patient-derived colon epithelial cells interfaced with matched fibroblasts cultured under flow. Use of heterotypic tissue recombinants revealed that IBD fibroblasts are the primary drivers of multiple IBD symptoms.

Cargo Quantification of Functionalized DNA Origami for Therapeutic Application.

In recent years, notable advances in nanotechnology-based drug delivery have emerged. A particularly promising platform in this field is DNA origami-based nanoparticles, which offer highly programmable surfaces, providing precise control over the nanoscale spacing and stoichiometry of various cargo. These versatile particles are finding diverse applications ranging from basic molecular biology to diagnostics and therapeutics.

Backpack-carrying macrophage immunotherapy for periodontitis.

Cell immunotherapy is a promising therapeutic modality to combat unmet medical needs. Macrophages offer a prominent cell therapy modality since their phenotypic plasticity allows them to perform a variety of roles including defending against pathogens, inducing/suppressing adaptive immunity, and aiding in wound healing. At the same time, this plasticity is a major hurdle in implementation of macrophage therapy.

IL-2/anti-IL-2 antibody complexes augment immune responses to therapeutic cancer vaccines.

One driver of the high failure rates of clinical trials for therapeutic cancer vaccines is likely the inability to sufficiently engage conventional dendritic cells (cDCs), the antigen-presenting cell (APC) subset that is specialized in priming antitumor T cells. Here, we demonstrate that, relative to vaccination with an injectable mesoporous silica rod (MPS) vaccine alone (Vax), combining MPS vaccines with CD122-biased IL-2/anti-IL-2 antibody complexes (IL-2cx) drives ~3-fold expansion of cDCs at the vaccination sites, vaccine-draining lymph nodes, and spleens of treated mice. Furthermore, relative to Vax alone, Vax+IL-2cx led to a ~3-fold increase in the numbers of CD8 T cells and ~15-fold increase in the numbers of NK cells at the vaccination site.

Hemostats in the clinic.

Given the prevalence of hematological conditions, surgeries, and trauma incidents, hemostats-therapeutics designed to control and arrest bleeding-are an important tool in patient care. The prophylactic and therapeutic use of hemostats markedly enhances survival rates and improves the overall quality of life of patients suffering from these conditions. Since their inception in the 1960s, hemostats have witnessed remarkable progress in terms of the active ingredients utilized, therapeutic outcomes, demonstrated efficacy, and the storage stability.

Hydrogels in the clinic: An update.

Hydrogels have been used in the clinic since the late 1980s with broad applications in drug delivery, cosmetics, tissue regeneration, among many other areas. The past three decades have witnessed rapid advances in the fields of polymer chemistry, crosslinking approaches, and hydrogel fabrication methods, which have collectively brought many new hydrogel products, either injectable or non-injectable, to clinical studies. In an article published in 2020 entitled "Hydrogels in the clinic", we reviewed the clinical landscape and translational challenges of injectable hydrogels.

Antibody drug conjugates in the clinic.

Antibody-drug conjugates (ADCs), chemotherapeutic agents conjugated to an antibody to enhance their targeted delivery to tumors, represent a significant advancement in cancer therapy. ADCs combine the precise targeting capabilities of antibodies and the potent cell-killing effects of chemotherapy, allowing for enhanced cytotoxicity to tumors while minimizing damage to healthy tissues. Here, we provide an overview of the current clinical landscape of ADCs, highlighting 11 U.

Measurement of circulating viral antigens post-SARS-CoV-2 infection in a multicohort study.

Objectives: To determine the proportion of individuals with detectable antigen in plasma or serum after SARS-CoV-2 infection and the association of antigen detection with postacute sequelae of COVID-19 (PASC) symptoms.

Methods: Plasma and serum samples were collected from adults participating in four independent studies at different time points, ranging from several days up to 14 months post-SARS-CoV-2 infection. The primary outcome measure was to quantify SARS-CoV-2 antigens, including the S1 subunit of spike, full-length spike, and nucleocapsid, in participant samples.

Identification of pharmacological inducers of a reversible hypometabolic state for whole organ preservation.

Drugs that induce reversible slowing of metabolic and physiological processes would have great value for organ preservation, especially for organs with high susceptibility to hypoxia-reperfusion injury, such as the heart. Using whole-organism screening of metabolism, mobility, and development in , we identified an existing drug, SNC80, that rapidly and reversibly slows biochemical and metabolic activities while preserving cell and tissue viability. Although SNC80 was developed as a delta opioid receptor activator, we discovered that its ability to slow metabolism is independent of its opioid modulating activity as a novel SNC80 analog (WB3) with almost 1000 times less delta opioid receptor binding activity is equally active.

Cargo quantification of functionalized DNA origami for therapeutic application.

In recent years, notable advances in nanotechnology-based drug delivery have emerged. A particularly promising platform in this field is DNA origami-based nanoparticles, which offer highly programmable surfaces, providing precise control over the nanoscale spacing and stoichiometry of various cargo. These versatile particles are finding diverse applications ranging from basic molecular biology to diagnostics and therapeutics.

Algorithms for Autonomous Formation of Multicellular Shapes from Single Cells.

Multicellular organisms originate from a single cell, ultimately giving rise to mature organisms of heterogeneous cell type composition in complex structures. Recent work in the areas of stem cell biology and tissue engineering has laid major groundwork in the ability to convert certain types of cells into other types, but there has been limited progress in the ability to control the morphology of cellular masses as they grow. Contemporary approaches to this problem have included the use of artificial scaffolds, 3D bioprinting, and complex media formulations; however, there are no existing approaches to controlling this process purely through genetics and from a single-cell starting point.

Bioelectric pharmacology of cancer: A systematic review of ion channel drugs affecting the cancer phenotype.

Cancer is a pernicious and pressing medical problem; moreover, it is a failure of multicellular morphogenesis that sheds much light on evolutionary developmental biology. Numerous classes of pharmacological agents have been considered as cancer therapeutics and evaluated as potential carcinogenic agents; however, these are spread throughout the primary literature. Here, we briefly review recent work on ion channel drugs as promising anti-cancer treatments and present a systematic review of the known cancer-relevant effects of 109 drugs targeting ion channels.

Scalable design of orthogonal DNA barcode libraries.

Orthogonal DNA barcode library design is an essential task in bioengineering. Here we present seqwalk, an efficient method for designing barcode libraries that satisfy a sequence symmetry minimization (SSM) heuristic for orthogonality, with theoretical guarantees of maximal or near-maximal library size under certain design constraints. Seqwalk encodes SSM constraints in a de Bruijn graph representation of sequence space, enabling the application of recent advances in discrete mathematics to the problem of orthogonal sequence design.

Uncovering the dynamics and consequences of RNA isoform changes during neuronal differentiation.

Static gene expression programs have been extensively characterized in stem cells and mature human cells. However, the dynamics of RNA isoform changes upon cell-state-transitions during cell differentiation, the determinants and functional consequences have largely remained unclear. Here, we established an improved model for human neurogenesis in vitro that is amenable for systems-wide analyses of gene expression.

Modulating Adjuvant Release Kinetics From Scaffold Vaccines to Tune Adaptive Immune Responses.

Increasing the potency, quality, and durability of vaccines represents a major public health challenge. A critical parameter that shapes vaccine immunity is the spatiotemporal context in which immune cells interact with antigen and adjuvant. While various material-based strategies demonstrate that extended antigen release enhances both cellular and humoral immunity, the effect of adjuvant kinetics on vaccine-mediated immunity remains incompletely understood.

Durable lymph-node expansion is associated with the efficacy of therapeutic vaccination.

Following immunization, lymph nodes dynamically expand and contract. The mechanical and cellular changes enabling the early-stage expansion of lymph nodes have been characterized, yet the durability of such responses and their implications for adaptive immunity and vaccine efficacy are unknown. Here, by leveraging high-frequency ultrasound imaging of the lymph nodes of mice, we report more potent and persistent lymph-node expansion for animals immunized with a mesoporous silica vaccine incorporating a model antigen than for animals given bolus immunization or standard vaccine formulations such as alum, and that durable and robust lymph-node expansion was associated with vaccine efficacy and adaptive immunity for 100 days post-vaccination in a mouse model of melanoma.

MRC1 and LYVE1 expressing macrophages in vascular beds of GNAQ p.R183Q driven capillary malformations in Sturge Weber syndrome.

Sturge-Weber syndrome (SWS), a neurocutaneous disorder, is characterized by capillary malformations (CM) in the skin, brain, and eyes. Patients may suffer from seizures, strokes, and glaucoma, and only symptomatic treatment is available. CM are comprised of enlarged vessels with endothelial cells (ECs) and disorganized mural cells.

Branching Crisscross Polymerization of Single-Stranded DNA Slats.

Controlling where and when self-assembly happens is crucial in both biological and synthetic systems as it optimizes the utilization of available resources. We previously reported strictly seed-initiated linear crisscross polymerization with alternating recruitment of single-stranded DNA slats that are aligned in a parallel versus perpendicular orientation with respect to the double-helical axes. However, for some applications, it would be advantageous to produce growth that is faster than what a linear assembly can provide.