Anisotropic growth of gold anchors on CdSe semiconductor quantum platelets for self-assembled architectures with well-connected electronic circuits for the electrochemical detection of enrofloxacin.

Anisotropic growth of nanomaterials enables advances in building diverse and complex architectures, which exhibit unique properties and enrich the choice of nano-building modules for electrochemical sensor devices. Herein, an anisotropic growth method was proposed to anchor gold nanoparticles (AuNPs) onto both ends of quasi-two-dimensional CdSe semiconductor quantum nanoplatelets (NPLs), appearing with a monodisperse and uniform nano-dumbbell shape. Then, these AuNPs were exploited as natural anchor points and further initiated self-assembly to create complex architectures via dithiol bridges. Detailed studies illustrated that the covalent Se-Au bonds facilitate effective charge transfer in the internal metal-semiconductor (M-S) electric field. The narrowed energy gap and up-shifted highest occupied molecular orbital were favored for electron removal during the electro-oxidation process. The ultrathin CdSe NPLs supplied a large specific surface area, carrying remaining holes and abundant active sites for target electro-catalysis. As a result, using the assembled complex as the electrode matrix with well-connected electronic circuits, a reliable electrochemical sensor was achieved for enrofloxacin detection. Under the optimal conditions, the current response exhibits two linear dynamic ranges, 0.01-10.0 µM and 10.0-250 µM, and the detection limit was calculated as 0.0026 µM. This work not only opens up broad application prospects for heterogeneous M-S combinations as effective electrochemical matrixes but also develops reliable antibiotic assays for food and environmental safety.

RNA editing enzymes: structure, biological functions and applications.

With the advancement of sequencing technologies and bioinformatics, over than 170 different RNA modifications have been identified. However, only a few of these modifications can lead to base pair changes, which are called RNA editing. RNA editing is a ubiquitous modification in mammalian transcriptomes and is an important co/posttranscriptional modification that plays a crucial role in various cellular processes. There are two main types of RNA editing events: adenosine to inosine (A-to-I) editing, catalyzed by ADARs on double-stranded RNA or ADATs on tRNA, and cytosine to uridine (C-to-U) editing catalyzed by APOBECs. This article provides an overview of the structure, function, and applications of RNA editing enzymes. We discuss the structural characteristics of three RNA editing enzyme families and their catalytic mechanisms in RNA editing. We also explain the biological role of RNA editing, particularly in innate immunity, cancer biogenesis, and antiviral activity. Additionally, this article describes RNA editing tools for manipulating RNA to correct disease-causing mutations, as well as the potential applications of RNA editing enzymes in the field of biotechnology and therapy.

A new index to measure the uniformity of remolded loess.

The uniformity of remolded loess is crucial for engineering stability and in laboratory testing, as it affects physical and mechanical properties. It is important to have an index which can accurately and conveniently evaluate the uniformity of remolded loess. This study demonstrated and verified the feasibility of using hydraulic conductivity (K) as an indicator for evaluating the uniformity of remolded loess through laboratory experiments and theoretical analysis. In laboratory research, nine loess samples under different preparation conditions were meticulously prepared in duplicate, which were divided into three sets according to the whole dry density (WDD) of approximately 1.3 g/cm3, 1.4 g/cm3, and 1.5 g/cm3 respectively. For the nine duplicate samples, two procedures were performed for each of the sample. One is the uniformity analysis by cutting the soil column and weighing. The other is the hydraulic conductivity experiment. Results showed that sample uniformity is affected by sample preparation conditions, and there are differences in the uniformity of the same WDD samples. The values of K positively correlate with the degree of sample uniformity. In theoretical analysis, based on Darcy's Law and Kozeny-Carman equation, it is found K is inversely proportional to the variance ( σ 2 ) of the sample dry density. That is, K is positively proportional to the sample uniformity. Since K can be easily determined in the laboratory, the application of this new index in the field of geotechnical engineering makes it very convenient and simple to evaluate the uniformity of remolded loess.

Brain functional connectivity alterations of Wernicke's area in individuals with autism spectrum conditions in multi-frequency bands: A mega-analysis.

Characterized by severe deficits in communication, most individuals with autism spectrum conditions (ASC) experience significant language dysfunctions, thereby impacting their overall quality of life. Wernicke's area, a classical and traditional brain region associated with language processing, plays a substantial role in the manifestation of language impairments. The current study carried out a mega-analysis to attain a comprehensive understanding of the neural mechanisms underpinning ASC, particularly in the context of language processing. The study employed the Autism Brain Image Data Exchange (ABIDE) dataset, which encompasses data from 443 typically developing (TD) individuals and 362 individuals with ASC. The objective was to detect abnormal functional connectivity (FC) between Wernicke's area and other language-related functional regions, and identify frequency-specific altered FC using Wernicke's area as the seed region in ASC. The findings revealed that increased FC in individuals with ASC has frequency-specific characteristics. Further, in the conventional frequency band (0.01-0.08 Hz), individuals with ASC exhibited increased FC between Wernicke's area and the right thalamus compared with TD individuals. In the slow-5 frequency band (0.01-0.027 Hz), increased FC values were observed in the left cerebellum Crus II and the right lenticular nucleus, pallidum. These results provide novel insights into the potential neural mechanisms underlying communication deficits in ASC from the perspective of language impairments.

Selenomethionine Suppress the Progression of Poorly Differentiated Thyroid Cancer via LncRNA NONMMUT014201/miR-6963-5p/Srprb Pathway.

BACKGROUND: Poorly differentiated thyroid cancer (PDTC) is a special type of thyroid cancer that threatens the life of the patients. Unfortunately, there are no effective treatments for PDTC right now, so it is urgent to search for new efficacious drugs. This experiment was designed to elucidate the effects of selenomethionine (SeMet) on PDTC in vitro and vivo. METHODS: A xenograft animal model was used to assay the volume and weight of PDTC. LncRNA NOMMMUT014201 expression was detected by fluorescence in situ hybridization and Real-time quantitative PCR (qRT-PCR). In vitro experiments were carried on in WRO cells. The Cell Counting Kit-8 assay was performed to test the effect of SeMet on the proliferation of cells. And the migration and invasion of WRO cells by the wound-healing assay, Transwell migration and invasion assays. The cell apoptosis was measured by flow cytometry. In addition, genes related to proliferation, migration, invasion and apoptosis were detected through qRT-PCR and Western Blot. RESULTS: SeMet inhibited the proliferation, migration and invasion and promoted the apoptosis of WRO cells in a dose-dependent manner. Then vivo, SeMet significantly suppressed the volume and weight of PDTC. And SeMet downregulated the expressions of Ki67, PCNA, MMP2, MMP9 and BCL2, but upregulated that of BAX and Cleaved-Caspase 3. Moreover, SeMet upregulated the level of LncRNA NOMMMUT014201 both vivo and in vitro. In addition, repression of LncRNA NOMMMUT014201 removed the inhibition effect of SeMet on WRO cell growth significantly (p<0.05). Further investigation showed that LncRNA NOMMMUT014201 downregulated the expression of miR-6963-5p in PDTC cells, but miR-6963-5p inhibited the level of Srprb. In addition, sh-LncRNA NOMMMUT014201 enhanced the proliferation, migration and invasion but inhibited the apoptosis of WRO cells. However, inhibited miR-6963-5p or overexpressed Srprb relieved the effects of sh-LncRNA NOMMMUT014201on WRO cells. CONCLUSION: Collectively, SeMet inhibits the growth of PDTC in a dose-dependent manner through LncRNA NONMMUT014201/miR-6963-5p/Srprb signal pathway, thus suggesting that SeMet might be a potential drug for PDTC treatment.

Directed assembly of fullerenols via electrostatic and coordination interactions to fabricate diverse and water-soluble metal cation-fullerene nanocluster complexes.

Metal ion-nanocluster coordination complexes can produce a variety of functional engineered nanomaterials with promising characteristics to enable widespread applications. Herein, the visualization observation of the interactions of metal ions and fullerene derivatives, particularly anionic fullerenols (Fol), were carried out in aqueous solutions. The alkali metal salts only resulted in salting out of Fol to gain re-soluble sediments, whereas multivalent metal cations (Mn+, n = 2, 3) modulated further assembly of Fol to produce insoluble hybrids. These provide crucial insights into the directed assembly of Fol that two major forces involved in actuation are electrostatic and coordination effects. Through the precise modulation of feed ratios of Fol to Mn+, a variety of water-soluble Mn+@Fol coordination complexes were facilely prepared and subsequently characterized by various measurements. Among them, X-ray photoelectron spectra validated the coordination effects through the metal cation and oxygen binding feature. Transmission electron microscopy delivered valuable information about diverse morphologies and locally-ordered microstructures at the nanoscale. This study opens a new opportunity for developing a preparation strategy to fabricate water-soluble metal cation-fullerenol coordination complexes with various merits for potential application in biomedical fields.

Advances and opportunities in methods to study protein translation - A review.

It is generally believed that the regulation of gene expression involves protein translation occurring before RNA transcription. Therefore, it is crucial to investigate protein translation and its regulation. Recent advancements in biological sciences, particularly in the field of omics, have revolutionized protein translation research. These studies not only help characterize changes in protein translation during specific biological or pathological processes but also have significant implications in disease prevention and treatment. In this review, we summarize the latest methods in ribosome-based translation omics. We specifically focus on the application of fluorescence imaging technology and omics technology in studying overall protein translation. Additionally, we analyze the advantages, disadvantages, and application of these experimental methods, aiming to provide valuable insights and references to researchers studying translation.

Efficient and Stable Perovskite Solar Modules Enabled by Inhibited Escape of Volatile Species.

The intrinsically weak bonding structure in halide perovskite materials makes components in the thin films volatile, leading to the decomposition of halide perovskite materials. The reactions within the perovskite film are reversible provided that components do not escape the thin films. Here, a holistic approach is reported to improve the efficiency and stability of PSMs by preventing the effusion of volatile components. Specifically, a method for in situ generation of channel barrier layers for perovskite photovoltaic modules is developed. The resulting PSMs attain a certified aperture PCE of 21.37%, and possess remarkable continuous operation stability for maximum power point tracking (MPPT) of T90 > 1100 h in ambient air, and damp heat (DH) tracking of T93 > 1400 h.

Development of mitochondrial gene-editing strategies and their potential applications in mitochondrial hereditary diseases: a review.

Mitochondrial DNA (mtDNA) is a critical genome contained within the mitochondria of eukaryotic cells, with many copies present in each mitochondrion. Mutations in mtDNA often are inherited and can lead to severe health problems, including various inherited diseases and premature aging. The lack of efficient repair mechanisms and the susceptibility of mtDNA to damage exacerbate the threat to human health. Heteroplasmy, the presence of different mtDNA genotypes within a single cell, increases the complexity of these diseases and requires an effective editing method for correction. Recently, gene-editing techniques, including programmable nucleases such as restriction endonuclease, zinc finger nuclease, transcription activator-like effector nuclease, clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated 9 and base editors, have provided new tools for editing mtDNA in mammalian cells. Base editors are particularly promising because of their high efficiency and precision in correcting mtDNA mutations. In this review, we discuss the application of these techniques in mitochondrial gene editing and their limitations. We also explore the potential of base editors for mtDNA modification and discuss the opportunities and challenges associated with their application in mitochondrial gene editing. In conclusion, this review highlights the advancements, limitations and opportunities in current mitochondrial gene-editing technologies and approaches. Our insights aim to stimulate the development of new editing strategies that can ultimately alleviate the adverse effects of mitochondrial hereditary diseases.

Frequency specific alterations of the degree centrality in patients with acute basal ganglia ischemic stroke: a resting-state fMRI study.

This study intended to investigate the frequency specific brain oscillation activity in patients with acute basal ganglia ischemic stroke (BGIS) by using the degree centrality (DC) method. A total of 34 acute BGIS patients and 44 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. The DC values in three frequency bands (conventional band: 0.01-0.08 Hz, slow­4 band: 0.027-0.073 Hz, slow­5 band: 0.01-0.027 Hz) were calculated. A two-sample t-test was used to explore the between-group differences in the conventional frequency band. A two-way repeated-measures analysis of variance (ANOVA) was used to analyze the DC differences between groups (BGIS patients, HCs) and bands (slow­4, slow­5). Moreover, correlations between DC values and clinical indicators were performed. In conventional band, the DC value in the right middle temporal gyrus was decreased in BGIS patients compared with HCs. Significant differences of DC were observed between the two bands mainly in the bilateral cortical brain regions. Compared with the HCs, the BGIS patients showed increased DC in the right superior temporal gyrus and the left precuneus, but decreased mainly in the right inferior temporal gyrus, right inferior occipital gyrus, right precentral, and right supplementary motor area. Furthermore, the decreased DC in the right rolandic operculum in slow-4 band and the right superior temporal gyrus in slow-5 band were found by post hoc two-sample t-test of main effect of group. There was no significant correlation between DC values and clinical scales after Bonferroni correction. Our findings showed that the DC changes in BGIS patients were frequency specific. Functional abnormalities in local brain regions may help us to understand the underlying pathogenesis mechanism of brain functional reorganization of BGIS patients.

Integration of mRNA and miRNA analysis reveals the molecular mechanisms of sugar beet (Beta vulgaris L.) response to salt stress.

The continuous increase of saline-alkali areas worldwide has led to the emergence of saline-alkali conditions, which are the primary abiotic stress or hindering the growth of plants. Beet is among the main sources of sugar, and its yield and sugar content are notably affected by saline-alkali stress. Despite sugar beet being known as a salt-tolerant crop, there are few studies on the mechanisms underlying its salt tolerance, and previous studies have mainly delineated the crop's response to stress induced by NaCl. Recently, advancements in miRNA-mRNA network analysis have led to an increased understanding of how plants, including sugar beet, respond to stress. In this study, seedlings of beet variety "N98122" were grown in the laboratory using hydroponics culture and were exposed to salt stress at 40 days of growth. According to the phenotypic adaptation of the seedlings' leaves from a state of turgidity to wilting and then back to turgidity before and after exposure, 18 different time points were selected to collect samples for analysis. Subsequently, based on the data of real-time quantitative PCR (qRT-PCR) of salt-responsive genes, the samples collected at the 0, 2.5, 7.5, and 16 h time points were subjected to further analysis with experimental materials. Next, mRNA-seq data led to the identification of 8455 differentially expressed mRNAs (DEMs) under exposure to salt stress. In addition, miRNA-seq based investigation retrieved 3558 miRNAs under exposure to salt stress, encompassing 887 known miRNAs belonging to 783 families and 2,671 novel miRNAs. With the integrated analysis of miRNA-mRNA network, 57 miRNA-target gene pairs were obtained, consisting of 55 DEMIs and 57 DEMs. Afterwards, we determined the pivotal involvement of aldh2b7, thic, and δ-oat genes in the response of sugar beet to the effect of salt stress. Subsequently, we identified the miRNAs novel-m035-5p and novel-m0365-5p regulating the aldh gene and miRNA novel-m0979-3p regulating the thic gene. The findings of miRNA and mRNA expression were validated by qRT-PCR.

Functional changes of default mode network and structural alterations of gray matter in patients with irritable bowel syndrome: a meta-analysis of whole-brain studies.

Background: Irritable bowel syndrome (IBS) is a brain-gut disorder with high global prevalence, resulting from abnormalities in brain connectivity of the default mode network and aberrant changes in gray matter (GM). However, the findings of previous studies about IBS were divergent. Therefore, we conducted a meta-analysis to identify common functional and structural alterations in IBS patients. Methods: Altogether, we identified 12 studies involving 194 IBS patients and 230 healthy controls (HCs) from six databases using whole-brain resting state functional connectivity (rs-FC) and voxel-based morphometry. Anisotropic effect-size signed differential mapping (AES-SDM) was used to identify abnormal functional and structural changes as well as the overlap brain regions between dysconnectivity and GM alterations. Results: Findings indicated that, compared with HCs, IBS patients showed abnormal rs-FC in left inferior parietal gyrus, left lingual gyrus, right angular gyrus, right precuneus, right amygdala, right median cingulate cortex, and left hippocampus. Altered GM was detected in the fusiform gyrus, left triangular inferior frontal gyrus (IFG), right superior marginal gyrus, left anterior cingulate gyrus, left rectus, left orbital IFG, right triangular IFG, right putamen, left superior parietal gyrus and right precuneus. Besides, multimodal meta-analysis identified left middle frontal gyrus, left orbital IFG, and right putamen as the overlapped regions. Conclusion: Our results confirm that IBS patients have abnormal alterations in rs-FC and GM, and reveal brain regions with both functional and structural alterations. These results may contribute to understanding the underlying pathophysiology of IBS. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42022351342.

Advances of Electrochemical and Electrochemiluminescent Sensors Based on Covalent Organic Frameworks.

Covalent organic frameworks (COFs), a rapidly developing category of crystalline conjugated organic polymers, possess highly ordered structures, large specific surface areas, stable chemical properties, and tunable pore microenvironments. Since the first report of boroxine/boronate ester-linked COFs in 2005, COFs have rapidly gained popularity, showing important application prospects in various fields, such as sensing, catalysis, separation, and energy storage. Among them, COFs-based electrochemical (EC) sensors with upgraded analytical performance are arousing extensive interest. In this review, therefore, we summarize the basic properties and the general synthesis methods of COFs used in the field of electroanalytical chemistry, with special emphasis on their usages in the fabrication of chemical sensors, ions sensors, immunosensors, and aptasensors. Notably, the emerged COFs in the electrochemiluminescence (ECL) realm are thoroughly covered along with their preliminary applications. Additionally, final conclusions on state-of-the-art COFs are provided in terms of EC and ECL sensors, as well as challenges and prospects for extending and improving the research and applications of COFs in electroanalytical chemistry.

Optimization of the proportions of advantageous components in the hypolipidemic "bioequivalent substance system" of Jiang-Zhi-Ning and its mechanism of action.

CONTEXT: Jiang-Zhi-Ning (JZN), a traditional Chinese medicinal formula, is used to treat hyperlipidemia in clinics. OBJECTIVE: To screen the hypolipidemic "bioequivalent substance system (BSS)" of JZN and elucidate the potential hypolipidemic mechanism. MATERIALS AND METHODS: In vitro, the TG content in HepG2 cells was determined after the intervention of the combination of advantageous components (CAC) by uniform design. In vivo, hyperlipidemia models were established by Triton WR-1339 (400 mg/kg; i.p.) in male ICR mice, and corresponding treatments were administered via oral administration once. The mice were divided into 12 groups (n = 5): control, hyperlipidemic model, simvastatin (positive control, 20 mg/kg), gradient doses of JZN granules (2, 4 and 8 g/kg) and the hypolipidemic effective extraction (HEE) of JZN (120, 240 and 480 mg/kg) and CAC groups (20, 40 and 160 mg/kg). Serum TC, TG, LDL-C and HDL-C were performed after 24 h. Transcriptomics and qRT-PCR technology were used to explore the mechanism of the "BSS" of JZN. RESULTS: In vitro, the ratio of CAC was determined. CAC could reduce the TG content in HepG2 cells (77.21%). Compared with the model group, the high dose of CAC could markedly decrease the levels of TC (61.86%), TG (105.54%) and LDL-C (39.38%) and increase the level of HDL-C (232.67%). CAC was proved to be the "BSS". Transcriptomics and qRT-PCR analysis revealed CAC regulated non-alcoholic fatty liver disease, bile secretion, PPAR and adipocytokine signalling pathway. DISCUSSION AND CONCLUSIONS: These findings provided new feasible ideas and methods for the elucidation of the pharmacodynamic material basis.

Generation of a human iPSC line CIPi003-A from a patient with focal epilepsy harboring a heterozygous mutation in DEPDC5 gene.

The DEPDC5 gene (OMIM 614191) has been proven to be a frequent cause of familial and sporadic focal epilepsy. A human induced pluripotent stem cell (iPSC) line was generated from a child diagnosed with focal epilepsy, which was caused by DEDPC5 mutation. The iPSC line expresses high pluripotency markers, carries the DEDPC5 mutation, and can differentiate into three germ layers in vitro. The iPSC lines offer a promising technique for studying the pathogenesis and conducting drug screening of DEDPC5-related epilepsy.

Static and dynamic resting-state brain activity patterns of table tennis players in 7-Tesla MRI.

Table tennis involves quick and accurate motor responses during training and competition. Multiple studies have reported considerably faster visuomotor responses and expertise-related intrinsic brain activity changes among table tennis players compared with matched controls. However, the underlying neural mechanisms remain unclear. Herein, we performed static and dynamic resting-state functional magnetic resonance imaging (rs-fMRI) analyses of 20 table tennis players and 21 control subjects using 7T ultra-high field imaging. We calculated the static and dynamic amplitude of low-frequency fluctuations (ALFF) of the two groups. The results revealed that table tennis players exhibited decreased static ALFF in the left inferior temporal gyrus (lITG) compared with the control group. Voxel-wised static functional connectivity (sFC) and dynamic functional connectivity (dFC) analyses using lITG as the seed region afforded complementary and overlapping results. The table tennis players exhibited decreased sFC in the right middle temporal gyrus and left inferior parietal gyrus. Conversely, they displayed increased dFC from the lITG to prefrontal cortex, particularly the left middle frontal gyrus, left superior frontal gyrus-medial, and left superior frontal gyrus-dorsolateral. These findings suggest that table tennis players demonstrate altered visuomotor transformation and executive function pathways. Both pathways involve the lITG, which is a vital node in the ventral visual stream. These static and dynamic analyses provide complementary and overlapping results, which may help us better understand the neural mechanisms underlying the changes in intrinsic brain activity and network organization induced by long-term table tennis skill training.

A de novo heterozygous variant in ACOX1 gene cause Mitchell syndrome: the first case in China and literature review.

BACKGROUND: Mitchell syndrome (MITCH) is a rare autosomal dominant hereditary disorder, characterized by episodic demyelination, sensorimotor polyneuropathy and hearing loss. MITCH is caused by heterozygous mutation in the ACOX1 gene, which encodes straight-chain acyl-CoA oxidase, on chromosome 17q25.1.  Only 5 unrelated patients have been reported so far, and no reports from China. Here, we describe the first MITCH case in a Chinese individual. CASE PRESENTATION: A 7-year-old girl initially presented with diffuse desquamatory rash at age 3. Her clinical symptoms in order of presentation were diffuse desquamatory rash, gait instability, ptosis with photophobia, hearing loss, abdominal pain, diarrhea, nausea, and dysuria. Genetic analysis demonstrated that the patient carried a heterozygous variant c.710A>G(p.Asp237Ser) in the ACOX1 gene, which can cause MITCH symptoms. This is the first MITCH case with gastrointestinal and urinary tract symptoms. After administrating N acetylcysteine amide (NACA), some symptoms were relieved and the patient's condition improved. CONCLUSION: This is the first MITCH case in the Chinese population, and we expanded the genotype spectrum of it. The p.Asp237Ser may be a mutational hotspot in ACOX1 regardless of race. In terms of diagnosis, patients with recurrent rash, gait instability, and hearing loss with some autonomic symptoms should raise the suspicion of MITCH and proper and prompt treatment should be given.

Exercise reduces hyperlipidemia-induced cardiac damage in apolipoprotein E-deficient mice via its effects against inflammation and oxidative stress.

Cardiovascular disease is a high incidence and mortality rate disease worldwide. Exercise training has become an established evidence-based treatment strategy that is beneficial for many cardiovascular diseases. This study aimed to investigate the effects of exercise on hyperlipidemia-induced cardiac damage in apolipoprotein E-deficient (ApoE-/-) mice. Male ApoE-/- mice were randomly divided into the following four groups: normal diet (ND), normal diet + exercise training (ND + E), high-fat diet (HFD), and high-fat diet + exercise training (HFD + E). Exercise training consisted of swimming for 40 min, 5 days/week for 12 weeks. After 12 weeks, histopathological alterations in cardiac tissue and the serum were measured. Furthermore, the NOX4, NRF2, SIRT1, TGF-ß, HO-1, collagen III, Smad3, Bax, Bak, Bcl-2, Bcl-xl, IL-1ß, IL-6, and IL-18 expression levels were evaluated using immunohistochemistry and western blotting; Results: the serum levels of SIRT1, GSH-Px, and SOD were lower in ApoE-/- HFD mice compared with those in ApoE-/- HFD + E mice. Significant pathological changes were observed in the ApoE-/- HFD + E group compared with those in the ApoE-/- HFD group. Increased levels of oxidative stress, fibrosis, and apoptosis, and decreased antioxidant expression in the ApoE-/- HFD group compared with those in ApoE-/- HFD + E mice. Exercise exerts protective effects against cardiac damage caused by hyperlipidemia.

miR­124 inhibits cardiomyocyte apoptosis in myocardial ischaemia­reperfusion injury by activating mitochondrial calcium uniporter regulator 1.

Mitochondria­mediated apoptosis is the primary cause of cardiomyocyte death. Therefore, mitochondria are a key target for treating myocardial injury. Mitochondrial calcium uniporter regulator 1 (MCUR1)­mediated mitochondrial calcium homeostasis markedly promotes cell proliferation and resistance to apoptosis. However, whether MCUR1 is involved in regulation of cardiomyocyte apoptosis during myocardial ischaemia­reperfusion remains unknown. microRNA­124 (miR­124) is upregulated in cardiovascular disease, suggesting a key role for miR­124 in the cardiovascular system. Whether miR­124 affects cardiomyocyte apoptosis and myocardial infarction is not well understood. Western blot showed that miR­124 and MCUR1 were upregulated in cardiomyocyte apoptosis induced by hydrogen peroxide (H2O2). Flow cytometry assay of cell apoptosis showed that miR­124 inhibited cardiomyocyte apoptosis by activating MCUR1 following H2O2 treatment. The dual­luciferase reporter assay confirmed binding of miR­124 to MCUR1 3'­UTR and subsequent activation of MCUR1. FISH assay revealed the entry of miR­124 into the cell nucleus. Therefore, MCUR1 was identified as a novel target of miR­124, and it was shown that the miR­124­MCUR1 axis modulated cardiomyocyte apoptosis induced by H2O2 in vitro. The results indicated induced expression of miR­124 during acute myocardial infarction and its transport to the nucleus. In the nucleus, miR­124 transcriptionally activated MCUR1 by binding to its enhancers. These findings reveal a role of miR­124 as a biomarker for myocardial injury and infarction.

Molecular mechanisms of eukaryotic translation fidelity and their associations with diseases.

Converting genetic information into functional proteins is a complex, multi-step process, with each step being tightly regulated to ensure the accuracy of translation, which is critical to cellular health. In recent years, advances in modern biotechnology, especially the development of cryo-electron microscopy and single-molecule techniques, have enabled a clearer understanding of the mechanisms of protein translation fidelity. Although there are many studies on the regulation of protein translation in prokaryotes, and the basic elements of translation are highly conserved in prokaryotes and eukaryotes, there are still great differences in the specific regulatory mechanisms. This review describes how eukaryotic ribosomes and translation factors regulate protein translation and ensure translation accuracy. However, a certain frequency of translation errors does occur in translation, so we describe diseases that arise when the rate of translation errors reaches or exceeds a threshold of cellular tolerance.