FORCE platform overcomes barriers of oligonucleotide delivery to muscle and corrects myotonic dystrophy features in preclinical models.

Background: We developed the FORCE platform to overcome limitations of oligonucleotide delivery to muscle and enable their applicability to neuromuscular disorders. The platform consists of an antigen-binding fragment, highly specific for the human transferrin receptor 1 (TfR1), conjugated to an oligonucleotide via a cleavable valine-citrulline linker. Myotonic dystrophy type 1 (DM1) is a neuromuscular disorder caused by expanded CUG triplets in the DMPK RNA, which sequester splicing proteins in the nucleus, lead to spliceopathy, and drive disease progression.

A PD-1-targeted, receptor-masked IL-2 immunocytokine that engages IL-2Rα strengthens T cell-mediated anti-tumor therapies.

The clinical use of interleukin-2 (IL-2) for cancer immunotherapy is limited by severe toxicity. Emerging IL-2 therapies with reduced IL-2 receptor alpha (IL-2Rα) binding aim to mitigate toxicity and regulatory T cell (Treg) expansion but have had limited clinical success. Here, we show that IL-2Rα engagement is critical for the anti-tumor activity of systemic IL-2 therapy.

Atomic insight into the effects of precursor clusters on monolayer WSe.

Two-dimensional (2D) transition metal dichalcogenides (TMDCs) have been attracting much attention due to their rich physical and chemical properties. At the end of the chemical vapor deposition growth of 2D TMDCs, the adsorption of excess precursor clusters onto the sample is unavoidable, which will have significant effects on the properties of TMDCs. This is a concern to the academic community.

Combined Treatment of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Endothelial Cells Regenerate the Infarcted Heart in Mice and Non-Human Primates.

Background: Remuscularization of the mammalian heart can be achieved after cell transplantation of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs). However, several hurdles remain before implementation into clinical practice. Poor survival of the implanted cells is related to insufficient vascularization, and the potential for fatal arrhythmogenesis is associated with the fetal cell-like nature of immature CMs.

Hemagglutination Assay via Optical Density Characterization in 3D Microtrap Chips.

Hemagglutination assay has been used for blood typing and detecting viruses, thus applicable for the diagnosis of infectious diseases, including COVID-19. Therefore, the development of microfluidic devices for fast detection of hemagglutination is on-demand for point-of-care diagnosis. Here, we present a way to detect hemagglutination in 3D microfluidic devices via optical absorbance (optical density, OD) characterization.

Intratumoral dendritic cell-CD4 T helper cell niches enable CD8 T cell differentiation following PD-1 blockade in hepatocellular carcinoma.

Despite no apparent defects in T cell priming and recruitment to tumors, a large subset of T cell rich tumors fail to respond to immune checkpoint blockade (ICB). We leveraged a neoadjuvant anti-PD-1 trial in patients with hepatocellular carcinoma (HCC), as well as additional samples collected from patients treated off-label, to explore correlates of response to ICB within T cell-rich tumors. We show that ICB response correlated with the clonal expansion of intratumoral CXCL13CH25HIL-21PD-1CD4 T helper cells ("CXCL13 T") and Granzyme K PD-1 effector-like CD8 T cells, whereas terminally exhausted CD39TOXPD-1CD8 T cells dominated in nonresponders.

Relationship of Plaque Features at Coronary CT to Coronary Hemodynamics and Cardiovascular Events.

Background Plaque assessments with coronary CT angiography (CCTA) and coronary flow indexes have prognostic implications. Purpose To investigate the association and additive prognostic value of plaque burden and characteristics at CCTA with coronary pressure and flow. Materials and Methods Data of patients with coronary artery disease who underwent CCTA within 90 days before physiologic assessments at tertiary cardiovascular centers between January 2011 and December 2018 were retrospectively analyzed, which included fractional flow reserve (FFR), resting distal coronary artery pressure (Pd)-to-aortic pressure (Pa) ratio (hereafter, Pd/Pa), coronary flow reserve (CFR), hyperemic flow (1/hyperemic mean transit time [Tmn]), resting flow (1/resting Tmn), and index of microcirculatory resistance (IMR).

Temperate performance and metabolic adaptations following endurance training performed under environmental heat stress.

Endurance athletes are frequently exposed to environmental heat stress during training. We investigated whether exposure to 33°C during training would improve endurance performance in temperate conditions and stimulate mitochondrial adaptations. Seventeen endurance-trained males were randomly assigned to perform a 3-week training intervention in 18°C (TEMP) or 33°C (HEAT).

Prostate-Specific Antigen Within the Reference Range, Subclinical Coronary Atherosclerosis, and Cardiovascular Mortality.

Rationale: Although PSA (prostate-specific antigen)-a tumor marker for prostate cancer-has been reported to be associated with cardiovascular disease (CVD) risk factors, studies on the association of PSA with subclinical and clinical CVD remain limited.

Objective: We examined the association of total serum PSA within the reference range with coronary artery calcium (CAC) score and CVD mortality.

Methods And Results: A cross-sectional study was performed in 88 203 Korean men who underwent a health checkup exam including cardiac tomography estimation of CAC score.

Tunable PEGylation of branch-type PEI/DNA polyplexes with a compromise of low cytotoxicity and high transgene expression: in vitro and in vivo gene delivery.

Although PEGylated polyplexes for gene delivery are widespread, there is a need for an in-depth investigation of the role of the PEGylation degree on the delivery efficiency of the systems. For this, a low-toxicity series of polymers for gene delivery were designed via Michael addition of poly(ethylene glycol)methyl ether methacrylate (PEGMA) onto branched polyethylenimine PEI. The goal was to finely tune the PEGylation degree in order to determine the system offering the best compromise between low cytotoxicity and high transfection efficiency under both in vitro and in vivo conditions.

Production of Live Offspring from Vitrified-Warmed Oocytes Collected at Metaphase I Stage.

Vitrification of matured oocytes is widely adopted in human clinics and animal research laboratories. Cryopreservation of immature oocytes, particularly those at metaphase I (MI), remains a challenge. In the present work, mouse MI oocytes denuded of cumulus cells were vitrified and warmed (V/W) either prior to (V/W-BEFORE-IVM, n = 562) or after (V/W-AFTER-IVM, n = 664) in vitro maturation (IVM).

Fiber-needle swept-source optical coherence tomography system for the identification of the epidural space in piglets.

Background: Epidural needle insertion is traditionally a blind technique whose success depends on the experience of the operator. The authors describe a novel method using a fiber-needle-based swept-source optical coherence tomography (SSOCT) to identify epidural space.

Methods: An optical fiber probe was placed into a hollow 18-gauge Tuohy needle.

Fast polyenergetic forward projection for image formation using OpenCL on a heterogeneous parallel computing platform.

Purpose: Simulated projection images of digital phantoms constructed from CT scans have been widely used for clinical and research applications but their quality and computation speed are not optimal for real-time comparison with the radiography acquired with an x-ray source of different energies. In this paper, the authors performed polyenergetic forward projections using open computing language (OpenCL) in a parallel computing ecosystem consisting of CPU and general purpose graphics processing unit (GPGPU) for fast and realistic image formation.

Methods: The proposed polyenergetic forward projection uses a lookup table containing the NIST published mass attenuation coefficients (μ∕ρ) for different tissue types and photon energies ranging from 1 keV to 20 MeV.

Proteomic analysis of differently cultured endemic medicinal mushroom Antrodia cinnamomea T.T. Chang et W.N. Chou from Taiwan.

Antrodia cinnamomea is peculiar to Taiwan. It only grows on one host and is highly valued as an important component of several traditional Chinese medicines. In this study, the different protein expression profiles of artificially cultivated vegetative mycelium and wild-type basidiomatal fruiting bodies were compared and unique protein spots from wild-type basidiomatal fruiting body were investigated using 2D polyacrylamide gel electrophoresis and LC-MS/MS protein identification.

Cyclodextrin-modified microemulsion electrokinetic chromatography for separation of alpha-, gamma-, delta-tocopherol and alpha-tocopherol acetate.

Different forms of tocopherols, together with tocotrienols, are collectively named as vitamin E, and each possesses different degree of medical, biological and physiochemical significance. The main difficulty of separating different forms of tocopherols lay in their highly structural similarities and hydrophobicities. Microemulsion electrokinetic chromatography (MEEKC), claimed to attain high peak efficiency with great solubilization power, has not previously been applied to the separation of tocopherols.

Investigation of solvent effects in capillary electrophoresis for the separation of biological porphyrin methyl esters.

The effects of organic solvents on the capillary electrophoresis (CE) separation of a number of important biological porphyrin methyl esters - six weakly basic, hydrophobic cyclic tetrapyrroles possessing two and four to eight methyl ester groups around the periphery of the porphyrin ring - were investigated in the mode of micellar electrokinetic chromatography (MEKC), microemulsion electrokinetic chromatography (MEEKC), and nonaqueous CE. In aqueous MEKC, partial separation of the six neutral porphyrin methyl esters was obtained with an organic modifier (acetonitrile) in the concentration range between 20 and 40%, in which sodium dodecyl sulfate (SDS) molecules might be present in the form of SDS micelles and/or SDS micelle-like aggregates. Relatively stable SDS micelles can be formed in nonaqueous MEKC using formamide as the separation medium, but the separation of the target analytes remained unsatisfactory.