USP7 V517F mutation as a mechanism of inhibitor resistance.

Anticipating and addressing resistance is essential for maximizing the potential of an oncology target and effectively addressing clinical needs. In this study, we aimed to proactively outline the resistance mechanisms of USP7 inhibitors. We discovered a key treatment-emergent heterozygous mutation (V517F) in USP7 in the binding pocket of compounds as the primary cause of resistance to the USP7 inhibitor USP7-797.

Altered functional network topology properties to detect anxiety and depression caused by Crohn's disease and disease severity.

Objective: Here we investigated changes in topological properties of functional brain networks among individuals with Crohn's disease (CD) and to determine whether these changes are related to CD severity, as well as CD-associated anxiety and depression, which are regulated by the brain-gut axis mechanism.

Methods: In total, 31 individuals with CD, 21 with irritable bowel syndrome (IBS), and 20 healthy controls underwent functional magnetic resonance imaging. Individuals with CD or IBS were also evaluated using the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) and Depression (HADS-D) scales, as well as the simple endoscopic score for CD (SES-CD).

Effect of Hot Junction Size on the Temperature Measurement of Proton Exchange Membrane Fuel Cells Using NiCr/NiSi Thin-Film Thermocouple Sensors.

In the process of using thin-film thermocouples for contact measurement of the reaction temperature in proton exchange membrane fuel cells (PEMFC), the impact of thin-film thermocouple volume on the system's reaction temperature field variation, reaction efficiency, and the lifespan of thermocouples under these conditions is not thoroughly studied. Using magnetron sputtering technology, NiCr/NiSi thin-film thermocouples (NiCr/NiSi TFTCs) with different junction sizes were fabricated on the proton exchange membrane (PEM). These NiCr/NiSi TFTCs exhibit excellent compactness, with thickness and planar dimensions in the micrometer range.

Secretory Phenotype in Peripheral Blood Mononuclear Cells of Elderly Patients with Rheumatoid Arthritis.

This study aims to investigate the expression differences of peripheral blood mononuclear cells (PBMCs) in patients with elderly rheumatoid arthritis (ERA). Differentially expressed genes (DEGs) of PBMCs between young patients with RA (RA_Y) and elderly patients with RA (RA_A) were identified by RNA sequencing using the package, followed by bioinformatics analysis. The overlapped targets of the current DEGs and proteomic differentially expressed proteins (another set of unpublished data) were identified and further validated.

A retrospective cohort study of Epstein-Barr virus infection status and systemic lupus erythematosus.

Objectives: Systemic lupus erythematosus (SLE) and the Epstein-Barr virus (EBV) are very closely related. This study estimated the impact of EBV infection status on clinical manifestations and disease remission in patients with SLE.

Method: A retrospective study was performed using electronic health records of patients with SLE.

Noncanonical functions of microRNAs in the nucleus.

MicroRNAs (miRNAs) are small noncoding RNAs (ncRNAs) that play their roles in the regulation of physiological and pathological processes. Originally, it was assumed that miRNAs only modulate gene expression posttranscriptionally in the cytoplasm by inducing target mRNA degradation. However, with further research, evidence shows that mature miRNAs also exist in the cell nucleus, where they can impact gene transcription and ncRNA maturation in several ways.

Integration of risk variants from GWAS with SARS-CoV-2 RNA interactome prioritizes FUBP1 and RAB2A as risk genes for COVID-19.

The role of host genetic factors in COVID-19 outcomes remains unclear despite various genome-wide association studies (GWAS). We annotate all significant variants and those variants in high LD (R > 0.8) from the COVID-19 host genetics initiative (HGI) and identify risk genes by recognizing genes intolerant nonsynonymous mutations in coding regions and genes associated with cis-expression quantitative trait loci (cis-eQTL) in non-coding regions.

Proposal for Observing XUV-Induced Rabi Oscillation Using Superfluorescent Emission.

Intense x-ray and extreme ultraviolet (XUV) light sources have been available for decades, however, due to weak nonlinear interaction in the XUV photon energy range, observation of Rabi oscillation induced by XUV pulse remains a very challenging experimental task. Here we suggest a scheme where photoionization of a He medium by an intense XUV pump pulse is followed by a strong population inversion and Rabi oscillation at the He^{+}(1s-3p) transition and is accompanied by superfluorescence (SF) of the 7.56 eV pulse at the He^{+}(3p-2s) transition.

Time-Resolved Resonant Auger Scattering Clocks Distortion of a Molecule.

Resonant Auger scattering (RAS) provides information on the core-valence electronic transition and impresses a rich fingerprint of the electronic structure and nuclear configuration at the time-initiating RAS process. Here, we suggest using a femtosecond X-ray pulse to trigger RAS in a distorted molecule, which is generated from the nuclear evolution on a valence excited state pumped by a femtosecond ultraviolet pulse. With the time delay varied, the amount of molecular distortion can be controlled and the RAS measurements imprint both their electronic structures and changing geometries.

Comparison of different assays for the detection of anticyclic citrullinated peptide antibodies in patients with rheumatoid arthritis.

Objective: To evaluate a novel fully automated immunoturbidimetric assay developed by Qiangsheng Biotechnology Company for the detection of anticyclic citrullinated peptide antibodies (anti-CCP) in serum of patients with rheumatoid arthritis (RA) and compare it to the conventional EUROIMMUN- anti-CCP ELISA. Two other commonly used automated assays, the Elecsys anti-CCP assay, an ECLIA that is run on the Modular Analystics E170 (Cobas Diagnostics, Germany), and an anti-CCP CLIA developed by YHLO that is run on the iFlash 3000 Chemiluminescence Immunoassay Analyzer, were included as reference standards.

Methods: A total of 264 serum samples were collected from patients attending the First People's Hospital of Wenling affiliated to Wenzhou Medical University between July 2020 and November 2020.

SOMCL-19-133, a novel, selective, and orally available inhibitor of NEDD8-activating enzyme (NAE) for cancer therapy.

Inhibition of the NEDD8-activating enzyme (NAE), the key E1 enzyme in the neddylation cascade, has been considered an attractive anticancer strategy with the discovery of the first-in-class NAE inhibitor, MLN4924. In this study, we identified SOMCL-19-133 as a highly potent, selective, and orally available NAE inhibitor, which is an analog to AMP. It effectively inhibited NAE with an IC value of 0.

Design, synthesis and pharmacological evaluation of new PARP1 inhibitors by merging pharmacophores of olaparib and the natural product alantolactone.

Based on the reported synthetic lethality of the combination of PARP inhibitor olaparib with the natural product alantolactone, we designed several series of new PARP1 inhibitors by structurally merging both compounds into a single hybrid compound. Among them, compounds 20e and 25a displayed not only high biochemical activity (IC = 2.99 nM and 5.

Predissociation resonances and accurate calculations of dication HF.

It is very interesting and challenging to investigate the electronic structures of diatomic dications, due to the nature of coulombic repulsive and bound attractive dissociation limits and their avoided diabatic interactions. Using the multi-reference configuration interaction approach, comprehensive calculations of the first 36 electronic states, corresponding to 15 dissociation limits, of dication HF are reported. Good agreements for the vertical excitation energies and dissociation limits are achieved with the available references.

Performance of a Low Energy Ion Source with Carbon Nanotube Electron Emitters under the Influence of Various Operating Gases.

Low energy ion measurements in the vicinity of a comet have provided us with important information about the planet's evolution. The calibration of instruments for thermal ions in the laboratory plays a crucial role when analysing data from in-situ measurements in space. A new low energy ion source based on carbon nanotube electron emitters was developed for calibrating the ion-mode of mass spectrometers or other ion detectors.

Design of a Compact Time-of-Flight Mass Spectrometer for Space Application.

A miniature reflectron time-of-flight mass spectrometer (TOF MS) with orthogonal extraction coupled with electron impact (EI) ionization source can be used to perform in situ gas composition analysis in a planetary environment. However, performances such as the mass resolution, sensitivity, limit of detection, mass range, and mass accuracy are often decreased because of miniaturization. Herein, a compact instrument for space applications has been developed, and its performance has been evaluated.

FOXM1/LINC00152 feedback loop regulates proliferation and apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via Wnt/β-catenin signaling pathway.

Rheumatoid arthritis (RA), a chronic systemic disease, is featured with inflammatory synovitis, which can lead to destruction on bone and cartilage and even cause disability. Emerging studies demonstrated that Fibroblast-like synoviocytes (FLS) is a vital cellular participant in RA progression. Long non-coding RNAs (lncRNAs) are also reported to participate in the pathogenesis of RA.

Residual Gas Adsorption and Desorption in the Field Emission of Titanium-Coated Carbon Nanotubes.

Titanium (Ti)-coated multiwall carbon nanotubes (CNTs) emitters based on the magnetron sputtering process are demonstrated, and the influences of modification to CNTs on the residual gas adsorption, gas desorption, and their field emission characteristic are discussed. Experimental results show that Ti nanoparticles are easily adsorbed on the surface of CNTs due to the "defects" produced by Ar irradiation pretreatment. X-ray photoelectron spectroscopy (XPS) characterization showed that Ti nanoparticles contribute to the adsorption of ambient molecules by changing the chemical bonding between C, Ti, and O.

Peniginsengins B⁻E, New Farnesylcyclohexenones from the Deep Sea-Derived Fungus sp. YPGA11.

Chemical examination of the EtOAc extract of the deep sea-derived fungus sp YPGA11 resulted in the isolation of four new farnesylcyclohexenones, peniginsengins B⁻E (⁻), and a known analog peniginsengin A (). The structures of compounds ⁻ were determined on the basis of comprehensive analyses of the nuclear magnetic resonance (NMR) and mass spectroscopy (MS) data, and the absolute configurations of , , and were determined by comparisons of experimental electronic circular dichroism (ECD) with calculated ECD spectra. Compounds ⁻, characterized by a highly oxygenated 1-methylcyclohexene unit and a (4,8)-4,8-dimethyldeca-4,8-dienoic acid side chain, are rarely found in nature.

Penicindopene A, a new indole diterpene from the deep-sea fungus sp. YPCMAC1.

A new indole diterpene, named penicindopene A (), together with seven known compounds (-), was isolated from the deep-sea fungus sp. YPCMAC1. The structure of penicindopene A was elucidated by extensive spectroscopic analyses (1 D and 2 D NMR, and HRESIMS data), in addition to the ECD calculations for the assignments of its absolute configuration.

[Poly(ADP-ribose) polymerases-1 inhibitor MRL-45696 alleviates DNA damage after myocardial ischemia-reperfusion in diabetic rats].

Objective: To study the protective effect of MRL-45696, an inhibitor of poly(ADP-ribose) polymerase-1 (PARP-1), against DNA damage after myocardial ischemia/reperfusion (I/R) in diabetic rats.

Methods: Rat models of type 2 diabetes mellitus were established by high-fat feeding and a single peritoneal dose of streptozotocin. Forty diabetic rats were randomized equally into diabetic group, sham-operated group, sham-operated group with MRL-45696 treatment, I/R injury model group and I/R injury group with MRL-45696 treatment.

Improving the sensitivity of miniature linear ion trap mass spectrometer by a DC voltage applied on the eject electrodes.

A miniaturized linear ion trap mass spectrometer with continuous atmospheric pressure interface has been built in our lab. Significant extension in mass range and reduction in power consumption have been realized by the supplemental alternating current frequency scan mode. However, relatively poor sensitivity has been witnessed, which is directly dominated by the detection efficiency of the ion detector.

Development of a low power miniature linear ion trap mass spectrometer with extended mass range.

A miniaturized ion trap mass spectrometer with continuous atmospheric pressure interface was built, which could be used in conjunction with internal ionization (in-vacuum plasma ionization) and external ionization (electrospray ionization). To improve its mass range, a supplemental AC signal frequency scan mode was performed for this miniature mass spectrometer, in which the fundamental RF signal was remained constant with an amplitude as low as several hundreds volts. Experiments showed that the upper limit of the mass range can be extended to 2500 Da for the miniature mass spectrometer developed in this work, and the power consumption can be reduced by 2/5, while maintaining good balance with performance parameters such as stability, sensitivity, and resolution.

Simulation of the influence of constant uniform magnetic field on a miniature LIT mass spectrometer.

In this paper, the effects of constant uniform magnetic fields on a miniature linear ion trap mass spectrometer with hyperbolic electrodes are simulated using SIMION 8.0 3D software. Magnetic fields in different directions have different effects on the trajectories of the trapped ions and the shape of the ion cloud.