S-acylation of p62 promotes p62 droplet recruitment into autophagosomes in mammalian autophagy.

p62 is a well-characterized autophagy receptor that recognizes and sequesters specific cargoes into autophagosomes for degradation. p62 promotes the assembly and removal of ubiquitinated proteins by forming p62-liquid droplets. However, it remains unclear how autophagosomes efficiently sequester p62 droplets. Herein, we report that p62 undergoes reversible S-acylation in multiple human-, rat-, and mouse-derived cell lines, catalyzed by zinc-finger Asp-His-His-Cys S-acyltransferase 19 (ZDHHC19) and deacylated by acyl protein thioesterase 1 (APT1). S-acylation of p62 enhances the affinity of p62 for microtubule-associated protein 1 light chain 3 (LC3)-positive membranes and promotes autophagic membrane localization of p62 droplets, thereby leading to the production of small LC3-positive p62 droplets and efficient autophagic degradation of p62-cargo complexes. Specifically, increasing p62 acylation by upregulating ZDHHC19 or by genetic knockout of APT1 accelerates p62 degradation and p62-mediated autophagic clearance of ubiquitinated proteins. Thus, the protein S-acylation-deacylation cycle regulates p62 droplet recruitment to the autophagic membrane and selective autophagic flux, thereby contributing to the control of selective autophagic clearance of ubiquitinated proteins.

Evaluation the value of H2FPEF score and HFA-PEFF step E score in the diagnosis of heart failure with preserved ejection fraction.

BACKGROUND: Clinical diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. The aim of the study is to evaluate the value of the H2FPEF score and HFA-PEFF step E score in the diagnosis of HFpEF. METHODS: 319 hospitalised patients with 'shortness of breath' or 'dyspnoea' were retrospectively collected and scored with the above two scores, respectively. They were divided into HFpEF group and non-HFpEF group in the study. RESULTS: Both the negative and positive predictive value of H2FPEF score and HFA-PEFF Step E score were 95.52%, 96.83% and 98.28%, 93.63%, respectively. However, there were 189 (59.25%) and 104 (32.60%) cases could not be diagnosed or excluded in the H2FPEF score and the HFA-PEFF step E score, respectively. CONCLUSIONS: Both scores of the H2FPEF and the HFA-PEFF step E may be used to effectively rule out or confirm HFpEF according to the score point. However, there are three fifths and one third patients in the H2FPEF score and the HFA-PEFF step E score, respectively, in the intermediate scores who are needed further invasive catheterisation or exercise stress tests.

Three novel SLC37A4 variants in glycogen storage disease type 1b and a literature review.

Glycogen storage disease type 1b (GSD1b) is a rare genetic disorder, resulting from mutations in the SLC37A4 gene located on chromosome 11q23.3. Although the SLC37A4 gene has been identified as the pathogenic gene for GSD1b, the complete variant spectrum of this gene remains to be fully elucidated. In this study, we present three patients diagnosed with GSD1b through genetic testing. We detected five variants of the SLC37A4 gene in these three patients, with three of these mutations (p. L382Pfs*15, p. G117fs*28, and p. T312Sfs*13) being novel variants not previously reported in the literature. We also present a literature review and general overview of the currently reported SLC37A4 gene variants. Our study expands the mutation spectrum of SLC37A4, which may help enable genetic testing to facilitate prompt diagnosis, appropriate intervention, and genetic counseling for affected families.

Legionella pneumophila-mediated host posttranslational modifications.

Legionella pneumophila is a Gram-negative bacterium ubiquitously present in freshwater environments and causes a serious type of pneumonia called Legionnaires' disease. During infections, L. pneumophila releases over 300 effector proteins into host cells through an Icm/Dot type IV secretion system to manipulate the host defense system for survival within the host. Notably, certain effector proteins mediate posttranslational modifications (PTMs), serving as useful approaches exploited by L. pneumophila to modify host proteins. Some effectors catalyze the addition of host protein PTMs, while others mediate the removal of PTMs from host proteins. In this review, we summarize L. pneumophila effector-mediated PTMs of host proteins, including phosphorylation, ubiquitination, glycosylation, AMPylation, phosphocholination, methylation, and ADP-ribosylation, as well as dephosphorylation, deubiquitination, deAMPylation, deADP-ribosylation, dephosphocholination, and delipidation. We describe their molecular mechanisms and biological functions in the regulation of bacterial growth and Legionella-containing vacuole biosynthesis and in the disruption of host immune and defense machinery.

Tethering ATG16L1 or LC3 induces targeted autophagic degradation of protein aggregates and mitochondria.

Proteolysis-targeting chimeras (PROTACs) based on the ubiquitin-proteasome system have made great progress in the field of drug discovery. There is mounting evidence that the accumulation of aggregation-prone proteins or malfunctioning organelles is associated with the occurrence of various age-related neurodegenerative disorders and cancers. However, PROTACs are inefficient for the degradation of such large targets due to the narrow entrance channel of the proteasome. Macroautophagy (hereafter referred to as autophagy) is known as a self-degradative process involved in the degradation of bulk cytoplasmic components or specific cargoes that are sequestered into autophagosomes. In the present study, we report the development of a generalizable strategy for the targeted degradation of large targets. Our results suggested that tethering large target models to phagophore-associated ATG16L1 or LC3 induced targeted autophagic degradation of the large target models. Furthermore, we successfully applied this autophagy-targeting degradation strategy to the targeted degradation of HTT65Q aggregates and mitochondria. Specifically, chimeras consisting of polyQ-binding peptide 1 (QBP) and ATG16L1-binding peptide (ABP) or LC3-interacting region (LIR) induced targeted autophagic degradation of pathogenic HTT65Q aggregates; and the chimeras consisting of mitochondria-targeting sequence (MTS) and ABP or LIR promoted targeted autophagic degradation of dysfunctional mitochondria, hence ameliorating mitochondrial dysfunction in a Parkinson disease cell model and protecting cells from apoptosis induced by the mitochondrial stress agent FCCP. Therefore, this study provides a new strategy for the selective proteolysis of large targets and enrich the toolkit for autophagy-targeting degradation.Abbreviations: ABP: ATG16L1-binding peptide; ATG16L1: autophagy related 16 like 1; ATTEC: autophagy-tethering compound; AUTAC: autophagy-targeting chimera; AUTOTAC: autophagy-targeting chimera; Baf A1: bafilomycin A1; BCL2: BCL2 apoptosis regulator; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CASP3: caspase 3; CPP: cell-penetrating peptide; CQ: chloroquine phosphate; DAPI: 4',6-diamidino-2-phenylindole; DCM: dichloromethane; DMF: N,N-dimethylformamide; DMSO: dimethyl sulfoxide; EBSS: Earle's balanced salt solution; FCCP: carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone; FITC: fluorescein-5-isothiocyanate; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; HEK293: human embryonic kidney 293; HEK293T: human embryonic kidney 293T; HPLC: high-performance liquid chromatography; HRP: horseradish peroxidase; HTT: huntingtin; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MFF: mitochondrial fission factor; MTS: mitochondria-targeting sequence; NBR1: NBR1 autophagy cargo receptor; NLRX1: NLR family member X1; OPTN: optineurin; P2A: self-cleaving 2A peptide; PB1: Phox and Bem1p; PBS: phosphate-buffered saline; PE: phosphatidylethanolamine; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; PROTACs: proteolysis-targeting chimeras; QBP: polyQ-binding peptide 1; SBP: streptavidin-binding peptide; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SPATA33: spermatogenesis associated 33; TIMM23: translocase of inner mitochondrial membrane 23; TMEM59: transmembrane protein 59; TOMM20: translocase of outer mitochondrial membrane 20; UBA: ubiquitin-associated; WT: wild type.

Nondestructive Monitoring Hydration of Belite Calcium Sulfoaluminate Cement by EIS Measurement.

In this study, the impact of water-to-cement (w/c) ratios of belite calcium sulfoaluminate cement (BCSA) on the hydration kinetics and the electrochemical impedance spectroscopy (EIS) parameters is studied. According to the analysis of classic hydration measurements, such as calorimetry tests, chemical shrinkage content, and chemically bound water content, it can be concluded that a higher w/c ratio clearly accelerates the hydration of BCSA cement paste. The electrical resistivity of BCSA0.35 cement paste is more than 4.5 times that of BCSA0.45 and BCSA0.5, due to the gradually densified micropore structure blocking the electrical signal transmission rather than the free charged-ion content. The porosity of BCSA0.5 is 27.5% higher than that of BCSA0.35 and 7.8% higher than that of BCSA0.45, which proves the resistivity is clearly related to the variation in microstructure, especially for the porosity and pore size distribution. The novelty of this study is the linear regression with logarithm terms of electrical resistivity and classic hydration parameters such as chemical shrinkage, cumulative hydration heat, and chemically bound water is established to extend the classical expression of cement hydration degree. It indicates that the electrochemical impedance spectroscopy can be taken as a nondestructive testing measurement to real-time monitor the cement hydration process of cement-based materials.

Variation of Volatile Compounds and Corresponding Aroma Profiles in Chinese Steamed Bread by Various Yeast Species Fermented at Different Times.

To control the fermentation process of yeast-Chinese steamed bread (CSB), the volatile compounds and odor profiles of yeast-CSBs during fermentation were comprehensively investigated by sensory evaluation, gas chromatography-mass spectrometry, gas chromatography-olfactometry (GC-O), and odor activity value (OAV). Eight sensory attributes were established, and quantitative descriptive analysis results showed that CF1303-CSB had intense sweet and sweet aftertaste attributes, CF1318-CSB was characterized by milky, wheaty, and yeasty attributes, while CL10138-CSB presented distinct sour, winy, and floury attributes. A total of 41 key aroma-active compounds were detected, and phenylethyl alcohol was the most potent aroma compound with a flavor dilution (FD) of 1024. CF1303-CSB, CF1318-CSB, and CL10138-CSB contained 24, 22, and 21 key aroma compounds, respectively, based on the OAV. These key aroma compounds can be used as the potential markers to monitor the yeast-CSBs during the fermentation process. Five compounds, including ß-myrcene, 2-phenoxyethanol, methyl cinnamate, guaiacol, and o-cresol, were first identified in CSB. These results provide theoretical basis for processing and quality control of yeast-CSBs.

Landscape of Peripheral Blood Mononuclear Cells and Soluble Factors in Severe COVID-19 Patients With Pulmonary Fibrosis Development.

Resulting from severe inflammation and cell destruction, COVID-19 patients could develop pulmonary fibrosis (PF), which remains in the convalescent stage. Nevertheless, how immune response participates in the pathogenesis of PF progression is not well defined. To investigate that question, 12 patients with severe COVID-19 were included in the study. Peripheral mononuclear cell (PBMC) samples were collected shortly after their admission and proceeded for single-cell RNA sequencing (scRNA-seq). After 14 days of discharge, the patients were revisited for chest CT scan. PF index (FI) was computed by AI-assisted CT images. Patients were categorized into FIhi and FIlo based on median of FI. By scRNA-seq analysis, our data demonstrated that frequency of CD4+ activated T cells and Treg cells were approximately 3-fold higher in FIhi patients compared with FIlo ones (p < 0.034 for all). By dissecting the differentially expressed genes, we found an overall downregulation of IFN-responsive genes (STAT1, IRF7, ISG15, ISG20, IFIs, and IFITMs) and S100s alarmins (S100A8, S100A9, S100A12, etc.) in all T-cell clusters, and cytotoxicity-related genes (GZMB, PRF1, and GNLY) in CTLs and γδ T cells in the FIhi cohort, compared with FIlo subjects. The GSEA analysis illustrated decreased expression of genes enriched in IFN signaling, innate immune response, adaptive immune response in T cells, NK cells, and monocytes in FIhi patients compared with FIlo ones. In conclusion, these data indicated that the attenuated IFN-responsive genes and their related signaling pathways could be critical for PF progression in COVID-19 patients.

Characterization of Aroma-Active Compounds in Four Yeast Extracts Using Instrumental and Sensory Techniques.

Gas chromatography-olfactometry coupled with sensory analysis and partial least-squares regression (PLSR) analysis led to the identification of the odorants responsible for the different flavors of four yeast extracts. Sensory analysis showed that LA00L had an intense sulfurous attribute, and LA00 was characterized by fatty and green notes, FA31 exhibited the floral odor, while KA02 had strong phenolic, animal, fermented, roasted, and caramellic notes. A total of 37 key aroma compounds with odor activity values greater than 1 were determined. 2,4-Di-tert-butylphenol and methional were the most potent aroma compounds. In addition, the key aroma compounds in LA00L were nonanal, dimethyl disulfide, and γ-decalactone. Octanal, dimethyl disulfide, and benzeneacetaldehyde were the key aroma compounds in LA00. In FA31, styrene, benzeneacetaldehyde, and acetophenone were the key aroma compounds, while indole, 2-methoxyphenol, benzeneacetaldehyde, and p-cresol contributed significantly to the aroma of KA02. PLSR showed that p-cresol and indole were significantly responsible for the phenolic and animal notes inducing the off-flavor (yeasty odor) of yeasty extracts. More significantly, indole was first reported to have an important effect on yeasty odor.

Correction: Core-shell Zn2GeO4 nanorods and their size-dependent photoluminescence properties.

Correction for 'Core-shell Zn2GeO4 nanorods and their size-dependent photoluminescence properties' by Songping Wu et al., Nanoscale, 2013, 5, 12335-12341.

CuGeO3 nanowires covered with graphene as anode materials of lithium ion batteries with enhanced reversible capacity and cyclic performance.

A facile one-step route was developed to synthesize crystalline CuGeO3 nanowire/graphene composites (CGCs). Crystalline CuGeO3 nanowires were tightly covered and anchored by graphene sheets, forming a layered structure. Subsequently, CGCs were exploited as electrode materials for lithium ion batteries (LIBs). The reversible formation of Li2O buffer layer and elastic graphene sheets accommodated the volume change during the charge and discharge processes. CGC containing 37 wt% graphene exhibited a superior electrochemical performance, that is, a remarkable reversible capacity (1265 mA h g(-1) for the first cycle), an outstanding cyclic performance (853 mA h g(-1) after 50 cycles under a current density of 200 mA g(-1)), a high coulombic efficiency, and an excellent rate capability. Clearly, CGCs may stand out as a promising anode material for LIBs.

Core-shell Zn2GeO4 nanorods and their size-dependent photoluminescence properties.

Size-tunable crystalline core-crystalline shell Zn2GeO4 nanorods were synthesized via a facile hydrothermal reaction. High purity Zn2GeO4 nanorods were obtained at pH = 7. The length of Zn2GeO4 nanorods (L = 50-100 nm) can be controlled through a one-step process, while micro-sized nanorods with an aspect ratio of the length to the diameter of 10 were yielded in a two-step process. The single crystalline nature of Zn2GeO4 nanorods with a core-shell structure was verified by high resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED) measurements. The Raman study revealed that there is no oxygen defect in Zn2GeO4 nanocrystals, suggesting that photoluminescence emission of Zn2GeO4 can be attributed to the presence of the interstitial Zn defect in Zn2GeO4 nanocrystals. As the diameter of nanorods decreased, the excitation and emission peaks appeared to be redshifted due to the quantum size effect.