Sub-bandgap photo-response of black silicon fabricated by femtosecond laser irradiation under water.

Here we propose a method to fabricate black Si without the need for any chalcogenide doping, accomplished by femtosecond (fs) laser irradiation in a liquid environment, aiming to fabricate the infrared detector and investigating their optoelectronic performance. Multi-scale laser-induced periodical surface structures (LIPSSs), containing micron sized grooves decorated with low spatial frequency ripples on the surface, can be clearly observed by SEM and 3D confocal microscope. The generated black Si demonstrates superior absorption capabilities across a broad wavelength range of 200-2500 nm, achieving an average absorptance of up to 71%. This represents a notable enhancement in comparison to untreated Si, which exhibits an average absorption rate of no more than 20% across the entire detectable spectrum. A metal-semiconductor-metal (MSM) type photodetector was fabricated based on this black Si, demonstrating remarkable optoelectronic properties, specifically, it attains a responsivity of 50.2 mA/W@10 V and an external quantum efficiency (EQE) of 4.02% at a wavelength of 1550 nm, significantly outperforming the unprocessed Si by more than five orders of magnitude. The great enhancement in infrared absorption as well as the optoelectronic performance can be ascribed to the synergistic effect of the multi-scale LIPSSs and the generated intermediate energy levels. On one hand, the multi-scale structures contribute to an anti-reflection and light trapping property; on the other hand, the defects levels generated through fs laser ablation process under water may narrow the band gap of the Si. The results therefore underscore the remarkable potential of black Si processed by fs laser under water for the application of photodetection, especially in the near-infrared band.

Platycodon grandiflorus polysaccharide inhibits the inflammatory response of 3D4/21 cells infected with PCV2.

Porcine circovirus type 2 (PCV2) infection cause multi-systemic inflammation in pigs. Platycodon grandiflorus polysaccharide (PGPSt) has been reported to have the effects of immune regulation and disease resistance. Nevertheless, the role and mechanism of PGPSt in the inflammatory response of 3D4/21 cells induced by PCV2 infection remain unclear. The present study aims to investigate effects of PGPSt on inflammatory response and its possible underlying mechanisms in vitro models. Cells were treated with PCV2 for 36 h to construct a cell inflammation model. The 3D4/21 cell lines were pretreated with or without PGPSt, and the changes of inflammation-related markers and the signaling pathway were detected by CCK-8, ELISA, qPCR and Western blot. The results showed that PGPSt was non-toxic to cells and protected PCV2-infected cells from inflammatory damage. PGPSt could significantly inhibit the high acetylation of histone H3 (AcH3) and histone H4 (AcH4), down-regulate HAT and up-regulate HDAC activity, and reduce the expression of pro-inflammatory enzymes iNOS and COX-2 proteins levels. Then the levels of IL-1ß, IL-6 and TNF-α were significantly inhibited, and the level of IL-10 was promoted. We also observed that PGPSt inhibited the phosphorylation of p65, p38 and Erk1/2, which subsequently inhibited nuclear translocation of NF-κB p65 to express pro-inflammatory factors. In conclusion, PGPSt can reduce the inflammatory response by regulating histone acetylation, reducing the release of inflammatory factors, reducing the expression of pro-inflammatory enzymes, and inhibiting the activation of NF-κB and MAPKs signaling pathways. This suggests that PGPSt had an anti-inflammatory effect on the inflammatory response caused by PCV2 infection, which provided theoretical data support for the research.

The surface morphology of Atractylodes macrocephala polysaccharide and its inhibitory effect on PCV2 replication.

BACKGROUND: Porcine infection with Porcine circovirus type 2 (PCV2) causes immunosuppression, which is easy to cause concurrent or secondary infection, making the disease complicated and difficult to treat, and causing huge economic losses to the pig industry. Total polysaccharide from the rhizoma of Atractylodes macrocephala Koidz. (PAMK) is outstanding in enhancing non-specific immunity and cellular immunity, and effectively improving the body's disease resistance, indicating its potential role in antiviral immunotherapy. RESULTS: PAMK had the characteristics of compact, polyporous and agglomerated morphology, but does not have triple helix conformation. PCV2 infection led to the increase in LC3-II, degradation of p62 and the increase of viral Cap protein expression and viral copy number. PAMK treatment significantly alleviated PCV2-induced autophagy and inhibited PCV2 replication. Moreover, PAMK treatment significantly attenuated the increase of PINK1 protein expression and the decrease of TOMM20 protein expression caused by PCV2 infection, alleviated Parkin recruitment from cytoplasm to mitochondria and intracellular reactive oxygen species accumulation, restored mitochondrial membrane charge, alleviated viral Cap protein expression. CONCLUSION: PAMK alleviates PCV2-induced mitophagy to suppress PCV2 replication by inhibiting the Pink 1/Parkin pathway. These findings may provide new insights into the prevention and treatment of PCV2. © 2023 Society of Chemical Industry.

Resolvin D1 attenuates mechanical allodynia after burn injury: Involvement of spinal glia, p38 mitogen-activated protein kinase, and brain-derived neurotrophic factor/tropomyosin-related kinase B signaling.

Resolvin D1 (RvD1) suppresses inflammatory, postoperative, and neuropathic pain. The present study assessed the roles and mechanisms of RvD1 in mechanical allodynia after burn injury. A rat model of burn injury was established for analyses, and RvD1 was injected intraperitoneally. Pain behavior and the expression levels of spinal dorsal horn Iba-1 (microglia marker), GFAP (astrocyte marker), p-p38 mitogen-activated protein kinase (MAPK), brain-derived neurotrophic factor (BDNF), and tropomyosin-related kinase B (TrkB) were detected by behavioral and immunocytochemical assays. The results showed that RvD1 attenuated mechanical allodynia after burn injury, prevented microglial and astroglial activation, and downregulated p-p38 MAPK in microglia and BDNF/TrkB following burn injury. Similarly, inhibition of p38 MAPK and BDNF/TrkB signaling attenuated mechanical allodynia after burn injury. In addition, inhibition of p38 MAPK prevented spinal microglial activation and downregulated BDNF/TrkB following burn injury. Furthermore, inhibition of BDNF/TrkB signaling prevented spinal microglial activation and downregulated p-p38 MAPK within spinal microglia. Taken together, this study demonstrated that RvD1 might attenuate mechanical allodynia after burn injury by inhibiting spinal cord glial activation, microglial p38 MAPK, and BDNF/TrkB signaling in the spinal dorsal horn.

Peptide aptamer-based time-resolved fluoroimmunoassay for CHIKV diagnosis.

BACKGROUND: Chikungunya virus (CHIKV) and Dengue virus (DENV) have similar clinical symptoms, which often induce misdiagnoses. Therefore, an antigen detection diagnostic system that can clearly identify these two viruses is desirable. METHODS: In this study, we developed a novel peptide with high affinity and specificity to CHIKV, and further constructed peptide aptamer-based TRFIA assay to efficiently detect CHIKV. Peptide aptamer B2 (ITPQSSTTEAEL) and B3 (DTQGSNWI) were obtained through computer-aided design and selected as CHIKV-specific peptide aptamers based on their high binding affinity, strong hydrogen bonding, and RMSD of molecular docking. Then, a sandwich-Time-Resolved Fluoroimmunoassay (TRFIA) was successfully constructed for the detection of the interaction between peptide aptamers and viruses. RESULTS: When using B2 as the detection element, highly specific detection of CHIKV E2 was achieved with detection limits of 8.5 ng/ml in PBS solution. Variation coefficient between inter-assay showed the disturbances received from the detection of clinical fluid specimens (including serum and urine), were also within acceptable limits. The detection limits for 10-fold dilution serum and urine were 57.8 ng/mL and 147.3 ng/mL, respectively. The fluorescent signal intensity exhibited a good linear correlation with E2 protein concentration in the range of 0-1000 ng/mL, indicating the potential for quantitative detection of E2 protein. CONCLUSIONS: These results demonstrate that the construction of peptide aptamers with high affinity and specificity provides an excellent method for rapid diagnostic element screening, and the developed peptide aptamer B2 contributed to better detection of CHIKV viral particles compared to traditional antibodies.

Highly Efficient Utilization of Ferrate(VI) Oxidation Capacity Initiated by Mn(II) for Contaminant Oxidation: Role of Manganese Species.

Manganese ion [Mn(II)] is a background constituent existing in natural waters. Herein, it was found that only 59% of bisphenol A (BPA), 47% of bisphenol F (BPF), 65% of acetaminophen (AAP), and 49% of 4-tert-butylphenol (4-tBP) were oxidized by 20 µM of Fe(VI), while 97% of BPA, 95% of BPF, 96% of AAP, and 94% of 4-tBP could be oxidized by the Fe(VI)/Mn(II) system [20 µM Fe(VI)/20 µM Mn(II)] at pH 7.0. Further investigations showed that bisphenol S (BPS) was highly reactive with reactive iron species (RFeS) but was sluggish with reactive manganese species (RMnS). By using BPS and methyl phenyl sulfoxide (PMSO) as the probe compounds, it was found that reactive iron species contributed primarily for BPA oxidation at low Mn(II)/Fe(VI) molar ratios (below 0.1), while reactive manganese species [Mn(VII)/Mn(III)] contributed increasingly for BPA oxidation with the elevation of the Mn(II)/Fe(VI) molar ratio (from 0.1 to 3.0). In the interaction of Mn(II) and Fe(VI), the transfer of oxidation capacity from Fe(VI) to Mn(III), including the formation of Mn(VII) and the inhibition of Fe(VI) self-decay, improved the amount of electron equivalents per Fe(VI) for BPA oxidation. UV-vis spectra and dominant transformation product analysis further revealed the evolution of iron and manganese species at different Mn(II)/Fe(VI) molar ratios.

Rapid Discovery of Substances with Anticancer Potential from Marine Fungi Based on a One Strain-Many Compounds Strategy and UPLC-QTOF-MS.

The secondary metabolites of marine fungi with rich chemical diversity and biological activity are an important and exciting target for natural product research. This study aimed to investigate the fungal community in Quanzhou Bay, Fujian, and identified 28 strains of marine fungi. A total of 28 strains of marine fungi were screened for small-scale fermentation by the OSMAC (One Strain-Many Compounds) strategy, and 77 EtOAc crude extracts were obtained and assayed for cancer cell inhibition rate. A total of six strains of marine fungi (P-WZ-2, P-WZ-3-2, P-WZ-4, P-WZ-5, P56, and P341) with significant changes in cancer cell inhibition induced by the OSMAC strategy were analysed by UPLC-QTOF-MS. The ACD/MS Structure ID Suite software was used to predict the possible structures with inhibitory effects on cancer cells. A total of 23 compounds were identified, of which 10 compounds have been reported to have potential anticancer activity or cytotoxicity. In this study, the OSMAC strategy was combined with an untargeted metabolomics approach based on UPLC-QTOF-MS to efficiently analyse the effect of changes in culture conditions on anticancer potentials and to rapidly find active substances that inhibit cancer cell growth.

Immune-related effects of compound astragalus polysaccharide and sulfated epimedium polysaccharide on newborn piglets.

This study aimed to evaluate the immune effects of compound astragalus polysaccharide and sulfated epimedium polysaccharide (APS-sEPS) on the peripheral blood lymphocyte and intestinal mucosa in newborn piglets. A total of 40 newborn piglets were randomly divided into four groups during a 25-day experiment, including APS-sEPS, APS, sEPS and control group. The results showed that supplementation with APS-sEPS to newborn piglets remarkably increased the physiological parameters, especially the WBC. In peripheral blood, piglets that received APS-sEPS showed the highest proliferation of T lymphocytes, the percentage of CD3 + CD4+ and CD3 + CD8+ cells were the highest on days 15 and 25 (p < 0.05). The serum concentrations of IFN-γ on days 7 and 15, and IL-4, IL-10, sIgA on days 7, 15 and 25 in APS-sEPS group were significantly higher than those in the control group (p < 0.05). Furthermore, the villus length and the ratio of villus length to crypt depth in APS-sEPS group were both significantly increased compared to that of control group (p < 0.05). In the duodenum, jejunum and illume, the concentrations of IFN-γ, IL-10, total IgG and sIgA in APS-sEPS group were all significantly higher than that in control group (p < 0.05). In intestinal mucosa, APS-sEPS significantly increased the expression of NF-κB and IRF-3 mRNA in each section of small intestine of piglets. Nevertheless, in the illume segment, the effect of APS-sEPS was more significant than that of APS and sEPS (p < 0.05). The expression of TLR4 was more significant than that of control group in duodenum only. The results from the present research provide evidence that the suckling piglets administered with APS-sEPS supplement exhibited enhanced immune function of peripheral blood lymphocyte and expression of specific antibodies, and ameliorated intestinal morphological development and increased activities of humoral immune response in the small intestine, which would be related to the activation of the TLR4-NF-κB signaling pathway and IRF3.

The Role of the Heat Shock Cognate Protein 70 Genes in Sex Determination and Differentiation of Chinese Tongue Sole (Cynoglossus semilaevis).

Fish sex determination can be affected by environmental temperature. This process relies on temperature-sensitive proteins such as heat shock proteins (HSPs). Our previous work found that heat shock cognate proteins (HSCs) may participate in high-temperature associated sex reversal of Chinese tongue sole (Cynoglossus semilaevis). However, the role of hsc genes in responding to high temperature and affecting sex determination/differentiation remains unclear. Here, by using C. semilaevis as model, we identified hsc70 and hsc70-like. hsc70 was abundant in the gonads with a testicular-higher expression at all gonadal development stages except for 6 months post fertilization (mpf). Intriguingly, hsc70-like showed higher expression in testes from 6 mpf on. Both long-term heat treatment during the temperature-sensitive sex-determining period and short-term heat stress at the end of this period caused different expression of hsc70/hsc70-like between sexes. The dual-luciferase assay results also suggested that these genes can respond to high temperature rapidly in vitro. Heat treatment of C. semilaevis testis cells overexpressed with hsc70/hsc70-like could affect the expression of sex-related genes sox9a and cyp19a1a. Our results indicated that hsc70 and hsc70-like were key regulators linking external high-temperature signals with sex differentiation in vivo and provide a new idea for understanding the mechanism by which high temperature affects sex determination/differentiation in teleosts.

Protective effects of agrimonolide on hypoxia-induced H9c2 cell injury by maintaining mitochondrial homeostasis.

Cardiomyocyte death caused by hypoxia is one of the main causes of myocardial infarction or heart failure, and mitochondria play an important role in this process. Agrimonolide (AM) is a monomeric component extracted from Agrimonia pilosa L. and has antioxidant, antitumor, and anti-inflammatory effects. This study aimed to investigate the role and mechanism of AM in improving hypoxia-induced H9c2 cell damage. The results showed that low AM concentrations promote H9c2 cell proliferation and increase cellular ATP content. Transcriptome sequencing showed that AM induces differential expression of genes in H9c2 cells. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that these genes were concentrated in mitochondrial function. Subsequent experiments confirmed that AM regulates hypoxia-induced cell cycle arrest. AM inhibited the rate of apoptosis by regulating the expression of apoptosis-related proteins, reducing the level of cleaved Caspase 3 and Bax, and increasing the level of Bcl2, thereby protecting H9c2 cells from hypoxia-induced apoptosis. AM restored the mitochondrial membrane potential, inhibited the generation of ROS, maintained the normal shape of the mitochondria, improved the level of the mitochondrial functional proteins OPA1, MFN1, MFN2, Tom20, and increased the level of ATP. In conclusion, AM protects H9c2 cells from hypoxia-induced cell damage.

The association between the prognostic nutritional index and 28-day mortality among atrial fibrillation patients in China over 80 years of age.

BACKGROUNDS AND AIMS: The most prevalent form of cardiac rhythm abnormality among older populations is atrial fibrillation (AF). The prognostic nutritional index (PNI) is a reliable predictor of mortality in various diseases. The association between the PNI and mortality among AF patients over 80 years remains uncleared. METHODS AND RESULTS: A retrospective assessment of AF cases admitted to a single cardiovascular disease unit in China between January 2015 and June 2020 was performed. The PNI at admission was defined as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). The association between PNI and cardiovascular disease (CVD)-related or all-cause mortality within 28 days was assessed via multivariable Cox regression. The analysis included 1141 patients. The CVD-related and all-cause mortality rates were 3.3% and 8.7%. Kaplan-Meier analyses revealed that cases with lower PNI tertiles exhibited higher all-cause mortality (T1: 7.6%; T2: 6.1%; T3: 2.4%, P < 0.001) or CVD mortality (T1: 6.3%; T2: 2.9%; T3: 0.8%, P < 0.001). After adjusting for potential confounders, continuous PNI was negatively related to the hazard of all-cause mortality (HR 0.92, 95% CI 0.89, 0.96) and CVD-related mortality (HR 0.90, 95% CI 0.84, 0.95). Compared to the T1 group, patients with a higher PNI exhibited a lower risk of all-cause mortality (P for trend 0.003) and CVD-related mortality (P for trend 0.005). Among most subgroups, CVD-related and all-cause mortality decreased with elevating PNI values. CONCLUSIONS: PNI is significantly negatively correlated with CVD-related and all-cause mortality among AF cases over 80 years.

Cloning of the Maternal Effector Gene org and Its Regulation by lncRNA ORG-AS in Chinese Tongue Sole (Cynoglossus semilaevis).

Maternal effector genes (MEGs) encode maternal RNA and protein, accumulating in the cytoplasm of oocytes. During oocyte development, MEGs participate in oocyte meiosis and promote oocyte development. And MEGs can also regulate maternal transcriptome stability and promote maternal-zygotic transition (MTZ) in early embryonic development. Long noncoding RNAs (lncRNAs), as new epigenetic regulators, can regulate gene expression at both the transcriptional and post-transcriptional levels through cis- or trans-regulation. The oogenesis-related gene org is a germ-cell-specific gene in fish, but the role of org in embryonic development and oogenesis has rarely been studied, and the knowledge of the lncRNA-mediated regulation of org is limited. In this study, we cloned and identified the org gene of Chinese tongue sole (Cynoglossus semilaevis), and we identified a lncRNA named lncRNA ORG-anti-sequence (ORG-AS), located at the reverse overlapping region of org. The results of qRT-PCR and FISH demonstrated that org was highly expressed during the early stages of embryonic development and oogenesis and was located in the cytoplasm of oocytes. ORG-AS was expressed at low levels in the ovary and colocalized with org in the cytoplasm of oocytes. In vitro experiments showed that overexpression of ORG-AS inhibited org expression. These results suggest that org, as a MEG in C. semilaevis, participates in the MTZ and the oogenesis. The lncRNA ORG-AS negatively regulates the gene expression of org through trans-regulation. These new findings broaden the function of MEGs in embryonic development and the oogenesis of bony fish and prove that lncRNAs are important molecular factors regulating org.

Evaluation of the differences between biofilm and planktonic Brucella abortus via metabolomics and proteomics.

This study analyzed the difference between biofilm and planktonic Brucella abortus using metabolomics and proteomics. Brucella abortus was cultured in different media to induce Brucella abortus biofilm formation and planktonic cells, followed by metabolomics and proteomics analyses for these two samples. Significant differential metabolites were identified, followed by KEGG pathway analysis. Differentially expressed proteins were identified, followed by subcellular localization, GO annotation, and KEGG pathway enrichment. Additionally, a correlation analysis of metabolomics and proteomics was performed. Metabolomics analysis showed 7682 positive and 4433 negative metabolites, including 188 positive and 117 negative significant differential metabolites. These differential metabolites were enriched in fatty acid/unsaturated fatty acid biosynthesis and linoleic acid metabolism. Proteomics analysis revealed 1759 proteins, including 486 differentially expressed proteins, which were enriched in various metabolic and degradation-related pathways. Subcellular localization showed that 74.3% of the differential proteins were cytoplasmic proteins. Correlation analysis showed that 1-palmitoyl-2-oleoyl-phosphatidylglycerol had the most significant correlations with proteins, followed by cytosine. Both metabolites correlated with the protein Q57EI7 (RbsB-1, ribose ABC transporter). One common pathway, fatty acid biosynthesis, was identified by both proteomics and metabolomics analyses that involved the metabolites, oleic acid, and protein Q57DK3 (biotin carboxylase). There were metabolomic and proteomic differences between Brucella abortus biofilm and planktonic cells, and these results provide novel insights into the biofilm-forming process of Brucella abortus.

Label-Free Probing of Molecule Binding Kinetics Using Single-Particle Interferometric Imaging.

Probing molecular interactions is critical for screening drugs, detecting pollutants, and understanding biological processes at the molecular level, but these interactions are difficult to detect, especially for small molecules. A label-free optical imaging technology that can detect molecule binding kinetics is presented, in which free-moving particles are driven into oscillations with an alternating electrical field and the interferometric scattering patterns of the particles are imaged via an optical imaging method. By tracking the charge-sensitive variations in the oscillation amplitude with sub-nanometer precision, the small molecules and metal ions binding to the surface as well as protein-protein binding kinetics were measured. The capability of the label-free measurement of molecular interactions can provide a promising platform for screening small-molecule drugs, probing conformational changes in proteins, and detecting environmental pollutants.

NAD+ administration decreases microvascular damage following cardiac ischemia/reperfusion by restoring autophagic flux.

Microvascular damage is a key pathological change in myocardial ischemia/reperfusion (I/R) injury. Using a rat model of myocardial I/R, our current study has provided the first evidence that nicotinamide adenine dinucleotide (NAD+) administration can significantly attenuate myocardial I/R-induced microvascular damage, including reduced regional blood perfusion, decreased microvessel density and integrity, and coronary microvascular endothelial cells (CMECs) injury. In studies with primary cultured CMECs under hypoxia/reoxygenation (HR) and a rat model of I/R, our results suggested that the protective effect of NAD+ on CMECs exposed to HR or I/R is at least partially mediated by the NAD+-induced restoration of autophagic flux, especially lysosomal autophagy: NAD+ treatment markedly induced transcription factor EB (TFEB) activation and attenuated lysosomal dysfunction in the I/R or HR-exposed cells. Collectively, our study has provided the first in vivo and in vitro evidence that NAD+ significantly rescued the impaired autophagic flux and cell apoptosis that was induced by I/R in rat CMECs, which is mediated in part through the action of TFEB-mediated lysosomal autophagy.

Platycodon grandifloras polysaccharides inhibit mitophagy injury induced by Cr (VI) in DF-1 cells.

This study aimed to investigate the role of Platycodon grandiflorus polysaccharide (PGPS) in chromium (VI)-induced autophagy in a chicken embryo fibroblast cell lines (DF-1 cells). DF-1 cells were exposed to Cr (VI), PGPSt, and Cr (VI) + PGPSt, and their effects on cell viability, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and autophagy-related proteins were examined. The results showed that the cell viability was reduced after Cr (VI) treatment, and 3-MA, CsA or PGPSt suppressed this decrease. Cr (VI) treatment increased the ROS levels and decreased the MMP, thereby enhancing the expression of mitochondrial autophagy marker proteins (PINK1, Parkin, and LC3-II), inhibiting mitophagy autophagy protein TOMM20 expression, and promoting the degradation of autophagy-related marker p62. These changes led to exceeding mitochondrial autophagy and cell trauma and could be mitigated by PGPSt. Overall, our research showed that Cr (VI) can induce exceeding mitochondrial autophagy in DF-1 cells, whereas PGPSt can improve Cr (VI)-induced mitochondrial autophagy by inhibiting ROS and restoring MMP.

Identification of Nanoparticles via Plasmonic Scattering Interferometry.

The development of optical imaging techniques has led to significant advancements in single-nanoparticle tracking and analysis, but these techniques are incapable of label-free selective nanoparticle recognition. A label-free plasmonic imaging technology that is able to identify different kinds of nanoparticles in water is now presented. It quantifies the plasmonic interferometric scattering patterns of nanoparticles and establishes relationships among the refractive index, particle size, and pattern both numerically and experimentally. Using this approach, metallic and metallic oxide particles with different radii were distinguished without any calibration. The ability to optically identify and size different kinds of nanoparticles can provide a promising platform for investigating nanoparticles in complex environments to facilitate nanoscience studies, such as single-nanoparticle catalysis and nanoparticle-based drug delivery.

Riboflavin attenuates myocardial injury via LSD1-mediated crosstalk between phospholipid metabolism and histone methylation in mice with experimental myocardial infarction.

The underlying mechanisms responsible for the cardioprotective effects of riboflavin remain elusive. Current study tested the hypothesis that riboflavin protects injured myocardium via epigenetic modification of LSD1. Here we showed that myocardial injury was attenuated and cardiac function was improved in riboflavin-treated mice with experimental myocardial infarction (MI), while these protective effects of riboflavin could be partly blocked by cotreatment with LSD1 inhibitor. Riboflavin also reduced apoptosis in hypoxic (1% oxygen) H9C2 cell lines. Results of ChIP-seq for H9C2 cells showed that riboflavin activated LSD1, as verified by decreased H3K4me2 levels of target genes. Subsequent LEGO bioinformatics analysis indicated that phospholipid metabolism genes Lpcat2 and Pld1 served as the potential target genes responsible for the LSD1 mediated protective effects. Overexpressions of Lpcat2 and Pld1 aggravated hypoxic injury in H9C2 cells, while these detrimental effects could be attenuated by overexpression of LSD1. We thus propose that riboflavin alleviates myocardial hypoxic/ischemic injury by activating LSD1 cellular activity and modulating the expression of phospholipid metabolism genes. LSD1-mediated crosstalk between phospholipid metabolism and histone methylation might thus be an important mechanism for the cardioprotective effects of riboflavin.

Novel idiopathic DCM-related SCN5A variants localised in DI-S4 predispose electrical disorders by reducing peak sodium current density.

BACKGROUND: Variants of SCN5A, encoding cardiac sodium channel, have been linked to the development of dilated cardiomyopathy (DCM). We aimed to explore novel SCN5A variants in patients with idiopathic DCM (iDCM) and to identify the distribute characteristics and pathological mechanisms as well as clinical phenotypes associated with the variants in patients with iDCM. METHODS: SCN5A exons sequencing was performed inpatients with iDCM (n=90) and two control cohorts (arrhythmias group, n=90, and healthy group, n=195). Clinical characteristics were compared between carriers and non-carriers. We then generated a novel heterozygous knock-in (KI) mouse by homologous recombination. Cardiac function, electrical parameters and histological characteristics were examined at basal or stimulating condition. RESULTS: We found three novel non-synonymous SCN5A variants associated with iDCM, including c.674G>A, c.677C>T, and c.4340T>A. The newly defined iDCM-related variants mainly located in the S4 segment of domain I (DI-S4). Incidence of atrioventricular block was significantly higher in mutant patients with iDCM than in non-carriers. Structural injuries were absent at both basal and stress condition in KI mice carrying c.674G>A (R225Q); however, this variant significantly prolonged PR intervals at baseline without affecting other ECG parameters, which was linked to decreased peak sodium current density in KI cardiomyocytes. Histological analysis of the atrioventricular node did not show any evidences of cell damages. CONCLUSION: Our results suggest that the iDCM-related SCN5A variants in the DI-S4 could predispose electrical disorders by reducing peak sodium current density.

Aldehyde dehydrogenase 2 deficiency negates chronic low-to-moderate alcohol consumption-induced cardioprotecion possibly via ROS-dependent apoptosis and RIP1/RIP3/MLKL-mediated necroptosis.

Previous studies evidenced the beneficial effects of low-to-moderate alcohol consumption on cardiovascular system by activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2), a key enzyme metabolizing acetaldehyde to innocuous acetic acid, in diabetic mice. It remains questionable whether people with inactive ALDH2 would also benefit from the drinking habit. Present study was therefore designed to examine the influence of ALDH2 deficiency on low-to-moderate alcohol consumption related myocardial alternations. Wildtype (WT) and ALDH2 knockout (KO) mice were exposed to low-to-moderate alcohol (EtOH) challenge for 6weeks. Cardiac function and cell death related pathways were then measured. Although EtOH exposure did not further improve cardiac function or reduce reactive oxygen species (ROS) levels in WT mice, levels of high density lipoprotein-cholesterol (HDL-c) and expression of heme oxygenase-1 (HO-1) were significantly elevated in WT-EtOH group. However, EtOH exposure in KO mice depressed cardiac function as indicated by reduced left ventricular ejection fraction (EF) and increased myocardial fibrosis deposition as well as the excessive ROS accumulation. Above changes were related to altered cell demise (apoptosis and necroptosis), as shown by upregulated expression of cleaved caspase 9, cleaved caspase 3 and RIP1/RIP3/MLKL cascade. Our results thus suggest that ALDH2 is indispensable for the favorable cardiac effect of low-to-moderate alcohol consumption and ALDH2 deficiency may lead to unexpected cardiac dysfunctions via enhancing myocardial apoptosis and necroptosis.