Distribution and adsorption-desorption of organophosphate esters from land to sea in the sediments of the Beibu Gulf, South China Sea: Impact of seagoing river input.

Organophosphate esters (OPEs) have been a class of emerging environmental contaminants. However, studies on their environmental behavior, specifically their adsorption-desorption behavior between sediment and seawater in estuarine and coastal areas, remain limited. To address this gap, our study focused on investigating the levels and behavior of 11 OPEs in sediment samples collected from the Beibu Gulf, South China Sea, encompassing estuaries and coastal regions. The total concentrations of 11 OPEs (Σ11OPEs) in the sediments exhibit a significant decrease in summer, both in seagoing rivers (4.67 ± 2.74 ng/g dw) and the coastal zone (5.11 ± 3.71 ng/g dw), compared to winter levels in seagoing rivers (8.26 ± 4.70 ng/g dw) and the coastal zone (7.71 ± 3.83 ng/g dw). Chlorinated OPEs dominated the sediments, constituting 63 %-76 % of the total. Particularly, port and mariculture areas showed the highest levels of OPEs. Through load estimation analysis, it was revealed that the sedimentary OPEs in Qinzhou Bay (221 ± 128 kg) had the highest load, with input from the Qin River identified as a significant source. Chlorinated OPEs showed a trend of desorption from sediments to the water column with increasing salinity, emphasizing the crucial role of land-based OPEs input through suspended particulate matter in rivers as a pathway to the ocean. The impact of strong flow in estuarine environments was highlighted, as it can scour sediments, generate suspended sediments, and release OPEs into the water bodies. Additionally, the results of the ecological risk assessment indicated that most of the OPEs posed low-risk levels. However, attention is warranted for the contamination levels of some chlorinated OPEs, emphasizing the need for ongoing monitoring and assessment.

Association of Novel Insulin Resistance Indices with Blood Pressure in New-Onset Hypertension and Elevated Blood Pressure Individuals: A Cross-Sectional Study.

Objective: Insulin resistance (IR) has a bearing on blood pressure (BP). Nevertheless, research on the relationships between surrogates for IR and BP is limited. In this study, we investigate the associations of these novel IR indices with BP in new-onset hypertension (HTN) and elevated BP individuals. Methods: An overall sample of 55,381 adult subjects was included in Hebei General Hospital. BP and other clinical indicators were measured. Triglyceride glucose (TyG) index, TyG-waist circumference (TyG-WC), TyG-body mass index (TyG-BMI), TyG-waist to height ratio (TyG-WHtR), triglyceride-to-high-density lipoprotein-cholesterol ratio (TG/HDL-C) and metabolic score for IR (METS-IR) were collected as dependable surrogates for IR. Examinees were categorized into four groups based on BP levels. Those involved were classified as quartiles according to the levels of six surrogate IR indices. Logistic regression analysis was adopted to evaluate the impact of substitute IR indicators on BP. The receiver operating characteristic curve (ROC) analysis was performed to explore the predictive ability of the parameters on BP. Results: The incidence of elevated BP, stage 1 HTN and stage 2 HTN was 7.86%, 24.05% and 23.76%, respectively. As the levels of six substitute IR indices rose, so did the BP. In the logistic regression analysis, after full adjustment, all alternative IR indicators were independently related to both stage 1 HTN and stage 2 HTN. Except for TG/HDL-C, other substitute IR indices were strongly associated with elevated BP. ROC curves analysis suggested TyG-WC and TyG-WHtR outperformed other indicators with higher odd ratios and area under the curve (AUC) in all the participants. Conclusion: Increased substitute IR indices were significantly associated with elevated BP in new-onset HTN and elevated BP individuals. TyG-WC and TyG-WHtR could better predict elevated BP, stage 1 HTN and stage 2 HTN.

Association Between Sensitivity to Thyroid Hormones and Metabolic Dysfunction-Associated Fatty Liver Disease in Euthyroid Subjects: A Cross-Sectional Study.

Objective: Thyroid hormones (THs) exert instrumental effects in regulating lipids metabolism. Whereas, research investigating the relationship between sensitivity indices to THs and metabolic dysfunction-associated fatty liver disease (MAFLD) have contradicted this. This study was designed to approach the correlation between sensitivity indices to THs and MAFLD in euthyroid subjects. Methods: An overall sample of 6356 euthyroid participants were enrolled in a Chinese hospital. Free triiodothyronine to free thyroxine ratio (FT3/FT4), thyrotropin triiodothyronine resistance index (TT3RI), thyrotropin thyroxine resistance index (TT4RI), thyroid stimulating hormone index (TSHI) and thyroid feedback quantile-based indices (TFQIFT3 and TFQIFT4) were collected as sensitivity indicators to THs. Participants were split into two groups based on whether they suffered with MAFLD or not. And participants were categorized into quartiles based on sensitivity indicators to THs. The effects of sensitivity indices to THs on MAFLD were analyzed using regression analysis. Bootstrap was performed to assess the mediation effect of triglyceride glucose (TyG) index on the relationship between sensitivity parameters to THs and MAFLD. Results: The incidence of MAFLD in euthyroid subjects was 34.47%. As FT3/FT4, TT3RI and TFQIFT3 levels rose, so did the MAFLD prevalence. After adjustment for confounders, logistic regression analyses indicated that the high-level FT3/FT4 and TFQIFT3 still remained risk factors for MAFLD. The relevance of FT3/FT4 and MAFLD was stronger among those whose age ≤ 40 years and had non-visceral obesity. And the interrelation between TFQIFT3 and MAFLD was stronger in subjects whose age ≤ 40 years. Mediation analyses suggested that TyG index had a noteworthy indirect impact on the relationship between FT3/FT4, TFQIFT3 and MAFLD. Conclusion: Increased FT3/FT4 and TFQIFT3 were significantly related to MAFLD prevalence in populations with normal thyroid function. TyG index partly mediated the relevance between FT3/FT4, TFQIFT3 and MAFLD.

Comprehensive evaluation method of stope stability and its application in deep metal mine.

The problem of high stress conditions is a critical challenge for mining activity in deep metal mines, and the difficulty and economic cost of maintaining stope stability also increases. In order to ensure stope stability in the mining process, it is necessary to evaluate stope stability for a more stable stope structure. However, there are many kinds of methods for rock stability assessment, and most of them are based on empirical and analytical methods, which lead to uncertain results. In this paper, a comprehensive evaluation method including factors of stope stability, self-stabilization time, maximum safety span, and support measure is determined, which is more likely to provide a comprehensive result. Finally, it was verified by the field application in Jiaojia Gold Mine. Results show that it can accurately evaluate the stope stability from different aspects compared with the traditional single evaluation method, and it leads to a more comprehensive and reliable result.

Occurrence, bioaccumulation and ecological risk of organic ultraviolet absorbers in multiple coastal and offshore coral communities of the South China Sea.

The occurrence of organic ultraviolet absorbers (OUVAs) in coral reef regions has aroused widespread concern. This study focused on the occurrence, distribution, bioaccumulation and ecological risk of ten OUVAs in both coastal and offshore coral reef regions in the South China Sea. While the Σ10OUVAs was 85 % lower in the offshore seawater (15.1 ng/L) than in the coastal seawater (102.1 ng/L), the Σ10OUVAs was 21 % lower in the offshore corals (1.82 µg/g dry weight (dw)) than in the coastal corals (2.31 µg/g dw). This difference was speculated to relate to the high intensity of human activities in the coastal regions. Moreover, the offshore corals showed higher bioaccumulative capability toward OUVAs (log bioaccumulation factors (BAFs): 1.22-5.07) than the coastal corals (log BAFs: 0.17-4.38), which was presumably the influence of varied physiological status under different environmental conditions. The results of the ecological risk assessment showed that BP-3 resulted in 73 % of coastal corals and 20 % of offshore corals at a risk of bleaching. Therefore, the usage and discharge of BP-3 should be managed and controlled by the countries adjacent to the South China Sea for the protection of coral reefs.

Relationship of Bone Turnover Markers with Serum Uric Acid-to-Creatinine Ratio in Men and Postmenopausal Women with Type 2 Diabetes.

Purpose: Accumulating evidence has shown that serum uric acid (UA) is associated with some chronic diseases owing to its antioxidant capacity; however, previous research has discrepant results regarding the relationship between UA and bone health. UA normalized by renal function can reflect endogenous UA levels more precisely than SUA levels. This study assessed the relationship between serum UA-to-creatinine (SUA/Cr) ratio and bone turnover markers (BTMs) in men and postmenopausal women with type 2 diabetes mellitus (T2DM). Patients and Methods: Overall, 1691 patients (1028 males and 663 postmenopausal females) with T2DM admitted to Hebei General Hospital between January and December 2020 were selected and divided into two groups according to their SUA/Cr ratio. One-way analysis of variance was used to compare groups. The relationship between the SUA/Cr ratio and BTMs (including osteocalcin [OC], procollagen I N-terminal peptide [PINP], and ß-isomerized type I collagen C-telopeptide breakdown products [ß-CTX]) was analyzed using multiple linear regression. Furthermore, subgroup analyses were performed to explore the differences between men and women in the relationship between SUA/Cr and BTMs. Mediation analysis was used to explore whether insulin resistance mediated the association between SUA/Cr and BTMs. Results: ß-CTX and PNIP levels of patients with T2DM in the low SUA/Cr group were significantly higher than those in the high SUA/Cr group, and the difference between the two groups was statistically significant (P < 0.05). Correlation analysis showed that SUA/Cr was negatively correlated with ß-CTX and PNIP. After adjusting for confounding factors, multivariate linear regression analysis revealed that the SUA/Cr level was negatively correlated with PINP and ß-CTX in male patients and postmenopausal women with T2DM. Stronger correlations were found in patients with 25(OH)D3 < 20ng/mL, course ≥ 5 years, HbA1c > 7%, or BMI < 28 kg/m2. Conclusion: SUA/Cr ratio was an independent influencing factor of BTMs in patients with T2DM.

Mediating effect analysis of visceral adiposity index on free triiodothyronine to free thyroxine ratio and non-alcoholic fatty liver disease in euthyroid population.

Background: The association between free triiodothyronine/free thyroxine (FT3/FT4) and non-alcoholic fatty liver disease (NAFLD) in euthyroid subjects is unclear. In addition, few studies have explored whether VAI mediates the association between FT3/FT4 ratio and NAFLD in the euthyroid population. We aimed to analyze the mediating effect of VAI on the FT3/FT4 ratio and NAFLD risk in the euthyroid population. Methods: This cross-sectional study included 7 946 annual health examinees from the Health Examination Center, Hebei General Hospital, from January to December 2020. The basic information and biochemical parameters, as well as calculated FT3/FT4 ratio and VAI were collected. NAFLD was diagnosed according to abdominal ultrasonography. The fibrosis score for NAFLD positive subjects (NFS) was calculated to reflect the extent of liver fibrosis. The risk of NAFLD was analyzed by quartiles of FT3/FT4 ratio (Q1-Q4 quartiles) and VAI (V1-V4 quartiles), respectively. Pearson correlation analysis was performed to investigate the correlation between FT3/FT4 ratio and VAI. Multivariate logistic regression analysis was applied to analyze the effect of FT3/FT4 ratio and VAI on NAFLD and NFS status. Bootstrap was conducted to explore whether VAI mediated the association between FT3/FT4 ratio and NAFLD. Results: Of the 7 946 participants, 2 810 (35.36%) had NAFLD and 5 136 (64.64%) did not. Pearson correlation analysis indicated that FT3/FT4 ratio was positively associated with VAI (P<0.05). Multivariate logistic regression analysis indicated that compared to the Q1 group, the risk of NAFLD significantly increased in Q3 group [OR=1.255, 95%CI (1.011, 1.559)] and Q4 group [OR=1.553, 95%CI (1.252, 1.926)](P<0.05). Compared to the V1 group, the risk of NAFLD notably increased in V2 group [OR=1.584, 95%CI (1.205, 2.083)], V3 group [OR=2.386, 95%CI (1.778, 3.202)] and V4 group [OR=4.104, 95%CI (2.835, 5.939)] (P<0.01). There was no relevance between FT3/FT4 ratio, VAI and NFS status. Mediating effect analysis showed that FT3/FT4 ratio significantly directly influenced NAFLD prevalence [ß=3.7029, 95%CI (2.9583, 4.4474)], and VAI partly mediated the indirect effect of the FT3/FT4 ratio on NAFLD prevalence [ß=2.7649, 95%CI (2.2347, 3.3466)], and the mediating effect accounted for 42.75% of the total effects. Conclusion: Both FT3/FT4 ratio and VAI were predictors of NAFLD, and VAI partly mediated the indirect effect of the FT3/FT4 ratio on NAFLD prevalence in the euthyroid population.

Bioaccumulation and trophic transfer of PAHs in tropical marine food webs from coral reef ecosystems, the South China Sea: Compositional pattern, driving factors, ecological aspects, and risk assessment.

Multiple environmental pressures caused by global warming and human activities have aroused widespread concern about PAHs pollution in tropical marine coral reef regions (CRRs). However, the trophodynamics of PAHs in the food webs of the CRRs and the related influence factors have not been reported. This study investigated the occurrence, trophic amplification, and transmission of PAHs in various organisms selecting between at least representative species for each level in CRRs of the South China Sea (SCS); revealed their driving mechanisms; and explored the trophodynamics of PAHs in the food web of the coral reef ecosystem. Results showed that more PAHs can be accumulated in the mantle tissue of Tridacnidae, and the proportion of mantle tissue of Tridacnidae increases with the increase of latitude (y = 0.01x + 0.17, R2 = 0.49, p < 0.05). Latitude drives the differential occurrence level and bioaccumulation of PAHs in tropical marine organisms, and also affects the trophodynamics of PAHs in aquatic ecosystem food webs. PAHs undergo trophic amplification in the food webs of tropical marine ecosystems represented by coral reefs, thus further aggravating the negative environmental impact on coral reef ecosystems. The cancer risk caused by accidental ingestion of PAHs by humans through consumption of seafood in CRRs is very low, but we should be alert to the biomagnification effect of PAHs.

What Makes Employees Green Advocates? Exploring the Effects of Green Human Resource Management.

Green advocacy has been the focus of both practitioners and theorists for decades. However, little attention has been paid to employee green advocacy despite its significance to employee green behaviors and the environmental sustainability of organizations. In an effort to contribute to this nascent field, this study investigates what promotes employee green advocacy and its psychological mechanisms. Based on cognitive consistency theory, we propose that green human resource management (GHRM) can influence employees' organization-based self-esteem, which motivates them to engage in employee green advocacy to sustain their positive self-image and avoid possible cognitive disorders. Perceived organizational support moderates the relationship between GHRM and employee organization-based self-esteem. Data from a sample of 135 employees and their chief human resource officer (CHO) supported our hypotheses. We discussed the theoretical and practical implications of our findings.

Identification of novel biomarkers involved in doxorubicin-induced acute and chronic cardiotoxicity, respectively, by integrated bioinformatics.

Background: The mechanisms of doxorubicin (DOX) cardiotoxicity were complex and controversial, with various contradictions between experimental and clinical data. Understanding the differences in the molecular mechanism between DOX-induced acute and chronic cardiotoxicity may be an ideal entry point to solve this dilemma. Methods: Mice were injected intraperitoneally with DOX [(20 mg/kg, once) or (5 mg/kg/week, three times)] to construct acute and chronic cardiotoxicity models, respectively. Survival record and ultrasound monitored the cardiac function. The corresponding left ventricular (LV) myocardium tissues were analyzed by RNA-seq to identify differentially expressed genes (DEGs). Gene Ontology (GO), Kyoto Encyclopedia of Gene and Genome (KEGG), and Gene Set Enrichment Analysis (GSEA) found the key biological processes and signaling pathways. DOX cardiotoxicity datasets from the Gene expression omnibus (GEO) database were combined with RNA-seq to identify the common genes. Cytoscape analyzed the hub genes, which were validated by quantitative real-time PCR. ImmuCo and ImmGen databases analyzed the correlations between hub genes and immunity-relative markers in immune cells. Cibersort analyzed the immune infiltration and correlations between the hub genes and the immune cells. Logistic regression, receiver operator characteristic curve, and artificial neural network analysis evaluated the diagnosis ability of hub genes for clinical data in the GEO dataset. Results: The survival curves and ultrasound monitoring demonstrated that cardiotoxicity models were constructed successfully. In the acute model, 788 DEGs were enriched in the activated metabolism and the suppressed immunity-associated signaling pathways. Three hub genes (Alas1, Atp5g1, and Ptgds) were upregulated and were negatively correlated with a colony of immune-activating cells. However, in the chronic model, 281 DEGs showed that G protein-coupled receptor (GPCR)-related signaling pathways were the critical events. Three hub genes (Hsph1, Abcb1a, and Vegfa) were increased in the chronic model. Furthermore, Hsph1 combined with Vegfa was positively correlated with dilated cardiomyopathy (DCM)-induced heart failure (HF) and had high accuracy in the diagnosis of DCM-induced HF (AUC = 0.898, P = 0.000). Conclusion: Alas1, Atp5g1, and Ptgds were ideal biomarkers in DOX acute cardiotoxicity. However, Hsph1 and Vegfa were potential biomarkers in the myocardium in the chronic model. Our research, first, provided bioinformatics and clinical evidence for the discovery of the differences in mechanism and potential biomarkers of DOX-induced acute and chronic cardiotoxicity to find a therapeutic strategy precisely.

Impacto da Concentração de Ácido Úrico Sérico no Risco de Doença Cardiovascular: Um Estudo Coorte Realizado no Norte da China / Impact of Serum Uric Acid Concentration on the Risk of Cardiovascular Disease: A Cohort Study Conducted in Northern China

Resumo Fundamento Os resultados de estudos anteriores sobre a relação entre ácido úrico sérico (AUS) e o risco de doença cardiovascular (DCV) até agora são inconsistentes devido aos fatores de confusão causados por outros fatores de risco cardiovascular conhecidos. Objetivos Este estudo tem o objetivo de avaliar a relação entre o AUS e as DCV incidentes em chineses de meia-idade e idosos, que foram estratificados de acordo com o índice de massa corporal (IMC). Métodos Recrutamos 5.721 participantes com idades entre 40 e 75 anos que não tinham diagnóstico de DCV na linha de base, e que foram monitorados de 2008 a 2017. Os participantes foram categorizados em quintis de AUS. A regressão de Cox e a análise de sobrevivência de Kaplan-Meier foram utilizadas para comparar a incidência de DCV entre os grupos de AUS. As correlações entre AUS e a incidência de DCV em grupos com IMC e circunferência de cintura (CC) variados também foram analisadas. Um P valor <0,05 foi considerado estatisticamente significativo. Resultados Durante um período médio de monitoramento de 7,6 anos, a incidência de DCV aumentou com o AUS (teste de Log-rank p<0,001). Em comparação com o primeiro quintil, as razões de risco padronizadas (intervalos de confiança de 95%) para p desenvolvimento de DCV foram 1,08 (0,78-1,65), 1,17 (0,88-1,77), 1,47 (1,12-2,21), e 1,68 (1,28-2,44) para o segundo, terceiro, quarto e quinto quintis, respectivamente. Essa relação ficou mais clara em participantes com IMC e CC normais. A razão de risco ajustada para cada aumento de 100 μmol/L de AUS foi de 1,13 (intervalo de confiança de 95%: 1,02-1,39) para eventos de DCV. Conclusões O AUS alto é um fator de risco de DCV independente em pessoas de meia-idade e idosas do norte da China. Esse efeito é mantido mesmo depois da estratificação de acordo com medidas de magreza/obesidade.

Abstract Background The results of previous studies of the relationship between serum uric acid (SUA) and the risk of cardiovascular disease (CVD) have been inconsistent due to confounding factors caused by other known cardiovascular risk factors. Objectives This study aimed to evaluate the relationship between SUA and incident CVD in middle-aged and elderly Chinese people, who were stratified according to body mass index (BMI). Methods This study recruited 5,721 participants of 40-75 years of age, who were free of CVD at baseline and who underwent follow-up from 2008 to 2017. Participants were categorized in SUA quintiles. Cox proportional hazard and Kaplan-Meier survival analysis were used to compare CVD incidence among the SUA groups. The correlations between SUA and CVD incidence in groups with differing BMI and waist circumference (WC) were also analyzed. A P value <0.05 was considered statistically significant. Results During a mean follow-up period of 7.6 years, CVD incidence increased with SUA (log-rank test p<0. 001). Compared with the first quintile, the adjusted hazard ratios (95% confidence interval (CI)) for the development of CVD were 1.08 (0.78-1.65), 1.17 (0.88-1.77), 1.47 (1.12-2.21), and 1.68 (1.28-2.44) for the second to fifth quintiles, respectively. This relationship was clearer in participants with normal BMI and WC. The adjusted hazard ratio for each 100 μmol/L increase in SUA was 1.13 (95% CI: 1.02-1.39) for CVD events. Conclusions High SUA is an independent risk factor for CVD in middle-aged and elderly northern Chinese people. This effect is maintained even after stratification according to measures of leanness/obesity.

Impact of Serum Uric Acid Concentration on the Risk of Cardiovascular Disease: A Cohort Study Conducted in Northern China. / Impacto da Concentração de Ácido Úrico Sérico no Risco de Doença Cardiovascular: Um Estudo Coorte Realizado no Norte da China.

BACKGROUND: The results of previous studies of the relationship between serum uric acid (SUA) and the risk of cardiovascular disease (CVD) have been inconsistent due to confounding factors caused by other known cardiovascular risk factors. OBJECTIVES: This study aimed to evaluate the relationship between SUA and incident CVD in middle-aged and elderly Chinese people, who were stratified according to body mass index (BMI). METHODS: This study recruited 5,721 participants of 40-75 years of age, who were free of CVD at baseline and who underwent follow-up from 2008 to 2017. Participants were categorized in SUA quintiles. Cox proportional hazard and Kaplan-Meier survival analysis were used to compare CVD incidence among the SUA groups. The correlations between SUA and CVD incidence in groups with differing BMI and waist circumference (WC) were also analyzed. A P value <0.05 was considered statistically significant. RESULTS: During a mean follow-up period of 7.6 years, CVD incidence increased with SUA (log-rank test p<0. 001). Compared with the first quintile, the adjusted hazard ratios (95% confidence interval (CI)) for the development of CVD were 1.08 (0.78-1.65), 1.17 (0.88-1.77), 1.47 (1.12-2.21), and 1.68 (1.28-2.44) for the second to fifth quintiles, respectively. This relationship was clearer in participants with normal BMI and WC. The adjusted hazard ratio for each 100 µmol/L increase in SUA was 1.13 (95% CI: 1.02-1.39) for CVD events. CONCLUSIONS: High SUA is an independent risk factor for CVD in middle-aged and elderly northern Chinese people. This effect is maintained even after stratification according to measures of leanness/obesity.

FUNDAMENTO: Os resultados de estudos anteriores sobre a relação entre ácido úrico sérico (AUS) e o risco de doença cardiovascular (DCV) até agora são inconsistentes devido aos fatores de confusão causados por outros fatores de risco cardiovascular conhecidos. OBJETIVOS: Este estudo tem o objetivo de avaliar a relação entre o AUS e as DCV incidentes em chineses de meia-idade e idosos, que foram estratificados de acordo com o índice de massa corporal (IMC). MÉTODOS: Recrutamos 5.721 participantes com idades entre 40 e 75 anos que não tinham diagnóstico de DCV na linha de base, e que foram monitorados de 2008 a 2017. Os participantes foram categorizados em quintis de AUS. A regressão de Cox e a análise de sobrevivência de Kaplan-Meier foram utilizadas para comparar a incidência de DCV entre os grupos de AUS. As correlações entre AUS e a incidência de DCV em grupos com IMC e circunferência de cintura (CC) variados também foram analisadas. Um P valor <0,05 foi considerado estatisticamente significativo. RESULTADOS: Durante um período médio de monitoramento de 7,6 anos, a incidência de DCV aumentou com o AUS (teste de Log-rank p<0,001). Em comparação com o primeiro quintil, as razões de risco padronizadas (intervalos de confiança de 95%) para p desenvolvimento de DCV foram 1,08 (0,78­1,65), 1,17 (0,88­1,77), 1,47 (1,12­2,21), e 1,68 (1,28­2,44) para o segundo, terceiro, quarto e quinto quintis, respectivamente. Essa relação ficou mais clara em participantes com IMC e CC normais. A razão de risco ajustada para cada aumento de 100 µmol/L de AUS foi de 1,13 (intervalo de confiança de 95%: 1,02­1,39) para eventos de DCV. CONCLUSÕES: O AUS alto é um fator de risco de DCV independente em pessoas de meia-idade e idosas do norte da China. Esse efeito é mantido mesmo depois da estratificação de acordo com medidas de magreza/obesidade.

KCNQ1OT1 lncRNA affects the proliferation, apoptosis, and chemoresistance of small cell lung cancer cells via the JAK2/STAT3 axis.

BACKGROUND: Small cell lung cancer (SCLC) is a devastating and aggressive neuroendocrine carcinoma characterized by high cellular proliferation and early metastatic spread. Numerous studies have demonstrated that long noncoding RNAs (lncRNAs) can regulate tumor generation and development, including in SCLC. The current study aimed to assess the effect of the lncRNA, KCNQ1OT1, on the proliferation, apoptosis, and chemoresistance of SCLC and the potential underlying molecular mechanism. METHODS: Matched chemo-resistant and sensitive cells were applied to RNA isolation and followed by expression profiling by microarray analysis and subsequent quantitative polymerase chain reaction (qPCR) validation. Cell viability and apoptosis were determined by Cell Counting Kit-8 and flow cytometry to examine the chemoresistance and apoptosis of KCNQ1OT1 knockdown with lentivirus-mediated RNA interference. Furthermore, cell proliferation was studied by colony formation, and invasion and migration were tested by Transwell cell invasion and wound-healing assays, respectively. A tumor xenograft model was established to determine the role of KCNQ1OT1 in tumor growth and chemoresistance in response to KCNQ1OT1 knockdown in vivo. Western blot analysis, qPCR, and immunohistochemistry were used to detect the levels of messenger RNA (mRNA) Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway-related markers. RESULTS: Higher expression of KCNQ1OT1 was detected in SCLC chemo-resistant verso chemo-sensitive cells. Knockdown of KCNQ1OT1 inhibited SCLC cell viability and cloning ability, hindered cell migration and invasion, induced apoptosis in vitro, and suppressed tumor growth and chemoresistance in vivo, by activating the JAK2/STAT3 signaling pathway. CONCLUSIONS: This is the first study to indicate that lncRNA KCNQ1OT1 promotes cell proliferation and invasion, and prevents apoptosis of SCLC by activating the JAK2/STAT3 pathway.

Inhibition of lncRNA KCNQ1OT1 Improves Apoptosis and Chemotherapy Drug Response in Small Cell Lung Cancer by TGF-ß1 Mediated Epithelial-to-Mesenchymal Transition.

PURPOSE: Drug resistance is one of the main causes of chemotherapy failure in patients with small cell lung cancer (SCLC), and extensive biological studies into chemotherapy drug resistance are required. MATERIALS AND METHODS: In this study, we performed lncRNA microarray, in vitro functional assays, in vivo models and cDNA microarray to evaluate the impact of lncRNA in SCLC chemoresistance. RESULTS: The results showed that KCNQ1OT1 expression was upregulated in SCLC tissues and was a poor prognostic factor for patients with SCLC. Knockdown of KCNQ1OT1 inhibited cell proliferation, migration, chemoresistance and promoted apoptosis of SCLC cells. Mechanistic investigation showed that KCNQ1OT1 can activate transforming growth factor-ß1 mediated epithelial-to-mesenchymal transition in SCLC cells. CONCLUSION: Taken together, our study revealed the role of KCNQ1OT1 in the progression and chemoresistance of SCLC, and suggested KCNQ1OT1 as a potential diagnostic and prognostic biomarker in SCLC clinical management.

Triboelectric-optical responsive cholesteric liquid crystals for self-powered smart window, E-paper display and optical switch.

Intelligent responsive devices are crucial for a variety of applications ranging from smart electronics to robotics. Electro-responsive cholesteric liquid crystals (CLC) have been widely applied in display panels, smart windows, and so on. In this work, we realize the mechanical stimuli-triggered optical responses of the CLC by integrating it with a triboelectric nanogenerator (TENG), which converts the mechanical motion into alternating current electricity and then tunes the different optical responses of the CLC. When the voltage applied on the CLC is relatively low (15-40 V), the TENG drives the switching between the bistable planar state and focal conic state of the CLC, which shows potential applications in self-powered smart windows or E-paper displays. When the voltage supplied by the TENG is larger than 60 V, a self-powered optical switch is demonstrated by utilizing the transformation between focal conic state and instantons homeotropic state of the CLC. This triboelectric-optical responsive device consumes no extra electric power and suggests a great potential for future smart electronics.

[Etiology and genetic diagnosis of short stature in children].

OBJECTIVE: To study the etiology and genetic diagnosis of children with short stature. METHODS: A retrospective analysis was performed to study the etiological distribution and clinical features of 86 children with short stature. RESULTS: A total of 6 causes were observed in these children, among which idiopathic short stature (ISS, 41%) and growth hormone deficiency (GHD, 29%) were the most common causes, followed by genetic diseases (14%). There were no significant differences in age at the time of diagnosis, body height, body length and weight at birth, body height of parents and insulin-like growth factor-1 levels between the genetic disease group and the ISS/GHD groups (P>0.05). Compared with the ISS group, the genetic disease group had significantly lower deviation from the 3rd percentile for the height of children of the same age and sex (ΔP3) and height standard deviation score (P<0.05), while there were no significant differences between the genetic disease and GHD groups (P>0.05). The analysis of the clinical manifestations for the genetic disease group showed heterogeneity and phenotypic overlap in children with different genetic diseases. CONCLUSIONS: ISS, GHD and genetic diseases are major causes of short stature in children. For children with severe short stature, genetic testing should be performed to make a definitive diagnosis after GHD has been excluded.

[Role of TGF-ß1 in multi-drug resistance in small cell lung cancer and its clinical significance].

OBJECTIVE: To investigate the role of transforming growth factor ß1 (TGF-ß1) in multi-drug resistance in small cell lung cancer and its clinical significance.
 Methods: The mRNA and protein expressions of TGF-ß1 in H69 and H69AR cells were detected by real-time PCR and Western blot, respectively. After silence of TGF-ß1, the sensitivity of H69AR to drugs was detected by CCK8 assay. The expressions of TGF-ß1 in lung cancer and paracarcinoma tissues were examined by QRT-PCR and immunohistochemistry. The relationship of TGF-ß1 expression with clinical pathological features and prognosis of patients was studied.
 Results: Compared to H69, the mRNA and protein expressions of TGF-ß1 in H69AR cells were significantly increased by (5.93±0.47) and (8.49±1.92) folds, respectively (P<0.01). Transfection of TGF-ß1 siRNA resulted in a decrease of TGF-ß1 expression by 70.432% in H69AR cells (F=21.20, P<0.01) and an increase insensitivity to chemotherapeutic agents of H69AR cells (t=4.576, P<0.05). Compare with the paracarcinoma tissues, the expression of TGF-ß1 was significantly increased in small cell lung cancer tissues (t=13.925, P<0.01), which was closely related with clinical stage, chemosensitivity and overall survival (all P<0.05), but not related with gender, age (both P>0.05).
 Conclusion: TGF-ß1 is involved in the regulation of small cell lung cancer multidrug resistance, which may be a potential marker to evaluate the chemosensitivity and clinical prognostic for small cell lung cancer.

Oct2 and Bob1 are sensitive and specific markers in lineage determination of B cell lymphomas with no expression of conventional B cell markers.

AIMS: Rare cases of B cell lymphomas do not express conventional B cell markers (CD20, CD79a and PAX5), and these types of lymphomas include anaplastic lymphoma kinase (ALK)-positive large B cell lymphoma, plasmablastic lymphoma, primary effusion lymphoma and the solid variant of primary effusion lymphoma, extracavitary human herpesvirus 8 (HHV8)-positive large B cell lymphoma. Establishing accurate diagnoses of these B cell lymphomas can be challenging, and often requires a large panel of immunohistochemical stains, molecular assays and cytogenetic studies. B cell-specific transcription factors, Oct2 and Bob1, have been shown to be expressed consistently in most, if not all, B cell lymphomas, and therefore we investigated the utility of Oct2 and Bob1 immunohistochemistry in lineage determination of the aforementioned B cell lymphomas. METHODS AND RESULTS: We selected 34 cases of previously diagnosed B cell lymphomas with no or weak expression of CD20, CD79a and PAX5. Oct2 and Bob1 were positive in 74% (25 of 34) and 85% (29 of 34) of the cases, respectively. When we combined the results of these two immunostains, 94% (32 of 34) cases expressed at least one of these two markers. We also included 51 control cases of non-B cell neoplasms, and none of them expressed either Oct2 or Bob1. CONCLUSIONS: Oct2 and Bob1 are very reliable in determining B cell lineage in the absence of expression of other pan-B cell markers, and it should provide great diagnostic benefit to include them both in a panel of immunohistochemistry to assess undifferentiated malignant neoplasms.

EPHA3 regulates the multidrug resistance of small cell lung cancer via the PI3K/BMX/STAT3 signaling pathway.

Multidrug resistance (MDR) is a major obstacle to the treatment of small cell lung cancer (SCLC). EPHA3 has been revealed to be the most frequently mutated Eph receptor gene in lung cancer with abnormal expression. Growing evidence indicates that the signaling proteins of EPHA3 downstream, including PI3K, BMX and STAT3, play crucial roles in tumorigenesis and cancer progression. To explore the possible role of EPHA3 in MDR, we assessed the influence of EPHA3 on chemoresistance, cell cycle, apoptosis, and tumor growth, as well as the relationship between EPHA3 and the expression of PI3K, BMX, and STAT3 in SCLC. We observed that overexpression of EPHA3 in SCLC cells decreased chemoresistance by increasing apoptosis and inducing G0/G1 arrest, accompanied by reduced phosphorylation of PI3K/BMX/STAT3 signaling pathway. Knockdown of EPHA3 expression generated a resistant phenotype of SCLC, as a result of decreased apoptosis and induced G2/M phase arrest. And re-expression of EPHA3 in these cells reversed the resistant phenotype. Meanwhile, increased phosphorylation of PI3K/BMX/STAT3 signaling pathway was observed in these cells with EPHA3 deficiency. Notably, both PI3K inhibitor (LY294002) and BMX inhibitor (LFM-A13) impaired the chemoresistance enhanced by EPHA3 deficiency in SCLC cell lines. Furthermore, EPHA3 inhibited growth of SCLC cells in vivo and was correlated with longer overall survival of SCLC patients. Thus, we first provide the evidences that EPHA3 is involved in regulating the MDR of SCLC via PI3K/BMX/STAT3 signaling and may be a new therapeutic target in SCLC.