Cephalopod-inspired jetting devices for gastrointestinal drug delivery.

Needle-based injections currently enable the administration of a wide range of biomacromolecule therapies across the body, including the gastrointestinal tract, through recent developments in ingestible robotic devices. However, needles generally require training, sharps management and disposal, and pose challenges for autonomous ingestible systems. Here, inspired by the jetting systems of cephalopods, we have developed and evaluated microjet delivery systems that can deliver jets in axial and radial directions into tissue, making them suitable for tubular and globular segments of the gastrointestinal tract.

Quantitative Evaluation of Type 1 and Type 2 Choroidal Neovascularization Components Under Treatment With Projection-Resolved OCT Angiography.

Purpose: To evaluate the response of type 1 and type 2 macular neovascularization (MNV) components under anti-vascular endothelial growth factor (VEGF) treatment in age-related macular degeneration (AMD) using projection-resolved optical coherence tomography angiography (PR-OCTA).

Methods: This retrospective study included eyes with treatment-naïve exudative AMD treated with anti-VEGF injections under a pro re nata (PRN) protocol over 1 year. Two-dimensional MNV areas and three-dimensional MNV volumes were derived from macular PR-OCTA scans using an automated convolutional neural network.

Multi-Plexus Nonperfusion Area Segmentation in Widefield OCT Angiography Using a Deep Convolutional Neural Network.

Purpose: To train and validate a convolutional neural network to segment nonperfusion areas (NPAs) in multiple retinal vascular plexuses on widefield optical coherence tomography angiography (OCTA).

Methods: This cross-sectional study included 202 participants with a full range of diabetic retinopathy (DR) severities (diabetes mellitus without retinopathy, mild to moderate non-proliferative DR, severe non-proliferative DR, and proliferative DR) and 39 healthy participants. Consecutive 6 × 6-mm OCTA scans at the central macula, optic disc, and temporal region in one eye from 202 participants in a clinical DR study were acquired with a 70-kHz OCT commercial system (RTVue-XR).

Multiomic profiling of breast cancer cells uncovers stress MAPK-associated sensitivity to AKT degradation.

More than 50% of human tumors display hyperactivation of the serine/threonine kinase AKT. Despite evidence of clinical efficacy, the therapeutic window of the current generation of AKT inhibitors could be improved. Here, we report the development of a second-generation AKT degrader, INY-05-040, which outperformed catalytic AKT inhibition with respect to cellular suppression of AKT-dependent phenotypes in breast cancer cell lines.

Anti-BCMA CAR T-cell therapy CT103A in relapsed or refractory AQP4-IgG seropositive neuromyelitis optica spectrum disorders: phase 1 trial interim results.

Chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA) have great potentials in autoimmune diseases and could be novel therapeutics for relapsed/refractory neuromyelitis optica spectrum disorder (NMOSD). To evaluate the safety and efficacy of the CT103A, a self-developed BCMA-targeting CAR construct against BCMA, in patients with AQP4-IgG seropositive NMOSD, an ongoing, investigator-initiated, open-label, single-arm, phase 1 clinical trial is conducted at our center. In total, 12 patients were administered with a CAR-BCMA infusion.

Modulation of intracellular kinase signaling to improve TIL stemness and function for adoptive cell therapy.

Introduction: Adoptive cellular therapy with tumor-infiltrating lymphocytes (TIL) has demonstrated promising clinical benefits in several solid tumors, but the efficacy of this therapy might be compromised by the "prone-to-exhaustion" phenotype of TIL and poor persistence in vivo. This calls for a robust expansion process to produce a large number of cells for clinical usage while at the same time maintaining favorable anti-tumor function and memory phenotype. Previous studies showed that the PI3K-AKT signaling pathway plays a key role in the regulation of T cell activation, differentiation and memory formation.

Immunogenicity and safety of an egg culture-based quadrivalent inactivated non-adjuvanted subunit influenza vaccine in subjects ≥3 years: A randomized, multicenter, double-blind, active-controlled phase III, non-inferiority trial.

Subunit influenza vaccine only formulated with surface antigen proteins has better safety profiles relative to split-virion influenza vaccine. Compared to the traditional quadrivalent split-virion influenza vaccine, a novel quadrivalent subunit influenza vaccine is urgently needed in China. We completed a phase 3, randomized, double-blind, active-controlled, non-inferiority clinical study at two sites in Henan Province, China.

Observation of the B_{c}^{+} Meson in Pb-Pb and pp Collisions at sqrt[s_{NN}]=5.02 TeV and Measurement of its Nuclear Modification Factor.

The B_{c}^{+} meson is observed for the first time in heavy ion collisions. Data from the CMS detector are used to study the production of the B_{c}^{+} meson in lead-lead (Pb-Pb) and proton-proton (pp) collisions at a center-of-mass energy per nucleon pair of sqrt[s_{NN}]=5.02  TeV, via the B_{c}^{+}→(J/ψ→μ^{+}μ^{-})μ^{+}ν_{μ} decay.

Geographic Atrophy Progression Is Associated With Choriocapillaris Flow Deficits Measured With Optical Coherence Tomographic Angiography.

Purpose: The purpose of this study was to assess the associations between baseline choriocapillaris (CC) flow deficits and geographic atrophy (GA) progression.

Methods: In this prospective cohort study, patients with GA underwent 3 × 3-mm macular spectral-domain optical coherence tomographic angiography (OCTA) at baseline and follow-up visits. Annual GA enlargement rate was defined as change of square root of GA area in 12 months.

Association Between Fluid Volume in Inner Nuclear Layer and Visual Acuity in Diabetic Macular Edema.

Purpose: In diabetic macular edema (DME), the correlation between visual acuity (VA) and central subfield thickness (CST) is weak. We hypothesize that fluid volume (FV) in the inner nuclear layer (INL) may correlate more strongly with VA.

Design: Retrospective, cross-sectional study.

Functional Connectivity as a Potential Mechanism for Language Plasticity.

Background And Objectives: Task fMRI is a clinical tool for language lateralization, but has limitations, and cannot provide information about network-level plasticity. Additional methods are needed to improve the precision of presurgical language mapping. We investigate language resting-state functional connectivity (RS fMRI; FC) in typically developing children (TD) and children with epilepsy.

Next-Generation Surrogate Wnts Support Organoid Growth and Deconvolute Frizzled Pleiotropy In Vivo.

Modulation of Wnt signaling has untapped potential in regenerative medicine due to its essential functions in stem cell homeostasis. However, Wnt lipidation and Wnt-Frizzled (Fzd) cross-reactivity have hindered translational Wnt applications. Here, we designed and engineered water-soluble, Fzd subtype-specific "next-generation surrogate" (NGS) Wnts that hetero-dimerize Fzd and Lrp6.

Classification based on mutations of TERT promoter and IDH characterizes subtypes in grade II/III gliomas.

Background: Grade II and III gliomas have variable clinical behaviors, showing the distinct molecular genetic alterations from glioblastoma (GBM), many of which eventually transform into more aggressive tumors. Since the classifications of grade II/III gliomas based on the genetic alterations have been recently emerging, it is now a trend to include molecular data into the standard diagnostic algorithm of glioma.

Methods: Here we sequenced TERT promoter mutational status (TERTp-mut) in the DNA of 377 grade II/III gliomas and analyzed the clinical factors, molecular aberrations, and transcriptome profiles.

Spatiotemporal expression profile of the Pumilio gene in the embryonic development of silkworm.

We previously identified a pumilio gene in silkworm (Bombyx mori L.), designated BmPUM, which was specifically expressed in the ovary and testis. To further characterize this gene's involvement in silkworm development, we have determined the spatiotemporal expression pattern of BmPUM during all embryonic stages.

MiR-124 governs glioma growth and angiogenesis and enhances chemosensitivity by targeting R-Ras and N-Ras.

Background: Glioma is one of the most aggressive and lethal human brain tumors. Accumulating evidence shows that microRNAs play important roles in cancers, including glioma. Previous studies reported that miR-124 levels were downregulated in glioma specimens.

19-substituted benzoquinone ansamycin heat shock protein-90 inhibitors: biological activity and decreased off-target toxicity.

Unlabelled: The benzoquinone ansamycins (BQAs) are a valuable class of antitumor agents that serve as inhibitors of heat shock protein (Hsp)-90. However, clinical use of BQAs has resulted in off-target toxicities, including concerns of hepatotoxicity. Mechanisms underlying the toxicity of quinones include their ability to redox cycle and/or arylate cellular nucleophiles.

Extraction of trace amount of severely degraded DNA.

DNA extraction from food is always problematic especially from highly processed samples which contain only trace amounts of severely degraded DNA fragments. In this work, to extract trace amounts of small DNA fragments of the traditional Chinese medicine (TCM) colla corii asini derived from highly processed Equus asinus skin, three strategies were compared for its authentication. With some optimizations, the modified QIAquick spin column method achieved higher DNA yield and purity in comparison with the "SDS/proteinase K" method and the "Wizard magnetic DNA purification system for food" method.

Expression of the endoplasmic reticulum chaperone GRP94 gene in ischemic gerbil brain.

GRP94 (glucose regulated protein 94) gene expression in the ischemic-hippocampus of gerbils, which was induced by a temporary occlusion of the bilateral common carotid arteries (CCAs), was tested by Northern blot analysis. The maximum GRP94 gene expression level was detected at the occipital lobe 10 min after the induction of ischemia. In the hippocampus, GRP94 gene expression reached a maximum 15 min after inducing ischemia.

Clusterin overexpression is responsible for the anti-apoptosis effect in a mouse neuroblastoma cell line, B103.

The functional role of clusterin in apoptosis was examined using flow cytometry. Clusterin cDNA was transfected into the mouse neuroblastoma cell line, B103, in order to determine if clusterin overexpression inhibits apoptosis. The increased clusterin expression level in the B103 cells tended to suppress the apoptotic index.

Phylogenetic relationship of Bombyx mori protein disulfide isomerase.

A cDNA that encodes protein disulfide isomerase was isolated from Bombyx mori (bPDI), in which an open reading frame of 494 amino acids contained two PDI-typical thioredoxin active sites of WCGHCK and an ER retention signal of the KDEL motif at its C-terminal. The bPDI protein shared less than 55% of the amino acid sequence homology with other reported PDIs. bPDI is most genetically similar to the D.