[Retracted] Effects of Grb2­associated binding protein 2­specific siRNA on the migration and invasion of MG­63 osteosarcoma cells.

[This retracts the article DOI: 10.3892/ol.2017.7375.].

Construction and validation of somatic mutation-derived long non-coding RNAs signatures of genomic instability to predict prognosis of hepatocellular carcinoma.

BACKGROUND: Long non-coding RNAs (LncRNAs) have been found to be a potential prognostic factor for cancers, including hepatocellular carcinoma (HCC). Some LncRNAs have been confirmed as potential indicators to quantify genomic instability (GI). Nevertheless, GI-LncRNAs remain largely unexplored. This study established a GI-derived LncRNA signature (GILncSig) that can predict the prognosis of HCC patients. AIM: To establish a GILncSig that can predict the prognosis of HCC patients. METHODS: Identification of GI-LncRNAs was conducted by combining LncRNA expression and somatic mutation profiles. The GI-LncRNAs were then analyzed for functional enrichment. The GILncSig was established in the training set by Cox regression analysis, and its predictive ability was verified in the testing set and TCGA set. In addition, we explored the effects of the GILncSig and TP53 on prognosis. RESULTS: A total of 88 GI-LncRNAs were found, and functional enrichment analysis showed that their functions were mainly involved in small molecule metabolism and GI. The GILncSig was constructed by 5 LncRNAs (miR210HG, AC016735.1, AC116351.1, AC010643.1, LUCAT1). In the training set, the prognosis of high-risk patients was significantly worse than that of low-risk patients, and similar results were verified in the testing set and TCGA set. Multivariate Cox regression analysis and stratified analysis confirmed that the GILncSig could be used as an independent prognostic factor. Receiver operating characteristic curve analysis of the GILncSig showed that the area under the curve (0.773) was higher than the two LncRNA signatures published recently. Furthermore, the GILncSig may have a better predictive performance than TP53 mutation status alone. CONCLUSION: We established a GILncSig that can predict the prognosis of HCC patients, which will help to guide prognostic evaluation and treatment decisions.

Improved Energy Storage Performance of Composite Films Based on Linear/Ferroelectric Polarization Characteristics.

The development and integration of high-performance electronic devices are critical in advancing energy storage with dielectric capacitors. Poly(vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) (PVTC), as an energy storage polymer, exhibits high-intensity polarization in low electric strength fields. However, a hysteresis effect can result in significant residual polarization, leading to a severe energy loss, which impacts the resultant energy storage density and charge/discharge efficiency. In order to modify the polarization properties of the polymer, a biaxially oriented polypropylene (BOPP) film with linear characteristics has been selected as an insulating layer and combined with the PVTC ferroelectric polarization layer to construct PVTC/BOPP bilayer films. The hetero-structure and polarization characteristics of the bilayer film have been systematically studied. Adjusting the BOPP volume content to 67% resulted in a discharge energy density of 10.1 J/cm3 and an energy storage efficiency of 80.9%. The results of this study have established the mechanism for a composite structure regulation of macroscopic energy storage performance. These findings can provide a basis for the effective application of ferroelectric polymer-based composites in dielectric energy storage.

Neutrophil Extracellular Traps Regulate Surgical Brain Injury by Activating the cGAS-STING Pathway.

Surgical brain injury (SBI), induced by neurosurgical procedures or instruments, has not attracted adequate attention. The pathophysiological process of SBI remains sparse compared to that of other central nervous system diseases thus far. Therefore, novel and effective therapies for SBI are urgently needed. In this study, we found that neutrophil extracellular traps (NETs) were present in the circulation and brain tissues of rats after SBI, which promoted neuroinflammation, cerebral edema, neuronal cell death, and aggravated neurological dysfunction. Inhibition of NETs formation by peptidylarginine deiminase (PAD) inhibitor or disruption of NETs with deoxyribonuclease I (DNase I) attenuated SBI-induced damages and improved the recovery of neurological function. We show that SBI triggered the activation of cyclic guanosine monophosphate-adenosine monophosphate synthase stimulator of interferon genes (cGAS-STING), and that inhibition of the cGAS-STING pathway could be beneficial. It is worth noting that DNase I markedly suppressed the activation of cGAS-STING, which was reversed by the cGAS product cyclic guanosine monophosphate-adenosine monophosphate (cGMP-AMP, cGAMP). Furthermore, the neuroprotective effect of DNase I in SBI was also abolished by cGAMP. NETs may participate in the pathophysiological regulation of SBI by acting through the cGAS-STING pathway. We also found that high-dose vitamin C administration could effectively inhibit the formation of NETs post-SBI. Thus, targeting NETs may provide a novel therapeutic strategy for SBI treatment, and high-dose vitamin C intervention may be a promising translational therapy with an excellent safety profile and low cost.

Taurine attenuates activation of hepatic stellate cells by inhibiting autophagy and inducing ferroptosis.

BACKGROUND: Liver fibrosis is a compensatory response during the tissue repair process in chronic liver injury, and finally leads to liver cirrhosis or even hepatocellular carcinoma. The pathogenesis of hepatic fibrosis is associated with the progressive accumulation of activated hepatic stellate cells (HSCs), which can transdifferentiate into myofibroblasts to produce an excess of the extracellular matrix (ECM). Myofibroblasts are the main source of the excessive ECM responsible for hepatic fibrosis. Therefore, activated hepatic stellate cells (aHSCs), the principal ECM producing cells in the injured liver, are a promising therapeutic target for the treatment of hepatic fibrosis. AIM: To explore the effect of taurine on aHSC proliferation and the mechanisms involved. METHODS: Human HSCs (LX-2) were randomly divided into five groups: Normal control group, platelet-derived growth factor-BB (PDGF-BB) (20 ng/mL) treated group, and low, medium, and high dosage of taurine (10 mmol/L, 50 mmol/L, and 100 mmol/L, respectively) with PDGF-BB (20 ng/mL) treated group. Cell Counting Kit-8 method was performed to evaluate the effect of taurine on the viability of aHSCs. Enzyme-linked immunosorbent assay was used to estimate the effect of taurine on the levels of reactive oxygen species (ROS), malondialdehyde, glutathione, and iron concentration. Transmission electron microscopy was applied to observe the effect of taurine on the autophagosomes and ferroptosis features in aHSCs. Quantitative real-time polymerase chain reaction and Western blot analysis were performed to detect the effect of taurine on the expression of α-SMA, Collagen I, Fibronectin 1, LC3B, ATG5, Beclin 1, PTGS2, SLC7A11, and p62. RESULTS: Taurine promoted the death of aHSCs and reduced the deposition of the ECM. Treatment with taurine could alleviate autophagy in HSCs to inhibit their activation, by decreasing autophagosome formation, downregulating LC3B and Beclin 1 protein expression, and upregulating p62 protein expression. Meanwhile, treatment with taurine triggered ferroptosis and ferritinophagy to eliminate aHSCs characterized by iron overload, lipid ROS accumulation, glutathione depletion, and lipid peroxidation. Furthermore, bioinformatics analysis demonstrated that taurine had a direct targeting effect on nuclear receptor coactivator 4, exhibiting the best average binding affinity of -20.99 kcal/mol. CONCLUSION: Taurine exerts therapeutic effects on liver fibrosis via mechanisms that involve inhibition of autophagy and trigger of ferroptosis and ferritinophagy in HSCs to eliminate aHSCs.

HyGAnno: hybrid graph neural network-based cell type annotation for single-cell ATAC sequencing data.

Reliable cell type annotations are crucial for investigating cellular heterogeneity in single-cell omics data. Although various computational approaches have been proposed for single-cell RNA sequencing (scRNA-seq) annotation, high-quality cell labels are still lacking in single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) data, because of extreme sparsity and inconsistent chromatin accessibility between datasets. Here, we present a novel automated cell annotation method that transfers cell type information from a well-labeled scRNA-seq reference to an unlabeled scATAC-seq target, via a parallel graph neural network, in a semi-supervised manner. Unlike existing methods that utilize only gene expression or gene activity features, HyGAnno leverages genome-wide accessibility peak features to facilitate the training process. In addition, HyGAnno reconstructs a reference-target cell graph to detect cells with low prediction reliability, according to their specific graph connectivity patterns. HyGAnno was assessed across various datasets, showcasing its strengths in precise cell annotation, generating interpretable cell embeddings, robustness to noisy reference data and adaptability to tumor tissues.

Construction of Hydration Layer for Proton Transport by Implanting the Hydrophilic Center Ag0 in Nickel Metal-Organic Frameworks.

The directional arrangement of H2O molecules can effectively regulate the ordered protons transfer to improve transport efficiency, which can be controlled by the interaction between materials and H2O. Herein, a strategy to build a stable hydration layer in metal-organic framework (MOF) platforms, in which hydrophilic centers that can manipulate H2O molecules are implanted into MOF cavities is presented. The rigid grid-Ni-MOF is selected as the supporting material due to the uniformly distributed cavities and rigid structures. The Ag0 possesses potential combination ability with the hydrophilic substances, so it is introduced into the MOF as hydration layer centers. Relying on the strong interaction between Ag0 and H2O, the H2O molecules can rearrange around Ag0 in the cavity, which is intuitively verified by DFT calculation and molecular dynamics simulation. The establishment of a hydration layer in Ag@Ni-MOF regulates the chemical properties of the material and gives the material excellent proton conduction performance, with a proton conductivity of 4.86 × 10-2 S cm-1.

The Value of the Prostate Health Index and Derived Indexes in the Diagnosis of Prostate Cancer with PI-RADS-3 Lesions.

INTRODUCTION: The purpose of this article was to evaluate the diagnostic value of prostate health index (PHI) and its derivatives in prostate cancer (PCa) with prostate imaging reporting and data system (PI-RADS)-3 lesions. METHODS: Patients with benign prostatic hyperplasia (BPH) (n = 155) were included in the BPH group, while all patients with PCa (n = 49) were enrolled in the PCa group. Between the groups, the serum concentrations of total prostate-specific antigen (TPSA), percent-free prostate-specific antigen (%fPSA), prostate health index (PHI), prostate health index density (PHID), and prostate-specific antigen density (PSAD) were compared. RESULTS: On average, 49 (24%) of 204 men had PCa on biopsy, with 81.63% of those cases being clinically serious. Age, prostate volume, TPSA, and PSAD did not significantly differ between the PCa group and the BPH group. In contrast, [-2]pro prostate-specific antigen (p2PSA) (17.10 ± 4.77 vs. 13.93 ± 3.22, p < 0.001), PHI (33.88 ± 8.81 vs. 25.83 ± 5.63, p < 0.001), and PHID (0.52 ± 0.15 vs. 0.38 ± 0.11, p < 0.001) showed a statistically significant difference between the two groups. Compared to conventional PSA, PHI (AUC = 0.786, 95% CI: 0.705-0.867) and PHID (AUC = 0.763, 95% CI: 0.684-0.843) were considerably better predictors of all PCa. The TPSA, %fPSA, p2PSA, PHI, PHID, and PSAD areas under the receiver operating characteristic for clinically significant PCa (csPCa) were 0.587, 0.650, 0.696, 0.823, 0.796, and 0.614, respectively. Out of all the various parameters, PHI and PHID performed very well in this cohort's biopsy outcome prediction. CONCLUSION: PHI offers the best diagnostic value for detecting PCa in cases of PI-RADS-3 lesions. Additionally, PHID raised the possibility of csPCa PI-RADS-3 lesions. However, more investigation is required to confirm our results by using multicenter collaboration.

DNA methylation-regulated LINC02587 inhibits ferroptosis and promotes the progression of glioma cells through the CoQ-FSP1 pathway.

BACKGROUND: Long noncoding RNAs (lncRNAs) are considered key players in the formation and development of tumors. Herein, Gene Expression Profiling Interactive Analysis (GEPIA) was employed as a bioinformatics technology. LINC02587 is differentially expressed in bladder urothelial cancer, glioblastoma, lung adenocarcinoma, lung SCC, melanoma, and other tumor tissue and cells. However, its impact on the emergence of glioma and its mechanism is remaining elusive. METHODS: Some of the in vitro assays employed in this study were the CCK-8 / Annexin-V / Transwell assays, colony formation, and wound healing, together with Western blot (WB) evaluation. MSP / BSP assays were employed for assessing the CpG island's methylation status in the LINC02587 promoter. Through transcriptome, ferroptosis-related experiments, and WB evaluation, it was confirmed that LINC02587 is correlated with the regulation of ferroptosis in tumor cells, and CoQ-Fsp1 is one of its regulatory pathways. Moreover, the underlined in-vitro results were further validated by in-vivo studies. RESULTS: The current study shows that the promoter sequence of LINC02587 is regulated by methylation. The silencing of LINC02587 can inhibit cellular proliferative, migrative, and invasive properties, and induce ferroptosis within gliomas through the CoQ-FSP1 pathway. CONCLUSIONS: LINC02587 is likely to be a novel drug target in treating glioma.

Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells.

Aged hematopoietic stem cells (HSC) exhibit compromised reconstitution capacity and differentiation-bias towards myeloid lineage, however, the molecular mechanism behind it remains not fully understood. In this study, we observed that the expression of pseudouridine (Ψ) synthase 10 is increased in aged hematopoietic stem and progenitor cells (HSPC) and enforced protein of Ψ synthase 10 (PUS10) recapitulates the phenotype of aged HSC, which is not achieved by its Ψ synthase activity. Consistently, we observed no difference of transcribed RNA pseudouridylation profile between young and aged HSPC. No significant alteration of hematopoietic homeostasis and HSC function is observed in young Pus10-/- mice, while aged Pus10-/- mice exhibit mild alteration of hematopoietic homeostasis and HSC function. Moreover, we observed that PUS10 is ubiquitinated by E3 ubiquitin ligase CRL4DCAF1 complex and the increase of PUS10 in aged HSPC is due to aging-declined CRL4DCAF1- mediated ubiquitination degradation signaling. Taken together, this study for the first time evaluated the role of PUS10 in HSC aging and function, and provided a novel insight into HSC rejuvenation and its clinical application.

Effectiveness of dexmedetomidine on postoperative cognitive dysfunction in elderly patients with fracture: A systematic review.

BACKGROUND: Previous studies have explored the effectiveness of dexmedetomidine on postoperative cognitive dysfunction (POCD) in elderly patients with fracture. However, no systematic review has addressed this issue. Thus, this systematic review investigated the effectiveness of dexmedetomidine on POCD in elderly patients with fracture. METHODS: In this study, we searched electronic databases of PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Wang Fang and China Science and Technology Journal Database from their initiation to July 1, 2022. We considered randomized controlled trials of dexmedetomidine on POCD in elderly patients with fracture in this study. Primary outcome was measured by mini-mental state examination. Secondary outcomes were measured by total occurrence rate of postoperative cognitive dysfunction, occurrence rate of delirium, visual analogue scale and occurrence rate of adverse events. RESULTS: A total of 10 studies involving 969 elderly patients with fracture are included in this study. Meta-analysis results showed that there were significant differences on mini-mental state examination at 1-day post-surgery [mean difference (MD) = 2.17; random 95% confidence interval (CI), 1.06, 3.28; P < .001; I²=98%], 3-day post-surgery (MD = 2.70; random 95% CI, 1.51, 3.89; P < .001; I²=98%), and 7-day post-surgery (MD = 1.21; random 95% CI, 0.50, 1.93; P < .001; I²=86%), total occurrence rate of postoperative cognitive dysfunction (odds ratio [OR] = 0.26; fixed 95% CI, 0.11, 0.60; P = .002; I²= 0%), occurrence rate of delirium (OR = 0.29; fixed 95% CI, 0.11, 0.78; P = .01; I²= 0%), visual analogue scale (MD = -1.23; random 95% CI, -1.74, -0.72; P < .001; I²=95%), and occurrence rate of adverse events (OR = 0.32; fixed 95% CI, 0.20, 0.50; P < .001; I²= 0%) between the 2 groups. CONCLUSION: The results of this study showed that dexmedetomidine could effectively manage POCD in elderly patients with fracture. However, the overall quality of included trials is not too high. Thus, the present findings should be cautiously referred.

Case report: Autosomal recessive bestrophinopathy with macular cysts and MNV over 13-year follow-up.

Purpose: To describe the phenotype and genotype of a patient with autosomal recessive bestrophinopathy (ARB) over a 13-year follow-up period. Methods: The phenotype of the subject was described after a complete ophthalmological examination, which included fundus photography, optical coherence tomography (OCT), fundus autofluorescence, fluorescein angiography (FA), indocyanine green angiography (ICGA), electroretinogram (EOG), electroretinography (ERG), and multifocal electroretinogram (mfERG). Genetic analyses were carried out by screening the variations via whole-exome sequencing. Results: This patient presented with retinoschisis and cystic changes when he was 7 years old and was diagnosed with X-linked retinoschisis. In the 13th year after the first presentation, enlarged macular cysts with retinoschisis, macular neovascularization (MNV), and subretinal fluid were displayed on OCT. Autofluorescence showed hyperfluorescence corresponding to the area of retinal pigment epithelium (RPE) change. EOG showed no light peak, and the Arden ratio was less than 2.0. Whole-exome sequencing revealed compound heterozygous sequence variations (p. [Arg47Leu; Trp287*]) in the coding sequence of the BEST1 allele inherited from his parents. Thus, a diagnosis of ARB combined with secondary MNV was made. Conclusion: Patients with compound heterozygous BEST1 mutations developed ARB, which could show significant retinoschisis at a young age. Genetic analyses, autofluorescence, and EOG are essential to diagnose ARB correctly in consequence of considerable phenotypic variations.

Transportation and Transformation of Legacy Pesticides, Currently Used Pesticides, and Degradation Products: From Corn Planting to Corn Flour Processing.

Pesticide residues in food are a critical issue affecting food safety. The pesticide contaminants in food include currently used, legacy pesticides, and degradation products. Thus, this study analyzed the effects of planting and processing on the transfer and degradation of pesticide residues in corn. Specifically, we studied the transportation and transformation of 26 organochlorine pesticides (OCPs), 6 currently used pesticides, and 2 degradation products throughout corn planting and flour processing. For the currently used pesticide, diquat applied in this study did not significantly affect its concentration in soils. Different from this, λ-cyhalothrin application increased its concentration in soils. Therein, λ-cyhalothrin degraded to 3-PBA in a short time, and 3-PBA degraded faster than λ-cyhalothrin. The concentrations of legacy, currently used pesticides, and degradation products were higher in bran than in corn flour, indicating that the outer portions of corn kernels accumulated more pesticides. However, the results for λ-cyhalothrin were the opposite, indicating that the surrounding of bran is more favorable for degrading λ-cyhalothrin. The short- and long-term risks of consumer exposure to these pesticide residues via corn consumption are relatively insignificant based on the implementation time and dose in this study.

Regional block anesthesia for adult patients with inguinal hernia repair: A systematic review.

BACKGROUND: Inguinal hernia repair (IHR) is a common surgical technique performed under regional block anesthesia (RBA). Although previous clinical trials have explored the effectiveness and safety of RBA for IHR, no systematic review has investigated its effectiveness and safety in adult patients with IHR. METHODS: This systematic review searched electronic databases (PubMed, Embase, Cochrane Library, CNKI, Wangfang, and VIP) from their inception to July 1, 2022. We included all potential randomized controlled trials that focused on the effects and safety of RBA in adult patients with IHR. Outcomes included operative time, total rescue analgesics, numerical rating scale at 24 hours, occurrence rate of nausea and vomiting, and occurrence rate of urinary retention (ORUCR). RESULTS: Five randomized controlled trials, involving 347 patients with IHR, were included in this study. Meta-analysis results showed that no significant differences were identified on operative time (MD = -0.20; fixed 95% confidence interval [CI], -3.87, 3.47; P = .92; I² = 0%), total rescue analgesics (MD = -8.90; fixed 95% CI, -20.36, 2.56; P = .13; I²â€…= 28%), and occurrence rate of nausea and vomiting (MD = 0.39; fixed 95% CI, 0.13, 1.16; P = .09; I²â€…= 0%) between 2 types of anesthesias. However, significant differences were detected in the numerical rating scale at 24 hours (MD = -1.53; random 95% CI, -2.35, -0.71; P < .001; I²â€…= 75%) and ORUCR (MD = 0.20; fixed 95% CI, 0.05, 0.80; P = .02; I²â€…= 0%) between the 2 management groups. CONCLUSION: The results of this study demonstrated that IHR patients with RBA benefit more from post-surgery pain relief at 24h and a decrease in the ORUCR than those with CSA.

Bibliometric analysis of research on immunogenic cell death in cancer.

Background: Immunotherapy is changing the way we treat cancer. Immunogenic cell death (ICD) has received considerable attention in the treatments of various cancer types, due to the long-lasting antitumor responses elicited in human body. However, to date, no relevant bibliometric research has been reported. Methods: Publications related to ICD in cancer research were collected from the Web of Science Core Collection. Using CiteSpace, VOSviewer and an online platform, the analyses of co-author, co-citation, and co-occurrence of terms retrieved from literatures were carried out. Results: A total of 1,577 publications were included in this study. The global research literatures on ICD in cancer research have been increasing from 2005 to 2021. China, the United States and France dominated in this area and had close collaborations with many countries. Six of the top 10 most contributive institutions were from France. When it comes to author analysis, Kroemer G, Zitvogel L, Kepp O, Garg AD and Galluzzi L were in both the top 10 most productive authors and top 10 most co-cited authors lists. The co-occurring author keywords could be grouped into three clusters: "biomarkers of ICD", "nanoparticles" and "combination therapy". In terms of promising hotspots, keywords (author keywords and KeyWords Plus) with recent citation bursts could be summarized into two aspects: "tumor microenvironment" and "nanoparticles". Conclusion: Increased attention has been paid to ICD in cancer treatment. However, there are still many unresolved domains in the field of ICD, such as clinical application and molecular mechanisms of this cell death process. ICD-inducing modalities combined with nanotechnology could potentiate the current immunotherapies, and will be hotspots for future research.

Orally Administered Brain Protein Combined With Probiotics Increases Treg Differentiation to Reduce Secondary Inflammatory Damage Following Craniocerebral Trauma.

Craniocerebral trauma is caused by external forces that can have detrimental effects on the vasculature and adjacent nerve cells at the site. After the mechanical and structural primary injury, a complex series of secondary cascades of injury exacerbates brain damage and cognitive dysfunction following mechanical and structural primary injury. Disruption of the blood-brain barrier and exposure of brain proteins following craniocerebral trauma, recognition by the immune system triggering autoimmune attack, and excessive secondary inflammatory responses causing malignant brain swelling, cerebral edema, and subsequent brain cell apoptosis provide a new direction for the suppression of brain inflammatory responses in the treatment of craniocerebral trauma. We observed that CD4+T/CD8+T in peripheral blood T cells of craniocerebral trauma rats were significantly higher than those of normal rats, and the ratio of CD4+CD25+Foxp3 (Foxp3)+Regulatory T cell (Treg) was significantly lower than that of normal rats and caused increased secondary inflammation. We constructed a rat model of post-surgical brain injury and orally administered brain protein combined with probiotics, which was observed to significantly reduce CD4+T/CD8+T and induce T-cell differentiation into CD4+CD25+Foxp3+Treg, thus, reducing secondary inflammatory responses following craniocerebral trauma. However, collecting intestinal stool and small intestinal tissues for broad target metabolomics, 16s rRNA bacteriomics, and the combined analysis of intestinal tissue proteomics revealed that oral administration of brain protein combined with probiotics activates glycerophospholipid and vitamin B6 metabolic pathways to promote the production of CD4+CD25+Foxp3+Treg. Therefore, we propose the novel idea that oral administration of brain protein combined with probiotics can induce immune tolerance by increasing Treg differentiation, thus, reducing secondary inflammatory injury following craniocerebral trauma.

Emission Characteristics and Health Risks of Volatile Organic Compounds (VOCs) Measured in a Typical Recycled Rubber Plant in China.

The continued development of the automotive industry has led to a rapid increase in the amount of waste rubber tires, the problem of "black pollution" has become more serious but is often ignored. In this study, the emission characteristics, health risks, and environmental effects of volatile organic compounds (VOCs) from a typical, recycled rubber plant were studied. A total of 15 samples were collected by summa canisters, and 100 VOC species were detected by the GC/MS-FID system. In this study, the total VOCs (TVOCs) concentration ranged from 1000 ± 99 to 19,700 ± 19,000 µg/m3, aromatics and alkanes were the predominant components, and m/p-xylene (14.63 ± 4.07%-48.87 ± 3.20%) could be possibly regarded as a VOCs emission marker. We also found that specific similarities and differences in VOCs emission characteristics in each process were affected by raw materials, production conditions, and process equipment. The assessment of health risks showed that devulcanizing and cooling had both non-carcinogenic and carcinogenic risks, yarding had carcinogenic risks, and open training and refining had potential carcinogenic risks. Moreover, m/p-xylene and benzene were the main non-carcinogenic species, while benzene, ethylbenzene, and carbon tetrachloride were the dominant risk compounds. In the evaluation results of LOH, m/p-xylene (25.26-67.87%) was identified as the most key individual species and should be prioritized for control. In conclusion, the research results will provide the necessary reference to standardize the measurement method of the VOCs source component spectrum and build a localized source component spectrum.

2-(Naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone induces apoptosis via ROS-mediated MAPK, AKT, and STAT3 signaling pathways in HepG2 human hepatocellular carcinoma cells.

1,4-naphthoquinone and its derivatives have attracted widespread attention due to their multiple biological activities, such as induction of cancer cell apoptosis; however, most of these compounds have high cytotoxicity. In this study, in order to reduce their toxicity and increase their potential anti-tumor effects, we synthesized a novel 1,4-naphthoquinone derivative named 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone (NTDMNQ), and investigated its apoptotic effects and underlying mechanism. Our results showed that NTDMNQ inhibited the viability of HepG2, Hep3B, and Huh7 human hepatocellular carcinoma (HCC) cells. It also increased the accumulation of cells in the G0/G1 phase of the cell cycle by increasing the expression levels of p-p53, p21 and p27, while decreasing the levels of Cyclin D1, Cyclin E, Cyclin-dependent kinase 2 (CDK2), CDK4, and CDK6. Inhibition of reactive oxygen species (ROS) by the ROS scavenger N-acetyl-L-cysteine (NAC) decreased apoptosis in NTDMNQ-treated cells. Western blot analysis showed that NTDMNQ increased the phosphorylation of p38 and c-Jun N-terminal kinase (JNK), and decreased the phosphorylation of extracellular signal-regulated kinase (ERK), AKT, and signal transducer and activator of transcription-3 (STAT3); these effects were blocked by NAC. Both the JNK inhibitor (SP600125) and p38 inhibitor (SB203580) reversed the phosphorylation of STAT3, and the ERK inhibitor (FR180204) and AKT inhibitor (LY294002) reduced the expression of STAT3. Taken together, these findings suggest that NTDMNQ induces apoptosis via ROS-mediated MAPK, AKT and STAT3 signaling pathways in HepG2 cells, and may be a potent anticancer agent.