Discovery, Characterization, and Structure of a Cell Active PAD2 Inhibitor Acting through a Novel Allosteric Mechanism.

Peptidyl arginine deiminases (PADs) are important enzymes in many diseases, especially those involving inflammation and autoimmunity. Despite many years of effort, developing isoform-specific inhibitors has been a challenge. We describe herein the discovery of a potent, noncovalent PAD2 inhibitor, with selectivity over PAD3 and PAD4, from a DNA-encoded library.

Change in prostate tissue gene expression following finasteride or doxazosin administration in the medical therapy for prostatic symptoms (MTOPS) study.

Benign prostatic hyperplasia (BPH) may decrease patient quality of life and often leads to acute urinary retention and surgical intervention. While effective treatments are available, many BPH patients do not respond or develop resistance to treatment. To understand molecular determinants of clinical symptom persistence after initiating BPH treatment, we investigated gene expression profiles before and after treatments in the prostate transitional zone of 108 participants in the Medical Therapy of Prostatic Symptoms (MTOPS) Trial.

Voltage-based magnetization switching and reading in magnetoelectric spin-orbit nanodevices.

As CMOS technologies face challenges in dimensional and voltage scaling, the demand for novel logic devices has never been greater, with spin-based devices offering scaling potential, at the cost of significantly high switching energies. Alternatively, magnetoelectric materials are predicted to enable low-power magnetization control, a solution with limited device-level results. Here, we demonstrate voltage-based magnetization switching and reading in nanodevices at room temperature, enabled by exchange coupling between multiferroic BiFeO and ferromagnetic CoFe, for writing, and spin-to-charge current conversion between CoFe and Pt, for reading.

Evaluation of Durability Performance for Chloride Ingress Considering Long-Term Aged GGBFS and FA Concrete and Analysis of the Relationship between Concrete Mixture Characteristic and Passed Charge Using Machine Learning Algorithm.

In this study, accelerated chloride diffusion tests are performed on ordinary Portland cement (OPC), ground granulated blast furnace slag (GGBFS), and fly ash (FA) concretes aged 4-6 years. Passed charge is evaluated according to ASTM-C-1202 for 12 mixtures, considering water-binder (W/B) ratios (0.37, 0.

Controlling the Interlayer Dzyaloshinskii-Moriya Interaction by Electrical Currents.

The recently discovered interlayer Dzyaloshinskii-Moriya interaction (IL-DMI) in multilayers with perpendicular magnetic anisotropy favors canting of spins in the in-plane direction. It could thus stabilize intriguing spin textures such as Hopfions. A key requirement for nucleation is to control the IL-DMI.

Multimodal Wearable Ionoskins Enabling Independent Recognition of External Stimuli Without Crosstalk.

Wearable ionoskins are one of the representative examples of the many useful applications offered by deformable stimuli-responsive sensory platforms. Herein, ionotronic thermo-mechano-multimodal response sensors are proposed, which can independently detect changes in temperature and mechanical stimuli without crosstalk. For this purpose, mechanically robust, thermo-responsive ion gels composed of poly(styrene-ran-n-butyl methacrylate) (PS-r-PnBMA, copolymer gelator) and 1-butyl-3-methylimidazolium bis(trifluoromethyl sulfonyl)imide ([BMI][TFSI], ionic liquid) are prepared.

Hypermethylation of PDX1, EN2, and MSX1 predicts the prognosis of colorectal cancer.

Despite numerous observations regarding the relationship between DNA methylation changes and cancer progression, only a few genes have been verified as diagnostic biomarkers of colorectal cancer (CRC). To more practically detect methylation changes, we performed targeted bisulfite sequencing. Through co-analysis of RNA-seq, we identified cohort-specific DNA methylation markers: CpG islands of the intragenic regions of PDX1, EN2, and MSX1.

ZNF204P is a stemness-associated oncogenic long non-coding RNA in hepatocellular carcinoma.

Hepatocellular carcinoma is a major health burden, and though various treatments through much research are available, difficulties in early diagnosis and drug resistance to chemotherapy-based treatments render several ineffective. Cancer stem cell model has been used to explain formation of heterogeneous cell population within tumor mass, which is one of the underlying causes of high recurrence rate and acquired chemoresistance, highlighting the importance of CSC identification and understanding the molecular mechanisms of CSC drivers. Extracellular CSCmarkers such as CD133, CD90 and EpCAM have been used successfully in CSC isolation, but studies have indicated that increasingly complex combinations are required for accurate identification.

SdhA blocks disruption of the Legionella-containing vacuole by hijacking the OCRL phosphatase.

Legionella pneumophila grows intracellularly within a replication vacuole via action of Icm/Dot-secreted proteins. One such protein, SdhA, maintains the integrity of the vacuolar membrane, thereby preventing cytoplasmic degradation of bacteria. We show here that SdhA binds and blocks the action of OCRL (OculoCerebroRenal syndrome of Lowe), an inositol 5-phosphatase pivotal for controlling endosomal dynamics.

Forward-Looking Ultrasound Wearable Scanner System for Estimation of Urinary Bladder Volume.

Accurate measurement of bladder volume is an important tool for evaluating bladder function. In this study, we propose a wearable bladder scanner system that can continuously measure bladder volume in daily life for urinary patients who need urodynamic studies. The system consisted of a 2-D array, which included integrated forward-looking piezoelectric transducers with thin substrates.

Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids.

Brain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids.

A simple method to improve the quality and yield of human pluripotent stem cell-derived cerebral organoids.

The development of cerebral organoid technology has allowed the human neural tissue to be collected for studying human brain development and neurological diseases. Human pluripotent stem cell-derived cerebral organoids (hCOs) are a theoretically infinite source of fresh human brain tissue for various research purposes. However, hCOs have limitations, including core necrotic cell death.

Mortality Rate of Patients With COVID-19 Based on Underlying Health Conditions.

Objective: The aim of this study was to evaluate the mortality rates of 566,602 patients with coronavirus disease (COVID-19) based on sex, age, and the presence or absence of underlying diseases and determine whether the underlying disease provides prognostic information specifically related to death.

Methods: The mortality rate was evaluated using conditional probability to identify the significant factors, and adjusted odds ratios (ORs) using a multivariable logistic regression analysis were estimated.

Results: The mortality rate of patients with underlying health conditions was 12%, which was 4 times higher than that of patients without underlying health conditions.

NEUROD1 Intrinsically Initiates Differentiation of Induced Pluripotent Stem Cells into Neural Progenitor Cells.

Cell type specification is a delicate biological event in which every step is under tight regulation. From a molecular point of view, cell fate commitment begins with chromatin alteration, which kickstarts lineage-determining factors to initiate a series of genes required for cell specification. Several important neuronal differentiation factors have been identified from ectopic over-expression studies.

Chromatin Interaction Changes during the iPSC-NPC Model to Facilitate the Study of Biologically Significant Genes Involved in Differentiation.

Given the difficulties of obtaining diseased cells, differentiation of neurons from patient-specific human induced pluripotent stem cells (iPSCs) with neural progenitor cells (NPCs) as intermediate precursors is of great interest. While cellular and transcriptomic changes during the differentiation process have been tracked, little attention has been given to examining spatial re-organization, which has been revealed to control gene regulation in various cells. To address the regulatory mechanism by 3D chromatin structure during neuronal differentiation, we examined the changes that take place during differentiation process using two cell types that are highly valued in the study of neurodegenerative disease - iPSCs and NPCs.

DNA Methylation of Intragenic CpG Islands are Required for Differentiation from iPSC to NPC.

The effects of gene body DNA methylation on gene regulation still remains highly controversial. In this study, we generated whole genome bisulfite sequencing (WGBS) data with high sequencing depth in induced pluripotent stem cell (iPSC) and neuronal progentior cell (NPC), and investigated the relationship between DNA methylation changes in CpG islands (CGIs) and corresponding gene expression during NPC differentiation. Interestingly, differentially methylated CGIs were more abundant in intragenic regions compared to promoters and these methylated intragenic CGIs (iCGIs) were associated with neuronal development-related genes.

Direct nanofluidic channels via hardening and wrinkling of thin polymer films.

In this study, we propose a rational route to create wrinkling patterns with individually controllable location and direction in thin polymer films. Optical and atomic force microscopy analysis confirmed the formation of straight wrinkles with a typical width of 1.51 to 1.

Ultra-Low Power Electrochromic Heat Shutters Through Tailoring Diffusion-Controlled Behaviors.

In this study, we propose low power consumption, all-in-one type electrochromic devices (ECDs) for effective heat shutters. Considering diffusion-controlled device operation, polymeric viologens (poly-viologens) are synthesized to lower the diffusivity of EC chromophores and to minimize self-bleaching. In comparison with devices based on mono-viologens corresponding to the monomer of poly-viologens, poly-viologen-containing ECDs exhibit advantages of lower coloration voltage (ca, -0.

Frequency modulation of laser ultrasound transducer using carbon nanotube-coated polyethylene microsphere.

An ultrasound transducer was fabricated by dropping a multi-walled carbon nanotube solution containing a mixture of carbon nanotubes and ethoxyethanol directly on the surface of polyethylene microspheres. The frequency modulation depended on the diameter of the polyethylene microspheres. To investigate this relationship, three types of polyethylene microspheres with different diameters were used in simulations and experiments.

Single-Shot Near-Field Volumetric Imaging System for Optical Ultrasound and Photoacoustics Using Capacitive Micromachined Ultrasonic Transducer Without Transmission Mode.

In this article, we present a single-shot dual-mode imaging system that uses optical ultrasound (US) as an ultrasonic pulser without a transmission circuit. The ultrasonic pulse-echo system comprises an optical US pulser generated by carbon nanotubes (CNTs), which generate a high-power photoacoustic (PA) signal and a capacitive micromachined ultrasonic transducer (CMUT) receiver. By fabricating a thin CNT-polydimethylsiloxane (PDMS) composite capable of semiabsorption of the laser, a single-shot imaging system was developed.

Comparison between Resonance and Non-Resonance Type Piezoelectric Acoustic Absorbers.

In this study, piezoelectric acoustic absorbers employing two receivers and one transmitter with a feedback controller were evaluated. Based on the target and resonance frequencies of the system, resonance and non-resonance models were designed and fabricated. With a lateral size less than half the wavelength, the model had stacked structures of lossy acoustic windows, polyvinylidene difluoride, and lead zirconate titanate-5A.