Visualization of Pulse-Wave Velocity on Arterial Wall of Mice Through High-Frequency Ultrafast Doppler Imaging.

Arterial pulse-wave velocity (PWV) is widely used in clinical applications to assess cardiovascular diseases. Ultrasound methods have been proposed for estimating regional PWV in human arteries. Furthermore, high-frequency ultrasound (HFUS) has been applied to perform preclinical small-animal PWV measurements; however, electrocardiogram (ECG)-gated retrospective imaging is required to achieve high-frame-rate imaging, which might be affected by arrhythmia-related problems. In this article, HFUS PWV mapping based on 40-MHz ultrafast HFUS imaging is proposed to visualize PWV on mouse carotid artery to measure arterial stiffness without ECG gating. In contrast to most other studies that used cross-correlation methods to detect arterial motion, ultrafast Doppler imaging was applied in this study to measure arterial wall velocity for PWV estimations. The performance of the proposed HFUS PWV mapping method was verified using a polyvinyl alcohol (PVA) phantom with various freeze-thaw cycles. Small-animal studies were then performed in wild-type (WT) mice and in apolipoprotein E knockout (ApoE KO) mice that were fed a high-fat diet (for 16 and 24 weeks). The Young's modulus of the PVA phantom measured through HFUS PWV mapping was 15.3 ± 0.81, 20.8 ± 0.32, and 32.2 ± 1.11 kPa for three, four, and five freeze-thaw cycles, respectively, and the corresponding measurement biases (relative to theoretical values) were 1.59%, 6.41%, and 5.73%, respectively. In the mouse study, the average PWVs were 2.0 ± 0.26, 3.3 ± 0.45, and 4.1 ± 0.22 m/s for 16-week WT, 16-week ApoE KO, and 24-week ApoE KO mice, respectively. The PWVs of ApoE KO mice increased during the high-fat diet feeding period. HFUS PWV mapping was used to visualize the regional stiffness of mouse artery, and a histology confirmed that the plaque formation in the bifurcation region increased the regional PWV. All the results indicate that the proposed HFUS PWV mapping method is a convenient tool for investigating arterial properties in preclinical small-animal studies.

XPF-ERCC1 Blocker Improves the Therapeutic Efficacy of 5-FU- and Oxaliplatin-Based Chemoradiotherapy in Colorectal Cancer.

5-FU-based chemoradiotherapy (CRT) and oxaliplatin-based CRT are commonly used therapies for advanced colorectal cancer (CRC). However, patients with a high expression of ERCC1 have a worse prognosis than those with a low expression. In this study, we investigated the effect of XPF-ERCC1 blockers on chemotherapy and 5-FU-based CRT and oxaliplatin (OXA)-based CRT in colorectal cancer cell lines. We investigated the half-maximal inhibitory concentration (IC50) of 5-FU, OXA, XPF-ERCC1 blocker, and XPF-ERCC1 blocker, and 5-FU or OXA combined and analyzed the effect of XPF-ERCC1 blocker on 5-FU-based CRT and oxaliplatin-based CRT. Furthermore, the expression of XPF and γ-H2AX in colorectal cells was analyzed. In animal models, we combined the XPF-ERCC1 blocker with 5-FU and OXA to investigate the effects of RC and finally combined the XPF-ERCC1 blocker with 5-FU- and oxaliplatin-based CRT. In the IC50 analysis of each compound, the cytotoxicity of the XPF-ERCC1 blocker was lower than that of 5-FU and OXA. In addition, the XPF-ERCC1 blocker combined with 5-FU or OXA enhanced the cytotoxicity of the chemotherapy drugs in colorectal cells. Furthermore, the XPF-ERCC1 blocker also increased the cytotoxicity of 5-FU-based CRT and OXA -based CRT by inhibiting the XPF product DNA locus. In vivo, the XPF-ERCC1 blocker was confirmed to enhance the therapeutic efficacy of 5-FU, OXA, 5-FU-based CRT, and OXA CRT. These findings show that XPF-ERCC1 blockers not only increase the toxicity of chemotherapy drugs but also increase the efficacy of combined chemoradiotherapy. In the future, the XPF-ERCC1 blocker may be used to improve the efficacy of 5-FU- and oxaliplatin-based CRT.

Estimation of Mouse Carotid Arterial Wall Shear Stress Using High-Frequency Ultrasound Imaging.

Wall shear stress (WSS) is a crucial hemodynamic factor that promotes atherosclerosis (plaque) development in arteries; although the relationship between WSS and arterial atherosclerosis has been explored in many animal studies, it is not fully understood. No suitable tool, however, exists for rapidly estimating dynamic WSS in small-animal studies. This study proposes a 40-MHz high-frequency ultrasound (HFUS) imaging system for dynamic WSS estimation based on mouse carotid artery blood flow velocity gradient measurements by vector Doppler imaging (VDI). Aliasing reduces the accuracy of Doppler measurements, which can be prevented by increasing the imaging frame rate. Conventionally, imaging is performed at two tilted angles by alternating between the angles; in the proposed method, the frame rate was doubled by imaging at each tilted angle sequentially and by then temporally aligning the sequences based on pulsatile flow characteristics. Velocity estimation using this method had low errors for both a steady-flow straight-tube and pulsatile flow 60%-stenosis phantom. The method was tested for wild-type (WT) C57BL/6 mice at 16 weeks old and apolipoprotein E knockout (ApoE KO) mice at 16 and 24 weeks old; differences in time-averaged and oscillatory WSS were observed, and histology confirmed that the 24-week ApoE KO mice with the highest oscillatory WSS had the greatest plaque formation. The proposed HFUS WSS imaging method can predict the location and extent of plaque development; thus, this method is useful for small-animal studies investigating the WSS effect on atherosclerotic plaque development.

Second harmonic generation and simplified bond hyperpolarizability model analyses on the intermixing of Si/SiGe stacked multilayers for gate-all-around structure.

Si/SiGe stacked multilayers are key elements in fabrication of gate-all-around (GAA) structures and improvement of electrical properties, with the evolution of the Si/SiGe interfaces playing a crucial role. In this work, a model is developed based on the simplified bond hyperpolarizability model (SBHM) to analysis the anisotropic reflective second harmonic generation (Ani-RSHG) on a three-period stacked Si/Si1-xGexmultilayer, which builds on Si(100) diamond structures. TheC4vsymmetry of the Si(100) structure enables the second harmonic generation (SHG) contribution from the bonds to be simplified and the effective hyperpolarizabilities of the interfacial and bulk sources to be obtained. The effective interface dipolar and bulk quadrupolar SHG hyperpolarizabilities in the Si1-xGexsample with various Ge concentration profiles are modeled by interpreting the concentration of a component element as the probability of the element occupying an atomic site. On the basis of the developed model, the Ani-RSHG spectra of the as-grown samples with various Ge ratios for each layer and the samples annealed at 850 °C and 950 °C are analyzed to inspect the change in Ge distribution and its gradient in depth. The ani-RSHG analysis on as-grown samples showed difference in Ge distribution in samples with the multi Si/SiGe structure, which is not well observed in synchrotron x-ray diffraction (XRD) spectra. For the annealed samples, the response to changes in Ge concentration and its gradient in depth reveal the Si/Si1-xGexinterface intermixing. Results of high-angle annular dark-field scanning transmission electron microscopy and energy dispersive x-ray spectroscopy agree well with the Ani-RSHG with SBHM findings. Compared with the Raman and synchrotron XRD spectra, the Ani-RSHG with SBHM simulation result demonstrates much better response to changes in compositions of the Si/Si1-xGexstacked multilayered structures, verifying the potential for characterizing the concentration distribution in stacked multilayered thin films for GAA structures.

HIF-1α Expression Increases Preoperative Concurrent Chemoradiotherapy Resistance in Hyperglycemic Rectal Cancer.

Purpose: Preoperative concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced rectal cancer patients. However, the poor therapeutic efficacy of CCRT was found in rectal cancer patients with hyperglycemia. This study investigated how hyperglycemia affects radiochemotherapy resistance in rectal cancer. Methods and Materials: We analyzed the correlation between prognosis indexes with hypoxia-inducible factor-1 alpha (HIF-1α) in rectal cancer patients with preoperative CCRT. In vitro, we investigated the effect of different concentrated glucose of environments on the radiation tolerance of rectal cancers. Further, we analyzed the combined HIF-1α inhibitor with radiation therapy in hyperglycemic rectal cancers. Results: The prognosis indexes of euglycemic or hyperglycemic rectal cancer patients after receiving CCRT treatment were investigated. The hyperglycemic rectal cancer patients (n = 13, glycosylated hemoglobin, HbA1c > 6.5%) had poorer prognosis indexes. In addition, a positive correlation was observed between HIF-1α expression and HbA1c levels (p = 0.046). Therefore, it is very important to clarify the relationship between HIF-1α and poor response in patients with hyperglycemia receiving pre-operative CCRT. Under a high glucose environment, rectal cancer cells express higher levels of glucose transport 1 (GLUT1), O-GlcNAc transferase (OGT), and HIF-1α, suggesting that the high glucose environment might stimulate HIF-1α expression through the GLUT1-OGT-HIF-1α pathway promoting tolerance to Fluorouracil (5-FU) and radiation. In the hyperglycemic rectal cancer animal model, rectal cancer cells confirmed that radiation exposure reduces apoptosis by overexpressing HIF-1α. Combining HIF-1α inhibitors was able to reverse radioresistance in a high glucose environment. Lower HIF-1α levels increased DNA damage in tumors leading to apoptosis. Conclusions: The findings here show that hyperglycemia induces the expression of GLUT1, OGT, and HIF-1α to cause CCRT tolerance in rectal cancer and suggest that combining HIF-1α inhibitors could reverse radioresistance in a high glucose environment. HIF-1α inhibitors may be useful for development as CCRT sensitizers in patients with hyperglycemic rectal cancer.

Biomarkers of Favorable vs. Unfavorable Responses in Locally Advanced Rectal Cancer Patients Receiving Neoadjuvant Concurrent Chemoradiotherapy.

Colorectal cancer is the second leading cause of cancer death globally. The gold standard for locally advanced rectal cancer (LARC) nowadays is preoperative concurrent chemoradiation (CCRT). Approximately three quarters of LARC patients do not achieve pathological complete response and hence suffer from relapse, metastases and inevitable death. The exploration of trustworthy and timely biomarkers for CCRT response is urgently called for. This review focused upon a broad spectrum of biomarkers, including circulating tumor cells, DNA, RNA, oncogenes, tumor suppressor genes, epigenetics, impaired DNA mismatch repair, patient-derived xenografts, in vitro tumor organoids, immunity and microbiomes. Utilizing proper biomarkers can assist in categorizing appropriate patients by the most efficient treatment modality with the best outcome and accompanied by minimal side effects. The purpose of this review is to inspect and analyze accessible data in order to fully realize the promise of precision oncology for rectal cancer patients.

Antiproliferation- and Apoptosis-Inducible Effects of a Novel Nitrated [6,6,6]Tricycle Derivative (SK2) on Oral Cancer Cells.

The benzo-fused dioxabicyclo[3.3.1]nonane core is the central framework in several natural products. Using this core, we had developed a novel nitrated [6,6,6]tricycle-derived compound containing an n-butyloxy group, namely, SK2. The anticancer potential of SK2 was not assessed. This study aimed to determine the antiproliferative function and investigated possible mechanisms of SK2 acting on oral cancer cells. SK2 preferentially killed oral cancer cells but caused no harmful effect on non-malignant oral cells. After the SK2 exposure of oral cancer cells, cells in the sub-G1 phase accumulated. This apoptosis-like outcome of SK2 treatment was validated to be apoptosis via observing an increasing annexin V population. Mechanistically, apoptosis signalers such as pancaspase, caspases 8, caspase 9, and caspase 3 were activated by SK2 in oral cancer cells. SK2 induced oxidative-stress-associated changes. Furthermore, SK2 caused DNA damage (γH2AX and 8-hydroxy-2'-deoxyguanosine). In conclusion, a novel nitrated [6,6,6]tricycle-derived compound, SK2, exhibits a preferential antiproliferative effect on oral cancer cells, accompanied by apoptosis, oxidative stress, and DNA damage.

Kinetics of Moisture Loss and Oil Absorption of Pork Rinds during Deep-Fat, Microwave-Assisted and Vacuum Frying.

The fat content of fried pork rinds is high, and alternative frying helps reduce the oil content and maintain their texture and taste. Different frying methods such as microwave-assisted, traditional deep frying and vacuum frying on the breaking force, color, microstructure, water loss and oil absorption attributes of fried pork rinds were evaluated in this study. The fat content of microwave-assisted and vacuum-fried pork rinds was lower (24.2 g/100 g dry weight basis (db) and 17.1 g/100 g db, respectively) than that (35.6 g/100 g db) of traditional deep-fat frying. Non-uniform, holy and irregular surface microstructures were obtained by vacuum frying due to rapid mass transfer at low pressure. The first-order kinetic models of water loss and oil absorption of traditional and microwave-assisted frying of pork rinds were established. Microwave frying caused a faster moisture loss rate, shorter frying time and lower pork rind oil content, makes it an attractive substitute for traditional deep-fat frying.

Cross-Cycled Uplink Resource Allocation over NB-IoT.

Before each user equipment (UE) can send data using the narrowband physical uplink shared channel (NPUSCH), each UE should periodically monitor a search space in the narrowband physical downlink control channel (NPDCCH) to decode a downlink control indicator (DCI) over narrowband Internet of Things (NB-IoT). This monitoring period, called the NPDCCH period in NB-IoT, can be flexibly adjusted for UEs with different channel qualities. However, because low-cost NB-IoT UEs operate in the half-duplex mode, they cannot monitor search spaces in NPDCCHs and transmit data in the NPUSCH simultaneously. Thus, as we observed, a percentage of uplink subframes will be wasted when UEs monitor search spaces in NPDCCHs, and the wasted percentage is higher when the monitored period is shorter. In this paper, to address this issue, we formulate the cross-cycled resource allocation problem to reduce the consumed subframes while satisfying the uplink data requirement of each UE. We then propose a cross-cycled uplink resource allocation algorithm to efficiently use the originally unusable NPUSCH subframes to increase resource utilization. Compared with the two resource allocation algorithms, the simulation results verify our motivation of using the cross-cycled radio resources to achieve massive connections over NB-IoT, especially for UEs with high channel qualities. The results also showcase the efficiency of the proposed algorithm, which can be flexibly applied for more different NPDCCH periods.

Expression pattern and prognostic impact of glycoprotein non-metastatic B (GPNMB) in triple-negative breast cancer.

Glycoprotein non-metastatic B (GPNMB) is a transmembrane protein overexpressed in numerous cancers including triple-negative breast cancers (TNBC). It has been linked to promote cancer aggressiveness and implicated as a novel target for GPNMB-expressing cancers. In current study, we aimed to explore the clinical significance of GPNMB in TNBC. Among 759 specimens, immunohistochemistry (IHC) exhibited GPNMB expressions were variable in different subtypes and significantly higher in TNBC. Kaplan-Meier analysis revealed GPNMB overexpression in TNBC was associated with worse prognosis especially distant metastasis (P = 0.020, HR = 2.515, CI 1.154-5.480). Multivariate analysis showed GPNMB expression was an independent prognostic factor in terms of recurrence and distant metastasis (P = 0.008, HR = 3.22, CI 1.36-7.61; P = 0.017, HR = 3.08, CI 1.22-7.74). In silico analysis showed high mRNA expression of GPNMB was associated with distant metastasis and GPNMB was overexpressed in TNBC. Furthermore, GPNMB positively correlated with epithelial-mesenchymal transition (EMT) regulators, mesenchymal marker vimentin, MMP and integrins. The protein levels of Twist and MMP2 were upregulated by GPNMB overexpression in TNBC cells. GPNMB-enhanced cell invasion was attenuated by broad spectrum MMP inhibitor (GM 6001) and the selective inhibitor of MMP-2 (ARP100). In summary, GPNMB expression is prevalent in TNBC and may be implicated as a prognostic biomarker in patients with TNBC.

Fluoroquinolones as an alternative treatment for Klebsiella pneumoniae liver abscess and impact on hospital length of stay.

Klebsiella pneumoniae liver abscess (KPLA) is an endemic disease in East Asia. Patients with KPLA usually require prolonged intravenous (i.v.) ß-lactam therapy and hospitalisation. Fluoroquinolones have high oral bioavailability and the potential to shorten the duration of i.v. therapy. The aim of this study was to investigate the feasibility of fluoroquinolones as an alternative treatment for KPLA in Taiwan. Consecutive patients with KPLA in a medical centre in Taiwan between July 2012 and August 2019 were retrospectively enrolled. Clinical characteristics and outcomes were compared between cases treated with ß-lactams and fluoroquinolones. A multivariate logistic regression model and propensity-score adjusted analysis were performed to identify independent risk factors for prolonged hospitalisation. A total of 234 patients with KPLA were identified during the study period. Most patients received ß-lactams (n = 199; 85.0%), whilst only 35 (15.0%) received fluoroquinolones as the major therapy. Fluoroquinolones had similar clinical efficacy to ß-lactams even in critically ill patients. Patients treated with fluoroquinolones had a shorter i.v. antibiotics duration (18.9 ± 7.6 days vs. 28.5 ± 14.7 days; P < 0.001) and hospital length of stay (LOS) (20.9 ± 8.3 days vs. 29.5 ± 16.2 days; P < 0.001) than patients treated with ß-lactams. Major therapy with fluoroquinolones was an independent protective factor for hospital LOS > 14 days in all patients and for hospital LOS > 21 days in critically ill patients. In conclusion, fluoroquinolones were an effective alternative treatment for KPLA that resulted in a shorter duration of i.v. therapy and hospital LOS.

Structural evolution of in situ boron-doped SiGe ultrathin film analyzed by multi-optical methods.

In situ boron (B)-doped SiGe (BSG) layer is extensively used in the source (S)/(D) drain of metal-oxide-semiconductor field-effect transistors. An unexpected structural evolution occurs in BSG during metallization and activation annealing during actual fabrication, which involves a correlated interaction between B and SiGe. Herein, the complicated phenomena of the structural evolution of BSG were analyzed by 325 nm micro-Raman spectroscopy, x-ray photoelectron spectroscopy (XPS), reflective second harmonic generation (RSHG), and synchrotron x-ray diffraction (XRD). Optical inspection was integrated into these processes to establish a multi-optical method. 325 nm micro-Raman spectroscopy was used to determine variations in Si-Si, Si-Ge, and Ge-Ge bonds in BSG. XPS exhibited the binding energy evolution of Ge3d during different annealing processes at varied Ge ratios and B concentrations. RSHG revealed the polar Si-B and Ge-B bonds formed during annealing. Synchrotron XRD provided the structure and strain changes of BSG. Secondary-ion mass spectrometer profiles provided the species distribution, which was used to examine the results of multi-optical method. Furthermore, double-layered BSG (DBSG) with different B concentrations were analyzed using the multi-optical method. Results revealed that Ge aggregated in the homogeneous interface of DBSG, and that B dopants in BSG served as carrier providers that strongly influenced the BSG structure. However, BSG with excessive B concentration was unstable and increased the B content (SiB3) through metallization. For BSG with a suitable B concentration, the formation of Si-B and Ge-B bonds suppressed the diffusion of Ge from SiGe, thereby reducing the possibility of Ge loss and further B pipe-up in the heavily doped S/D region.

A compact and portable laser radioactive decontamination system using passive Q-switched fiber laser and polygon scanner.

We designed a compact and portable laser radioactive decontamination system using a passive Q-switched fiber laser and a polygon scanner. The passive Q-switched fiber laser produced average power of 15 W at a repetition rate of 60 kHz. The scanner system contained a 12-sided spinning polygon mirror driven by a DC motor. By varying the spinning speed of the polygon mirror, we achieved a processing speed of up to 88,500 mm/s. This system was demonstrated to be very efficient for radioactive decontamination on surfaces of various metals: stainless steel, brass, iron, and aluminum.

SET Overexpression is Associated with Worse Recurrence-Free Survival in Patients with Primary Breast Cancer Receiving Adjuvant Tamoxifen Treatment.

Adjuvant tamoxifen reduces the recurrence rate of estrogen receptor (ER)-positive breast cancer. Previous in vitro studies have suggested that tamoxifen can affect the cancerous inhibitor of protein phosphatase 2A (CIP2A)/protein phosphatase 2A (PP2A)/phosphorylation Akt (pAkt) signaling in ER-negative breast cancer cells. In addition to CIP2A, SET nuclear proto-oncogene (SET) oncoprotein is another intrinsic inhibitor of PP2A, participating in cancer progression. In the current study, we explored the clinical significance of SET, CIP2A, PP2A, and Akt in patients with ER-positive breast cancer receiving adjuvant tamoxifen. A total of 218 primary breast cancer patients receiving adjuvant tamoxifen with a median follow-up of 106 months were analyzed, of which 17 (7.8%) experienced recurrence or metastasis. In an immunohistochemical (IHC) stain, SET overexpression was independently associated with worse recurrence-free survival (RFS) (hazard ratio = 3.72, 95% confidence interval 1.26⁻10.94, p = 0.017). In silico analysis revealed mRNA expressions of SET, PPP2CA, and AKT1 significantly correlated with worse RFS. In vitro, SET overexpression reduced tamoxifen-induced antitumor effects and drove luciferase activity in an Estrogen receptor element (ERE)-dependent manner. In conclusion, SET is a prognostic biomarker in patients with primary ER-positive breast cancer receiving adjuvant tamoxifen and may contribute to the failure of the tamoxifen treatment by modulating the ER signaling. Our study warrants further investigation into the potential role of SET in ER-positive breast cancer.

Protective effect of indigo naturalis extract against oxidative stress in cultured human keratinocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Indigo naturalis is used in traditional Chinese medicine to treat various skin disorders. AIM OF THE STUDY: The aims were to explore the effect of indigo naturalis on suppressing oxidative stress and protein modifications by hydrogen peroxide (H(2)O(2)) and 4-hydroxy-2-nonenal (HNE), a lipid peroxidation product, in cultured primary human keratinocytes. MATERIALS AND METHODS: Indigo naturalis extract at a dose that did not cause cytotoxicity was added to cultured keratinocytes in the absence or the presence of H(2)O(2) or HNE. The degree of cytotoxicity, levels of reactive oxygen species (ROS), and amount of protein carbonyl groups were evaluated. RESULTS: Indigo naturalis extract at the concentration of 10µg/ml had no protective effect against H(2)O(2) or HNE-induced cytotoxicity, but decreased intracellular levels of ROS after H(2)O(2) treatment and suppressed the increase of protein carbonyl groups induced by HNE. CONCLUSION: Indigo naturalis possesses an inhibitory effect on formation of intracellular ROS induced by exogenous ROS and protein modification induced by HNE in human keratinocytes, which is relevant to the alleviation of inflammatory skin diseases.

Up-regulation of antioxidant enzymes and coenzyme Q(10) in a human oral cancer cell line with acquired bleomycin resistance.

Bleomycin (BLM) is an anti-cancer drug that can induce formation of reactive oxygen species (ROS). To investigate the association between up-regulation of antioxidant enzymes and coenzyme Q(10) (CoQ(10)) in acquired BLM resistance, one BLM-resistant clone, SBLM24 clone, was selected from a human oral cancer cell line, SCC61 clone. The BLM resistance of SBLM24 clone relative to a sub-clone of SCC61b cells was confirmed by analysis of clonogenic ability and cell cycle arrest. CoQ(10) levels and levels of Mn superoxide dismutase, glutathione peroxidase 1, catalase and thioredoxin reductase 1 were augmented in SBLM24 clone although there was also a mild increase in the expression of BLM hydrolase. Suppression of CoQ(10) levels by 4-aminobenzoate sensitized BLM-induced cytotoxicity. The results of suppression on enhanced ROS production by BLM and the cross-resistance to hydrogen peroxide in SBLM24 clone further demonstrated the development of adaptation to oxidative stress during the formation of acquired BLM resistance.

Effect of mitochondrial dysfunction and oxidative stress on endogenous levels of coenzyme Q(10) in human cells.

Little is known about the regulation of endogenous CoQ(10) levels in response to mitochondrial dysfunction or oxidative stress although exogenous CoQ(10) has been extensively used in humans. In this study, we first demonstrated that acute treatment of antimycin A, an inhibitor of mitochondrial complex III, and the absence of mitochondrial DNA suppressed CoQ(10) levels in human 143B cells. Because these two conditions also enhanced formation of reactive oxygen species (ROS), we further investigated whether oxidative stress or mitochondrial dysfunction primarily contributed to the decrease of CoQ(10) levels. Results showed that H(2)O(2) augmented CoQ(10) levels, but carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP), a chemical uncoupler, decreased CoQ(10) levels in 143B cells. However, H(2)O(2) and FCCP both increased mRNA levels of multiple COQ genes for biosynthesis of CoQ(10) . Our findings suggest that ROS induced CoQ(10) biosynthesis, whereas mitochondrial energy deficiency caused secondary suppression of CoQ(10) levels possibly due to impaired import of COQ proteins into mitochondria.