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Obstructive hypertrophic cardiomyopathy (oHCM) is a subtype of HCM characterized by left ventricular outflow tract obstruction resulting from cardiac muscle hypertrophy and anatomic alterations in the mitral valve and apparatus. Mavacamten, a cardiac myosin inhibitor metabolized primarily by CYP2C19 in the liver, is the first and only targeted medication approved for the treatment of symptomatic New York Heart Association (NYHA) class II–III oHCM. Previous pharmacokinetic (PK) results of mavacamten in healthy Caucasian, Japanese, and Asian participants demonstrated that mavacamten exposure was affected by CYP2C19 metabolism status. This open‐label, parallel‐group, phase I trial aimed to determine the PK and safety of mavacamten in healthy Chinese participants with different CYP2C19 genotypes. The primary outcome was to define the PK of mavacamten in healthy Chinese participants; the secondary outcome was to examine safety and tolerability. After a single oral dose of 15 or 25 mg mavacamten in fasted healthy adult Chinese individuals, Cmax was reached within a median Tmax of 0.6–1.5 h, indicating rapid absorption. Inter‐individual variability was moderate, and individuals carrying non‐functional CYP2C19 alleles (*2/*2, *3/*3, or *2/*3) exhibited longer half‐life and increased total exposure. After stratification of CYP2C19 genotypes, total mavacamten exposures were similar among different ethnic groups when compared with prior PK studies. No significant adverse events were observed in this study. Single oral administration of mavacamten at 15 mg was well tolerated across all CYP2C19 genotypes, and 25 mg dose was well tolerated in healthy participants with CYP2C19 genotypes UM/RM/NM. The PK profile of mavacamten in the healthy Chinese population was consistent with that in other healthy populations. [ABSTRACT FROM AUTHOR]

BACKGROUND: Temperature is a primary factor that determines the eco‐geographical distribution and population development of invasive insects. Temperature stress leads to various negative effects, including excess reactive oxygen species (ROS), and catalase (CAT) is a key enzyme against ROS in the antioxidant pathway. The whitefly Bemisia tabaci MED is a typical invasive pest that causes damage worldwide. Our previous studies have shown that CAT promotes whitefly adaptation to high temperature by eliminating ROS. However, the mechanism underlying the low‐temperature adaptation of whiteflies is still unknown. RESULTS: In this study, we investigated the role of CAT in the low‐temperature tolerance of B. tabaci MED by analyzing its survival rate, reproduction, and ROS levels at 25 °C (as a control, suitable temperature), 20 °C (moderately decreased temperature), and 4 °C (severely decreased temperature). Silencing of BtCAT1, BtCAT2, or BtCAT3 reduced the viability of whiteflies under a short‐term severely decreased temperature (4 °C), which manifested as decreases in survival and fecundity accompanied by significant increases in ROS levels. Moreover, even at a moderately decreased temperature (20 °C), silencing of BtCAT1 led to high ROS levels and low survival rates in adults. CONCLUSION: Silencing of BtCATs significantly increased the sensitivity of B. tabaci MED to low temperatures. BtCAT1 is likely more essential than other BtCATs for low‐temperature tolerance in whiteflies. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Development of highly efficient and metal‐free photocatalysts for bacterial inactivation under natural light is a major challenge in photocatalytic antibiosis. Herein, we developed an acidizing solvent‐thermal approach for inserting a non‐conjugated ethylenediamine segment into the conjugated planes of 3,4,9,10‐perylene tetracarboxylic anhydride to generate a photocatalyst containing segregated π‐conjugation units (EDA‐PTCDA). Under natural light, EDA‐PTCDA achieved 99.9 % inactivation of Escherichia coli and Staphylococcus aureus (60 and 45 min), which is the highest efficiency among all the natural light antibacterial reports. The difference in the surface potential and excited charge density corroborated the possibility of a built‐in electron‐trap effect of the non‐conjugated segments of EDA‐PTCDA, thus forming a highly active EDA‐PTDA/bacteria interface. In addition, EDA‐PTCDA exhibited negligible toxicity and damage to normal tissue cells. This catalyst provides a new opportunity for photocatalytic antibiosis under natural light conditions. [ABSTRACT FROM AUTHOR]

Porcine embryonic fibroblasts (PEFs) can be directly reprogrammed into porcine induced pluripotent stem cells (piPSCs). However, the reprogramming process is generally lengthy and inefficient. Here, we established a fast and efficient induction system of piPSCs from porcine Sertoli cells (SCs) via forced expression of pig Yamanaka factors. The alkaline phosphatase (AP)‐positive colonies from SCs developed on Day 3 after lentivirus infection, and were expanded and then picked up on Day 7, whereas reprogramming process from PEFs did not show any colonies in the same period. The picked piPSCs strongly expressed pluripotent genes, had the differentiation capacity to three germ layers, and could be also induced into primordial germ cell‐like cells. Screening for transcription factor combinations showed that POU class 5 homeobox 1 (OCT4) is the core factor for AP‐positive colony formation, and two factors (OCT4 and c‐MYC) could successfully reprogram SCs into piPSCs. We then compared the RNA‐sequencing data of piPSCs derived from SCs and PEFs, and found that the most significant difference was the activation of Transforming Growth Factor β signaling pathway. We also compared the RNA levels of SCs and PEFs, and found that SCs exhibited higher Wnt signaling activity and Bone Morphogenetic Protein 4 expression than PEFs, which might be correlated with higher cell proliferation rate and reprogramming efficiency. In summary, the data demonstrated that starting cell sources of piPSCs significantly affect reprogramming dynamics and SCs could serve as cell sources for efficient reprogramming. [ABSTRACT FROM AUTHOR]

Near‐infrared (NIR) light‐driven overall water splitting beyond 800 nm remains a high‐priority target yet great challenge. Here we report that efficient utilization of photogenerated electrons in a photosensitized system prepared by site‐selective photodeposition of platinum single atoms/clusters (Pt‐SACs) on Ni‐phytate (PA‐Ni)‐sensitized polymeric carbon nitride (PCN). The optimal catalyst presents simultaneous hydrogen (H2) and oxygen (O2) evolution with an H2 evolution amount of 1.4 μmol at λ>800 nm for 24 hours, which its activity was approximately 140 times higher than that of a system without Pt‐SAC modification (PA‐Ni1.1@PCN). This work represents the first NIR‐light responsive photosensitized system for overall water splitting, and may open an avenue for precisely manipulating cocatalyst positions at the atomic level to improve NIR‐light‐driven overall water splitting via photosensitization. [ABSTRACT FROM AUTHOR]

The objectives of this phase I study are to assess the safety, tolerability, and pharmacokinetics (PKs) of RO7049389 in healthy Chinese volunteers (HVs) and evaluate potential ethnic differences in the safety and PKs using data from this study and the first‐in‐human study (in which most of the HVs were non‐Asian). HVs randomly received a single dose of 200–600 mg of RO7049389 or a placebo in a single ascending dose (n = 28) or multiple doses of 200–400 mg of RO7049389 or a placebo in multiple ascending doses (n = 24). Safety and tolerability were monitored throughout the study. Serial blood samples were collected for PK analysis. RO7049389 was safe and well‐tolerated in the HVs. The time to maximum concentration ranged from 1.5 to 3.0 h, and terminal half‐life ranged from 3.66 to 14.6 h. A single dose of 200–600 mg and multiple doses of 200–400 mg exhibited nonlinear PKs. In general, the safety profiles were comparable between non‐Asian and Asian HVs, but the plasma exposure of RO7049389 in Chinese HVs was higher than that in non‐Asian HVs. The data generated from this study will provide guidance for future clinical studies on RO7049389 in Chinese/Asian patients with hepatitis B virus. [ABSTRACT FROM AUTHOR]

Distinguished from the former researchers, this article aims at researching the effect of the stator fundamental negative sequence current in turbo‐generators on the electromagnetic torque both from theoretical analysis and finite element simulation. Firstly, based on three sequence component analysis, coordinate system transform and interaction analysis of magneto‐motive force vectors, the concrete expression of direct component of the electromagnetic torque is given, and the concrete expression of second harmonic electromagnetic torque is presented by a new vectorial approach proposed in this article. Further, the impact of the stator fundamental negative sequence current on the electromagnetic torque has been discussed in details by the new approach proposed in this article. In order to prove the correctness of the analytical analysis by the new approach proposed in this article, two turbo‐generators have been taken as examples, and their finite element simulation models have been built up and tested through experimental data. Moreover, the simulation result verifies the effectiveness of the analytical expression and analytic analysis proposed in this article. © 2021 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

LCL‐type resonant dual‐active‐bridge (LCL‐DAB) DC–DC converters have more significant advantages in eliminating backflow power and achieving higher voltage gain compared with traditional dual active bridge (DAB) DC–DC converters. Therefore, LCL‐DAB DC–DC converters have a broad application prospect in DC micro‐grids, electric vehicles, uninterruptible power supplies etc. Since at this stage only a few researches on LCL‐DAB DC–DC converters have been done, here, the specific system operation region with triple‐phase‐shift (TPS) modulation scheme designed under no backflow power is presented. Furthermore, a dynamic compensation based feedforward control method under no backflow power is proposed, which enables the LCL‐DAB DC–DC converter to operate under no backflow power in wide region and achieve outstanding dynamic performance against output/input disturbance. Finally, the experimental results verify the feasibility and effectiveness of the proposed control method. [ABSTRACT FROM AUTHOR]