Multi-stage aeration regime to regulate organic conversion toward gas alleviation and humification in food waste digestate composting.

Aerobic composting has been considered as a pragmatic technique to convert food waste digestate into high-quality biofertiliser. Nevertheless, massive gaseous emission and immature product remain the primary challenges in food waste digestate composting. Thus, the performance of multi-stage aeration regimes to improve gaseous emissions and organic humification during food waste digestate composting was investigated in this study. In addition to continuous aeration with a constant intensity of 0.3 L kg·dry mass (DM)-1·min-1, two multi-stage decreased aeration regimes were designed as "0.3-0.2-0.1" and "0.3-0.1-0.1" L·kg·DM-1·min-1 from the thermophilic to cooling and then mature stages, respectively. Results showed that the decreased aeration regimes could alleviate nitrous oxide (N2O) and ammonia (NH3) emission and slightly enhance humification during composting. The alleviated N2O and NH3 emission were mainly contributed by abiotically reducing gaseous release potential as well as biotically inactivating denitrifers (Pusillimonas and Pseudidiomarina) and proliferating Atopobium to reduce nitrate availability under lower aeration supply. The "0.3-0.2-0.1 L kg·DM-1·min-1" regime exhibited a more excellent performance to alleviate N2O and NH3 emission by 27.5% and 16.3%, respectively. Moreover, the decreased aeration regimes also favored the enrichment of functional bacteria (Caldicoprobacter and Syntrophomonas) to accelerate lignocellulosic biodegradation and thus humic acid synthesis by 6.5%-11.2%. Given its better performance to improve gaseous emissions and humification, the aeration regime of "0.3-0.2-0.1 L kg·DM-1·min-1" are recommended in food waste digestate composting in practice.

Prospects of focal adhesion kinase inhibitors as a cancer therapy in preclinical and early phase study.

INTRODUCTION: FAK, a nonreceptor cytoplasmic tyrosine kinase, plays a crucial role in tumor metastasis, drug resistance, tumor stem cell maintenance, and regulation of the tumor microenvironment. FAK has emerged as a promising target for tumor therapy based on both preclinical and clinical data. AREAS COVERED: This paper aims to summarize the molecular mechanisms underlying FAK's involvement in tumorigenesis and progression. Encouraging results have emerged from ongoing clinical trials of FAK inhibitors. Additionally, we present an overview of clinical trials for FAK inhibitors, examining their potential as promising treatments. The pertinent studies gathered from databases including PubMed, ClinicalTrials.gov. EXPERT OPINION: Since the first finding in 1990s, targeting FAK has became the focus of interests in many pharmaceutical companies. Through 30 years' discovery, the industry and academy gradually realized the features of FAK target which may not be a driver gene but a solid defense system for the cancer initiation and development. Currently, the ongoing clinical regimens involving FAK inhibition are all the combination strategies in which FAK inhibitors can further strengthen the cancer cell killing effects of other testing agents. The emerging positive signal in clinical trials foresee targeting FAK as class will be an effective mean to fight against cancers.

Superconductivity in a Layered Cobalt Oxychalcogenide Na2CoSe2O with a Triangular Lattice.

Unconventional superconductivity in bulk materials under ambient pressure is extremely rare among the 3d transition metal compounds outside the layered cuprates and iron-based family. It is predominantly linked to highly anisotropic electronic properties and quasi-two-dimensional (2D) Fermi surfaces. To date, the only known example of a Co-based exotic superconductor is the hydrated layered cobaltate, NaxCoO2·yH2O, and its superconductivity is realized in the vicinity of a spin-1/2 Mott state. However, the nature of the superconductivity in these materials is still a subject of intense debate, and therefore, finding a new class of superconductors will help unravel the mysteries of their unconventional superconductivity. Here, we report the discovery of superconductivity at ∼6.3 K in our newly synthesized layered compound Na2CoSe2O, in which the edge-shared CoSe6 octahedra form [CoSe2] layers with a perfect triangular lattice of Co ions. It is the first 3d transition metal oxychalcogenide superconductor with distinct structural and chemical characteristics. Despite its relatively low TC, this material exhibits very high superconducting upper critical fields, µ0HC2(0), which far exceeds the Pauli paramagnetic limit by a factor of 3-4. First-principles calculations show that Na2CoSe2O is a rare example of a negative charge transfer superconductor. This cobalt oxychalcogenide with a geometrical frustration among Co spins shows great potential as a highly appealing candidate for the realization of unconventional and/or high-TC superconductivity beyond the well-established Cu- and Fe-based superconductor families and opens a new field in the physics and chemistry of low-dimensional superconductors.

Berberine modulates the immunometabolism and differentiation of CD4+ T cells alleviating experimental arthritis by suppression of M1-exo-miR155.

BACKGROUND: The inflammatory cascade mediated by macrophages and T cells is considered to be an important factor in promoting the progression of rheumatoid arthritis (RA). Our previous study found that berberine (BBR) can therapeutically impact adjuvant arthritis (AA) in rats through the regulation of macrophage polarization and the balance of Th17/Treg. However, whether BBR's effects on CD4+T cells response are related to its suppression of M1 macrophage still unclear. PURPOSE: The study aimed to estimate the mechanism of BBR in regulating the immunometabolism and differentiation of CD4+T cells are related to exosome derived from M1-macrophage (M1-exo). STUDY-DESIGN/METHODS: Mice model of collagen-induced arthritis (CIA) was established to investigate the antiarthritic effect of BBR was related with regulation of M1-exo to balance T cell subsets. Bioinformatics analysis using the GEO database and meta-analysis. In vitro, we established the co-culture system involving M1-exo and CD4+ T cells to examine whether BBR inhibits CD4+T cell activation and differentiation by influencing M1-exo-miR155. Exosome was characterized using transmission electron microscopy and western blot analysis, macrophage and CD4+T cell subpopulation were detected by flow cytometry. Further, the metabolic profiles of CD4+T cells were assessed by ECAR, OCR, and the level of glucose, lactate, intracellular ATP. RESULT: BBR reinstates CD4+ T cell homeostasis and reduces miR155 levels in both M1-exo and CD4+ T cells obtained from mice with CIA. In vitro, we found exosomes are indispensable for M1-CM on T lymphocyte activation and differentiation. BBR reversed M1-exo facilitating the activation and differentiation of CD4+T cells. Furthermore, BBR reversed glycolysis reprogramming of CD4+T cells induced by M1-exo, while these regulation effects were significantly weakened by miR155 mimic. CONCLUSION: The delivery of miR-155 by M1-exo contributes to CD4+ T cell immunometabolism dysfunction, a process implicated in the development of RA. The anti-arthritic effect of BBR is associated with the suppression of glycolysis and the disruption of CD4+ T cell subsets balance, achieved by reducing the transfer of M1-exo-miR155 into T cells.

Berberine ameliorates collagen-induced arthritis in mice by restoring macrophage polarization via AMPK/mTORC1 pathway switching glycolytic reprogramming.

Dysfunction of macrophage polarization majorly contributes to the progression of rheumatoid arthritis (RA). Polarization and functions of activated macrophages are closely associated with the reprogramming of intracellular metabolisms. Previously, we demonstrated that the anti-arthritis effect of berberine (BBR) in rats with adjuvant-induced arthritis (AA) may be related to AMP-activated protein kinase (AMPK) activation (a key regulator in the biological energy metabolism), and balanced macrophage polarization. However, the specific molecular mechanism of BBR in macrophage metabolism is yet to be elucidated. In this study, we clarified that BBR ameliorated articular inflammation and restored M1/M2 ratio in collagen-induced arthritis (CIA) mice in an AMPK-dependent manner. Mechanistically, BBR reversed the effects of mTORC1 agonist leucine (Leu) on regulating macrophage polarization through activation of AMPK to switch glycolytic reprogramming. Furthermore, BBR inhibition of mTORC1 rely on activation of AMPK to phosphorylate raptor and TSC2 instead of destroying its structure. Our study revealed that the activation of AMPK is required for the BBR-mediated anti-arthritis effect by downregulating mTORC1/HIF-1α and inhibiting the glycolysis in M1 macrophages.

Sodium alginate hydrogel integrated with type III collagen and mesenchymal stem cell to promote endometrium regeneration and fertility restoration.

A thinner endometrium has been linked to implantation failure, and various therapeutic strategies have been attempted to improve endometrial regeneration, including the use of mesenchymal stem cells (MSCs). However, low survival and retention rates of transplanted stem cells are main obstacles to efficient stem cell therapy in thin endometrium. Collagen type III is a key component of the extracellular matrix, plays a crucial role in promoting cell proliferation and differentiation, and has been identified as the major collagen expressed at the implantation site. Herein, composite alginate hydrogel containing recombinant type III collagen (rCo III) and umbilical cord mesenchymal stem cells are developed. rCo III serves as favorable bioactive molecule, displaying that rCo III administration promotes MSCs proliferation, stemness maintenance and migration. Moreover, rCo III administration enhances cell viability and migration of mouse endometrial stromal cells (ESCs). In a mouse model of thin endometrium, the Alg-rCo III hydrogel loaded with MSCs (MSC/Alg-rCo III) significantly induces endometrial regeneration and fertility enhancement in vivo. Further studies demonstrate that the MSC/Alg-rCo III hydrogel promoted endometrial function recovery partly by regulating mesenchymal-epithelial transition of ESCs. Taken together, the combination of Alg-rCo III hydrogel and MSCs has shown promising results in promoting endometrium regeneration and fertility restoration, and may provide new therapeutic options for endometrial disease.

Intermittent aeration to reduce gaseous emission and advance humification in food waste digestate composting: Performance and mechanisms.

This study investigated the performance and mechanisms of intermittent aeration to regulate gaseous emission and humification during food waste digestate composting. In addition to continuous aeration, three intermittent aeration regimes were conducted with the on-off interval ratio at 3:1, 2:1, and 1:1 within each 30 min, respectively. Results showed that intermittent aeration regimes reduced gaseous emission and enhanced humification during composting. In particular, intermittent aeration with the on/off ratio of 1:1 was more effective to reduce organic mineralization than other regimes, which alleviated the emission of nitrous oxide and ammonia by 63.1% and 75.7% in comparison with continuous aeration, respectively. In addition, this aeration regime also enhanced the content of humic acid by 24.1%. Further analysis demonstrated that prolonging aeration-off intervals could enrich facultative bacteria (e.g. Atopobium and Clostridium) from digestate and inhibit the proliferation of several aerobic bacteria (e.g. Caldicoprobacter and Marinimicrobium) to retard organic mineralization for humification.

A Novel apaQTL-SNP for the Modification of Non-Small-Cell Lung Cancer Susceptibility across Histological Subtypes.

Background: Alternative polyadenylation (APA) events may be modulated by single nucleotide polymorphisms (SNPs). Therefore, this study aims to evaluate the association between APA quantitative trait loci (apaQTLs)-related SNPs (apaQTL-SNPs) and non-small-cell lung cancer (NSCLC) risk. Methods: APA-related genes associated with NSCLC (LUAD and LUSC) were first identified, and the respective apaQTL-SNPs of those genes were selected. Then, a two-phase case-control study was performed to evaluate the association between candidate apaQTL-SNPs and NSCLC risk. Results: A total of 7 LUAD- and 21 LUSC-associated apaQTL-SNPs were selected. In the first phase, the apaQTL-SNP rs10138506 was significantly associated with LUAD risk (p < 0.05), whereas the other two apaQTL-SNPs (rs1130698 and rs1130719) were significantly associated with LUSC risk (p < 0.05). In the second phase, the variant G allele of rs10138506 was still significantly associated with an increased risk of LUAD (OR = 1.42, 95%CI = 1.02−1.98, p = 0.038). Functional annotation indicated that the variant G allele of rs10138506 was significantly associated with a higher PDUI value of CHURC1. Meanwhile, 3'RACE experiments verified the presence of two poly(A) sites (proximal and distal) in CHURC1, while qRT-PCR results indicated that different genotypes of rs1127968 which, in perfect LD with rs10138506, can mediate changes in the lengths of the 3'UTR of CHURC1 isoforms. Conclusion: The variant G allele of rs10138506 in CHURC1 was correlated with a longer 3'UTR of CHURC1 mRNA and an increased LUAD risk. Further studies should evaluate the interaction between rs10138506 and different 3'UTR lengths of CHURC1 that regulate LUAD development.

Immunosenescence of T cells: a key player in rheumatoid arthritis.

INTRODUCTION: The incidence of rheumatoid arthritis (RA) and its complications are expected to increase with age. Remarkably, RA patients were identified features of accelerated aging, particularly in immunosenescence. As is known, T cells in RA patients readily differentiate into pro-inflammatory phenotypes that maintain chronic and persistent inflammatory changes in joints and many other organ systems. Recent evidence suggests that T cells are most sensitive to aging, and aged CD4+ T cells contribute to inflammaging, which plays a crucial role in accelerating the disease process. In recent years, the molecular mechanisms of T cell immunosenescence were beginning to be understood. Immune aging in RA T cells is associated with thymus insufficiency, metabolic abnormalities, shortened telomere length, and chronic energy stress. Therefore, we summarized the role and mechanism of T cell immunosenescence in RA. METHODS: A computer-based online search was performed using the PubMed database for published articles concerning T cells aging and rheumatoid arthritis. RESULTS: In this review, we assess the roles of CD4+ T cells in the center of inflammaging especially in RA and emphasize arthritogenic effector functions of senescent T cell; also we discuss the possible molecular mechanisms of senescent T cells and therapeutic targets to intervene T cells immunosenescence for improvement of RA.

Emission of volatile sulphur compounds during swine manure composting: Source identification, odour mitigation and assessment.

This study aimed to identify the sources of volatile sulphur compounds (VSCs) and evaluate their mitigation by ferric oxide (Fe2O3) during swine manure composting. Four chemicals, including l-cysteine, l-methionine, sodium sulphite, and sodium sulphate, were further added to simulate organic and inorganic sulphur-containing substances in swine manure to track VSC sources during composting. Results show that sulphur simulants induced the emission of six common VSCs, including methyl sulphide (Me2S), dimethyl sulphide (Me2SS), carbonyl sulphide (COS), carbon disulphide (CS2), methyl mercaptan (MeSH), and ethyl mercaptan (EtSH), during swine manure composting. Of them, COS, CS2, MeSH and Me2SS were predominantly contributed by the biodegradation of methionine and cysteine, while Me2S and EtSH were dominated by the reduction of sulphite and sulphate. Further Fe2O3 addition at 1.5 % of total wet weight of composting materials immobilized elemental sulphur and inhibited sulphate reduction to reduce the emission of VSCs by 46.7-80.9 %. Furthermore, odour assessment indicated that adding Fe2O3 into composting piles significantly reduced the odour intensity level to below 4, the odour value of VSCs by 47.1-81.3 %, and thus the non-carcinogenic risk by 68.4 %.

An Enhanced Steganography Network for Concealing and Protecting Secret Image Data.

The development of Internet technology has provided great convenience for data transmission and sharing, but it also brings serious security problems that are related to data protection. As is detailed in this paper, an enhanced steganography network was designed to protect secret image data that contains private or confidential information; this network consists of a concealing network and a revealing network in order to achieve image embedding and recovery separately. To reduce the system's computation complexity, we constructed the network's framework using a down-up structure in order to compress the intermediate feature maps. In order to mitigate the input's information loss caused by a sequence of convolution blocks, the long skip concatenation method was designed to pass the raw information to the top layer, thus synthesizing high-quality hidden images with fine texture details. In addition, we propose a novel strategy called non-activated feature fusion (NAFF), which is designed to provide stronger supervision for synthetizing higher-quality hidden images and recovered images. In order to further boost the hidden image's visual quality and enhance its imperceptibility, an attention mechanism-based enhanced module was designed to reconstruct and enhance the salient target, thus covering up and obscuring the embedded secret content. Furthermore, a hybrid loss function that is composed of pixel domain loss and structure domain loss was designed to boost the hidden image's structural quality and visual security. Our experimental results demonstrate that, due to the elaborate design of the network structure and loss function, our proposed method achieves high levels of imperceptibility and security.

Meaningful secret image sharing for JPEG images with arbitrary quality factors.

JPEG is the most common format for storing and transmitting photographic images on social network platforms. JPEG image is widely used in people's life because of their low storage space and high visual quality. Secret image sharing (SIS) technology is important to protect image data. Traditional SIS schemes generally focus on spatial images, however there is little research on frequency domain images. In addition, the current tiny research on SIS for JPEG images only focuses on JPEG images with a compression quality factor (QF) of 100. To overcome the limitation of JPEG images in SIS, we propose a meaningful SIS for JPEG images to operate the quantized DCT coefficients of JPEG images. The random elements utilization model is applied to achieve meaningful shadow images. Our proposed scheme has a better quality of the shadow images and the recovered secret image. Experiment results and comparisons indicate the effectiveness of the scheme. The scheme can be used for JPEG images with any compression QF. Besides, the scheme has good characteristics, such as (k,n) threshold, extended shadow images.

Bacterial dynamics for gaseous emission and humification during bio-augmented composting of kitchen waste with lime addition for acidity regulation.

This study investigated the impacts of lime addition and further microbial inoculum on gaseous emission and humification during kitchen waste composting. High-throughput sequencing was integrated with Linear Discriminant Analysis Effect Size (LEfSe) and Functional Annotation of Prokaryotic Taxa (FAPROTAX) to decipher bacterial dynamics in response to different additives. Results showed that lime addition enriched bacteria, such as Taibaiella and Sphingobacterium as biomarkers, to strengthen organic biodegradation toward humification. Furthermore, lime addition facilitated the proliferation of thermophilic bacteria (e.g. Bacillus and Symbiobacterium) for aerobic chemoheterotrophy, leading to enhanced organic decomposition to trigger notable gaseous emission. Such emission profile was further exacerbated by microbial inoculum to lime-regulated condition given the rapid enrichment of bacteria (e.g. Caldicoprobacter and Pusillimonas as biomarkers) for fermentation and denitrification. In addition, microbial inoculum slightly hindered humus formation by narrowing the relative abundance of bacteria for humification. Results from this study show that microbial inoculum to feedstock should be carefully regulated to accelerate composting and avoid excessive gaseous emission.

Meaningful Secret Image Sharing with Saliency Detection.

Secret image sharing (SIS), as one of the applications of information theory in information security protection, has been widely used in many areas, such as blockchain, identity authentication and distributed cloud storage. In traditional secret image sharing schemes, noise-like shadows introduce difficulties into shadow management and increase the risk of attacks. Meaningful secret image sharing is thus proposed to solve these problems. Previous meaningful SIS schemes have employed steganography to hide shares into cover images, and their covers are always binary images. These schemes usually include pixel expansion and low visual quality shadows. To improve the shadow quality, we design a meaningful secret image sharing scheme with saliency detection. Saliency detection is used to determine the salient regions of cover images. In our proposed scheme, we improve the quality of salient regions that are sensitive to the human vision system. In this way, we obtain meaningful shadows with better visual quality. Experiment results and comparisons demonstrate the effectiveness of our proposed scheme.

Metabolite transporters as regulators of macrophage polarization.

Macrophages are myeloid immune cells, present in virtually all tissues which exhibit considerable functional plasticity and diversity. Macrophages are often subdivided into two distinct subsets described as classically activated (M1) and alternatively activated (M2) macrophages. It has recently emerged that metabolites regulate the polarization and function of macrophages by altering metabolic pathways. These metabolites often cannot freely pass the cell membrane and are therefore transported by the corresponding metabolite transporters. Here, we reviewed how glucose, glutamate, lactate, fatty acid, and amino acid transporters are involved in the regulation of macrophage polarization. Understanding the interactions among metabolites, metabolite transporters, and macrophage function under physiological and pathological conditions may provide further insights for novel drug targets for the treatment of macrophage-associated diseases. In Brief Recent studies have shown that the polarization and function of macrophages are regulated by metabolites, most of which cannot pass freely through biofilms. Therefore, metabolite transporters required for the uptake of metabolites have emerged seen as important regulators of macrophage polarization and may represent novel drug targets for the treatment of macrophage-associated diseases. Here, we summarize the role of metabolite transporters as regulators of macrophage polarization.

The glycolysis inhibitor 2-deoxyglucose ameliorates adjuvant-induced arthritis by regulating macrophage polarization in an AMPK-dependent manner.

Macrophages are highly plastic cells critical for the development of rheumatoid arthritis (RA). Macrophages exhibit a high degree of pro-inflammatory plasticity in RA, accompanied by a metabolic reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis. 2-deoxyglucose (2-DG), a glycolysis inhibitor, has previously been shown to exhibit anti-inflammatory and anti-arthritic properties. However, the specific mechanisms of inflammatory modulation by 2-DG remain unclear. This study used 2-DG to treat rats with adjuvant arthritis (AA) and investigated its specific anti-arthritic mechanisms in the murine-derived macrophage cell line RAW264.7 in vitro. 2-DG reduced the arthritis index as well as alleviated cellular infiltration, synovial hyperplasia, and bone erosion in AA rats. Moreover, 2-DG treatment modulated peritoneal macrophage polarization, increasing levels of the arginase1 (Arg1) and decreasing expression of the inducible nitric oxide synthase (iNOS). 2-DG activated AMP-activated protein kinase (AMPK) via phosphorylation and reduced activation of the nuclear factor κB (NF-κB) in peritoneal macrophages of AA rats. In vitro, we verified that 2-DG promoted macrophage transition from M1 to M2-type by upregulating the expression of p-AMPKα and suppressing NF-κB activation in LPS-stimulated RAW264.7 cells. LPS-induced macrophages exhibited a metabolic shift from glycolysis to OXPHOS following 2-DG treatment, as observed by reduced extracellular acidification rate (ECAR), lactate export, glucose consumption, as well as an elevated oxygen consumption rate (OCR) and intracellular ATP concentration. Importantly, changes in polarization and metabolism in response to 2-DG were dampened after AMPKα knockdown. These findings indicate that the anti-arthritic 2-DG effect is mediated by a modulation of macrophage polarization in an AMPK-dependent manner.

A novel regQTL-SNP and the risk of lung cancer: a multi-dimensional study.

RegQTL, a novel concept, indicates that different genotypes of some SNPs have differential effects on the expression patterns of miRNAs and their target mRNAs. We aimed to identify the association between regQTL-SNPs and lung cancer risk and to explore the underlying mechanisms. The two-stage case-control study included the first stage in a Chinese population (626 lung cancer cases and 667 healthy controls) and the second stage in a European population (18,082 lung cancer cases and 13,780 healthy controls). Functional annotations were conducted based on the GTEx and the TCGA databases. Functional experiments were performed to explore the underlying biological mechanisms in vitro and vivo. After strict screening, five candidate regQTL-SNPs (rs7110737, rs273957, rs6593210, rs3768617, and rs6836432) were selected. Among them, the variant T allele of rs3768617 in LAMC1 was found to significantly increase the risk of lung cancer (first stage: P = 0.044; second stage: P = 0.007). The eQTL analysis showed that LAMC1 expression level was significantly higher in subjects with the variant T allele of rs3768617 (P = 1.10 × 10-14). In TCGA paired database, the regQTL annotation indicated the different expression patterns between LAMC1 and miRNA-548b-3p for the distinct genotypes of rs3768617. Additionally, LAMC1 knockdown significantly inhibited malignant phenotypes in lung cancer cell lines and suppressed tumor growth. A novel regQTL-SNP, rs3768617, might affect lung cancer risk by modulating the expression patterns of miRNA-548b-3p and LAMC1. RegQTL-SNPs could provide a new perspective for evaluating the regulatory function of SNPs in lung cancer development.

Different polymorphisms in HIF-1α may exhibit different effects on cancer risk in Asians: evidence from nearly forty thousand participants.

The effect of different SNPs in HIF-1α and cancer susceptibility remain indistinct. Here, we evaluated the association between all identified SNPs (rs11549465, rs11549467 and rs2057482) in HIF-1α and the overall risk of cancer in all case-control studies published before April 2020. A total of 54 articles including 56 case-control studies were included in this analysis. We found that variant genotypes of rs11549465 and rs11549467 were associated with a significantly increased overall cancer risk. In contrast, the variant T allele of rs2057482 showed a significantly reduced risk of overall cancer. In addition, variant genotypes of the three studied SNPs exhibited a significant association with cancer risk in Asians and specific cancer types. Meanwhile, HIF-1α was significantly highly expressed in head and neck squamous cell carcinoma and pancreatic cancer tissues. More importantly, survival analysis indicated that the high expression of HIF-1α was associated with a poor survival in patients with lung cancer. These findings further provided evidence that different SNPs in HIF-1α may exhibit different effects on overall cancer risk; these effects were ethnicity and type-specific. Further studies with functional evaluations are required to confirm the biological mechanisms underlying the role of HIF-1α SNPs in cancer development and progression.

Isoniazid causes heart looping disorder in zebrafish embryos by the induction of oxidative stress.

BACKGROUND: The cardiotoxicity of isoniazid on zebrafish embryos and its underlying mechanism is unclear. METHODS: Here, we exposed zebrafish embryos at 4 h post-fertilization to different levels of isoniazid and recorded the morphology and number of malformed and dead embryos under the microscope. RESULTS: The high concentration of isoniazid group showed more malformed and dead embryos than the low concentration of isoniazid group and control group. The morphology of the heart and its alteration were visualized using transgenic zebrafish (cmlc2: GFP) and confirmed by in situ hybridization. The negative effects of isoniazid on the developing heart were characterized by lower heart rate and more heart looping disorders. Mechanistically, PCR showed decreased expression of heart-specific transcription factors when exposed to isoniazid. Oxidative stress was induced by isoniazid in cardiomyocytes, mediated by decreased activities of catalase and superoxide dismutase, which were rescued by scavengers of reactive oxygen species. CONCLUSION: In conclusion, this study demonstrated that isoniazid led to heart looping disturbance by the downregulation of cardiac-specific transcription factors and induction of cardiomyocyte apoptosis.