Precise programming of multigene expression stoichiometry in mammalian cells by a modular and programmable transcriptional system.

Context-dependency of mammalian transcriptional elements has hindered the quantitative investigation of multigene expression stoichiometry and its biological functions. Here, we describe a host- and local DNA context-independent transcription system to gradually fine-tune single and multiple gene expression with predictable stoichiometries. The mammalian transcription system is composed of a library of modular and programmable promoters from bacteriophage and its cognate RNA polymerase (RNAP) fused to a capping enzyme.

Pectin based biologic Velcro effectively seals traumatic solid organ and small bowel injuries.

Introduction: Injuries to the liver and small bowel are common in multiple injuries. While there are currently a variety of accepted damage-control techniques to expeditiously manage such injuries, morbidity and mortality remain high. Pectin polymers have previously been shown to effectively seal visceral organ injuries ex vivo through physiochemical entanglement with the glycocalyx.

Early Stroke and Mortality After Percutaneous Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation.

Background: Percutaneous endocardial left atrial appendage occlusion (LAAO) is an alternative therapy for stroke prevention in patients with atrial fibrillation who are poor candidates for oral anticoagulants. Oral anticoagulation is generally discontinued 45 days following successful LAAO. Real-world data on early stroke and mortality following LAAO are lacking.

Simultaneous T1, T2, and T2* Mapping of Carotid Plaque: The SIMPLE* Technique.

Background Quantitative T1, T2, and T2* measurements of carotid atherosclerotic plaque are important in evaluating plaque vulnerability and monitoring its progression. Purpose To develop a sequence to simultaneously quantify T1, T2, and T2* of carotid plaque. Materials and Methods The simultaneous T1, T2, and T2* mapping of carotid plaque (SIMPLE*) sequence is composed of three modules with different T2 preparation pulses, inversion-recovery pulses, and acquisition schemas.

Secretome of hESC-Derived MSC-like Immune and Matrix Regulatory Cells Mitigate Pulmonary Fibrosis through Antioxidant and Anti-Inflammatory Effects.

Oxidative stress and inflammation are major drivers in the pathogenesis and progression of pulmonary fibrosis (PF). The mesenchymal stem cell (MSC) secretome has regenerative potential and immunomodulatory functions. Human embryonic stem cell (hESC)-derived MSC-like immune and matrix regulatory cells (IMRCs) are manufacturable with large-scale good manufacturing practice (GMP) preparation.

Multivariate genomic architecture of cortical thickness and surface area at multiple levels of analysis.

Recent work in imaging genetics suggests high levels of genetic overlap within cortical regions for cortical thickness (CT) and surface area (SA). We model this multivariate system of genetic relationships by applying Genomic Structural Equation Modeling (Genomic SEM) and parsimoniously define five genomic brain factors underlying both CT and SA along with a general factor capturing genetic overlap across all brain regions. We validate these factors by demonstrating the generalizability of the model to a semi-independent sample and show that the factors align with biologically and functionally relevant parcellations of the cortex.

A visual bi-layer sensor based on Agar/TiO/butterfly bean flower anthocyanin/κ-carrageenan with photostability for monitoring Penaeus chinensis freshness.

Visual indicator bi-layer films were manufactured incorporating κ-carrageenan, butterfly pea flower anthocyanin, varying Nano‑titanium dioxide (TiO) content and agar for Penaeus chinensis (Chinese white shrimp) freshness detection. The κ-carrageenan-anthocyanin (CA) layer served as indicator, while the TiO-agar (TA) layer functioned as the protective layer to improve the photostability of film. The bi-layer structure was characterized by scanning electron microscopy (SEM).

 (Asparagaceae), a new species from mid-eastern China revealed by morphological and molecular evidence.

A new species, Y.F.Hu & J.

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.

Simultaneous sequencing of genetic and epigenetic bases in DNA.

DNA comprises molecular information stored in genetic and epigenetic bases, both of which are vital to our understanding of biology. Most DNA sequencing approaches address either genetics or epigenetics and thus capture incomplete information. Methods widely used to detect epigenetic DNA bases fail to capture common C-to-T mutations or distinguish 5-methylcytosine from 5-hydroxymethylcytosine.

Enhancing CAR-T cell functionality in a patient-specific manner.

Patient responses to autologous CD19 chimeric antigen receptor (CAR) T-cell therapies are limited by insufficient and inconsistent cellular functionality. Here, we show that controlling the precise level of stimulation during T-cell activation to accommodate individual differences in the donor cells will dictate the functional attributes of CAR-T cell products. The functionality of CAR-T cell products, consisting of a diverse set of blood samples derived from healthy donors, acute lymphoblastic leukemia (ALL), and chronic lymphocytic lymphoma (CLL) patient samples, representing a range of patient health status, is tested upon culturing on artificial antigen-presenting cell scaffolds to deliver T-cell stimulatory ligands (anti-CD3/anti-CD28) at highly defined densities.

Mechanisms of response and resistance to combined decitabine and ipilimumab for advanced myeloid disease.

The challenge of eradicating leukemia in patients with acute myelogenous leukemia (AML) after initial cytoreduction has motivated modern efforts to combine synergistic active modalities including immunotherapy. Recently, the ETCTN/CTEP 10026 study tested the combination of the DNA methyltransferase inhibitor decitabine together with the immune checkpoint inhibitor ipilimumab for AML/myelodysplastic syndrome (MDS) either after allogeneic hematopoietic stem cell transplantation (HSCT) or in the HSCT-naïve setting. Integrative transcriptome-based analysis of 304 961 individual marrow-infiltrating cells for 18 of 48 subjects treated on study revealed the strong association of response with a high baseline ratio of T to AML cells.

Higher-Order Aberrations and Visual Performance in Myopic Children Treated With Aspheric Base Curve-Designed Orthokeratology.

Objectives: To investigate the impact of aspheric base curve (BC)-designed orthokeratology (ortho-k) (AOK) lenses on higher-order aberrations (HOA) at different pupil diameters and visual performance.

Methods: This prospective clinical study included subjects randomized to wear spherical BC-designed ortho-k (SOK) or AOK lenses. The Pediatric Refractive Error Profile (PREP) questionnaire was completed before and after 3 months of lens wear.

Futibatinib for -Rearranged Intrahepatic Cholangiocarcinoma.

Background: Alterations in fibroblast growth factor receptor 2 () have emerged as promising drug targets for intrahepatic cholangiocarcinoma, a rare cancer with a poor prognosis. Futibatinib, a next-generation, covalently binding FGFR1-4 inhibitor, has been shown to have both antitumor activity in patients with -altered tumors and strong preclinical activity against acquired resistance mutations associated with ATP-competitive FGFR inhibitors.

Methods: In this multinational, open-label, single-group, phase 2 study, we enrolled patients with unresectable or metastatic fusion-positive or rearrangement-positive intrahepatic cholangiocarcinoma and disease progression after one or more previous lines of systemic therapy (excluding FGFR inhibitors).

Temporal pain processing in the primary somatosensory cortex and anterior cingulate cortex.

Pain is known to have sensory and affective components. The sensory pain component is encoded by neurons in the primary somatosensory cortex (S1), whereas the emotional or affective pain experience is in large part processed by neural activities in the anterior cingulate cortex (ACC). The timing of how a mechanical or thermal noxious stimulus triggers activation of peripheral pain fibers is well-known.

Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer.

Despite neoadjuvant/conversion chemotherapy, the prognosis of cT4a/bN+ gastric cancer is poor. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents have shown activity in late-stage gastric cancer, but their efficacy in the neoadjuvant/conversion setting is unclear. In this single-armed, phase II, exploratory trial (NCT03878472), we evaluate the efficacy of a combination of ICI (camrelizumab), antiangiogenesis (apatinib), and chemotherapy (S-1 ± oxaliplatin) for neoadjuvant/conversion treatment of cT4a/bN+ gastric cancer.

Alternating Early Afterdepolarizations Underlying Bradycardia-Dependent Macroscopic T Wave and Discordant Mechanical Alternans.

Background: Macroscopic T wave alternans (macro-TWA) often heralds the onset of Torsades de Pointes in patients with QT prolongation. However, the mechanisms underlying macro-TWA remain unclear. We examined the cellular and ionic basis for macro-TWA in rabbits with left ventricular hypertrophy (LVH).

Borneol-driven meningeal lymphatic drainage clears amyloid-β peptide to attenuate Alzheimer-like phenotype in mice.

The accumulation and clearance of amyloid-β (Aβ) peptides play a crucial role in the pathogenesis of Alzheimer's disease (AD). The (re)discovery of meningeal lymphatic vessels in recent years has focused attention on the lymphatic clearance of Aβ and has become a promising therapeutic target for such diseases. However, there is a lack of small molecular compounds that could clearly regulate meningeal lymphatic drainage to remove Aβ from the brain.