Circ_0007432 promotes non-small cell lung cancer progression and macrophage M2 polarization through SRSF1/KLF12 axis.

Circular RNAs (circRNAs) plays critical roles in non-small cell lung cancer (NSCLC) development. Herein, we illustrated the effects of circ_0007432 on malignant features of NSCLC. We found that circ_0007432 played a promoting role in NSCLC progression, lying in accelerating cell viability, migration and invasion of NSCLC cells, promoting M2 macrophage polarization, suppressing cell apoptosis of NSCLC cells, and enhancing tumor growth in vivo. Mechanistically, the interactions among circ_0007432, SRSF1, KLF12, and IL-8 were validated by RNA-binding protein immunoprecipitation (RIP), electrophoretic mobility shift assay (EMSA), RNA pull-down, dual luciferase reporter assay and chromatin immunoprecipitation (ChIP) assays. Circ_0007432 upregulated KLF12 by recruiting SRSF1. KLF12 facilitated IL-8 expression and release by binding to IL-8 promoter. Furthermore, the role of circ_0007432/SRSF1/KLF12/IL-8 axis in malignant phenotypes of tumor cells or macrophage polarization was investigated using rescue experiments. In conclusion, circ_0007432 bound with SRSF1 to stabilize KLF12 and then promote IL-8 release, thus promoting malignant behaviors of NSCLC cells and M2 macrophage polarization.

Ferroptosis in hepatocellular carcinoma, from mechanism to effect.

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor worldwide, characterized by high malignancy and rapid progression. Most cases are diagnosed at intermediate to advanced stages. Current treatment methods have limited efficacy, resulting in high recurrence rates and poor prognosis. Radical hepatectomy remains the primary treatment for HCC, complemented by radiotherapy, chemotherapy, targeted therapy, and immunotherapy. Despite significant improvement in patient prognosis with radical hepatectomy, the five-year survival rate post-surgery remains low; thus necessitating exploration of more effective therapeutic approaches. Ferroptosis is a recently discovered form of cell death that can modulate the occurrence and development of HCC through various mechanisms. This article aims to elucidate the mechanism of ferroptosis and its impact on HCC development to provide novel insights for diagnosis and treatment.

Effect of Repetitive Peripheral Magnetic Stimulation on Patients With Low Back Pain: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: The purpose of this meta-analysis was to investigate the effects of repetitive peripheral magnetic stimulation (rPMS) on pain intensity, functional mobility, and kinesiophobia in individuals with low back pain (LBP). DATA SOURCES: The PubMed, Physiotherapy Evidence Database, Embase, Cochrane Library, and Web of Science databases were systematically searched from inception until November 25, 2022. STUDY SELECTION: Eligible randomized controlled trials contained information on the population (LBP), intervention (rPMS), and outcomes (pain intensity, functional mobility, and kinesiophobia). Participants in the rPMS intervention group were compared with those in sham or other control groups. Two independent researchers searched for, screened, and qualified the articles. DATA EXTRACTION: Two independent researchers extracted key information from each eligible study. The authors' names, year of publication, setting, total sample size, rPMS parameters, baseline/mean difference (MD), and 95% confidence interval (CI) were extracted using a standardized form, and the methodological quality was assessed using the Physiotherapy Evidence Database score and GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system. DATA SYNTHESIS: Of 733 studies identified, 6 randomized controlled trials (n = 139) were included for meta-analysis. Compared with sham rPMS or other therapy, rPMS showed significant efficacy in reducing pain intensity (visual analog scale: MD, -1.89; 95% CI, -3.32 to -0.47; P<.05; very low-quality evidence). Significant efficacy was also found in terms of functional disability (Oswestry Disability Index: MD, -8.39; 95% CI, -13.65 to -3.12; P<.001; low-quality evidence). However, there was no statistically significant between-group difference on the Tampa scale of kinesiophobia (MD, -1.81; 95% CI, -7.60 to 3.98; P>.05; very low-quality evidence). CONCLUSIONS: This meta-analysis found very low- to low-quality evidence that rPMS can be used to reduce pain intensity and improve functional disability in individuals with LBP. However, no significant effect of rPMS on kinesiophobia was found.

Bibliometric analysis of electroencephalogram research in mild cognitive impairment from 2005 to 2022.

Background: Electroencephalogram (EEG), one of the most commonly used non-invasive neurophysiological examination techniques, advanced rapidly between 2005 and 2022, particularly when it was used for the diagnosis and prognosis of mild cognitive impairment (MCI). This study used a bibliometric approach to synthesize the knowledge structure and cutting-edge hotspots of EEG application in the MCI. Methods: Related publications in the Web of Science Core Collection (WosCC) were retrieved from inception to 30 September 2022. CiteSpace, VOSviewer, and HistCite software were employed to perform bibliographic and visualization analyses. Results: Between 2005 and 2022, 2,905 studies related to the application of EEG in MCI were investigated. The United States had the highest number of publications and was at the top of the list of international collaborations. In terms of total number of articles, IRCCS San Raffaele Pisana ranked first among institutions. The Clinical Neurophysiology published the greatest number of articles. The author with the highest citations was Babiloni C. In descending order of frequency, keywords with the highest frequency were "EEG," "mild cognitive impairment," and "Alzheimer's disease". Conclusion: The application of EEG in MCI was investigated using bibliographic analysis. The research emphasis has shifted from examining local brain lesions with EEG to neural network mechanisms. The paradigm of big data and intelligent analysis is becoming more relevant in EEG analytical methods. The use of EEG to link MCI to other related neurological disorders, and to evaluate new targets for diagnosis and treatment, has become a new research trend. The above-mentioned findings have implications in the future research on the application of EEG in MCI.

Design and Implementation of a Chain-Type Direct Push Drilling Rig for Contaminated Sites.

For sites where volatile organic compounds are present, the direct push method, in combination with other sensors for investigation, is a powerful method. The investigation process is an integrated drilling and sensing process, but the trajectory of the probe carrying the sensor is ambiguous. This paper explores and introduces the application of a chain-type direct push drilling rig by designing and building a chain-type direct push miniature drilling rig. This rig allows for indoor experimental studies of direct push trajectories. The chain-type direct push drilling model is proposed based on the mechanism of chain transmission. The drilling rig provides a steady direct thrust through the chain, which is driven by a hydraulic motor. In addition, the drilling tests and results described prove that the chain could be applied to direct push drilling. The chain-type direct push drilling rig can drill to a depth of 1940 mm in single-pass and up to 20,000 mm in multiple passes. The test results also indicate that it drills a total length of 462.461 mm and stops after 87.545 s of operation. The machine can provide a drilling angle of 0-90° and keep the borehole angle fluctuating within 0.6° with the characteristics of strong adjustability, flexibility, continuity, stability, and low disturbance, which is of great value and significance for studying the drilling trajectory of direct push tools and obtaining more accurate investigation data.

Circulating Metabolic Markers Related to the Diagnosis of Hepatocellular Carcinoma.

Primary liver carcinoma is the sixth most common cancer worldwide, while hepatocellular carcinoma (HCC) is the most dominant cancer type. Chronic hepatitis B and C virus infections and aflatoxin exposure are the main risk factors, while nonalcoholic fatty liver disease caused by obesity, diabetes, and metabolic syndrome are the more common risk factors for HCC. Metabolic disorders caused by these high-risk factors are closely related to the tumor microenvironment of HCC, revealing a possible cause-and-effect relationship between the two. These metabolic disorders involve many complex metabolic pathways, such as carbohydrate, lipid, lipid derivative, amino acid, and amino acid derivative metabolic processes. The resulting metabolites with significant abnormal changes in the concentration level in circulating blood may be used as biomarkers to guide the diagnosis, treatment, or prognosis of HCC. At present, there are high-throughput technologies that can quickly detect small molecular metabolites in many samples. Compared to tissue biopsy, blood samples are easier to obtain, and patients' willingness to participate is higher, which makes it possible to study blood HCC biomarkers. Over the past few years, a substantial body of research has been performed worldwide, and other potential biomarkers have been identified. Unfortunately, due to the limitations of each study, only a few markers have been widely verified and are suitable for clinical use. This review briefly summarizes the potential blood metabolic markers related to the diagnosis of HCC, mainly focusing on amino acids and their derivative metabolism, lipids and their derivative metabolism, and other possible related metabolisms.

Alteration of network connectivity in stroke patients with apraxia of speech after tDCS: A randomized controlled study.

Objective: This study aimed to examine the changes in the functional connectivity of the cortical speech articulation network after anodal transcranial direct current stimulation (A-tDCS) over the left lip region of the primary motor cortex (M1) in subacute post-stroke patients with apraxia of speech (AoS), and the effect of A-tDCS on AoS. Methods: A total of 24 patients with post-stroke AoS were randomized into two groups and received A-tDCS over the left lip region of M1 (tDCS group)/ sham tDCS (control group) as well as speech and language therapy two times per day for 5 days. Before and after the treatment, the AoS assessments and electroencephalogram (EEG) were evaluated. The cortical interconnections were measured using the EEG non-linear index of cross approximate entropy (C-ApEn). Results: The analysis of EEG showed that, after the treatment, the activated connectivity was all in the left hemisphere, and not only regions in the speech articulation network but also in the dorsal lateral prefrontal cortex (DLPFC) in the domain-general network were activated in the tDCS group. In contrast, the connectivity was confined to the right hemisphere and between bilateral DLPFC and bilateral inferior frontal gyrus (IFG) in the control group. In AoS assessments, the tDCS group improved significantly more than the control group in four of the five subtests. The results of multivariate linear regression analyses showed that only the group was significantly associated with the improvement of word repetition (P = 0.002). Conclusion: A-tDCS over the left lip region of M1 coupled with speech therapy could upregulate the connectivity of both speech-specific and domain-general networks in the left hemisphere. The improved articulation performance in patients with post-stroke AoS might be related to the enhanced connectivity of networks in the left hemisphere induced by tDCS. Clinical trial registration: ChiCTR-TRC-14005072.

tDCS-EEG for Predicting Outcome in Patients With Unresponsive Wakefulness Syndrome.

Objectives: We aimed to assess the role of transcranial direct current stimulation (tDCS) combined with electroencephalogram (EEG) for predicting prognosis in UWS cases. Methods: This was a historical control study that enrolled 85 patients with UWS. The subjects were assigned to the control (without tDCS) and tDCS groups. Conventional treatments were implemented in both the control and tDCS groups, along with 40 multi-target tDCS sessions only in the tDCS group. Coma Recovery Scale-Revised (CRS-R) was applied at admission. The non-linear EEG index was evaluated after treatment. The modified Glasgow Outcome Scale (mGOS) was applied 12 months after disease onset. Results: The mGOS improvement rate in the tDCS group (37.1%) was higher than the control value (22.0%). Linear regression analysis revealed that the local and remote cortical networks under unaffected pain stimulation conditions and the remote cortical network under affected pain stimulation conditions were the main relevant factors for mGOS improvement. Furthermore, the difference in prefrontal-parietal cortical network was used to examine the sensitivity of prognostic assessment in UWS patients. The results showed that prognostic sensitivity could be increased from 54.5% (control group) to 84.6% (tDCS group). Conclusions: This study proposes a tDCS-EEG protocol for predicting the prognosis of UWS. With multi-target tDCS combined with EEG, the sensitivity of prognostic assessment in patients with UWS was improved. The recovery might be related to improved prefrontal-parietal cortical networks of the unaffected hemisphere.

Contaminant migration and the retention behavior of a laterite-bentonite mixture engineered barrier in a landfill.

Groundwater pollution has become increasingly severe in recent years, particularly owing to leachate leakage in landfills. In this study, the migration of Cu2+ in a landfill and the retention behavior of a compacted laterite-bentonite engineered barrier system toward the contaminant were analyzed by a numerical simulation based on laboratory and field test results. The results show that the hydraulic conductivity of the laterite-bentonite mixture decreased with an increase in the bentonite ratio: The hydraulic conductivities of the laterite-bentonite mixture were 4.718 × 10-7, 2.103 × 10-7, 7.899 × 10-8, 3.918 × 10-8, and 1.614 × 10-8 cm/s when the bentonite ratios were 0, 2%, 5%, 10%, and 20%, respectively. The hydraulic conductivity of laterite and of the mixture with a bentonite ratio of 2% decreased gradually under infiltration of deionized water and CuSO4 solutions with concentrations of 0.01 and 0.1 mol/L. This could be attributed to the increased degree of flocculation of laterite with the increase in the solution concentration. The results of the numerical simulation indicate that the migration range of Cu2+ after 3650 days was approximately 1500 m. The retention efficiency of a 0.5 m engineered barrier for Cu2+ was 67%. However, the retention efficiency exceeded 83% when the engineered barrier thickness was increased to 1.0 m. The results of the laboratory tests and numerical simulation demonstrate that a compacted laterite-bentonite engineered barrier system has a good retention effect on Cu2+. These observations may provide effective concepts for the prevention and control of groundwater pollution in landfills.

Upregulation of Nei-Like DNA Glycosylase 3 Predicts Poor Prognosis in Hepatocellular Carcinoma.

BACKGROUND: Accumulating evidence has suggested that Nei-like DNA glycosylase 3 (NEIL3) is associated with human tumors. However, there are few studies on the role of NEIL3 in hepatocellular carcinoma (HCC). The aim of this study was to investigate the expression profile of NEIL3 and its clinical relevance in HCC. MATERIALS AND METHODS: A total of 130 HCC and corresponding nontumor tissues were collected to perform immunohistochemistry (IHC). The clinical relevance and prognostic value of NEIL3 in HCC were analyzed by the chi-square test, Kaplan-Meier analysis, the Cox proportional hazard model, and nomogram. RESULTS: IHC showed that the NEIL3 protein level was remarkably upregulated in tumor tissues compared with nontumor tissues (fold change = 1.24; P < 0.001). High NEIL3 expression was significantly correlated with BCLC stage (P=0.004) and TNM stage (P=0.005). Overall survival (OS) and disease-free survival (DFS) rates in the high NEIL3 expression group were significantly worse than those in the low NEIL3 expression group (P=0.007 and P=0.004, respectively). Furthermore, subgroup analysis showed that high NEIL3 expression predicted worse OS and DFS for HCC patients with advanced TNM stage, poorly differentiated tumor, HBsAg positive, or cirrhosis. Multivariate analysis and the prognostic nomograms revealed that tumor NEIL3 level may serve as a promising prognostic indicator for OS and DFS in HCC patients. CONCLUSION: Our findings suggested that NEIL3 might be a potential prognosis assessment marker and therapeutic target for HCC patients.

Multi-Target and Multi-Session Transcranial Direct Current Stimulation in Patients With Prolonged Disorders of Consciousness: A Controlled Study.

Objectives: To investigate the effect of multi-session transcranial direct current stimulation (tDCS) over the prefrontal area, left dorsolateral prefrontal cortex (DLPFC), and bilateral fronto-temporo-parietal cortices (FTPCs) in patients with prolonged disorders of consciousness (DOC) and to examine the altered cortical interconnections using non-linear electroencephalography (EEG). Methods: In this open-label controlled study, conventional treatments were implemented in both the control and tDCS groups, together with 80 tDCS sessions only in the tDCS group. The order of tDCS targets was as follows: prefrontal area, left FTPC, right FTPC, and left DLPFC. The Coma Recovery Scale-Revised (CRS-R) and non-linear EEG index were evaluated before and after the treatment. Additionally, the modified Glasgow Outcome Scale (mGOS) was used as a follow-up evaluation at 12 months after the disease onset. Results: The CRS-R improved significantly in both groups after the treatment. However, the CRS-R and mGOS were more significantly improved in the tDCS group than in the control group. Among the cross approximate entropy (C-ApEn) indices, the local CA-PA and CA-FA under the affected painful stimulus condition and all local and remote indices of the unaffected side under the unaffected painful stimulus condition were significantly higher in the tDCS group than in the control group. Multivariate logistic regression analysis revealed that group and type were the main relevant factors based on mGOS improvement. Multivariate linear regression analysis revealed that group, CA-FA, and CU-MTU were the main relevant factors based on CRS-R improvement under the affected painful stimulus conditions, whereas only CU-MTU and CU-FPU were relevant under the unaffected painful stimulus condition. Conclusion: Multi-target and multi-session tDCS could improve the cortical connections between the primary sensorimotor and frontal cortices of the affected hemisphere and the prefrontal-parietal and temporo-parietal associative cortical networks of the unaffected hemisphere. Thus, this tDCS protocol may be used as an add-on treatment for prolonged DOC.

Outcome Prediction in Unresponsive Wakefulness Syndrome and Minimally Conscious State by Non-linear Dynamic Analysis of the EEG.

Objectives: This study aimed to investigate the role of non-linear dynamic analysis (NDA) of the electroencephalogram (EEG) in predicting patient outcome in unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS). Methods: This was a prospective longitudinal cohort study. A total of 98 and 64 UWS and MCS cases, respectively, were assessed. During admission, EEGs were acquired under eyes-closed and pain stimulation conditions. EEG nonlinear indices, including approximate entropy (ApEn) and cross-ApEn, were calculated. The modified Glasgow Outcome Scale (mGOS) was employed to assess functional prognosis 1 year following brain injury. Results: The mGOS scores were improved in 25 (26%) patients with UWS and 42 (66%) with MCS. Under the painful stimulation condition, both non-linear indices were lower in patients with UWS than in those with MCS. The frontal region, periphery of the primary sensory area (S1), and forebrain structure might be the key points modulating disorders of consciousness. The affected local cortical networks connected to S1 and unaffected distant cortical networks connecting S1 to the prefrontal area played important roles in mGOS score improvement. Conclusions: NDA provides an objective assessment of cortical excitability and interconnections of residual cortical functional islands. The impaired interconnection of the residual cortical functional island meant a poorer prognosis. The activation in the affected periphery of the S1 and the increase in the interconnection of affected local cortical areas around the S1 and unaffected S1 to the prefrontal and temporal areas meant a relatively favorable prognosis.

Transcranial Direct Current Stimulation Over Prefrontal Areas Improves Psychomotor Inhibition State in Patients With Traumatic Brain Injury: A Pilot Study.

OBJECTIVES: Many post-traumatic patients with minimally conscious state are complicated by psychomotor inhibition state (PIS), which impedes further rehabilitation. The treatment of PIS is not satisfactory. This pilot study aimed to investigate effects of anodal transcranial direct current stimulation (A-tDCS) on PIS in post-traumatic patients and examine the altered cortical activation after tDCS using non-linear electroencephalogram (EEG). METHODS: The study included 10 patients with post-traumatic PIS. An A-B design was used. The patients received 4 weeks of sham tDCS during Phase A, and they received A-tDCS over the prefrontal area and left dorsolateral prefrontal cortex (DLPFC) for 4 weeks (40 sessions) during Phase B. Conventional treatments were administered throughout both phases. JFK Coma Recovery Scale-Revised (CRS-R), apathy evaluation scale (AES), and the EEG non-linear indices of approximate entropy (ApEn) and cross approximate entropy (C-ApEn) were measured before Phase A, before Phase B, and after Phase B. RESULTS: After A-tDCS treatment, CRS-R and AES were improved significantly. ApEn and C-ApEn results showed that the local cortical connection of bilateral sensorimotor areas with their peripheral areas could be activated by affected painful stimuli, while bilateral cerebral hemispheres could be activated by the unaffected painful-stimuli condition. Linear regression analysis revealed that the affected sensorimotor cortex excitability and unaffected local and distant cortical networks connecting the sensorimotor area to the prefrontal area play a major role in AES improvement. CONCLUSION: A-tDCS over the prefrontal area and left DLPFC improves PIS. The recovery might be related to increased excitability in local and distant cortical networks connecting the sensorimotor area to the prefrontal area. Thus, tDCS may be an alternative treatment for post-traumatic PIS.

Effects of Transcranial Direct Current Stimulation on Apraxia of Speech and Cortical Activation in Patients With Stroke: A Randomized Sham-Controlled Study.

Purpose The study aims to investigate, using anodal transcranial direct current stimulation (A-tDCS), over which site, the left lip region of primary motor cortex (M1) or the Broca's area, there would be better recovery from apraxia of speech (AoS) in patients with poststroke aphasia and to examine for altered activation in speech-related areas after tDCS with nonlinear electroencephalography (EEG). Method Fifty-two patients with AoS were randomized into A-tDCS over the left M1 (A-tDCS-M1), Broca's area, and sham tDCS groups who underwent 10 sessions of tDCS and speech treatment for 5 days. The EEG nonlinear index of approximate entropy was calculated for 6 subjects in each group before and after treatment. Results After treatment, the change in speech-language performance improved more significantly in the A-tDCS-M1 group than the other 2 groups (p < .05). EEG approximate entropy indicated that both A-tDCS groups could activate the stimulated sites; the improvement in the A-tDCS-M1 group was correlated with high activation in the dorsal lateral prefrontal cortex and Broca's areas of the left hemisphere in addition to the stimulated site. Conclusion A-tDCS over the left M1 can improve the speech function in patients with poststroke aphasia and severe AoS and excite and recruit more areas in the motor speech network.

Effect of Transcutaneous Vagus Nerve Stimulation in Dysphagia After Lateral Medullary Infarction: A Case Report.

Purpose Severe dysphagia with weak pharyngeal peristalsis after dorsal lateral medullary infarction (LMI) requires long-term tube feeding. However, no study is currently available on therapeutic effectiveness in severe dysphagia caused by nuclear damage of vagus nerve after dorsal LMI. The purpose of the present investigation was to explore the potential of transcutaneous vagus nerve stimulation (tVNS) to improve severe dysphagia with weak pharyngeal peristalsis after dorsal LMI. Method We assessed the efficacy of 6-week tVNS in a 28-year-old woman presented with persisting severe dysphagia after dorsal LMI who had been on nasogastric feeding for 6 months. tVNS was applied for 20 min twice a day, 5 days a week, for 6 weeks. The outcome measures included saliva spitted, Swallow Function Scoring System, Functional Oral Intake Scale, Clinical Assessment of Dysphagia With Wallenberg Syndrome, Yale Pharyngeal Residue Severity Rating Scale, and upper esophagus X-ray examination. Results After tVNS, the patient was advanced to a full oral diet without head rotation or spitting. No saliva residue was found in the valleculae and pyriform sinuses. Contrast medium freely passed through the upper esophageal sphincter. Conclusion Our findings suggest that tVNS might provide a useful means for recovery of severe dysphagia with weak pharyngeal peristalsis after dorsal LMI. Supplemental Material https://doi.org/10.23641/asha.9755438.

The Impact of the Epigenetic Cancer Drug Azacitidine on Host Immunity: The Role of Myelosuppression, Iron Overload and tp53 Mutations in a Zebrafish Model.

The unsatisfactory real-world efficacy of the hypomethylating agent azacitidine in treating myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) has prompted us to investigate the hematological adverse events and host variables that may compromise the use of this epigenetic drug. Using the zebrafish, we found that azacitidine destroyed their myeloid precursors and impaired myeloid function by inhibiting antigen processing, allogeneic response and phagocytic activity, resulting in increased susceptibility to infection even by the normal flora E. coli. In addition, iron overload, a MDS-associated condition following repeated transfusions, exacerbated bacterial infection especially by V. vulnificus with known iron dependence. Furthermore, we show that the tp53M214K mutant zebrafish survived longer than the wild-type (WT) when challenged with bacteria following azacitidine treatment. This was attributed to the mutant's hematopoietic cells rather than its general genetic background, since the WT animals reconstituted with the tp53M214K mutant kidney marrow became more resistant to bacterial infection following treatment with azacitidine. The clinical relevance of our findings was indicated by a MDS case with severe azacitidine-induced bone marrow suppression and by the association of hyperferritinemia with bacteremia in azacitidine-treated patients, while tp53M214K-mediated resistance to azacitidine-induced myelosuppression may explain the survival advantage of malignant MDS and AML clones over their normal counterparts under azacitidine treatment. Together, we propose that myelosuppression, iron overload and TP53 mutations may represent the host variables that compromise the azacitidine efficacy.

Synthesis and properties of hyperbranched polymers for polymer light emitting devices with sunlight-style white emission.

A new series of hyperbranched polymers consisting of fluorene-alt-carbazole as the branches and the three-dimensional-structured spiro[3.3]heptane-2,6-dispirofluorene (SDF) as the core were designed and synthesized by one-pot Suzuki coupling polycondensation. A phosphor group with broad full width at half maximum (FWHM) bis(1-phenyl-isoquinoline)(acetylacetonato)iridium(iii) (Ir(Brpiq)2acac, 0.08 mol%) as the red-light emitting unit and bis(2-(4-bromophenyl)-1-[6-(9-carbazolyl)hexyl]-imidazole)(2-(5-(4-fluorinated phenyl)-1,3,4-triazole)pyridine)iridium(iii) ((CzhBrPI)2Ir(fpptz)) as the green-light emitting unit were introduced into the backbones to obtain sunlight-style white-light emission by adjusting the feeding ratios of (CzhBrPI)2Ir(fpptz) (0.08 to 0.32 mol%). The results indicate the synthesized polymers show high thermal stabilities and good amorphous film morphology because of the hyperbranched structures. Besides, the lowest unoccupied molecular orbital (LUMO) levels of polymers were reduced and the electron injection was improved because of excellent electron-transporting ability of the triazole unit in the green group. The hyperbranched structures can effectively suppress the polymers' chain distortion and aggregation, and promote the incomplete Förster resonance energy transfer (FRET) efficiency from fluorene-alt-carbazole segments to Ir complex units. As a result, the devices with hyperbranched polymer light-emitting layers realize white light emission, and the optimized device also exhibits good electroluminescent (EL) performance with Commission Internationale de l'Eclairage (CIE) coordinates at (0.32, 0.31), a maximum luminance of 9054 cd m-2, a maximum current efficiency of 3.59 cd A-1 and a maximum Color Rendering Index (CRI) of 91. The hyperbranched polymers based on fluorene-alt-carbazole branches and a SDF core and high-efficiency phosphor groups with broad full width at half maximum are attractive candidates for sunlight-style white polymer light-emitting device.

Polyfluorene-based white light conjugated polymers incorporating orange iridium(iii) complexes: the effect of steric configuration on their photophysical and electroluminescent properties.

Different kinds of polyfluorene-based white light conjugated polymers with phosphorescent iridium(iii) complexes as orange emission groups and polyfluorene as blue emission groups were designed and synthesized. On the basis of adjusting substituent positions on iridium(iii) complexes, the conjugated polymers exhibited different steric configurations, i.e. hyperbranched and linear structures, and the PL emission peaks of iridium(iii) complexes had a significant change. Compared to linear conjugated polymers, hyperbranched white light conjugated polymers showed the best thermal stability and film forming properties. The white light single-emissive-layer devices with simplified configuration were also prepared in a wet process. All these devices realized good electroluminescence, especially the hyperbranched conjugated polymers in which the roll off phenomenon at high current density was effectively suppressed. Furthermore, EL spectra of hyperbranched polymers exhibited good stability at different driving voltages. A maximum luminance of 2469 cd m-2, a maximum current efficiency of 1.73 cd A-1 and the commission internationale de l'Eclairage (CIE) coordinates of (0.25, 0.23) showed white light was achieved from the HPF-Ir10 devices.

Bortezomib-induced miRNAs direct epigenetic silencing of locus genes and trigger apoptosis in leukemia.

MicroRNAs (miRNAs) have been suggested to repress transcription via binding the 3'-untranslated regions of mRNAs. However, the involvement and details of miRNA-mediated epigenetic regulation, particularly in targeting genomic DNA and mediating epigenetic regulation, remain largely uninvestigated. In the present study, transcription factor CCAAT/enhancer binding protein delta (CEBPD) was responsive to the anticancer drug bortezomib, a clinical and highly selective drug for leukemia treatment, and contributed to bortezomib-induced cell death. Interestingly, following the identification of CEBPD-induced miRNAs, we found that miR-744, miR-3154 and miR-3162 could target CpG islands in the 5'-flanking region of the CEBPD gene. We previously demonstrated that the Yin Yang 1 (YY1)/polycomb group (PcG) protein/DNA methyltransferase (DNMT) complex is important for CCAAT/enhancer binding protein delta (CEBPD) gene inactivation; we further found that Argonaute 2 (Ago2) interacts with YY1 and binds to the CEBPD promoter. The miRNA/Ago2/YY1/PcG group protein/DNMT complex linked the inactivation of CEBPD and genes adjacent to its 5'-flanking region, including protein kinase DNA-activated catalytic polypeptide (PRKDC), minichromosome maintenance-deficient 4 (MCM4) and ubiquitin-conjugating enzyme E2 variant 2 (UBE2V2), upon bortezomib treatment. Moreover, we revealed that miRNA binding is necessary for YY1/PcG group protein/DNMT complex-mediated epigenetic gene silencing and is associated with bortezomib-induced methylation on genomic DNA. The present study successfully characterized the interactions of the miRNA/Ago2/YY1/PcG group protein/DNMT complex and provided new insights for miRNA-mediated epigenetic regulation in bortezomib-induced leukemic cell arrest and cell death.