14-3-3σ downregulation sensitizes pancreatic cancer to carbon ions by suppressing the homologous recombination repair pathway.

This study explored the role of 14-3-3σ in carbon ion-irradiated pancreatic adenocarcinoma (PAAD) cells and xenografts and clarified the underlying mechanism. The clinical significance of 14-3-3σ in patients with PAAD was explored using publicly available databases. 14-3-3σ was silenced or overexpressed and combined with carbon ions to measure cell proliferation, cell cycle, and DNA damage repair. Immunoblotting and immunofluorescence (IF) assays were used to determine the underlying mechanisms of 14-3-3σ toward carbon ion radioresistance. We used the BALB/c mice to evaluate the biological behavior of 14-3-3σ in combination with carbon ions. Bioinformatic analysis revealed that PAAD expressed higher 14-3-3σ than normal pancreatic tissues; its overexpression was related to invasive clinicopathological features and a worse prognosis. Knockdown or overexpression of 14-3-3σ demonstrated that 14-3-3σ promoted the survival of PAAD cells after carbon ion irradiation. And 14-3-3σ was upregulated in PAAD cells during DNA damage (carbon ion irradiation, DNA damaging agent) and promotes cell recovery. We found that 14-3-3σ resulted in carbon ion radioresistance by promoting RPA2 and RAD51 accumulation in the nucleus in PAAD cells, thereby increasing homologous recombination repair (HRR) efficiency. Blocking the HR pathway consistently reduced 14-3-3σ overexpression-induced carbon ion radioresistance in PAAD cells. The enhanced radiosensitivity of 14-3-3σ depletion on carbon ion irradiation was also demonstrated in vivo. Altogether, 14-3-3σ functions in tumor progression and can be a potential target for developing biomarkers and treatment strategies for PAAD along with incorporating carbon ion irradiation.

UBA2 as a Prognostic Biomarker and Potential Therapeutic Target in Glioma.

BACKGROUND: Gliomas are characterized by aggressive behavior, leading to severe disability and high mortality. Ubiquitin-like modifier activating enzyme 2 (UBA2) is a subunit of the E1-activating enzyme involved in the SUMOylation (SUMO, small ubiquitin-related modifier) of numerous proteins. Although the abnormality of UBA2 is linked to the progression of various tumor types, the role of UBA2 in glioma is still unknown. METHODS: A bioinformatic analysis using several public databases was conducted to examine the expression level, clinicopathological correlations, and prognostic significance of UBA2 in glioma. The correlation between UBA2 expression and drug sensitivity in cancers was also explored. Multiple cellular experiments were conducted to validate the role of UBA2 in glioma. RESULTS: Analysis of multiple databases and cellular experiments revealed that UBA2 was overexpressed in glioma tissues and cell lines, respectively. UBA2 expression in gliomas correlated with World Health Organization (WHO) grade, IDH gene status, 1p19q deletion, histological type, and immune cell infiltration in glioma. UBA2 expression in carcinomas also correlated with drug sensitivity. Kaplan-Meier analysis revealed that high expression of UBA2 predicted poorer survival in glioma patients. A nomogram model containing UBA2 expression was constructed for clinical practice. Knockdown of UBA2 was observed to suppress glioma cell progression and sensitize glioma cells to irradiation in vitro. CONCLUSION: Overall, this research showed that UBA2 might be involved not only in the development of glioma but also in the regulation of immunity, drug sensitivity, and radiosensitivity. Therefore, UBA2 may be a potential target for therapy and a candidate biomarker for glioma diagnosis and prognosis.

Radiosensitization of Osteosarcoma Cells Using the PARP Inhibitor Olaparib Combined with X-rays or Carbon Ions.

Objective: Osteosarcomas are derived from bone-forming mesenchymal cells that are insensitive to radiation. This study aimed to investigate the radiosensitization of osteosarcoma cells (U2OS and K7M2) using the PARP inhibitor olaparib combined with X-rays or carbon ions (C-ions). Methods: The effect of olaparib on the proliferation of osteosarcoma cells after irradiation was assessed using CCK-8 and clone formation assays. Cells were treated with olaparib and/or radiation and the effects of olaparib on the cell cycle and apoptosis were analysed by flow cytometry after 48h. Immunofluorescence was used to stain the nuclei, γ-H2AX, 53BP1, and Rad51 proteins, and the number of γ-H2AX, 53BP1, and Rad51 foci was observed under a fluorescence microscope. The effect of olaparib combined with radiation on double-stranded DNA breaks in osteosarcoma cells was evaluated. Results: At the same radiation dose, olaparib reduced the proliferation and colony formation ability of irradiated osteosarcoma cells (P < 0.05). Olaparib monotherapy induced minimal apoptotic effects and G2/M phase arrest in osteosarcoma cells and irradiation alone induced moderate apoptosis and G2/M phase arrest. However, radiation combined with olaparib significantly increased the percentage of apoptotic cells and G2/M phase arrest in osteosarcoma cells (P < 0.05). Immunofluorescence experiments showed that compared to the radiation group, the formation of γ-H2AX and 53BP1 foci was significantly increased in the combined group (P < 0.05). The expression levels of Rad51 foci in the irradiated group were higher than those in the control group (P < 0.05). However, the number of Rad51 foci in the combined group was significantly decreased (P < 0.05). Conclusion: The PARP inhibitor olaparib combined with irradiation (X-rays or C-ions) enhanced the radiosensitivity of osteosarcoma cell lines (U2OS and K7M2). Our findings provide a potential theoretical basis for the clinical application of olaparib in overcoming radiation resistance in osteosarcoma.

Efficacy and safety of carbon ion radiotherapy for chordomas: a systematic review and meta-analysis.

OBJECTIVE: Carbon ion radiotherapy (C-ion RT) for chordomas has been gradually performed in several research centres. This study aimed to systematically review the results of clinical reports from these institutions and to evaluate the safety and efficacy of C-ion RT. METHODS: In accordance with the PRISMA guidelines and set search strategies, we searched four databases for articles from their inception to February 11, 2023. These articles were screened, and data were extracted independently by two researchers. STATA 14.0 was used for statistical analysis of survival results. RESULTS: A total of 942 related articles were retrieved, 11 of which were included. Regarding lesion location, 57% (n = 552) originated in the sacral region, 41% (n = 398) in the skull base, and 2% (n = 19) in the spine (upper cervical). The local control (LC) rates at 1, 2, 3, 5, 9, and 10 years in these studies were 96%, 93%, 83%, 76%, 71%, and 54%, respectively. The overall survival (OS) rates at 1, 2, 3, 5, 9, and 10 years in these studies were 99%, 100%, 93%, 85%, 76%, and 69%, respectively. Acute and late toxicities were acceptable, acute toxicities were mainly grade 1 to grade 2 and late toxicities were mainly grade 1 to grade 3. CONCLUSION: C-ion RT has attractive clinical application prospects and is an important local treatment strategy for chordomas. Encouraging results were observed in terms of LC and OS. Meanwhile, the acute and late toxicities were acceptable. PROSPERO registration number: CRD42023398792.

Charged particle therapy for high-grade gliomas in adults: a systematic review.

High-grade gliomas are the most common intracranial malignancies, and their current prognosis remains poor despite standard aggressive therapy. Charged particle beams have unique physical and biological properties, especially high relative biological effectiveness (RBE) of carbon ion beam might improve the clinical treatment outcomes of malignant gliomas. We systematically reviewed the safety, efficacy, and dosimetry of carbon-ion or proton radiotherapy to treat high-grade gliomas. The protocol is detailed in the online PROSPERO database, registration No. CRD42021258495. PubMed, EMBASE, Web of Science, and The Cochrane Library databases were collected for data analysis on charged particle radiotherapy for high-grade gliomas. Until July 2022, two independent reviewers extracted data based on inclusion and exclusion criteria. Eleven articles were eligible for further analysis. Overall survival rates were marginally higher in patients with the current standard of care than those receiving concurrent intensity-modulated radiotherapy plus temozolomide. The most common side effects of carbon-ion-related therapy were grade 1-2 (such as dermatitis, headache, and alopecia). Long-term toxicities (more than three to six months) usually present as radiation necrosis; however, toxicities higher than grade 3 were not observed. Similarly, dermatitis, headache, and alopecia are among the most common acute side effects of proton therapy treatment. Despite improvement in survival rates, the method of dose-escalation using proton boost is associated with severe brain necrosis which should not be clinically underestimated. Regarding dosimetry, two studies compared proton therapy and intensity-modulated radiation therapy plans. Proton therapy plans aimed to minimize dose exposure to non-target tissues while maintaining target coverage. The use of charged-particle radiotherapy seems to be effective with acceptable adverse effects when used either alone or as a boost. The tendency of survival outcome shows that carbon ion boost is seemingly superior to proton boost. The proton beam could provide good target coverage, and it seems to reduce dose exposure to contralateral organs at risk significantly. This can potentially reduce the treatment-related dose- and volume-related side effects in long-term survivors, such as neurocognitive impairment. High-quality randomized control trials should be conducted in the future. Moreover, Systemic therapeutic options that can be paired with charged particles are necessary.

Efficacy and safety of proton beam therapy for rhabdomyosarcoma: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate and conduct a meta-analysis on the efficacy and safety of proton beam therapy (PBT) for rhabdomyosarcoma (RMS). METHODS: We searched for articles using PubMed, Embase, Cochrane Library, and Web of Science databases from their inception to December 22, 2022. Two researchers independently screened literature and extracted data. Statistical analyses were performed using STATA version 14.0. RESULTS: We got 675 candidate articles, of which 11 studies were included in our study according to the inclusion and exclusion criteria. Of the 544 RMS patients who received PBT. The local control (LC) rate at 1, 2, 3, 4, and 5 years were 96% (95% confidence interval (CI) 0.91-1.01), 93% (95% CI 0.86-1.00), 78% (95% CI 0.71-0.85), 85% (95% CI 0.78-0.92), and 84% (95% CI 0.74-0.95), respectively. The progression-free survival (PFS) rate at 1, 2, 3, 4, and 5 years were 82% (95% CI 0.72-0.92), 73% (95% CI 0.61-0.84), 63% (95% CI 0.47-0.79), 64% (95% CI 0.54-0.74), and 76% (95% CI 0.59-0.94), respectively. The overall survival (OS) rate at 1, 2, 3, 4, and 5 years were 93% (95% CI 0.86-1.00), 85% (95% CI 0.76-0.95), 80% (95% CI 0.63-0.96), 71% (95% CI 0.62-0.80), and 82% (95% CI 0.71-0.94), respectively. Acute and late toxicities were mainly grades 1 to 2 in all studies. CONCLUSION: As an advantageous RT technique, PBT is an emerging option for patients with RMS, particularly children and adolescents patients. The data showed that PBT is a feasible, safe, and effective modality for RMS, showing promising LC, OS, PFS, and lower acute and late toxicities. PROSPERO registration number: CRD42022329154.

Efficacy and safety of carbon ion radiotherapy for bone sarcomas: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to systematically evaluate and conduct a meta-analysis of the efficacy and safety of carbon ion radiotherapy for bone sarcomas. METHODS: We searched for articles using the PubMed, Embase, Cochrane Library, and the Web of Science databases from their inception to January 12, 2022. Two researchers independently screened the literature and extracted data based on the inclusion and exclusion criteria. Statistical analyses were performed using STATA version 14.0. RESULTS: We searched for 4378 candidate articles, of which 12 studies were included in our study according to the inclusion and exclusion criteria. Of the 897 BSs patients who received carbon ion radiotherapy in the studies, 526 patients had chordoma, 255 patients had chondrosarcoma, 112 patients had osteosarcoma, and 4 patients had other sarcomas. The local control rate at 1, 2, 3, 4, 5, and 10 years in these studies were 98.5% (95% confidence interval [CI] = 0.961-1.009, I2 = 0%), 85.8% (95% CI = 0.687-1.030, I2 = 91%), 86% (95% CI = 0.763-0.957, I2 = 85.3%), 91.1% (95% CI = 0.849-0.974), 74.3% (95% CI = 0.666-0.820, I2 = 85.2%), and 64.7% (95% CI = 0.451-0.843, I2 = 95.3%), respectively. The overall survival rate at 1, 2, 3, 4, 5, and 10 years in these studies were 99.9% (95% CI = 0.995-1.004, I2 = 0%), 89.6% (95% CI = 0.811-0.980, I2 = 96.6%), 85% (95% CI = 0.750-0.950, I2 = 89.4%), 92.4% (95% CI = 0.866-0.982), 72.7% (95% CI = 0.609-0.844, I2 = 95.3%), and 72.1% (95% CI = 0.661-0.781, I2 = 46.5%), respectively. Across all studies, the incidence of acute and late toxicities was mainly grade 1 to grade 2, and grade 1 to grade 3, respectively. CONCLUSION: As an advanced radiotherapy, carbon ion radiotherapy is promising for patients with bone sarcomas that are unresectable or residual after incomplete surgery. The data indicated that carbon ion radiotherapy was safe and effective for bone sarcomas, showing promising results for local control, overall survival, and lower acute and late toxicity. PROSPERO REGISTRATION NUMBER: CRD42021258480.

The Effects of Angry Expressions and Fearful Expressions on Duration Perception: An ERP Study.

Little is known about the electrophysiological basis of the effect of threat-related emotional stimuli with different motivational direction on duration perception. Thus, event-related potentials were employed to examine the effects of angry expressions and fearful expressions on perception of different duration (490-910 ms). Behavioral results showed there was a greater underestimation of the duration of angry expressions (approach-motivated negative stimuli) than fearful expressions (withdrawal-motivated negative stimuli), compared with neutral expressions. Event-related potentials results showed that, the area of Contingent Negative Variation (CNV) evoked by angry expression, fearful expression and neutral expression gradually increased. These results indicated that specific electrophysiological mechanisms may underlie the attention effects of angry and fearful expressions on timing. Specifically, compared with neutral expressions, fearful expressions and angry expressions both are likely to distract more attentional resources from timer, in particular, angry expressions attract more attention resources than fearful expressions from timer. The major contribution of the current study is to provide electrophysiological evidences of fear vs. anger divergence in the aspect of time perception and to demonstrate beyond the behavioral level that the categorization of threat-related emotions should be refined so to highlight the adaptability of the human defense system.

Charged Particle Irradiation for Pancreatic Cancer: A Systematic Review of In Vitro Studies.

PURPOSE: Given the higher precision accompanied by optimized sparing of normal tissue, charged particle therapy was thought of as a promising treatment for pancreatic cancer. However, systematic preclinical studies were scarce. We aimed to investigate the radiobiological effects of charged particle irradiation on pancreatic cancer cell lines. METHODS: A systematic literature search was performed in EMBASE (OVID), Medline (OVID), and Web of Science databases. Included studies were in vitro English publications that reported the radiobiological effects of charged particle irradiation on pancreatic cancer cells. RESULTS: Thirteen carbon ion irradiation and seven proton irradiation in vitro studies were included finally. Relative biological effectiveness (RBE) values of carbon ion irradiation and proton irradiation in different human pancreatic cancer cell lines ranged from 1.29 to 4.5, and 0.6 to 2.1, respectively. The mean of the surviving fraction of 2 Gy (SF2) of carbon ion, proton, and photon irradiation was 0.18 ± 0.11, 0.48 ± 0.11, and 0.57 ± 0.13, respectively. Carbon ion irradiation induced more G2/M arrest and a longer-lasting expression of γH2AX than photon irradiation. Combination therapies enhanced the therapeutic effects of pancreatic cell lines with a mean standard enhancement ratio (SER) of 1.66 ± 0.63 for carbon ion irradiation, 1.55 ± 0.27 for proton irradiation, and 1.52 ± 0.30 for photon irradiation. Carbon ion irradiation was more effective in suppressing the migration and invasion than photon irradiation, except for the PANC-1 cells. CONCLUSIONS: Current in vitro evidence demonstrates that, compared with photon irradiation, carbon ion irradiation offers superior radiobiological effects in the treatment of pancreatic cancer. Mechanistically, high-LET irradiation may induce complex DNA damage and ultimately promote genomic instability and cell death. Both carbon ion irradiation and proton irradiation confer similar sensitization effects in comparison with photon irradiation when combined with chemotherapy or targeted therapy.

Integration of conflict resolution and positive emotions: Electrophysiological evidence.

Previous studies have shown that conflict monitoring is integrated with negative emotions. However, the idea that conflict resolution facilitates positive stimuli processing has not reached a consistent conclusion. We suggested that conflict resolution was integrated with positive emotions. The present study used ERPs, took the flanker task as primes, set different durations (i.e., 600 ms and 1200 ms) between the resolution of conflicts and the presentation of targets, and chose affective words as targets to investigate the affective effect of cognitive conflict during the resolution stage. Participants' task was to react to the flanker task and then evaluate the valence of the target words. The findings of experiment1 (600 ms) and experiment2 (1200 ms) were consistent. Behavioral results showed that the conflict effect was significant, and the positive signal effect of conflict resolution was found. In ERPs results, the enhanced N2 amplitudes for incongruent primes showed a significant conflict effect. The enhanced conflict SP amplitudes for incongruent primes reflected conflict resolution. As expected, the enhanced N400 amplitudes for positive targets after incongruent primes indicated that conflict resolution facilitated positive stimuli processing. Time-frequency analyses showed that incongruent primes elicited larger theta (4-8 Hz) power than congruent primes over the frontal areas. More importantly, we found that theta (4-8 Hz) power for positive targets after incongruent primes was lower than those after congruent primes over the central areas. These findings suggested that conflict resolution facilitated positive stimulus processing, and this positive effect was a carry-over effect, which indicated that conflict resolution was integrated with positive emotions.

Low-Dose Radiation Therapy Promotes Radiation Pneumonitis by Activating NLRP3 Inflammasome.

PURPOSE: To determine the role of NLRP3 inflammasome activation in low-dose radiation-induced radiation pneumonitis (RP) and to assess whether inhibition or deletion of the NLRP3 inflammasome is critical for conferring protection against RP. METHODS AND MATERIALS: The human monocytic THP-1 cells were treated with increasing doses of radiation to assess the activation of NLRP3 by Western blot and enzyme-linked immunosorbent assay. Reactive oxygen species (ROS) production was measured by flow cytometry, with or without ROS inhibitor treatment. A mouse thoracic radiation model that received different doses of radiation was used, and the lung tissues of thoracic-irradiated nlrp3-/- and wild-type C57BL/6 mice were examined by hematoxylin and eosin and immunofluorescence staining. The concentrations of cytokines in the bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay and Luminex multiplex assays. Lipopolysaccharide (LPS) was administered intranasally 28 days after thoracic irradiation, and NLRP3 inhibitor, MCC950 was administered intraperitoneally after irradiation at 2 different doses. RESULTS: (1) The NLRP3 inflammasome was activated in 2 Gy irradiated THP-1 cells; NLRP3 and cleaved-caspase-1 levels were not associated with dose escalation of irradiation. (2) Activation of the NLRP3 inflammasome was mediated by ROS, and ROS inhibitor treatment decreased the production of IL-1ß and IL-18 in vitro. (3) NLRP3 was activated in mouse lungs by irradiation at 2 Gy, 4 Gy, and 16 Gy, and NLRP3 activation was continuous for 8 weeks. (4) NLRP3 deletion protects against LPS-mediated monocyte infiltration in the mouse lung. (5) The administration of MCC950 decreased the inflammation score of the mice irradiated with 2 Gy or 16 Gy in vivo. CONCLUSIONS: Our results indicate that the NLRP3 inflammasome is activated by low-dose irradiation both in vitro and in vivo. Inhibition or deletion of NLRP3 can specifically alleviate the mouse lung inflammation caused by radiation and LPS treatment. This study reveals the mechanism of low-dose radiation therapy-induced RP and offers a possible treatment strategy.

Reward Modulates Affective Priming Effect in Cognitive Conflict Processing: Electrophysiological Evidence.

Previous research demonstrated that cognitive conflict could induce an affective priming effect, and the stage (detection/resolution) of conflict processing led to different directions (positive/negative) of the affective priming effect. We suggested that rewards play a critical role in the affective priming effect on conflict resolution. The present study used event-related potentials (ERPs), using the arrow flanker task as primes and choosing specific affective words as targets to investigate the affective priming effect induced by cognitive conflict during the resolution stage. Our question was whether rewards created a modulating effect. Participants were asked to judge the congruency of the prime stimuli and then evaluate the valence of the target words. For behavioral results, the conflict effect was significant, and the reward promoted the behavioral performance of participants. For ERP results, enhanced N2 amplitudes for incongruent primes indicated a significant conflict effect. More importantly, as expected, in the rewarded condition, the enhanced N400 amplitudes for positive targets following incongruent primes were found, indicating a positive priming effect. However, in the unrewarded condition, the reduced N400 amplitudes for positive targets following incongruent primes were found, indicating conflict resolution hindered the processing of positive stimuli. These findings suggested that cognitive conflict-induced the positive priming effect during the resolution stage and that rewards had a moderating effect on the positive priming effect.

The audio-visual integration effect on music emotion: Behavioral and physiological evidence.

Previous research has indicated that, compared to audio-only presentation, audio-visual congruent presentation can lead to a more intense emotional response. In the present study, we investigated the audio-visual integration effect on emotions elicited by positive or negative music and the role of visual information presentation durations. The participants were presented with audio-only condition, audio-visual congruent condition, and audio-visual incongruent condition and then required to judge the intensity of emotional experience elicited by the music. Their emotional responses to the music were measured using self-ratings and physiological aspects, including heart rate, skin temperature, EMG root mean square and prefrontal EEG. Relative to the audio-only presentation, the audio-visual congruent presentation led to a more intense emotional response. More importantly, the audio-visual integration occurred both in the positive music and in the negative music. Furthermore, the audio-visual integration effect was larger for positive music than for negative music; meanwhile the audio-visual integration effect was strongest with the visual information presented within 80s for negative music, which indicated that this integration effect was more likely to occur in the negative music. These results suggest that when the music was positive, the effect of audio-visual integration was greater. When the music was negative, the modulation effect of the presentation durations of visual information on the music-induced emotion was more significant.

[Silencing Effect of APE1 on the Radiosensitivity of Non-small Cell Lung Cancer Cells].

OBJECTIVE: To determine the effect of apurinic/apyrimidinic endonuclease-1(APE1) on the radiosensitivity of non-small cell lung cancer cells. METHODS: The expression of APE1 was detected by immunohistochemistry in 20 surgical specimen of non-small cell lung cancer tissues and 5 cases of pericarcinous lung tissues.The expressions of APE1 protein and mRNA in non-small cell lung cancer cell lines(A549, H460, H1299)and normal lung epithelial cell lines was detected by Western blot and qRT-PCR. The A549 and H460 stable cell lines with silencing of APE1 were constructed.The expression of APE1 in the silenced and non-silenced cells after exposure to 0-6 Gy radiation was detected by Western blot. The effect of silencing of APE1 was measured by colony formation assay, the proliferation of non-small cell lung cancer cells detected by CCK-8 assay, and the apoptosis of non-small cell lung cancer cells detected by Annexin Ⅴ/PI flow cytometry. RESULTS: The expression of APE1 was upregulated in non-small cell lung cancer tissues and cell lines.Radiation induced the expression of APE1 in non-small cell lung cancer cells in a dose responsive way. The silencing of APE1 inhibited the expression of APE1 induced by radiation in A549 and H460 cells. Exposure to radiation of the cells with silenced APE1 further inhibited cell colony formation and cell proliferation, and promoted the apoptosis of non-small cell lung cancer cells ( P<0.05). CONCLUSION: Silencing of APE1 enhances the radiosensitivity of non-small cell lung cancer cells.

Cognitive conflict could facilitate negative stimulus processing: evidence from trait anxiety in the flanker paradigm.

The present study used event-related potentials to investigate the affective priming effect of cognitive conflict and the influence of trait anxiety during the early stage of conflict processing. Participants with relatively high-trait or low-trait anxiety were tested using a combination of flanker task (congruent or incongruent arrows) as primes presented 200 ms before positive or negative words as targets. Behavioral results showed that response times were shorter for negative targets following incongruent primes relative to congruent primes, and vice versa, suggesting that conflicts facilitated the processing of negative targets. Event-related potential results revealed that the N2 amplitudes (280-320 ms) for incongruent stimuli were significantly more negative than those for congruent stimuli, indicating a significant conflict effect. Moreover, the N400 amplitudes (580-680 ms) for positive targets after congruent primes were significantly more negative than those after incongruent primes, but no significant difference was found in the N400 amplitudes after congruent primes and incongruent primes for negative targets, indicating that conflicts had a negative effect on the subsequent processing. In addition, in the high-trait anxiety, the N400 amplitudes for negative targets after incongruent primes were significantly more negative than those after incongruent primes, and vice versa, indicating that conflicts facilitated the processing of negative targets. These findings showed that conflicts could facilitate the processing of negative targets and be viewed as aversive signals during the early stage of conflict processing and that high-trait anxiety promoted the negative effect induced by conflicts.

Vascular endothelial growth receptor 1 acts as a stress-associated protein in the therapeutic response to thalidomide.

Thalidomide (THD) exhibits antitumor effects in several types of cancer. However, the failure of THD to inhibit tumor growth has also been observed in a number of murine models in vivo. The mechanism involved in the therapeutic failure of THD remains unclear. The present study demonstrated that, accompanied by growth-arresting and apoptosis-inducing effects (P<0.05), THD upregulated vascular endothelial growth factor receptor 1 (VEGFR1) expression levels in CT26 murine colorectal carcinoma cell lines. This in vitro phenomenon was also observed in various other cell lines, including human umbilical vein endothelial cells, SW480, SW620 and HCT116. Reactive oxygen species (ROS) levels were increased compared with those in the untreated control when cells were exposed to THD (P<0.05). Furthermore, results suggested that ROS suppression may have provoked the induction of VEGFR1 expression to some extent. In addition, the results revealed that THD failed to inhibit CT26 tumor growth in vivo and the expression of VEGFR1 protein was elevated by THD treatment compared with the control group in the murine colorectal tumor model (P<0.05). The results of further experiments suggested that VEGFR1 was elevated in response to various stress-associated situations, including chemotherapy, radiotherapy and thermotherapy, which indicate that it may act as a stress-associated protein. The present findings provide a foundation for the future study of VEGFR1-targeted therapy to enhance the efficacy of current therapies.

Inhibition of Return Is Modulated by Negative Stimuli: Evidence from Subliminal Perception.

Inhibition of return (IOR) is considered as a "blindness mechanism" that emotional stimuli have no impact on it. Most previous studies suggested that IOR was not modulated by emotional cues. However, one key question they ignored was that only supraliminal presentation of emotional stimuli was used in their experiments. The present experiment is aimed at exploring the possible interaction between the IOR effect and subliminal emotional process. We manipulated three different kinds of valence strength of negative stimuli (high negative, HN; moderate negative, MN; low negative, LN) which were presented under the subliminal perception level and an event-related potentials (ERPs) recording was adopted. The results showed that, compared to MN and HN, the IOR effect triggered by peripheral cues was more significant for LN with aspects of behavioral and electrophysiological data (a reduction P1 effect, more negative on cued trials than on uncued trials for both early posterior Nd and Nd components). This indicated that IOR can be modulated by emotionally relevant stimuli. The automatic processing that was triggered by subliminally negative stimuli of peripheral cues had an influence on the shifting of spatial attention that was triggered by IOR. These two mechanisms may occur in the perceptual stage simultaneously.