Pgam5-mediated PHB2 dephosphorylation contributes to endotoxemia-induced myocardial dysfunction by inhibiting mitophagy and the mitochondrial unfolded protein response.

Numerous mitochondrial abnormalities are reported to result from excessive inflammation during endotoxemia. Prohibitin 2 (PHB2) and phosphoglycerate mutase 5 (Pgam5) have been associated with altered mitochondrial homeostasis in several cardiovascular diseases; however, their role in endotoxemia-related myocardial dysfunction has not been explored. Our experiments were aimed to evaluate the potential contribution of Pgam5 and PHB2 to endotoxemia-induced mitochondrial dysfunction in cardiomyocytes, with a focus on two endogenous protective programs that sustain mitochondrial integrity, namely mitophagy and the mitochondrial unfolded protein response (UPRmt). We found that PHB2 transgenic mice are resistant to endotoxemia-mediated myocardial depression and mitochondrial damage. Our assays indicated that PHB2 overexpression activates mitophagy and the UPRmt, which maintains mitochondrial metabolism, prevents oxidative stress injury, and enhances cardiomyocyte viability. Molecular analyses further showed that Pgam5 binds to and dephosphorylates PHB2, resulting in cytosolic translocation of mitochondrial PHB2. Silencing of Pgam5 or transfection of a phosphorylated PHB2 mutant in mouse HL-1 cardiomyocytes prevented the loss of mitochondrially-localized PHB2 and activated mitophagy and UPRmt in the presence of LPS. Notably, cardiomyocyte-specific deletion of Pgam5 in vivo attenuated LPS-mediated myocardial dysfunction and preserved cardiomyocyte viability. These findings suggest that Pgam5/PHB2 signaling and mitophagy/UPRmt are potential targets for the treatment of endotoxemia-related cardiac dysfunction.

Serum levels of n-3 PUFA and colorectal cancer risk in Chinese population.

Circulating n-3 PUFA, which integrate endogenous and exogenous n-3 PUFA, can be better used to investigate the relationship between n-3 PUFA and disease. However, studies examining the associations between circulating n-3 PUFA and colorectal cancer (CRC) risk were limited, and the results remained inconclusive. This case­control study aimed to examine the association between serum n-3 PUFA and CRC risk in Chinese population. A total of 680 CRC cases and 680 sex- and age-matched (5-year interval) controls were included. Fatty acids were assayed by GC. OR and 95 % CI were calculated using multivariable logistic regression after adjustment for potential confounders. Higher level of serum α-linolenic acid (ALA), docosapentaenoic acid (DPA), DHA, long-chain n-3 PUFA and total n-3 PUFA were associated with lower odds of CRC. The adjusted OR and 95 % CI were 0·34 (0·24, 0·49, Pfor trend < 0·001) for ALA, 0·57 (0·40, 0·80, Pfor trend < 0·001) for DPA, 0·48 (0·34, 0·68, Pfor trend < 0·001) for DHA, 0·39 (0·27, 0·56, Pfor trend < 0·001) for long-chain n-3 PUFA and 0·31 (0·22, 0·45, Pfor trend < 0·001) for total n-3 PUFA comparing the highest with the lowest quartile. However, there was no statistically significant association between EPA and odds of CRC. Analysis stratified by sex showed that ALA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of CRC in both sexes. This study indicated that serum ALA, DPA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of having CRC in Chinese population.

Association of plant-based dietary patterns with the risk of colorectal cancer: a large-scale case-control study.

Plant-based diets are associated with a lower risk of colorectal cancer, but the risk might differ by the quality of plant-based diets. This study aimed to investigate the association between different types of plant-based dietary patterns and colorectal cancer risk in the Chinese population. We conducted a case-control study with 2799 eligible colorectal cancer cases and 2799 sex- and age-matched controls in Guangzhou, China. A validated food frequency questionnaire was used to collect dietary data, from which we derived plant-based diet indices, including the plant-based diet index (PDI), the healthy PDI (hPDI), and the unhealthy PDI (uPDI). The PDI, hPDI, and uPDI assess the adherence to overall, healthy, and unhealthy plant-based dietary patterns, respectively. The odds ratios (ORs) and 95% confidence intervals (CIs) for colorectal cancer risk were estimated using unconditional logistic regression models. Higher adherence to the PDI, particularly the hPDI, was associated with a lower risk of colorectal cancer, whereas greater adherence to the uPDI was associated with a higher risk of colorectal cancer. Compared with the lowest quintile, the adjusted ORs in the highest quintile were 0.79 (95% CI: 0.66-0.95) for the PDI, 0.45 (95% CI: 0.38-0.55) for the hPDI, and 1.45 (95% CI: 1.18-1.78) for the hPDI, respectively. In stratified analysis, the inverse association between the PDI and colorectal cancer risk was not observed in women, and the positive association between the uPDI and colorectal cancer risk was not observed in men. In conclusion, these results support recommendations that shifting to a healthy plant-based dietary pattern is important for the prevention of colorectal cancer, particularly in the Chinese population that habitually consumes plant foods.

Mitochondrial quality control in diabetic cardiomyopathy: from molecular mechanisms to therapeutic strategies.

In diabetic cardiomyopathy (DCM), a major diabetic complication, the myocardium is structurally and functionally altered without evidence of coronary artery disease, hypertension or valvular disease. Although numerous anti-diabetic drugs have been applied clinically, specific medicines to prevent DCM progression are unavailable, so the prognosis of DCM remains poor. Mitochondrial ATP production maintains the energetic requirements of cardiomyocytes, whereas mitochondrial dysfunction can induce or aggravate DCM by promoting oxidative stress, dysregulated calcium homeostasis, metabolic reprogramming, abnormal intracellular signaling and mitochondrial apoptosis in cardiomyocytes. In response to mitochondrial dysfunction, the mitochondrial quality control (MQC) system (including mitochondrial fission, fusion, and mitophagy) is activated to repair damaged mitochondria. Physiological mitochondrial fission fragments the network to isolate damaged mitochondria. Mitophagy then allows dysfunctional mitochondria to be engulfed by autophagosomes and degraded in lysosomes. However, abnormal MQC results in excessive mitochondrial fission, impaired mitochondrial fusion and delayed mitophagy, causing fragmented mitochondria to accumulate in cardiomyocytes. In this review, we summarize the molecular mechanisms of MQC and discuss how pathological MQC contributes to DCM development. We then present promising therapeutic approaches to improve MQC and prevent DCM progression.

Associations between coping styles, gender, their interaction and non-suicidal self-injury among middle school students in rural west China: A multicentre cross-sectional study.

Background: To investigate the association between coping styles, gender, their interactions and non-suicidal self-injurious (NSSI) behaviors among middle school students in rural western China under COVID-19. Methods: A multicentre cross-sectional study method was used to conduct an online survey of 8,361 students from 23 middle schools in the northern Sichuan region by clustering sampling, using the General Information Questionnaire, the Ottawa Self-Injury Inventory, and the Coping Style Scale for Middle School Students. Results: The past year prevalence of NSSI among middle school students in rural west China was 5.7%. The differences in scores between those with and without NSSI on all dimensions of coping styles were statistically significant (p < 0.001). Multivariate logistic regression analysis revealed that vocational high school (OR = 1.67), girls (OR = 2.5), single parent with divorced parents (OR = 1.89), remarriage with divorced parents (OR = 1.81), and tolerance (OR = 1.17), venting emotions (OR = 1.15) and fantasy/denial (OR = 1.07) in coping styles may increase the risk of NSSI among middle school students, while problem solving (OR = 0.9) and seeking social support (OR = 0.9) among coping styles may reduce the risk of NSSI among middle school students. The interaction results show that gender has a moderating role in the process of endurance, avoidance, venting of emotions, and fantasy/denial influencing non-suicidal self-injury in middle school students. Conclusion: There is an association between coping styles and self-injury among middle school students in rural areas in western China, with gender playing a moderating role. Active attention should be paid to students' coping styles and encouraging them to adopt positive coping styles as well as avoid negative coping styles, especially in the case of girls, which can help prevent self-injury.

Empagliflozin activates Wnt/ß-catenin to stimulate FUNDC1-dependent mitochondrial quality surveillance against type-3 cardiorenal syndrome.

OBJECTIVES: Cardiorenal syndrome type-3 (CRS-3) is an abrupt worsening of cardiac function secondary to acute kidney injury. Mitochondrial dysfunction is a key pathological mechanism of CRS-3, and empagliflozin can improve mitochondrial biology by promoting mitophagy. Here, we assessed the effects of empagliflozin on mitochondrial quality surveillance in a mouse model of CRS-3. METHODS: Cardiomyocyte-specific FUNDC1-knockout (FUNDC1CKO) mice were subjected to CRS-3 prior to assessment of mitochondrial homeostasis in the presence or absence of empagliflozin. RESULTS: CRS-3 model mice exhibited lower heart function, increased inflammatory responses and exacerbated myocardial oxidative stress than sham-operated controls; however, empagliflozin attenuated these alterations. Empagliflozin stabilized the mitochondrial membrane potential, suppressed mitochondrial reactive oxygen species production, increased mitochondrial respiratory complex activity and restored the oxygen consumption rate in cardiomyocytes from CRS-3 model mice. Empagliflozin also normalized the mitochondrial morphology, mitochondrial dynamics and mitochondrial permeability transition pore opening rate in cardiomyocytes. Cardiomyocyte-specific ablation of FUN14 domain-containing protein 1 (FUNDC1) in mice abolished the protective effects of empagliflozin on mitochondrial homeostasis and myocardial performance. Empagliflozin activated ß-catenin and promoted its nuclear retention, thus increasing FUNDC1-induced mitophagy in heart tissues; however, a ß-catenin inhibitor reversed these effects. CONCLUSIONS: In summary, empagliflozin activated Wnt/ß-catenin to stimulate FUNDC1-dependent mitochondrial quality surveillance, ultimately improving mitochondrial function and cardiac performance during CRS-3. Thus, empagliflozin could be considered for the clinical management of heart function following acute kidney injury.

KLF16 enhances stress tolerance of colorectal carcinomas by modulating nucleolar homeostasis and translational reprogramming.

Translational reprogramming is part of the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress, which acts to the advantage of cancer growth and development in different stress conditions, but the mechanism of ER stress-related translational reprogramming in colorectal carcinoma (CRC) progression remains unclear. Here, we identified that Krüppel-like factor 16 (KLF16) can promote CRC progression and stress tolerance through translational reprogramming. The expression of KLF16 was upregulated in CRC tissues and associated with poor prognosis for CRC patients. We found that ER stress inducers can recruit KLF16 to the nucleolus and increase its interaction with two essential proteins for nucleolar homeostasis: nucleophosmin1 (NPM1) and fibrillarin (FBL). Moreover, knockdown of KLF16 can dysregulate nucleolar homeostasis in CRC cells. Translation-reporter system and polysome profiling assays further showed that KLF16 can effectively promote cap-independent translation of ATF4, which can enhance ER-phagy and the proliferation of CRC cells. Overall, our study unveils a previously unrecognized role for KLF16 as an ER stress regulator through mediating translational reprogramming to enhance the stress tolerance of CRC cells and provides a potential therapeutic vulnerability.

Factors associated with adherence to colonoscopy among individuals who were positive in the preliminary screening for colorectal neoplasms.

OBJECTIVES: This study aimed to investigate the potential factors associated with adherence to colonoscopy among participants who were preliminarily screened positive in a community-based colorectal cancer screening program in China. METHODS: This study analyzed data from 1219 out of 6971 community residents who were identified as positive cases by the well-validated high-risk factor questionnaire (HRFQ) or fecal immunochemical test (FIT) in the preliminary screening stage for colorectal neoplasms. Patients showing adherence to colonoscopy were defined as those who received positive results in a preliminary screening for colorectal neoplasms and later received a colonoscopy examination as required. The associations of social-demographic factors, lifestyle behaviors, history of diabetes, body mass index (BMI), and risk factors in the HRFQ with adherence to colonoscopy were evaluated using logistic regression models. RESULTS: Among 1219 participants who preliminarily screened positive, the top five risk factors reported by the participants were chronic constipation (25.9%), hematochezia (23.5%), family history of CRC in first-degree relatives (22.1%), chronic diarrhea (21.8%), and history of polyps (16.6%). Around 14.2% of participants who preliminarily screened positive reported three or more risk factors, and the proportion was 26.2% among participants who were positive according to both HRFQ and FIT. Among all participants who were preliminarily screened positive, the multivariable results showed that those who were married (OR = 1.58, 95% CI: 1.12, 2.25, p = 0.01), had chronic diarrhea (OR = 1.34, 95% CI: 1.00, 1.78, p = 0.047), and had a positive FIT (OR = 1.60, 95% CI: 1.21, 2.10, p < 0.001 for patients who were negative according to HRFQ but positive according to FIT; OR = 2.12, 95% CI: 1.33, 2.78, p = 0.002 for patients who were positive for both HRFQ and FIT) were more likely to adhere to colonoscopy, while participants with a history of cancer (OR: 0.50, 95% CI: 0.31, 0.79, p = 0.003) were less likely to adhere to colonoscopy. The results among participants who were tested positive according to only HRFQ were similar to those among all participants who were tested positive according to HRFQ or FIT. However, among participants who were tested positive according to only FIT, we only found that those who were married (OR = 2.52, 95% CI: 1.08, 5.90, p = 0.033) had a higher odds of adhering to colonoscopy, while those with a history of diabetes (OR = 0.35, 95% CI: 0.13, 0.96, p = 0.042) were less likely to adhere to colonoscopy. CONCLUSION: Our findings provide evidence supporting the development of tailored interventional strategies that aim to improve adherence to colonoscopy for individuals with a high risk of colorectal neoplasms. Both barriers and facilitators associated with adherence to colonoscopy should be considered in supportive systems and health policies. However, further well-designed prospective studies are warranted to confirm our findings.

Factors associated with positive predictive value of preliminary screening in a two-step screening strategy for colorectal neoplasms in China.

BACKGROUND: The positive predictive value (PPV) of high risk factor questionnaire (HRFQ) plus fecal immunochemical test (FIT) as preliminary screening strategy for colorectal-related neoplasia is relatively low. We aim to explore independent factors associated with PPVs of HRFQ combined FIT for selecting high risk individuals for colonoscopy. METHODS: A total of 6971 residents were enrolled in a community-based screening program. Participants who had positive results of HRFQ and/or FIT and subsequently received colonoscopy were involved. The associations of socio-demographic factors, lifestyle behaviors, and high risk factors of colorectal cancer with PPVs of HRFQ, FIT, and their combination were evaluated by multivariable logistic regression models. RESULTS: Among 572 involved cases, 249 (43.5%) colorectal neoplasms were detected by colonoscopy, including 71 advanced adenoma (12.4%) and 9 colorectal cancer (CRC) (1.6%). The PPVs of preliminary screening were 43.5% for total colorectal neoplasms, 14.0% for advanced neoplasm, and 1.6% for CRC. Adding positive HRFQ to FIT could improve the PPV from 3.5 to 8.0% for detecting CRC. Preliminarily screened positive individuals who were males [adjusted odds ratio (AOR): 1.95, 95% CI 1.31, 2.90; p < 0.001], elders (> 60 years) (AOR: 1.70, 95% CI 1.17, 2.46; p = 0.005), or ex-/current smokers (AOR: 3.04, 95% CI 1.31, 7.09; p = 0.10) had higher odds of PPVs of detecting colorectal neoplasms. CONCLUSIONS: Combining HRFQ and FIT could largely improve PPVs for screening advanced neoplasm and CRC. Gender and age-specific FIT cut-off values as well as initiating ages for CRC screening might be recommended to improve the accuracy and effectiveness of current screening algorithm.

Effects of ex vivo Extracorporeal Membrane Oxygenation Circuits on Sequestration of Antimicrobial Agents.

Objectives: Our ex vivo study was designed to determine the sequestration of teicoplanin, tigecycline, micafungin, meropenem, polymyxin B, caspofungin, cefoperazone sulbactam, and voriconazole in extracorporeal membrane oxygenation (ECMO) circuits. Methods: Simulated closed-loop ECMO circuits were prepared using 2 types of blood-primed ECMO. After the circulation was stabilized, the study drugs were injected into the circuit. Blood samples were collected at 2, 5, 15, 30 min, 1, 3, 6, 12, and 24 h after injection. Drug concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. Control groups were stored at 4°C after 3, 6, 12, and 24 h immersing in a water bath at 37°C to observe spontaneous drug degradation. Results: Twenty-six samples were analyzed. The average drug recoveries from the ECMO circuits and control groups at 24 h relative to baseline were 67 and 89% for teicoplanin, 100 and 145% for tigecycline, 67 and 99% for micafungin, 45 and 75% for meropenem, 62 and 60% for polymyxin B, 83 and 85% for caspofungin, 79 and 98% for cefoperazone, 75 and 87% for sulbactam, and 60 and 101% for voriconazole, respectively. Simple linear regression showed no significant correlation between lipophilicity (r 2 = 0.008, P = 0.225) or the protein binding rate (r 2 = 0.168, P = 0.479) of drugs and the extent of drug loss in the ECMO circuits. Conclusions: In the two ECMO circuits, meropenem and voriconazole were significantly lost, cefoperazone was slightly lost, while tigecycline and caspofungin were not lost. Drugs with high lipophilicity were lost more in the Maquet circuit than in the Sorin circuit. This study needs more in vivo studies with larger samples for further confirmation, and it suggests that therapeutic drug concentration monitoring should be strongly considered during ECMO.

Programmed death-ligand 1 expression in the tumour stroma of colorectal liver oligometastases and its association with prognosis after liver resection.

BACKGROUND: The clinical value of programmed death-ligand 1 (PD-L1) expression in colorectal liver oligometastases (CLOs) remains undefined. This study aimed to detect PD-L1 in the microenvironment of CLOs and determine its association with patient prognosis. METHODS: We collected 126 liver-resection specimens from CLO patients who underwent curative liver resection between June 1999 and December 2016. Immunohistochemistry (IHC) was performed to assess PD-L1 expression in paraffin-embedded specimens. Overall survival (OS) and recurrence-free survival (RFS) were analysed using the Kaplan-Meier method and log-rank test. RESULTS: PD-L1 was mainly expressed in the stroma of liver oligometastases. Patients with high PD-L1 expression had a higher proportion of clinical-risk scores (CRSs) of 2-4 (67.7% vs 40.4%; P = 0.004). With a median 58-month follow-up, patients with high PD-L1 expression had a significantly lower 3-year OS rate (65.5% vs 92.7%; P = 0.001) and 3-year RFS rate (34.7% vs 83.8%; P < 0.001) than patients with low PD-L1 expression. Multivariate Cox analysis demonstrated that high PD-L1 expression (hazard ratio [HR] = 3.581; 95% confidence interval [CI] 2.301-9.972; P = 0.015), CRS 2-4 (HR = 6.960; 95% CI 1.135-42.689; P = 0.036) and increased preoperative CA19-9 (HR = 2.843; 95% CI 1.229-6.576; P = 0.015) were independent risk factors for OS. High PD-L1 expression (HR = 4.815; 95% CI 2.139-10.837; P < 0.001) and lymph-node metastasis (HR = 2.115; 95% CI 1.041-4.297; P = 0.038) were independent risk factors for RFS. CONCLUSION: This study found that PD-L1 was commonly expressed in the tumour stroma of CLOs and high PD-L1 expression was associated with poor prognosis.

Multifunctional Silver Nanoparticle Interlayer-Modified ZnO as the Electron-Injection Layer for Efficient Inverted Organic Light-Emitting Diodes.

The insufficient electron injection constitutes the major obstacle to achieving high-performance inverted organic light-emitting diodes (OLEDs). Here, a facile electron-injection architecture featuring a silver nanoparticle (AgNPs) interlayer-modified sol-gel-derived transparent zinc oxide (ZnO) ultrathin film is proposed and demonstrated. The optimized external quantum efficiencies of the developed inverted fluorescent and phosphorescent OLEDs capitalized on our proposed electron-injection structure reached 4.0 and 21.2% at a current density of 20 mA cm-2 and increased by a factor of 1.90 and 2.86 relative to a reference device without the AgNP interlayer, while simultaneously reducing the operational voltage and substantially ameliorating the device efficiency. Detailed analyses reveal that the local surface plasmon resonance emanated from AgNPs plays three meaningful roles simultaneously: suppressing the surface plasmon polariton mode loss, aiding in energy-level alignments, and inducing and reinforcing the local exciton-plasmon coupling electric field. Among these interesting and multifunctional roles, the enhanced local exciton-plasmon coupling electric field dominates the electron injection enhancement and substantial increases the device efficiency. Additionally, the light-scattering effect also helps in recovering the trapped light energy flux and thus improves the device efficiency. The proposed approach and findings provide an alternative path to fabricate high-performance inverted OLEDs and other related organic electronic or optoelectronic devices.

Circulating Tissue Factor-Positive Procoagulant Microparticles in Patients with Type 1 Diabetes.

AIM: To investigate the count of circulating tissue factor-positive (TF+) procoagulant microparticles (MPs) in patients with type 1 diabetes mellitus (T1DM). METHODS: This case-control study included patients with T1DM and age and sex-matched healthy volunteers. The counts of phosphatidylserine-positive (PS+) MPs and TF+PS+MPs and the subgroups derived from different cell types were measured in the peripheral blood sample of the two groups using multicolor flow cytometric assay. We compared the counts of each MP between groups as well as the ratio of the TF+PS+MPs and PS+MPs (TF+PS+MPs/PS+MPs). RESULTS: We recruited 36 patients with T1DM and 36 matched healthy controls. Compared with healthy volunteers, PS+MPs, TF+PS+MPs and TF+PS+MPs/PS+MPs were elevated in patients with T1DM (PS+MPs: 1078.5 ± 158.08 vs 686.84 ± 122.04/µL, P <0.001; TF+PS+MPs: 202.10 ± 47.47 vs 108.33 ± 29.42/µL, P <0.001; and TF+PS+MPs/PS+MPs: 0.16 ± 0.04 vs 0.19 ± 0.05, P = 0.004), mostly derived from platelet, lymphocytes and endothelial cells. In the subgroup analysis, the counts of total and platelet TF+PS+MPs were increased in patients with diabetic retinopathy (DR) and with higher HbA1c, respectively. CONCLUSION: Circulating TF+PS+MPs and those derived from platelet, lymphocytes and endothelial cells were elevated in patients with T1DM.

Universal screening for Lynch syndrome in a large consecutive cohort of Chinese colorectal cancer patients: High prevalence and unique molecular features.

The prevalence of Lynch syndrome (LS) varies significantly in different populations, suggesting that ethnic features might play an important role. We enrolled 3330 consecutive Chinese patients who had surgical resection for newly diagnosed colorectal cancer. Universal screening for LS was implemented, including immunohistochemistry for mismatch repair (MMR) proteins, BRAFV600E mutation test and germline sequencing. Among the 3250 eligible patients, MMR protein deficiency (dMMR) was detected in 330 (10.2%) patients. Ninety-three patients (2.9%) were diagnosed with LS. Nine (9.7%) patients with LS fulfilled Amsterdam criteria II and 76 (81.7%) met the revised Bethesda guidelines. Only 15 (9.7%) patients with absence of MLH1 on IHC had BRAFV600E mutation. One third (33/99) of the MMR gene mutations have not been reported previously. The age of onset indicates risk of LS in patients with dMMR tumors. For patients older than 65 years, only 2 patients (5.7%) fulfilling revised Bethesda guidelines were diagnosed with LS. Selective sequencing of all cases with dMMR diagnosed at or below age 65 years and only of those dMMR cases older than 65 years who fulfill revised Bethesda guidelines results in 8.2% fewer cases requiring germline testing without missing any LS diagnoses. While the prevalence of LS in Chinese patients is similar to that of Western populations, the spectrum of constitutional mutations and frequency of BRAFV600E mutation is different. Patients older than 65 years who do not meet the revised Bethesda guidelines have a low risk of LS, suggesting germline sequencing might not be necessary in this population.

Laser speckle formed disordered micro-meander structures for light extraction enhancement of flexible organic light-emitting diodes.

A new approach for efficiently recovering the wasted light energy in conventional flexible organic light-emitting diodes (FOLEDs) is developed by implementing disordered micro-meander structures (DMMs) via laser speckle holography technology. Compared to conventional flat device architecture, the structured FOLEDs with DMMs result in substantial improvement of the device efficiency and superior angular color stability. The resulting current efficiency (CE) and external quantum efficiency (EQE) are 1.31 and 1.39 times that of a common flat structure, respectively. Moreover, the proposed DMMs micro-structure simultaneously offers the unique characteristics of angular color stability with a wide viewing angle, which is usually considered as the criteria of the high-quality lighting applications. We hope that the demonstrated method could provide an alternative way for the development of high efficiency flexible OLEDs.

Evidence for an Association of ERCC1 Expression and Mismatch Repair Status with Overall Survival in Colorectal Cancer Patients.

BACKGROUND: The aim in this study was to determine if an association of excision repair cross-complementing group 1 (ERCC1) gene and mismatch repair (MMR) status with overall survival (OS) could be found from our analysis of a large cohort of Chinese colorectal cancer patients (CRC). METHODS: In total, 2,233 tissue samples isolated from individual CRC tumors were assessed by immunohistochemistry for the expression of ERCC1 and 4 MMR genes. RESULTS: The rates of proficient MMR (pMMR) and ERCC1 expression were 89.6 and 90.7%, respectively. We found that patients with positive ERCC1 expression and deficient (d)MMR status had higher overall survival (OS) than those with either positive ERCC1 and pMMR, negative ERCC1 and dMMR, or negative ERCC1 expression and pMMR status (OS 79 vs. 69 vs. 66 vs. 61%, hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.80-1.00; p = 0.043). Despite this finding, we found no statistical difference in OS between ERCC1-positive and -negative CRC patients when ERCC1 expression was considered alone (OS 70 vs. 62%, HR 0.82, 95% CI 0.65-1.04; p = 0.11). CONCLUSION: Our results indicate that the combined examination of ERCC1 expression and dMMR status can be used to aid OS assessment in CRC patients.

Endocrine therapy inhibits proliferation and migration, promotes apoptosis and suppresses survivin protein expression in colorectal cancer cells.

The majority of colorectal cancers (CRCs) are hormone­dependent. Thus, endocrine therapy has become an attractive strategy to treat CRC. The aim of the present study was to investigate the inhibitory effect of combined tamoxifen (TAM) plus ß­estradiol (E2) treatment on human DLD­1 CRC cells. The human DLD­1 CRC cell line was treated with different concentrations of TAM, ß­estradiol, or a combination of these two agents. Cell viability was assessed using an MTT assay, while apoptosis was detected using flow cytometry analysis. Alterations in the RNA and protein levels of the apoptosis­associated factors cyclin D1 and survivin were measured in the treated DLD­1 cells using semi­quantitative polymerase chain reaction (sqPCR) and western blot analyses. Alterations in cellular migration ability were monitored using a Transwell migration assay. Treatment with TAM, ß­estradiol and TAM plus ß­estradiol inhibited DLD­1 cell viability. The flow cytometry results revealed that these drugs promoted cell apoptosis, and the Transwell migration assay results indicated that the reduction in cell migration was greater in the TAM+E2 treatment group when compared with each treatment alone. sqPCR and western blot analysis results demonstrated that TAM, E2 and a combination of the two affected survivin expression based on the drug concentration and the treatment duration; however, they demonstrated no significant effect on cyclin D1 expression. In conclusion, treatment of DLD­1 cells with TAM, ß­estradiol, or a combination of these two drugs, inhibited cell viability and migration, promoted cell apoptosis, and reduced the mRNA and protein expression levels of survivin in a dose­ and time­dependent manner. These results provide novel experimental basis for hormonal adjuvant therapy for the treatment of CRC.

Transparent organic light-emitting diodes with balanced white emission by minimizing waveguide and surface plasmonic loss.

It is challenging in realizing high-performance transparent organic light-emitting diodes (OLEDs) with symmetrical light emission to both sides. Herein, an efficient transparent OLED with highly balanced white emission to both sides is demonstrated by integrating quasi-periodic nanostructures into the organic emitter and the metal-dielectric composite top electrode, which can simultaneously suppressing waveguide and surface plasmonic loss. The power efficiency and external quantum efficiency are raised to 83.5 lm W-1 and 38.8%, respectively, along with a bi-directional luminance ratio of 1.26. The proposed scheme provides a facile route for extending application scope of transparent OLEDs for future transparent displays and lightings.

Impact of age and mismatch repair status on survival in colorectal cancer.

Previous studies have suggested that deficiencies in mismatch repair genes (dMMR) often occur in patients with colorectal cancer (CRC) and contribute to disease etiology. Here, we looked for a correlation of MMR status to disease outcomes from a large number of Chinese CRC patients stratified by the age of onset of disease. A total of 2233 CRC patients were analyzed and tissue biopsies of surgically removed tumors scored for MMR gene status. The patient distribution after classification consisted of 188 younger aged patients (20-39 years of age), 1024 middle aged patients (40-59 years of age), and 1020 older aged patients (60-85 years of age). In this analysis, the expression of four MMR genes was assessed by immunohistochemistry (IHC). We found that the young group of CRC patients with dMMR had higher overall survival (OS) than the young group of patients with proficient MMR (pMMR) (77% vs. 56%, P = 0.03). Middle-aged patients with dMMR also had higher OS than middle-aged group patients with pMMR (78% vs. 68%, P = 0.012). However, we found no statistical difference in OS between dMMR and pMMR status in the older group of patients (75% vs. 71%, P = 0.224). Finally, the middle- and older-aged group set of patients had higher OS than the young group of patients (69% vs. 71% vs. 59%, P = 0.008). These data demonstrated that the age of disease onset can be an important factor to help evaluate the prognosis of CRC when combined with the analysis of MMR status within tumor biopsied tissue.

Association between Ki67 Index and Clinicopathological Features in Colorectal Cancer.

BACKGROUND: Conflicting results have been reported about the association between the Ki67 labeling index (Ki67-Li) and clinical outcome in patients with colorectal cancer (CRC). PATIENTS AND METHODS: Ki67 expression was assessed by immunohistochemistry (IHC) in 2,233 consecutive CRC cases. RESULTS: We determined 992 cases to have a low and 1,241 cases to have a high Ki67-Li (representing an approximately 44-56% breakdown in distribution between low versus high patients designated by phenotype). Stage III patients with a high Ki67-Li had higher 3-year disease-free survival (DFS) and overall survival (OS) than those with a low Ki67-Li (DFS 70 vs. 61%; p = 0.02 and OS 75 vs. 64%; p = 0.008). We also found significantly improved 3-year progression-free survival (PFS) for stage IV patients in the high versus the low Ki67-Li group (PFS 14 vs. 10%; p = 0.02). Yet, we found no statistical differences in prognosis for stage I and II patients and in OS for stage IV patients between high versus low Ki67-Li (p > 0.05). CONCLUSION: Our results suggest that high Ki67-Li can be an independent prognostic biomarker to aid the assessment of patient outcomes in both stage III and IV CRC.