enhancing-density-maps-removing-majority-particles-single-particle

Enhancing Density Maps by Removing the Majority of Particles in Single Particle Cryogenic Electron Microscopy Final Stacks

Over the past decade, advancements in technology and methodology within the field of cryogenic electron microscopy (cryo-EM) single-particle analysis ...

Tsinghua University

Genistein and daidzein are two major isoflavonoids in dietary soybean that have inhibition effect on the cell growth of different tumor cell lines. We previously reported the anti-tumor activities of genistein and daidzein in human co1on tumor (HCT) cells and their different ability to enhance the activation of murine lymphocytes. In the present study, the effect of genistein and daidzein on the cell growth, cell cycle progression, and differentiation of murine K1735M2 and human WM451 cel1s was investigated. It was found that genistein could inhibit the cell growth of two metastatic melanoma cell lines, murine Kl735M2 and human WM45l in a dose-dependent manner. Flow cytometry showed that genistein could cause arrest of both Kl735M2 and WM45l at G(2)/M phase, while daidzein increased the cell numbers at S phase, decreased the cell numbers at G(1) phase. Detection of melanin and morphological observation showed that genistein can induce Kl735M2 and WM45l to produce dendrite-like structure and produce more melanin by 80%. In contrast, daidzein only retarded the growth of K1735M2 and did not induce differentiation in either K1735M2 or WM451. These results suggest that genistein and daidzein in soybean can inhibit certain malignant phenotype of melanoma via different mechanisms and be potential medical candidates for melanoma cancer therapy.

Effects of genistein and daidzein on the cell growth, cell cycle, and differentiation of human and murine melanoma cells(1).

Type 2 diabetes (T2D) is a risk factor for dysregulation of glomerular filtration rate (GFR) and albuminuria. However, whether the association is causal remains unestablished.

Type 2 Diabetes, Diabetes Genetic Score and Risk of Decreased Renal Function and Albuminuria: A Mendelian Randomization Study.

This study aimed to determine whether community-acquired pneumonia (CAP) had a metabolic profile and whether this profile can be used for disease severity assessment.

Metabolic profiles in community-acquired pneumonia: developing assessment tools for disease severity.

A( syn)-T and G( syn)-C Hoogsteen base pairs in protein-bound DNA duplexes can be difficult to resolve by X-ray crystallography due to ambiguous electron density and by nuclear magnetic resonance (NMR) spectroscopy due to poor chemical shift dispersion and size limitations with solution-state NMR spectroscopy. Here we describe an NMR strategy for characterizing Hoogsteen base pairs in protein-DNA complexes, which relies on site-specifically incorporating C- and N-labeled nucleotides into DNA duplexes for unambiguous resonance assignment and to improve spectral resolution. The approach was used to resolve the conformation of an A-T base pair in a crystal structure of an ∼43 kDa complex between a 34 bp duplex DNA and the integration host factor (IHF) protein. In the crystal structure (Protein Data Bank entry 1IHF ), this base pair adopts an unusual Hoogsteen conformation with a distorted sugar backbone that is accommodated by a nearby nick used to aid in crystallization. The NMR chemical shifts and interproton nuclear Overhauser effects indicate that this base pair predominantly adopts a Watson-Crick conformation in the intact DNA-IHF complex under solution conditions. Consistent with these NMR findings, substitution of 7-deazaadenine at this base pair resulted in only a small (∼2-fold) decrease in the IHF-DNA binding affinity. The NMR strategy provides a new approach for resolving crystallographic ambiguity and more generally for studying the structure and dynamics of protein-DNA complexes in solution.

Characterizing Watson-Crick versus Hoogsteen Base Pairing in a DNA-Protein Complex Using Nuclear Magnetic Resonance and Site-Specifically C- and N-Labeled DNA.

Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Antibiotics are losing their effectiveness due to the emerging infectious diseases, the scarcity of novel antibiotics, and the contributions of antibiotic misuse and overuse to resistance. Characterization of the lipidomic response to pneumonia and exploring the "lipidomic phenotype" can provide new insight into the underlying mechanisms of pathogenesis and potential avenues for diagnostic and therapeutic treatments.

Inflammatory responses relate to distinct bronchoalveolar lavage lipidome in community-acquired pneumonia patients: a pilot study.

Prognostic biomarkers help triage initial patients and inform targeted therapy selection. Here, we explored the role of progranulin (PGRN)-implicated in processes ranging from inflammation to neurodegeneration-in patients with community-acquired pneumonia (CAP).

Elevated progranulin as a novel biomarker to predict poor prognosis in community-acquired pneumonia.

Quantum error correction is an essential ingredient for universal quantum computing. Despite tremendous experimental efforts in the study of quantum error correction, to date, there has been no demonstration in the realisation of universal quantum error-correcting code, with the subsequent verification of all key features including the identification of an arbitrary physical error, the capability for transversal manipulation of the logical state and state decoding. To address this challenge, we experimentally realise the [5, 1, 3] code, the so-called smallest perfect code that permits corrections of generic single-qubit errors. In the experiment, having optimised the encoding circuit, we employ an array of superconducting qubits to realise the [5, 1, 3] code for several typical logical states including the magic state, an indispensable resource for realising non-Clifford gates. The encoded states are prepared with an average fidelity of [Formula: see text] while with a high fidelity of [Formula: see text] in the code space. Then, the arbitrary single-qubit errors introduced manually are identified by measuring the stabilisers. We further implement logical Pauli operations with a fidelity of [Formula: see text] within the code space. Finally, we realise the decoding circuit and recover the input state with an overall fidelity of [Formula: see text], in total with 92 gates. Our work demonstrates each key aspect of the [5, 1, 3] code and verifies the viability of experimental realisation of quantum error-correcting codes with superconducting qubits.

Experimental exploration of five-qubit quantum error-correcting code with superconducting qubits.

Community-acquired pneumonia (CAP) is a respiratory disease that frequently requires hospital admission, and is a significant cause of death worldwide. Plasma fetuin-A levels were significantly lower in patients with sepsis, but data regarding CAP are scarce. This study aimed to evaluate the usefulness of fetuin-A as a prognostic biomarker of CAP.

Decreased plasma fetuin-A level as a novel bioindicator of poor prognosis in community-acquired pneumonia: A multi-center cohort study.

Neonatal heart undergoes metabolic conversion and cell cycle arrest preparing for the increased workload during adulthood. Herein, we report that neonatal ketone body elevation is a critical regulatory factor for postnatal heart development. Through multiomics screening, we found that the expression of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), the rate-limiting enzyme of ketogenesis, was transiently induced by colostrum in the neonatal heart. Hmgcs2 knockout caused mitochondrial maturation defects. Meanwhile, postnatal heart development was compromised and cardiomyocytes reacquired proliferation capacity in Hmgcs2 knockout mice. Consequently, over 40% of newborn Hmgcs2 knockout mice died before weaning. The heart function of surviving Hmgcs2 knockout mice was also impaired, which could be rescued by ketone body supplementation during the suckling stage. Mechanistically, ketone body deficiency inhibited β-hydroxybutyrylation but enhanced acetylation of mitochondrial proteins, which might be responsible for the inhibition of the enzyme activity in mitochondria. These observations suggest that ketone body is critical for postnatal heart development through regulating mitochondrial maturation and metabolic reprogramming.

Neonatal ketone body elevation regulates postnatal heart development by promoting cardiomyocyte mitochondrial maturation and metabolic reprogramming.

Hepatocellular carcinoma (HCC) is one of the most invasive cancers with a low 5-year survival rate. Pyroptosis, a specialized form of cell death, has shown its association with cancer progression. However, its role in the prognosis of HCC has not been fully understood.

Article	Year
Effects of genistein and daidzein on the cell growth, cell cycle, and differentiation of human and murine melanoma cells(1). The Journal of nutritional biochemistry\| PubMed ID: 12121829	2002
Type 2 Diabetes, Diabetes Genetic Score and Risk of Decreased Renal Function and Albuminuria: A Mendelian Randomization Study. EBioMedicine\| PubMed ID: 27211558	2016
Metabolic profiles in community-acquired pneumonia: developing assessment tools for disease severity. Critical care (London, England)\| PubMed ID: 29759075	2018
Characterizing Watson-Crick versus Hoogsteen Base Pairing in a DNA-Protein Complex Using Nuclear Magnetic Resonance and Site-Specifically C- and N-Labeled DNA. Biochemistry\| PubMed ID: 30950607	2019
Inflammatory responses relate to distinct bronchoalveolar lavage lipidome in community-acquired pneumonia patients: a pilot study. Respiratory research\| PubMed ID: 31046764	2019
Elevated progranulin as a novel biomarker to predict poor prognosis in community-acquired pneumonia. The Journal of infection\| PubMed ID: 31837341	2020
Experimental exploration of five-qubit quantum error-correcting code with superconducting qubits. National science review\| PubMed ID: 35070323	2022
Decreased plasma fetuin-A level as a novel bioindicator of poor prognosis in community-acquired pneumonia: A multi-center cohort study. Frontiers in medicine\| PubMed ID: 35966877	2022
Neonatal ketone body elevation regulates postnatal heart development by promoting cardiomyocyte mitochondrial maturation and metabolic reprogramming. Cell discovery\| PubMed ID: 36220812	2022
A pyroptosis-related gene signature for prognosis prediction in hepatocellular carcinoma. Frontiers in oncology\| PubMed ID: 37051536	2023

Yu Xu

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