The mechanisms, regulations, and functions of histone lysine crotonylation.

Histone lysine crotonylation (Kcr) is a new acylation modification first discovered in 2011, which has important biological significance for gene expression, cell development, and disease treatment. In the past over ten years, numerous signs of progress have been made in the research on the biochemistry of Kcr modification, especially a series of Kcr modification-related "reader", "eraser", and "writer" enzyme systems are identified. The physiological function of crotonylation and its correlation with development, heredity, and spermatogenesis have been paid more and more attention. However, the development of disease is usually associated with abnormal Kcr modification. In this review, we summarized the identification of crotonylation modification, Kcr-related enzyme system, biological functions, and diseases caused by abnormal Kcr. This knowledge supplies a theoretical basis for further exploring the function of crotonylation in the future.

Long- versus short-duration systemic corticosteroid regimens for acute exacerbations of COPD: A systematic review and meta-analysis of randomized trials and cohort studies.

While systemic corticosteroids quicken patient recovery during acute exacerbations of COPD, they also have many adverse effects. The optimal duration of corticosteroid administration remains uncertain. We performed a systematic review and meta-analysis to compare patient outcomes between short- (≤7 days) and long- (>7 days) corticosteroid regimens in adults with acute exacerbations of COPD. MEDLINE, EMBASE, CENTRAL, and hand searches were used to identify eligible studies. Risk of bias was assessed using the Cochrane RoB 2.0 tool and ROBINS-I. Data were summarized as ORs (odds ratios) or MDs (mean differences) whenever possible and qualitatively described otherwise. A total of 11532 participants from eight RCTs and three retrospective cohort studies were included, with 1296 from seven RCTs and two cohort studies eligible for meta-analyses. Heterogeneity was present in the methodology and settings of the studies. The OR (using short duration as the treatment arm) for mortality was 0.76 (95% CI = 0.40-1.44, n = 1055). The MD for hospital length-of-stay was -0.91 days (95% CI = -1.81--0.02 days, n = 421). The OR for re-exacerbations was 1.31 (95% CI = 0.90-1.90, n = 552). The OR for hyperglycemia was 0.90 (95% CI = 0.60-1.33, n = 423). The OR for infection incidence was 0.96 (95% CI = 0.59-1.156, n = 389). The MD for one-second forced expiratory volume change was -18.40 mL (95% CI = -111.80-75.01 mL, n = 161). The RCTs generally had low or unclear risks of bias, while the cohort studies had serious or moderate risks of bias. Our meta-analyses were affected by imprecision due to insufficient data. Some heterogeneity was present in the results, suggesting population, setting, and treatment details are potential prognostic factors. Our evidence suggests that short-duration treatments are not worse than long-duration treatments in moderate/severe exacerbations and may lead to considerably better outcomes in milder exacerbations. This supports the current GOLD guidelines. Trial registration: Our protocol is registered in PROSPERO: CRD42023374410.

Isolation and Culture of Primary Cochlear Hair Cells from Neonatal Mice.

Cochlear hair cells are the sensory receptors of the auditory system. These cells are located in the organ of Corti, the sensory organ responsible for hearing, within the osseous labyrinth of the inner ear. Cochlear hair cells consist of two anatomically and functionally distinct types: outer and inner hair cells. Damage to either of them results in hearing loss. Notably, as inner hair cells cannot regenerate, and damage to them is permanent. Hence, in vitro cultivation of primary hair cells is indispensable for investigating the protective or regenerative effects of cochlear hair cells. This study aimed to discover a method for isolating and cultivating mouse hair cells. After manual removal of the cochlear lateral wall, the auditory epithelium was meticulously dissected from the cochlear modiolus under a microscope, incubated in a mixture consisting of 0.25% trypsin-EDTA for 10 min at 37 °C, and gently suspended in culture medium using a 200 µL pipette tip. The cell suspension was passed through a cell filter, the filtrate was centrifuged, and cells were cultured in 24-well plates. Hair cells were identified based on their capacity to express a mechanotransduction complex, myosin-VIIa, which is involved in motor tensions, and via selective labeling of F-actin using phalloidin. Cells reached >90% confluence after 4 d in culture. This method can enhance our understanding of the biological characteristics of in vitro cultured hair cells and demonstrate the efficiency of cochlear hair cell cultures, establishing a solid methodological foundation for further auditory research.

Fe-doping and oxygen vacancy achieved by electrochemical activation and precipitation/dissolution equilibrium in NiOOH for oxygen evolution reaction.

The poor conductivities and instabilities of accessible nickel oxyhydroxides hinder their use as oxygen evolution reaction (OER) electrocatalysts. Herein, we constructed Fe-NiOOH-OV-600, an Fe-doped nickel oxide hydroxide with abundant oxygen vacancies supported on nickel foam (NF), using a hydrothermal method and an electrochemical activation strategy involving 600 cycles of cyclic voltammetry, assisted by the precipitation/dissolution equilibrium of ferrous sulfide (FeS) in the electrolyte. This two-step method endows the catalyst with abundant Fe-containing active sites while maintaining the ordered structure of nickel oxide hydroxide (NiOOH). Characterization and density functional theory (DFT) calculations revealed that synergy between trace amounts of the Fe dopant and the oxygen vacancies not only promotes the generation of reconstructed active layers but also optimizes the electronic structure and adsorption capacity of the active sites. Consequently, the as-prepared Fe-NiOOH-OV-600 delivered large current densities of 100 and 1000 mA cm-2 for the OER at overpotentials of only 253 and 333 mV in 1 mol/L KOH. Moreover, the catalyst is stable for at least 100 h at 500 mA cm-2. This work provides insight into the design of efficient transition-metal-based electrocatalysts for the OER.

Clinical significance of anti-rheumatoid arthritis 33 antibody in patients with systemic lupus erythematosus.

Although anti-rheumatoid arthritis (RA) 33 antibodies have been reported to be present in various connective tissue diseases (CTDs), the clinical significance of anti-RA33 in CTDs is still obscure. This study was performed to explore the clinical significance of anti-RA33 in CTDs, especially systemic lupus erythematosus (SLE). A total of 565 patients with positive anti-nuclear antibodies who had been tested for anti-RA33 were included in this study and were further classified into RA33-positive and RA33-negative groups. The association between anti-RA33 and the clinical features of CTDs was examined. Receiver operating characteristic (ROC) analysis was performed to explore the diagnostic value of anti-RA33 in SLE and SLE-related organ involvement. The results showed that SLE was the most common disease in CTD patients positive for anti-RA33 (48.8%). Compared with the RA33-negative group, higher proportions of SLE-associated antibodies and SLE patients with a high disease activity as well as lower levels of serum complement components were observed in the RA33-positive group (all p < 0.05). Furthermore, CTD patients with positive anti-RA33 were more likely to suffer from mucocutaneous and hematological involvement as well as interstitial lung disease (all p < 0.05). ROC analysis revealed an area under the curve value of 0.634 (95% confidence interval: 0.587-0.681) for anti-RA33 in the diagnosis of SLE, with a specificity and sensitivity of 92.9% and 13.5%, respectively. Taken together, this study reveals a significant association between anti-RA33 and the clinical features of CTDs, especially SLE, indicating a potential clinical significance of anti-RA33 in the management of SLE.

Case Report: IgA Nephropathy in a Patient With Anti-Transcription Intermediary Factor-1γ Antibody-Positive Dermatomyositis.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis characterized by IgA deposits in the mesangial area of glomeruli. Connective tissue disorders are some of the most frequent causes of secondary IgAN. Nevertheless, IgAN rarely occurs in systemic autoimmune myopathies (SAMs). The present case study reports on a 58-year-old patient with dermatomyositis with positive anti-transcription intermediary factor (TIF)-1γ antibodies who was diagnosed with IgAN during standard immunosuppressive therapy. Moreover, we have made a systematic review regarding the association of SAMs and IgAN. To the best of the authors' knowledge, this is the first case study describing a patient with anti-TIF1γ antibody-positive dermatomyositis who developed IgAN, which demonstrates a potential relationship between anti-TIF1γ-positive dermatomyositis and IgAN. It is important for clinicians to be aware of the possibility of renal involvement in patients with SAMs, even in those with anti-TIF1γ-positive dermatomyositis.

Amorphous-crystalline cobalt phosphide hollow nanocubes induced by dual ligand environment for highly efficient hydrogen evolution.

CoP is one of the most promising catalysts for catalyzing hydrogen evolution reaction. The foremost issue is how to improve intrinsic activity by regulating electronic structure at the molecular level. Herein, utilizing selective combination of EDTA and Co2+, an amorphous-crystalline CoP with lower valence cobalt and hollow porous structure which induced by dual ligand environment is successfully synthesized via microwave heating and following phosphating process. Synthesize CoPBA from EDTA3+ and Co3+ in a ratio of 1:1 and followed by phosphating (ECP-1) exhibits excellent performance for HER in alkaline media, requiring 173 mV to achieve 10 mA cm-2. The enhanced catalytic activity may be ascribed to the amorphous-crystalline crystal structure with enlarged exposure of active sites and the hollow porous framework induced by EDTA, as well as the homogeneously distribution of (111) plane, on which the change of free energy on both Co bridge sites and P top sites is close to zero when adsorbing hydrogen. Besides, its great catalytic stability has been evaluated via 1000 cycles of CV measurement. The possible mechanism of valence state regulation of cobalt ions in CoP is discussed in detail. Furthermore, the optimal ratio of EDTA to Co2+ and different precursor states are explored reasonably.

Fe(Co)OOH Dynamically Stable Interface Based on Self-Sacrificial Reconstruction for Long-Term Electrochemical Water Oxidation.

FeOOH on the real catalytic interface for the oxygen evolution reaction (OER) is chemically unstable to dissolve in alkaline media. Herein, based on the perspective of the dynamically stable interface, we purposely design the well-dispersed nanorod arrays of CoMoO4 as a host on activated iron foam (IF) to realize the optimal redeposition of FeOOH, constructing a self-sacrificial template rich in the FeOOH surface. Notably, at long-time oxidation potential, the precatalyst FeOOH-CoMoO4 can realize MoO42- dissolution and redeposition of Co oxyhydroxides on FeOOH host simultaneously, constructing a dynamically stable Fe(Co)OOH interface. The introduction of CoOOH improves conductivity and provides synergistic effect with FeOOH to lower the energy barrier for OER and maintain long-time stability, eventually exhibiting a low overpotential of 298 mV to reach the current density of 100 mA cm-2 and high stability over 60 h. This work demonstrates the feasibility of manipulating metal dissolution-redeposition process for a dynamically stable interface.

NFATc3-dependent expression of miR-153-3p promotes mitochondrial fragmentation in cardiac hypertrophy by impairing mitofusin-1 expression.

Mitochondrial dysfunction is involved in the pathogenesis of various cardiovascular disorders. Although mitochondrial dynamics, including changes in mitochondrial fission and fusion, have been implicated in the development of cardiac hypertrophy, the underlying molecular mechanisms remain mostly unknown. Here, we show that NFATc3, miR-153-3p, and mitofusion-1 (Mfn1) constitute a signaling axis that mediates mitochondrial fragmentation and cardiomyocyte hypertrophy. Methods: Isoprenaline (ISO) was used to stimulate the hypertrophic response and mitochondrial fragmentation in cultured cardiomyocytes and in vivo. We performed immunoblotting, immunofluorescence, and quantitative real-time PCR to validate the function of Mfn1 in cardiomyocyte hypertrophy. Bioinformatic analyses, a luciferase reporter assay, and gain- and loss-of-function studies were used to demonstrate the biological function of miR-153-3p, which regulates mitochondrial fragmentation and hypertrophy by targeting Mfn1. Moreover, ChIP-qPCR and a luciferase reporter assay were performed to identify transcription factor NFATc3 as an upstream regulator to control the expression of miR-153-3p. Results: Our results show that ISO promoted mitochondrial fission and enhanced the expression of miR-153-3p in cardiomyocytes. Knockdown of miR-153-3p attenuated ISO-induced mitochondrial fission and hypertrophy in cultured primary cardiomyocytes. miR-153-3p suppression inhibited mitochondrial fragmentation in ISO-induced cardiac hypertrophy in a mouse model. We identified direct targeting of Mfn1, a key protein of the mitochondrial fusion process, by miR-153-3p. Also, miR-153-3p promoted ISO-induced mitochondrial fission by suppressing the translation of Mfn1. We further found that NFATc3 activated miR-153-3p expression. Knockdown of NFATc3 inhibited miR-153-3p expression and blocked mitochondrial fission and hypertrophic response in cardiomyocytes. Conclusions: Our data revealed a novel signaling pathway, involving NFATc3, miR-153-3p, and Mfn1, which could be a therapeutic target for the prevention and treatment of cardiac hypertrophy.

Surface construction of loose Co(OH)2 shell derived from ZIF-67 nanocube for efficient oxygen evolution.

The rational design of nanostructure is very important for improving the number and effective utilization of active sites of the electrocatalysts. Here, a core-shell nanostructure composed of ZIF-67 core and Co(OH)2 shell (ZIF-67@Co(OH)2) has been obtained by subjecting ZIF-67 nanocube to the optimal high temperature etching process. After refluxing and etching in ethanol/water mixed solution, the loose Co(OH)2 shell can be constructed based on the surface of etched ZIF nanocube, which provides the obviously abundant active cobalt sites and better contact for oxygen evolution reaction (OER). Compared to the whole hollow Co(OH)2 nanocube, the solid ZIF-67 core in ZIF-67@Co(OH)2 can be favorable for charge transfer and provide the stable structure. The synergistic effect between Co(OH)2 shell and ZIF-67 core under suitable etching regulation can realize the optimized electrocatalysis for OER. The performance measurements show that Co(OH)2-1 after refluxing 1 h demonstrates the excellent activity requiring 354 mV overpotential at the current density of 10 mA cm-2 and the good stability. The enhanced mechanism may be due to the formation of loose Co(OH)2 as shell with fully exposed active sites, as well as the synergistic effect between ZIF-67 core and Co(OH)2 shell. Therefore, the surface construction of active composites based on ZIF precursor may be a new strategy for efficient electrocatalysis for water splitting.

N-Doped Sandwich-Structured Mo2C@C@Pt Interface with Ultralow Pt Loading for pH-Universal Hydrogen Evolution Reaction.

Designing a unique electrochemical interface to exhibit Pt-like activity and good stability is indispensable for the efficient hydrogen evolution reaction (HER). Herein, we synthesize well-defined Mo2C@NC@Pt nanospheres with a sandwich-structured interface through a facile organic-inorganic pyrolysis and following reduction process. The obtained Mo2C@NC@Pt heterostructures with ultralow Pt loading are composed of well-dispersed Mo2C nanoparticles (NPs) inner layer, N-doped carbon layer, and ultrafine Pt NPs outer layer. Electrochemical measurements demonstrate that Mo2C@NC@Pt heterostructures not only exhibit superior HER activities than commercial Pt/C with small overpotentials of only 27, 47, and 25 mV to achieve a current density of 10 mA cm-2 in acidic, alkaline, and neutral media, respectively, but also possess favorable long-term stability in pH-universal solution. The improved reaction kinetics of Mo2C@NC@Pt heterostructures are mainly attributed to the unique sandwich-structured interface with well-defined Mo2C NPs encapsulated by carbon layers and Pt NPs well-dispersed on the carbon support, synergistic effects among Mo2C NPs, NC, and Pt NPs, high specific surface area, and N-doping into the catalysts. This facile approach not only provides a new pathway for preparing well-defined carbides but also gives insight into the development of low-Pt catalysts for the efficient HER.