Genome-Wide Identification of Detoxification Genes in Wild Silkworm Antheraea pernyi and Transcriptional Response to Coumaphos.

For a half-century, the commercial wild silkworm, Antheraea pernyi, has been protected by coumaphos, which is an internal organophosphorus insecticide used to kill the potential parasitic fly larvae inside. Knowledge about the detoxification genes of A. pernyi as well as the detoxification mechanism for this species remains severely limited. In this study, we identified 281 detoxification genes (32 GSTs, 48 ABCs, 104 CYPs, and 97 COEs) in the genome of this insect, which are unevenly distributed over 46 chromosomes. When compared to the domesticated silkworm, Bombyx mori, a lepidopteran model species, A. pernyi has a similar number of ABCs, but a greater number of GSTs, CYPs, and COEs. By transcriptome-based expression analysis, we found that coumaphos at a safe concentration level significantly changed the pathways related to ATPase complex function and the transporter complex in A. pernyi. KEGG functional enrichment analysis indicated that protein processing in the endoplasmic reticulum was the most affected pathway after coumaphos treatment. Finally, we identified four significantly up-regulated detoxification genes (ABCB1, ABCB3, ABCG11, and ae43) and one significantly down-regulated detoxification gene (CYP6AE9) in response to coumaphos treatment, suggesting that these five genes may contribute to detoxification of coumaphos in A. pernyi. Our study provides the first set of detoxification genes for wild silkworms from Saturniidae and highlights the importance of detoxification gene repertoire in insect pesticide tolerance.

First complete mitochondrial genome of Rhodinia species (Lepidoptera: Saturniidae): genome description and phylogenetic implication.

To explore the characteristics of the mitochondrial genome (mitogenome) of the squeaking silkmoths Rhodinia, a genus of wild silkmoths in the family Saturniidae of Lepidoptera, and reveal phylogenetic relationships, the mitogenome of Rhodinia fugax Butler was determined. This wild silkmoth spins a green cocoon that has potential significance in sericulture, and exhibits a unique feature that its larvae can squeak loudly when touched. The mitogenome of R. fugax is a circular molecule of 15,334 bp long and comprises 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and an A + T-rich region, consistent with previous observations of Saturniidae species. The 370-bp A + T-rich region of R. fugax contains no tandem repeat elements and harbors several features common to the Bombycidea insects, but microsatellite AT repeat sequence preceded by the ATTTA motif is not present. Mitogenome-based phylogenetic analysis shows that R. fugax belongs to Attacini, instead of Saturniini. This study presents the first mitogenome for Rhodinia genus.

Mitochondrial Genome Architecture and Evolutionary Origin of the Yao Silkworm, a Living Fossil of the Domestic Silkworm Bombyx mori (Lepidoptera: Bombycidae).

The Yao silkworm is a unique silkworm resource producing yellow flat plate silk that has only been reared by the Baiku Yao ethnic group in Nandan County, Guangxi Province, China for a thousand years. Here, we report the mitochondrial genomes (mitogenomes) of five Yao silkworm strains and 10 local Guangxi strains of the domestic silkworm (Bombyx mori) L. (Lepidoptera: Bombycidae), and use the resulting mitogenomes and the available Bombyx mitogenomes to characterize their genome architecture and trace the evolutionary origin of the Yao silkworm. The five Yao silkworm mitogenomes exhibited genome architectures identical to typical set of 37 mitochondrial genes (13 protein-coding genes, 22 transfer RNAs, and two ribosomal RNAs) and a high level of genome sequence similarity with the domestic silkworm. Mitogenome-based phylogenetic reconstruction provided solid evidence that the Yao silkworm shares a common ancestor with the domestic silkworm. Sliding window analysis uncovered a distinct variation pattern in the mitogenome between the Yao silkworm and the other domestic silkworm strains. The phylogenetic analyses revealed a basal placement of the Yao silkworm among all available domestic silkworm strains, indicating that the Yao silkworm is an ancient population of the domestic silkworm. Our data indicated that the Yao silkworm (B. mori) is a lineage of the domestic silkworm, which for the first time provides insights into the origin of the Yao silkworm.

Five metastasis-related mRNAs signature predicting the survival of patients with liver hepatocellular carcinoma.

BACKGROUNDS: Liver hepatocellular carcinoma (HCC) is one of the most malignant tumors, of which prognosis is unsatisfactory in most cases and metastatic of HCC often results in poor prognosis. In this study, we aimed to construct a metastasis- related mRNAs prognostic model to increase the accuracy of prediction of HCC prognosis. METHODS: Three hundred seventy-four HCC samples and 50 normal samples were downloaded from The Cancer Genome Atlas (TCGA) database, involving transcriptomic and clinical data. Metastatic-related genes were acquired from HCMBD website at the same time. Two hundred thirty-three samples were randomly divided into train dataset and test dataset with a proportion of 1:1 by using caret package in R. Kaplan-Meier method and univariate Cox regression analysis and lasso regression analysis were performed to obtain metastasis-related mRNAs which played significant roles in prognosis. Then, using multivariate Cox regression analysis, a prognostic prediction model was established. Transcriptome and clinical data were combined to construct a prognostic model and a nomogram for OS evaluation. Functional enrichment in high- and low-risk groups were also analyzed by GSEA. An entire set based on The International Cancer Genome Consortium(ICGC) database was also applied to verify the model. The expression levels of SLC2A1, CDCA8, ATG10 and HOXD9 are higher in tumor samples and lower in normal tissue samples. The expression of TPM1 in clinical sample tissues is just the opposite. RESULTS: One thousand eight hundred ninety-five metastasis-related mRNAs were screened and 6 mRNAs were associated with prognosis. The overall survival (OS)-related prognostic model based on 5 MRGs (TPM1,SLC2A1, CDCA8, ATG10 and HOXD9) was significantly stratified HCC patients into high- and low-risk groups. The AUC values of the 5-gene prognostic signature at 1 year, 2 years, and 3 years were 0.786,0.786 and 0.777. A risk score based on the signature was a significantly independent prognostic factor (HR = 1.434; 95%CI = 1.275-1.612; P < 0.001) for HCC patients. A nomogram which incorporated the 5-gene signature and clinical features was also built for prognostic prediction. GSEA results that low- and high-risk group had an obviously difference in part of pathways. The value of this model was validated in test dataset and ICGC database. CONCLUSION: Metastasis-related mRNAs prognostic model was verified that it had a predictable value on the prognosis of HCC, which could be helpful for gene targeted therapy.

Characterization of an Ecdysteroid-Regulated 16 kDa Protein Gene in Chinese Oak Silkworm, Antheraea pernyi (Lepidoptera: Saturniidae).

A large number of ecdysteroid-regulated 16 kDa proteins (ESR16s) of insects have been isolated and annotated in GenBank; however, knowledge on insect ESR16s remain limited. In the present study, we characterized an ecdysteroid-regulated 16 kDa protein gene isolated in Chinese oak silkworm, Antheraea pernyi Guérin-Méneville ('ApESR16' in the following), an important silk-producing and edible insect. The obtained cDNA sequence of ApESR16 is 1,049 bp, harboring an open reading frame of 441 bp that encodes a polypeptide of 146 amino acids. CD-search revealed that ApESR16 contains the putative cholesterol/lipid binding sites on conserved domain Npc2_like (Niemann-Pick type C-2) belonging to the MD-2-related lipid-recognition superfamily. Sequence comparison revealed that ApESR16 exhibits 51-57% identity to ESR16s of lepidopteran insects, 36-41% identity to ESR16 or NPC2a of nonlepidopteran insects, and 28-32% identity to NPC2a of vertebrates, indicating a high sequence divergence during the evolution of animals. Phylogenetic analysis found that the used sequences were divided into two groups corresponding to vertebrates and invertebrates, and the used insect sequences were also well clustered according to their families. The A. pernyi ESR16 mRNA is expressed during all four developmental stages and in all tested tissues. Injection of 20-hydroxyecdysone (20-E) into A. pernyi diapausing pupae triggering diapause termination induced upregulation of ESR16 mRNA compared to the diapausing pupae, with the highest expression level at day 2 in the ovaries but day 12 in the fat body. Our results suggested that ApESR16 might be a diapause-related gene and plays a vital role in the pupal diapause of A. pernyi.

Anatomical Study of the Compositions and Internal Connections of the Chiasma Plantare (Master Knot of Henry): Exploring Its Possible Clinical Impact.

The purposes of this study were to integrate the types of interconnecting fibers among components of the chiasma plantare and to deduce their flexion actions. The chiasma plantare and the long flexor tendons in 52 cadaveric feet (26 left feet and 25 right feet) were dissected and removed via gross anatomic dissection. The connections among the flexor digitorum longus (FDL), flexor hallucis longus (FHL), and quadratus plantae (QP) were then classified and analyzed. The connection between the FHL and FDL was type I in 43 (86%) cases, type III in 2 (4%) cases, and type V in 5 (10%) cases, with the FHL manipulating the first through third toes and the FDL manipulating the first through the fifth toes. The shape of the QP in 28 (56%) cases exhibited a 2-headed QP, and in 22 (44%) cases, a medial-headed QP. The composition of the chiasma plantare was 2 layers in 28 (56%) cases and 3 layers in 22 (44%) cases: 9 (18%) cases were type a, 2 (4%) cases were type b1, and 1 (2%) case each was classified as type b2 and b3. The FHL controlled the second toe in 10 (20%) cases; both the second and third toes in 27 (54%) cases; and the second, third, and fourth toes in 13 (26%) cases. The QP manipulated the third and fourth toes in all cases, the second toe in 38 (76%) cases, and the fifth toe in 11 (22%) cases. These data suggest that such variations might result from tendon transfer. In conclusion, we considered the FDL to be more advanced for the recovery of both the ankle and the forefoot based on this study.

The Complete Mitochondrial Genome of the Longhorn Beetle Dorysthenes paradoxus (Coleoptera: Cerambycidae: Prionini) and the Implication for the Phylogenetic Relationships of the Cerambycidae Species.

The longhorn beetle Dorysthenes paradoxus (Faldermann, 1833) (Coleoptera: Cerambycidae) is not only a serious agricultural pest but also a traditionally edible insect in China. However, no genetic information on this species has been acquired. In the present study, we report the mitochondrial genome (mitogenome) of Do. paradoxus, as the first complete mitogenome of Prioninae. The circular mitogenome of 15,922 bp encodes 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), and two ribosomal RNAs (rRNAs), and it contains an A+T-rich region. This mitogenome exhibits the lowest A+T content (71.13%) but harbors the largest AT skew (0.116) among the completely sequenced Cerambycidae species. Eleven of the 13 PCGs have a typical ATN start codon, whereas COI and ND1 are tentatively designated by AAT and TTG, respectively. Only 4 of the 13 PCGs harbor a complete termination codon, and the remaining 9 possess incomplete termination codons (T or TA). Apart from tRNASer(AGN), the other 21 tRNAs can fold into a typical clover-leaf secondary structures. The Do. paradoxus A+T-rich region contains two poly-T stretches and a tandem repeat that comprises two 47-bp-long copies. Both Bayesian inference and Maximum likelihood analyses confirmed the subfamily ranks of Cerambycidae ([Prioninae + Cerambycinae] + Lamiinae) and the close relationship between Philinae and Prioninae/Cerambycinae. However, the data did not support the monophyly of Prioninae and Cerambycinae. The mitogenome presented here provides basic genetic information for this economically important species.

Effect of Information of Patients' Coping Style on Pregastroscopy Anxiety.

Examination of the relationship between patients' coping style, pregastroscopy information, and anxiety associated with gastroscopy in China was the aim of this study. A pretest, post-test, nonrandom assignment study with a two by two design was conducted. One hundred forty-five patients who underwent initial gastroscopy without sedation were classified into 2 groups on the basis of the coping style: information seekers or information avoiders using the Information Subscale of the Krantz Health Opinion Survey (KHOS-I). All participants were given standardized procedural information about gastroscopy as routine care. Half of each group was assigned to receive additional sensory information describing what sensation they would experience and how to cooperate to alleviate the discomfort. State anxiety assessed by the State Anxiety Scale of Spielberg's State-Trait Anxiety Inventory, blood pressure, and pulse were measured at enrollment and before gastroscopy. The information seekers and avoiders who received additional sensory information experienced significantly less state anxiety after the intervention. In contrast, the information seekers and avoiders who received standardized procedural information maintained their preintervention state anxiety level. Most patients reported their preference for sensory information. In conclusion, the provision of sensory information could significantly reduce patients' pregastroscopy anxiety regardless of patients' information coping style.

Recent developments in nanomedicine for melanoma treatment.

Melanoma is a most aggressive skin cancer with limited therapeutic options and its incidence is increasing rapidly in recent years. The discovery and application of new targeted therapy agents have shown significant benefits. However, adverse side-effects and resistance to chemotherapy remain formidable challenges in the clinical treatment of malignant melanoma. Nanotherapeutics offers an important prospect of overcoming these drawbacks. The anti-tumoral applications of nanomedicine are varied, including those in chemotherapy, RNA interference, photothermal therapy, and photodynamic therapy. Furthermore, nanomedicine allows delivery of the effector structures into the tumor site via passive or active targeting, thereby allowing increased therapeutic specificity and reduced side effects. In this review, we summarize the latest developments in the application of nanocarrier-mediated targeted drug delivery to melanoma and nanomedicine-related clinical trials in melanoma treatment. We also discuss existing problems and opportunities for future developments, providing direction and new thoughts for further studies.

Effect of diet and exercise intervention in Chinese pregnant women on gestational weight gain and perinatal outcomes: A quasi-experimental study.

Aim To determine the effect of a diet and exercise intervention in pregnant women on total gestational weight gain, weekly weight gain, 42-days postpartum weight retention, mode of delivery, and infant birth weight. METHODS: One hundred and one eligible Chinese pregnant women whose pre-pregnancy body mass index ranged from 18.5 to 24.9 were recruited between June 2013 and June 2014 from a tertiary hospital. Ninety participants, 45 in each group, completed the study. Intervention women received three face-to-face interventions and three follow-up phone calls which were developed based on the Transtheoretical Model. Gestational weight was measured at each prenatal check. Mode of delivery and infant birth weight were collected from the medical record. The 42-days postpartum weight was measured during the postpartum visits. RESULTS: (1) The total gestational weight gain and mean weight gain per week in the intervention group were significantly less than the control group (P=0.045 and P=0.008 respectively). (2) Infant birth weight was significantly lower in the intervention group (P=0.012). (3) Postpartum weight retention was significantly less in the intervention group (P=0.001). 4) There were not significant differences in mode of delivery. 5) Infant birth weight was significantly less than the control group (P=0.012). CONCLUSIONS: The lifestyle intervention significantly reduced gestational weight gain, optimized infant weight and lowered postpartum weight retention. Promotion of gestational weight management is needed and cultural health beliefs about pregnancy and postpartum practices should be considered when developing the intervention plan.

DNA methylation and histone acetylation regulate the expression of MGMT and chemosensitivity to temozolomide in malignant melanoma cell lines.

Malignant melanoma is an aggressive, highly lethal dermatological malignancy. Chemoresistance and rapid metastasis limit the curative effect of multimodal therapies like surgery or chemotherapy. The suicide enzyme O6-methylguanine-DNA methyltransferase (MGMT) removes adducts from the O6-position of guanine to repair DNA damage. High MGMT expression is associated with resistance to therapy in melanoma. However, it is unknown if MGMT is regulated by DNA methylation or histone acetylation in melanoma. We examined the effects of the DNA methylation inhibitor 5-Aza-2'-deoxycytidine and histone deacetylase inhibitor Trichostatin A alone or in combination on MGMT expression and promoter methylation and histone acetylation in A375, MV3, and M14 melanoma cells. This study demonstrates that MGMT expression, CpG island methylation, and histone acetylation vary between melanoma cell lines. Combined treatment with 5-Aza-2'-deoxycytidine and Trichostatin A led to reexpression of MGMT, indicating that DNA methylation and histone deacetylation are associated with silencing of MGMT in melanoma. This study provides information on the role of epigenetic modifications in malignant melanoma that may enable the development of new strategies for treating malignant melanoma.

Five new phorbol esters with cytotoxic and selective anti-inflammatory activities from Croton tiglium.

Five new phorbol esters, (four phorbol diesters, 1-4, and one 4-deoxy-4α-phorbol diester, 5), as well as four known phorbol esters analogues (6-9) were isolated and identified from the branches and leaves of Croton tiglium. Their structures were elucidated mainly by extensive NMR spectroscopic, and mass spectrometric analysis. Among them, compound (1) was the first example of a naturally occurring phorbol ester with the 20-aldehyde group. Compounds 2-5, and 7-9 showed potent cytotoxicity against the K562, A549, DU145, H1975, MCF-7, U937, SGC-7901, HL60, Hela, and MOLT-4 cell lines, with IC50 values ranging from 1.0 to 43 µM, while none of the compounds exhibited cytotoxic effects on normal human cell lines 293T and LX-2, respectively. In addition, compound 3 exhibited moderate COX-1 and COX-2 inhibition, with IC50 values of 0.14 and 8.5 µM, respectively.

Lignans from the bark of Zanthoxylum simulans.

Investigation on the EtOAc extract of the bark of Zanthoxylum simulans led to the isolation of four new lignans including zanthoxylumin A (1), zanthoxylumin B (2), ( - )-magnolin (3), and ( - )-pinoresinol-di-3,3-dimethylallyl ether (4). Their structures were established by comprehensive analysis of the spectral data, especially 1D and 2D NMR spectra.

"Doing the month": Postpartum practices in Chinese women.

This review describes the traditional ancient Chinese postpartum practice of "doing the month" or "zuoyuezi", the evidence for specific practices, maternal adherence to practices, and their effect upon the maternal postpartum physical and psychological health. A comprehensive search yielded 38 English or Chinese publications about common practices, adherence to practices, and their effects upon Chinese women's physical and psychological health. Doing the month involves a series of practices related to the maternal role, physical activity, maintenance of body warmth, and food consumption that are believed to restore maternal postpartum health and prevent future disease. Strengths of these practices include acknowledgment of the woman's societal and familial contribution to childbearing and the provision of consistent family support. There is concern for the effect of some practices upon both maternal physical and psychological health, particularly for postpartum depression. Current evidence about the effects of doing-the-month practices upon maternal health needs to be integrated into the traditional practices of doing the month to improve maternal health.

Efficacy and safety between temozolomide alone and temozolomide-based double therapy for malignant melanoma: a meta-analysis.

Temozolomide (TMZ) has received much attention, notably in the treatment of malignant glioma and malignant melanoma. The objective of this study was to compare the clinical efficacy and safety of TMZ alone and TMZ-based combination drug therapy in patients with melanoma. Using "temozolomide" as a keyword combined with "melanoma" and "randomized controlled trials" as Medical Subject Headings, the following electronic databases were searched: the Cochrane library, MEDLINE, EBSCO, EMBASE, Ovid, cNKI, and cBMDisc. The evaluating indicators were overall response rate (ORR), 1-year survival rate, and several of the most frequent adverse events. Five randomized controlled trials met our criteria and were included in the meta-analysis, with a total of 703 participants (309 patients received TMZ alone, and 394 patients received combined regimens). The meta-analysis showed that the ORR for TMZ-based drug therapy was higher than TMZ alone [relative risk (RR) = 1.44; 95% confidence interval (CI), 1.06-1.95], but the 1-year survival rate was not significantly different between the two groups (RR = 1.13; 95% CI, 0.92-1.40). These results suggested that the impact of these increased response rates was not translated into a survival benefit. Moreover, we found no difference in the incidence of adverse events analyzed. The currently available evidence showed that the TMZ-combination therapy may moderately improve the response rate, but there was no corresponding increased toxicity. Future large-scale, high-quality, placebo-controlled, double-blind trials are needed.

Characterization and biological evaluation of six new dimeric lignans with an unusual α,ß-unsaturated ketone motif from Zanthoxylum simulans.

Investigation of the bark of Zanthoxylum simulans afforded six new dimeric lignans zanthpodocarpins C-H (1-6) bearing an unusual α,ß-unsaturated ketone group. The new structures of 1-6 were determined by using detailed spectroscopic analysis. All of the isolated compounds were examined for their inhibitory effects against rat joint synovial cell and splenocyte proliferation. Compounds 1-6 showed potent anti-inflammatory activities with IC50 values ranging from 18.6 to 36.1µM, and 13.8 to 74.3µM.

Molecular characterization and phylogenetic analysis of the eukaryotic translation initiation factor 4A gene in Antheraea pernyi (Lepdoptera: Saturniidae).

Eukaryotic initiation factor 4A (eIF-4A) is an essential component for protein translation in eukaryotes. The eIF-4A gene (ApeIF-4A) was isolated and characterized from Antheraea pernyi (Guérin-Méneville) (Lepidoptera: Saturniidae). The obtained cDNA sequence was 1,435-bp long with an open reading frame of 1,266 bp encoding 421 amino acids. The predicted amino acid sequence shared several conserved features as found in known eIF-4As and revealed 74 and 78% identities with eIF-4As of Homo sapiens L. and Drosophila melanogaster (Meigen), respectively. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that ApeIF-4A was transcribed at four developmental stages and in all tissues tested, suggesting that it plays an important role in development of A. pernyi. Homologous alignment suggested that eIF-4As are highly conserved throughout evolution of eukaryote organisms. Phylogenetic trees based on the amino acid and nucleotide sequences of eIF-4A demonstrated a similar topology with the classical systematics, suggesting that it has the potential value in phylogenetic inference of eukaryotes.

More potential uses of specific perforator flaps in the calf - A cadaveric study on the subdermal vascular structure of the lower leg.

BACKGROUND: The perforator flap has garnered significant interest since its inception due to its advantage of not needing a vascular network at the deep fascial level. Perforator flaps are commonly utilized in different flap transplant surgeries, and the thigh flap is presently the most widely used perforator flap. Is it possible for the calf to replace the thigh as a more suitable site for harvesting materials? Currently, there is a lack of relevant anatomical research. This study aims to address this question from an anatomical and imaging perspective. METHODS: This study used cadavers to observe the branches and courses of perforators on the calf and the distribution of skin branches using microdissection techniques, digital X-ray photography, and micro-computed tomography techniques. RESULTS: The perforators had three main branches: the vertical cutaneous branch, the oblique cutaneous branch, and the superficial fascial branch. The superficial fascial branch traveled in the superficial fascia and connected with the nearby perforators. The vertical and oblique cutaneous branches entered the subdermal layer and connected with each other to create the subdermal vascular network. CONCLUSIONS: We observed an intact calf cutaneous branch chain between the cutaneous nerve and the perforator of the infrapopliteal main artery at the superficial vein site. Utilizing this anatomical structure, the calfskin branch has the potential to serve as a substitute for thigh skin flap transplantation and may be applied to perforator flap transplantation in more locations.

Selective pressure dominates the synonymous codon usage in parvoviridae.

Parvoviridae is a family of small non-enveloped viruses and divided into two subfamilies. The family members infect a wide range of organisms from insects to humans and some of the members (e.g., nonpathogenic adeno-associated viruses) are effective gene therapy delivery vectors. We detailed the synonymous codon usage pattern of Parvoviridae family from the available 58 sequenced genomes through multivariate statistical methods. Our results revealed that nine viruses showed some degree of strong codon bias, and the others possessed a general weak trend of codon bias. ENc-plot and neutrality plot results showed that selective pressure dominated over mutation in shapes coding sequence's composition. The overall GC content and GC content at the third synonymous codon position were the principal determinants behind the variations within the codon usage patterns, as they both significantly correlated with the first axis of correspondence analysis. In addition, gene length had no direct influence on the codon usage pattern. Densovirinae subfamily and Parvovirinae subfamily possessed nine identical preferred codons, though most of the two subfamilies codon usage frequencies were significantly different. The result of cluster analysis based on synonymous codon usage was discordant with that of taxonomic classification. Adeno-associated viruses formed a separated clade far from other Parvoviridae members in the dendrogram. Thus, we concluded that natural selection rather than mutation pressure accounts for the main factor that affects the codon bias in Parvoviridae family.

Inhibition of DNA-dependent protein kinase catalytic subunit by small molecule inhibitor NU7026 sensitizes human leukemic K562 cells to benzene metabolite-induced apoptosis.

Benzene is an established leukotoxin and leukemogen in humans. We have previously reported that exposure of workers to benzene and to benzene metabolite hydroquinone in cultured cells induced DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to mediate the cellular response to DNA double strand break (DSB) caused by DNA-damaging metabolites. In this study, we used a new, small molecule, a selective inhibitor of DNA-PKcs, 2-(morpholin-4-yl)-benzo[h]chomen-4-one (NU7026), as a probe to analyze the molecular events and pathways in hydroquinone-induced DNA DSB repair and apoptosis. Inhibition of DNA-PKcs by NU7026 markedly potentiated the apoptotic and growth inhibitory effects of hydroquinone in proerythroid leukemic K562 cells in a dose-dependent manner. Treatment with NU7026 did not alter the production of reactive oxygen species and oxidative stress by hydroquinone but repressed the protein level of DNA-PKcs and blocked the induction of the kinase mRNA and protein expression by hydroquinone. Moreover, hydroquinone increased the phosphorylation of Akt to activate Akt, whereas co-treatment with NU7026 prevented the activation of Akt by hydroquinone. Lastly, hydroquinone and NU7026 exhibited synergistic effects on promoting apoptosis by increasing the protein levels of pro-apoptotic proteins Bax and caspase-3 but decreasing the protein expression of anti-apoptotic protein Bcl-2. Taken together, the findings reveal a central role of DNA-PKcs in hydroquinone-induced hematotoxicity in which it coordinates DNA DSB repair, cell cycle progression, and apoptosis to regulate the response to hydroquinone-induced DNA damage.