Bacterial Cell Wall Quality Control during Environmental Stress.

Single-celled organisms must adapt their physiology to persist and propagate across a wide range of environmental conditions. The growth and division of bacterial cells depend on continuous synthesis of an essential extracellular barrier: the peptidoglycan cell wall, a polysaccharide matrix that counteracts turgor pressure and confers cell shape. Unlike many other essential processes and structures within the bacterial cell, the peptidoglycan cell wall and its synthesis machinery reside at the cell surface and are thus uniquely vulnerable to the physicochemical environment and exogenous threats.

Literature review and meta-analysis of the efficacy of cilostazol on limb salvage rates after infrainguinal endovascular and open revascularization.

Background: Current clinical guidelines recommend the use of cilostazol in the treatment of patients with infrainguinal peripheral artery disease (PAD) who experience intermittent claudication. However, the role of cilostazol therapy in patients with advanced PAD and critical limb ischemia (CLI) remains unclear. To conduct a meta-analysis of randomized controlled trials and cohort studies that evaluated the effect of cilostazol vs standard antiplatelet therapy on limb-related and arterial patency-related outcomes.

Adenoviral vectors for in vivo delivery of CRISPR-Cas gene editors.

Harnessing the bacterial clustered regularly interspaced short palindromic repeats (CRISPR) system for genome editing in eukaryotes has revolutionized basic biomedical research and translational sciences. The ability to create targeted alterations of the genome through this easy to design system has presented unprecedented opportunities to treat inherited disorders and other diseases such as cancer through gene therapy. A major hurdle is the lack of an efficient and safe in vivo delivery system, limiting most of the current gene therapy efforts to ex vivo editing of extracted cells.

Consistent apparent Young's modulus of human embryonic stem cells and derived cell types stabilized by substrate stiffness regulation promotes lineage specificity maintenance.

Background: Apparent Young's modulus (AYM), which reflects the fundamental mechanical property of live cells measured by atomic force microscopy and is determined by substrate stiffness regulated cytoskeletal organization, has been investigated as potential indicators of cell fate in specific cell types. However, applying biophysical cues, such as modulating the substrate stiffness, to regulate AYM and thereby reflect and/or control stem cell lineage specificity for downstream applications, remains a primary challenge during in vitro stem cell expansion. Moreover, substrate stiffness could modulate cell heterogeneity in the single-cell stage and contribute to cell fate regulation, yet the indicative link between AYM and cell fate determination during in vitro dynamic cell expansion (from single-cell stage to multi-cell stage) has not been established.

Functional connectivity within glioblastoma impacts overall survival.

Background: Glioblastoma (GBM; World Health Organization grade IV) assumes a variable appearance on MRI owing to heterogeneous proliferation and infiltration of its cells. As a result, the neurovascular units responsible for functional connectivity (FC) may exist within gross tumor boundaries, albeit with altered magnitude. Therefore, we hypothesize that the strength of FC within GBMs is predictive of overall survival.

Systems Biology Will Direct Vascular-Targeted Therapy for Obesity.

Healthy adipose tissue expansion and metabolism during weight gain require coordinated angiogenesis and lymphangiogenesis. These vascular growth processes rely on the vascular endothelial growth factor (VEGF) family of ligands and receptors (VEGFRs). Several studies have shown that controlling vascular growth by regulating VEGF:VEGFR signaling can be beneficial for treating obesity; however, dysregulated angiogenesis and lymphangiogenesis are associated with several chronic tissue inflammation symptoms, including hypoxia, immune cell accumulation, and fibrosis, leading to obesity-related metabolic disorders.

Assessment of Supra-Cervical Fetal Membrane by MRI 3D CISS: A Preliminary Study.

In approximately 8% of term births and 33% of pre-term births, the fetal membrane (FM) ruptures before delivery. studies of FMs after delivery have suggested the series of events leading to rupture, but no studies have confirmed this model. In this study, we used a three-dimensional constructive interference in steady state (3D-CISS) sequence to examine the FM at the cervical internal os zone during pregnancy; 18 pregnant women with one to three longitudinal MRI scans were included in this study.

The acoustic radiation force of a focused ultrasound beam on a suspended eukaryotic cell.

Although ultrasound tools for manipulating and permeabilizing suspended cells have been available for nearly a century, accurate prediction of the distribution of acoustic radiation force (ARF) continues to be a challenge. We therefore developed an analytical model of the acoustic radiation force (ARF) generated by a focused Gaussian ultrasound beam incident on a eukaryotic cell immersed in an ideal fluid. The model had three layers corresponding to the nucleus, cytoplasm, and membrane, of a eukaryotic cell.

SEQUIN Multiscale Imaging of Mammalian Central Synapses Reveals Loss of Synaptic Connectivity Resulting from Diffuse Traumatic Brain Injury.

The brain's complex microconnectivity underlies its computational abilities and vulnerability to injury and disease. It has been challenging to illuminate the features of this synaptic network due to the small size and dense packing of its elements. Here, we describe a rapid, accessible super-resolution imaging and analysis workflow-SEQUIN-that quantifies central synapses in human tissue and animal models, characterizes their nanostructural and molecular features, and enables volumetric imaging of mesoscale synaptic networks without the production of large histological arrays.

Self-Assembly of Block Heterochiral Peptides into Helical Tapes.

Patterned substitution of d-amino acids into the primary sequences of self-assembling peptides influences molecular-level packing and supramolecular morphology. We report that block heterochiral analogs of the model amphipathic peptide KFE8 (Ac-FKFEFKFE-NH), composed of two FKFE repeat motifs with opposite chirality, assemble into helical tapes with dimensions greatly exceeding those of their fibrillar homochiral counterparts. At sufficient concentrations, these tapes form hydrogels with reduced storage moduli but retain the shear-thinning behavior and consistent mechanical recovery of the homochiral analogs.

Dissecting the Functional Contributions of the Intrinsically Disordered C-terminal Tail of Bacillus subtilis FtsZ.

FtsZ is a bacterial GTPase that is central to the spatial and temporal control of cell division. It is a filament-forming enzyme that encompasses a well-folded core domain and a disordered C-terminal tail (CTT). The CTT is essential for ensuring proper assembly of the cytokinetic ring, and its deletion leads to mis-localization of FtsZ, aberrant assembly, and cell death.

Patient-derived small intestinal myofibroblasts direct perfused, physiologically responsive capillary development in a microfluidic Gut-on-a-Chip Model.

The development and physiologic role of small intestine (SI) vasculature is poorly studied. This is partly due to a lack of targetable, organ-specific markers for in vivo studies of two critical tissue components: endothelium and stroma. This challenge is exacerbated by limitations of traditional cell culture techniques, which fail to recapitulate mechanobiologic stimuli known to affect vessel development.

Targeting CD47 as a Novel Immunotherapy for Multiple Myeloma.

Multiple myeloma (MM) remains to be incurable despite recent therapeutic advances. CD47, an immune checkpoint known as the "don't eat me" signal, is highly expressed on the surface of various cancers, allowing cancer cells to send inhibitory signals to macrophages and impede phagocytosis and immune response. In this study, we hypothesized that blocking the "don't eat me" signaling using an anti-CD47 monoclonal antibody will induce killing of MM cells.

Development and Human Factors Considerations for Extended Reality Applications in Medicine: The Enhanced ELectrophysiology Visualization and Interaction System (ĒLVIS).

With the rapid expansion of hardware options in the extended realities (XRs), there has been widespread development of applications throughout many fields, including engineering, entertainment and medicine. Development of medical applications for the XRs have a unique set of considerations during development and human factors testing. Additionally, understanding the constraints of the user and the use case allow for iterative improvement.

Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer.

Reprogramming the tumor microenvironment to increase immune-mediated responses is currently of intense interest. Patients with immune-infiltrated "hot" tumors demonstrate higher treatment response rates and improved survival. However, only the minority of tumors are hot, and a limited proportion of patients benefit from immunotherapies.

Trait-like variants in human functional brain networks.

Resting-state functional magnetic resonance imaging (fMRI) has provided converging descriptions of group-level functional brain organization. Recent work has revealed that functional networks identified in individuals contain local features that differ from the group-level description. We define these features as network variants.

Phase separation in biology and disease-a symposium report.

Phase separation of multivalent protein and RNA molecules enables cells the formation of reversible nonstoichiometric, membraneless assemblies. These assemblies, referred to as biomolecular condensates, help with the spatial organization and compartmentalization of cellular matter. Each biomolecular condensate is defined by a distinct macromolecular composition.

Muscle relaxant induced pancreatitis leading to hyperosmolar hyperglycemic state.

Muscle relaxants are commonly prescribed in the United States but may have deleterious side effects that are unrecognized by physicians. Here, we report a 55-year-old Caucasian man who developed pancreatitis and a subsequent hyperosmolar hyperglycemic state after being prescribed tizanidine. The patient had untreated hypertriglyceridemia, unbeknownst to the prescribing physician.