ATP13A1 engages SEC61 to facilitate substrate-specific translocation.

The accurate targeting of proteins to their designated cellular compartments is essential for maintaining proper cellular architecture and function. However, interpreting and sorting the highly variable targeting sequences in secreted and membrane proteins present a substantial challenge for achieving precise localization within the secretory pathway. In this study, we demonstrate that atypical signal sequences, characterized by high hydrophobicity and/or the absence of characteristic charges, are recognized by the signal recognition particle and targeted to the endoplasmic reticulum in a reverse orientation.

MSBack: Multiscale Backmapping of Highly Coarse-Grained Proteins Using Constrained Diffusion.

Coarse-grained (CG) molecular dynamics is a powerful tool for simulating the collective behavior of biomolecules. However, the structural information lost during coarse-graining prevents the CG configurations from being more widely useful (e.g.

Tunable topological edge states based on anomalous scattering.

The present work combines traditional dielectric materials with metal foils to form composite scatterers and constructs a two-dimensional square lattice photonic crystal, from which its band topology is achieved. Photonic bandgap (PBG) arises from local Mie scattering resonances between adjacent structures, analogous to the role of atomic energy levels in a crystal. The energy levels of the composite scatterers can be controlled by rotation, thus manipulating the PBG and topological properties.

The impact of perceived life stress and online social support on university students' mental health during the post-COVID era in Northwestern China: gender-specific analysis.

Background: Before the pandemic, research had already established the potential impact of perceived life stress and social support on the mental health status of Chinese students. However, in the Post-COVID Era, the specific mechanisms linking these variables and the distinct role of online social support remain relatively unexplored.

Methods: After the cessation of China's dynamic zeroing policy, a total of 1180 university students from Northwestern China participated in this study by completing a demographic questionnaire, as well as self-report measures assessing mental health, perceived life stress, and online social support.

Enhancement of recombinant human interleukin-22 production by fusing with human serum albumin and supplementing N-acetylcysteine in Pichia Pastoris.

Interleukin-22 (IL-22) plays an important role in the treatment of organ failure, which can induce anti-apoptotic and proliferative signaling pathways; Nevertheless, the practical utilization of IL-22 is hindered by the restricted efficacy of its production. Pichia pastoris presents a viable platform for both industrial and pharmaceutical applications. In this study, we successfully generated a fusion protein consisting of truncated human serum albumin and human IL-22 (HSA-hIL-22) using P.

Cell reprogramming in a predictable manner on the superhydrophobic microwell array chip.

Reprogramming of somatic cells into the pluripotent state is stochastic and inefficient using the conventional culture plates. Novel micro-culture systems employing precisely controlled biophysical cues can improve the reprogramming efficiencies dramatically. Here we perform iPSC induction on our previously developed superhydrophobic microwell array chip (SMAR-chip) where cells undergo distinctive morphology change, switching from 2D monolayers to 3D clumps, and develop into bona fide colonies in more than 90% of the microwells.

Effect of -acetyl-l-cysteine on Cell Phenotype and Autophagy in Expressing Human Serum Albumin and Porcine Follicle-Stimulating Hormone Fusion Protein.

is widely used for the production of recombinant proteins, but the low secretion efficiency hinders its wide application in biopharmaceuticals. Our previous study had shown that -acetyl-l-cysteine (NAC) promotes human serum albumin and porcine follicle-stimulating hormone fusion protein (HSA-pFSHβ) secretion by increasing intracellular GSH levels, but the downstream impact mechanism is not clear. In this study, we investigated the roles of autophagy as well as cell phenotype in NAC promoting HSA-pFSHβ secretion.

Functional cooperation between IK and TRPC1 channels regulates serum-induced vascular smooth muscle cell proliferation via mediating Ca influx and ERK1/2 activation.

The increased proliferation of vascular smooth muscle cells (VSMCs) contributes to the pathogenesis of vascular diseases. The intermediate conductance calcium-activated potassium (IK ) channel plays a critical role in VSMC proliferation by raising the intracellular calcium concentration ([Ca ] ), but the underlying mechanism is still not unclear. Here we investigated the cooperation between IK and transient receptor potential canonical 1 (TRPC1) channels in mediating extracellular Ca entry, which in turn activates downstream Ca signalling in the regulation of VSMC proliferation using serum-induced cell proliferation model.

Cancer-derived exosomal circ_0038138 enhances glycolysis, growth, and metastasis of gastric adenocarcinoma via the miR-198/EZH2 axis.

This study aims to decipher the impact and downstream mechanisms of the bioinformatically identified circ_0038138 delivered by cancer-derived exosomes in gastric adenocarcinoma (GAC). Expression of circ_0038138 in clinical GAC tissues and exosomes (Exos) from clinical plasma samples (plasma-Exos) was predicted by bioinformatics analysis and validated by RT-qPCR. The binding affinity between circ_0038138, miR-198 and EZH2 was identified using luciferase activity, RIP, and RNA pull-down assays.

Mechanism of reactivation of the peroxidase catalytic activity of human cyclooxygenases by reducing cosubstrate quercetin.

Our earlier studies show that the peroxidase activity of cyclooxygenase 1 and 2 (COX-1 and COX-2) can be reactivated in vitro and in vivo by the presence of certain naturally-occurring flavonoids such as quercetin and myricetin, which serve as reducing cosubstrates. These compounds can activate COX at nanomolar concentrations. In the present study, quercetin is used as a representative model compound to investigate the chemical mechanism by which the peroxidase activity of human COX-1 and COX-2 is reactivated after each catalytic cycle.

Ligand-Controlled Regiodivergent Nickel-Catalyzed Hydrocyanation of Silyl-Substituted 1,3-Diynes.

A regiodivergent nickel-catalyzed hydrocyanation of 1-aryl-4-silyl-1,3-diynes is reported. When appropriate bisphosphine and phosphine-phosphite ligands are applied, the same starting materials can be converted into two different enynyl nitriles with good yields and high regioselectivities. The DFT calculations unveiled that the structural features of different ligands bring divergent alkyne insertion modes, which in turn lead to different regioselectivities.

Inhibition of cyclooxygenase by blocking the reducing cosubstrate at the peroxidase site: Discovery of galangin as a novel cyclooxygenase inhibitor.

Earlier we have shown that certain flavonoids (e.g., quercetin) are high-affinity reducing cosubstrates for cyclooxygenase (COX) 1 and 2.

Mechanism for the reactivation of the peroxidase activity of human cyclooxygenases: investigation using phenol as a reducing cosubstrate.

It has been known for many years that the peroxidase activity of cyclooxygenase 1 and 2 (COX-1 and COX-2) can be reactivated in vitro by the presence of phenol, which serves as a reducing compound, but the underlying mechanism is still poorly understood. In the present study, we use phenol as a model compound to investigate the mechanism by which the peroxidase activity of human COXs is reactivated after each catalytic cycle. Molecular docking and quantum mechanics calculations are carried out to probe the interaction of phenol with the peroxidase site of COXs and the reactivation mechanism.

Baicalein, as a Prooxidant, Triggers Mitochondrial Apoptosis in MCF-7 Human Breast Cancer Cells Through Mobilization of Intracellular Copper and Reactive Oxygen Species Generation.

Background: Baicalein, a natural flavonoid derived from traditional Chinese herb (known as Huang Qin in Chinese), has been reported to exhibit notable antitumor activity in various cancer cells, including breast cancer. However, the detailed mechanisms underlying its induced apoptosis as a prooxidant in breast cancer cells are still unknown.

Materials And Methods: In this study, we investigated the effect of endogenous copper on cytotoxic activity of baicalin against human breast cancer MCF-7 cells in vitro.

Digital phenotyping by consumer wearables identifies sleep-associated markers of cardiovascular disease risk and biological aging.

Sleep is associated with various health outcomes. Despite their growing adoption, the potential for consumer wearables to contribute sleep metrics to sleep-related biomedical research remains largely uncharacterized. Here we analyzed sleep tracking data, along with questionnaire responses and multi-modal phenotypic data generated from 482 normal volunteers.

Apatinib for advanced nonsmall-cell lung cancer: A retrospective case series analysis.

Objectives: Apatinib, a tyrosine kinase inhibitor which selectively inhibits vascular endothelial growth factor receptor-2, has been shown to be beneficial to patients with a variety of cancers, including advanced nonsmall-cell lung cancer (NSCLC). Thus, this study was aimed to retrospectively assess the efficacy and safety of apatinib in patients with advanced/metastatic NSCLC who failed more than two lines of treatment.

Methods: Twenty-three NSCLC patients were involved in this study, who received oral apatinib at a daily dose of 250/500/750 mg, with the progression after the failure of second-line therapy.

Thermal equilibrium control by frequent bang-bang modulation.

In this paper, we investigate the non-Markovian heat transfer between a weakly damped harmonic oscillator (system) and a thermal bath. When the system is initially in a thermal state and not correlated with the environment, the mean energy of the system always first increases, then oscillates, and finally reaches equilibrium with the bath, no matter what the initial temperature of the system is. Moreover, the heat transfer between the system and the bath can be controlled by fast bang-bang modulation.