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A new sensitive fluorescent probe (CDs-AgNP/H2O2) for detecting sulfite and bisulfite (SO32− and HSO3−) based on the inner-filter effect (IFE) between silver nanoparticles (AgNPs) and carbon dots (CDs) was developed. Because of the spectral overlap between the absorption of AgNPs and the excitation of CDs, the fluorescence of CDs can be quenched by AgNPs owing to the IFE. H2O2 weakens the IFE and restores the fluorescence due to the oxidation of AgNPs by H2O2. However, the existence of SO32−/HSO3− can quench the fluorescence again as a result of redox reaction between SO32−/HSO3− and H2O2. The results showed a broad linear range of 20–200 μM with a low limit of detection (3.02 μM) toward SO32−/HSO3−. The combination of IFE and redox reaction led to improvement of the sensitivity and selectivity. The probe was implemented to measure SO32−/HSO3− in various agricultural products and foods with acceptable results (80.6 to 118.9% recovery). [ABSTRACT FROM AUTHOR]

Microbial glycerol dialkyl glycerol tetraethers (GDGTs) in lacustrine sediments are widely used to reconstruct terrestrial paleoenvironments. However, lipids of diverse origin in lakes make it difficult to decipher environmental information, appealing for the necessity to evaluate the impact of terrigenous input on the distribution of GDGTs through long-term monitoring. In this study, we conducted two-year monitoring of GDGTs along the river, estuary, near shore, to the center of Lake Liangzi in central China. By comparing the spatiotemporal changes of GDGT distribution in suspended particulate matter (SPM) and surface sediments, we found that the archaeal isoprenoid GDGTs (isoGDGTs) were mainly produced in situ in the river-lake systems, and not affected by the soil input. In contrast, the bacterial branched GDGTs (brGDGTs) were affected, to some extent, by soil input, depending on the distance to the lakeshore. The soil input of brGDGTs was enhanced during an episode of abnormal rainfall (flood). Moreover, the large variation of isoGDGTs indicates the in situ production under the anoxic condition in lake water. The paired increase in the GDGT-0/Cren ratio and GDGT concentration might be diagnostic of flooding events in ancient times. [ABSTRACT FROM AUTHOR]

Besides natural climate variations, human activities can also cause significant changes in regional vegetation composition, especially during the late Holocene period. Southwest China has experienced a long history of human activities in terms of deforestation and agricultural development. Here we present a continuous fossil pollen record covering the past 2,100 years from Beihai Wetland in western Yunnan Province, for a better understanding of regional vegetation history and potential human activities. The pollen results indicate that the forest components show decreasing trends, including Alnus dominated deciduous broadleaved forest and evergreen broadleaved forest represented by evergreen Quercus. On the other hand, herbs such as Poaceae and Artemisia expanded along with the decline of forest, especially during the period after ad 1120. The results of ordination analysis further confirm such a pattern in which the first PCA component (PC1, capturing 42.2% of total variance) represents an increasing trend, which is subsequently interpreted as an index of human activities. Our findings show broadly identical patterns to previously published sedimentary records from Yunnan as well as historical documents. The human activities increased following the expansion in regional population, in the form of deforestation and regional agricultural development. They may also have caused the expansion of herbs, especially Poaceae, which replaced forest. Therefore, as indicated by the fossil pollen record from the Beihai Wetland, human activities in southwest China increased gradually during the past 2,100 years and more rapidly after ad 1120. Results of sediment influx and grain size analyses showed generally consistent patterns with the signs of summer monsoons captured by stable oxygen isotope records from stalagmites, indicating limited influence from human activities within the wetland system compared to the regional landscape. [ABSTRACT FROM AUTHOR]

Aims: The association between type 2 diabetes mellitus (T2DM) and risk of head and neck cancer (HNC) remains unclear. This study aims to perform a system review and meta-analysis to explore this relationship. Methods: PubMed, Web of Science, and Embase databases were searched for studies published up to July 31, 2020, regarding the association between T2DM and HNC risk. A random-effects model was utilized to calculate summary relative risks (RRs) with corresponding 95% confidence intervals (CIs). Results: Fourteen case–control studies and thirteen cohort studies were included in our analysis. We observed a weak association between T2DM and risk of HNC overall, but there was no statistical significance (RR, 1.04; 95% CI, 0.88–1.23; I2 = 83.2%). Interestingly, there was a strong association in East Asia (RR, 1.46; 95% CI, 1.21-1.77; I2 = 36.6%). For HNC subtypes, T2DM conferred a significantly elevated risk in oral cancer (RR, 1.22; 95% CI, 1.01–1.47; I2 = 89.0%). However, in subgroup analyses of smoking, alcohol use, and body mass index (BMI)/obesity adjustments, the association between T2DM and oral cancer risk became insignificant. In addition, T2DM was not associated with a statistically elevated risk of pharyngeal cancer (RR, 1.18; 95% CI, 0.94–1.49; I2 = 72.9%) and laryngeal cancer (RR, 1.03; 95% CI, 0.88–1.22; I2 = 71.2%). Conclusions: This meta-analysis indicates that T2DM is associated with an increased risk of HNC in East Asia. As for site-specific cancer types, the risk of oral cancer was significantly increased in T2DM patients, which appear to be mediated or confounded by smoking, alcohol use, or BMI/obesity. [ABSTRACT FROM AUTHOR]

Aims: Diabetes mellitus (DM) is widely recognized as a risk factor for diverse cancers in adults. However, the association between maternal diabetes and risk of childhood cancer in the offspring has so far not been well studied. We thus conducted a meta-analysis to evaluate the role of maternal diabetes on the risk of childhood cancer. Methods: We performed a comprehensive literature search to identify eligible studies published up to June 20, 2020, including the PubMed, Web of science and Embase databases. Summary odds ratios (OR) and 95% confidence intervals (CI) were computed using a random-effects model (I2 ≥ 25%) or a fixed-effect model (I2 < 25%). Results: Totally, sixteen case–control and six cohort studies on the risk of childhood cancer associated with maternal diabetes were included. Overall, children of diabetic women had a significantly increased risk in childhood malignancy (OR, 1.30; 95% CI, 1.10–1.53). Notably, a significantly elevated risk of childhood cancer in the offspring was found for women with pre-existing diabetes (OR, 1.41; 95% CI, 1.17–1.70), but not for women with gestational diabetes mellitus (GDM) (OR, 1.10; 95% CI, 0.94–1.28). For site-specific cancers, maternal diabetes was associated with a higher risk of leukemia in offspring (OR, 1.30; 95% CI, 1.15–1.48), especially for acute lymphoblastic leukemia (OR, 1.44; 95% CI, 1.27–1.64). However, no significant associations were observed between maternal diabetes and the risk of lymphomas and retinoblastoma. Conclusions: Our meta-analysis indicates that maternal diabetes is associated with an increased risk of childhood cancer in the offspring, particularly for acute lymphoblastic leukemia. Future study should investigate the underlying biological mechanisms behind the association. [ABSTRACT FROM AUTHOR]

The evolution of the Indian Summer Monsoon (ISM) has been widely investigated and traditionally interpreted as consequences of orbital forcing change and the migration of the Intertropical Convergent Zone (ITCZ). The potential influence of sea-surface temperature (SST) on ISM variation at millennial time scales has been progressively proposed in recent studies. Towards a better understanding of Holocene evolution of ISM, especially the potential response to variations in SST, a 643 cm continuous sediment sequence covering the past 11.1 ka was recovered from Beihai Wetland in western Yunnan Plateau. Fossil pollen analysis revealed that evergreen broadleaved forest dominated the regional vegetation in the early Holocene, which represented a warm and humid period associated with strong ISM. Expansions of deciduous broadleaved forest and grassland from 5.2 cal. ka BP to the present, together with the appearance of abundant plant remains, indicate the formation of the wetland system. Ordination analysis of the pollen assemblages further confirmed the abrupt vegetation turnover at ca. 5.2 cal. ka BP, which is consistent with the abrupt decline in reconstructed mean annual precipitation (Pann, from ca. 1400 to 1100 mm), and indicates an abrupt decline in the summer monsoon. We performed a climate regime shift test on various records from the ISM domain and eastern Africa and found this phenomenon as well, which could not be explained by changes in solar insolation or the migration of the ITCZ. A mid-Holocene cooling was detected from the Indian Ocean, especially a decreased SST in the tropical Indian Ocean ca. 5.5 cal. ka BP. Cooling of the tropical Indian Ocean possibly caused the abrupt retreat of the summer monsoon by restraining the duration of the monsoonal season and the convergent process, which was supported by an abrupt monsoon decline based on results from a minimal concept model. [ABSTRACT FROM AUTHOR]

Aims: The objective is to investigate the effects of liraglutide on nonalcoholic fatty liver disease in type 2 diabetes mellitus. Materials and methods: Thirty-two patients with T2DM and NAFLD admitted to the Third Affiliated Hospital of Dalian Medical University from December 2014 to December 2016 were selected, including 11 females and 21 males, aged 39.34 ± 8.54 years old. The patients were given liraglutide on the basis of their original hypoglycemic regimen. Results: After 3 months treatment of liraglutide, FPG was reduced from 8.54 ± 2.21 mmol/L to 6.90 ± 1.73 mmol/L. HbA1c was reduced from 9.72 ± 1.95 to 7.78 ± 1.99. WC was reduced from 103.27 ± 9.92 kg to 93.97 ± 8.35 kg. BMI was reduced from 30.56 ± 4.06 kg/m2 to 28.01 ± 3.12 kg/m2. FLI was reduced from 79.23 ± 16.56 to 58.83 ± 19.75. The differences were statistically significant (p < 0.001). TG was reduced from 2.95 ± 2.13 mmol/L to 2.27 ± 1.31 mmol/L. The difference was significant (p < 0.01). Meanwhile, HOMA-IR was reduced from 1.504 ± 0.002 to 1.503 ± 0.002. GGT was reduced from 62.63 ± 71.61 U/L to 38.13 ± 30.13 U/L. AST was reduced from 27.25 ± 13.74 U/L to 25.44 ± 16.69 U/L. The differences were statistically significant (p < 0.05). After treatment, FCP, TC, HDL-C, LDL-C, ALT, and HOMA-β were also improved compared with before treatment, but the difference was not statistically significant (p > 0.05). Conclusion: In addition to effectively lowering glucose and improving islet resistance, liraglutide could also improve obesity and adjust blood lipids. However, the improvement of islet function might not be significant after 3 months of treatment. Liraglutide could reduce liver fat accumulation in patients with T2DM and NAFLD. [ABSTRACT FROM AUTHOR]

RNA splicing dysregulation is widespread in cancer. Accumulating evidence demonstrates that splicing defects resulting from splicing dysregulation play critical roles in cancer pathogenesis and can serve as new biomarkers and therapeutic targets for cancer intervention. These findings have greatly deepened the mechanistic understandings of the regulation of alternative splicing in cancer cells, leading to rapidly growing interests in targeting cancer-related splicing defects as new therapies. Here we summarize the current research progress on splicing dysregulation in cancer and highlight the strategies available or under development for targeting RNA splicing defects in cancer. [ABSTRACT FROM AUTHOR]

Ventricular tachycardia (VT) causes sudden cardiac death, however, the majority of risk genes for VT remain unknown. SCN4B encodes a β-subunit, Navβ4, for the voltage-gated cardiac sodium channel complex involved in generation and conduction of the cardiac action potential. We hypothesized that genomic variants in SCN4B increase the risk of VT. We used high-resolution melt analysis followed by Sanger sequencing to screen 199 VT patients to identify nonsynonymous variants in SCN4B. Two nonsynonymous heterozygous variants in SCN4B were identified in VT patients, including p.Gly8Ser in four VT patients and p.Ala145Ser in one VT patient. Case–control association studies were used to assess the association between variant p.Gly8Ser and VT in two independent populations for VT (299 VT cases vs. 981 controls in population 1 and 270 VT patients vs. 639 controls in population 2). Significant association was identified between p.Gly8Ser and VT in population 1 (P = 1.21 × 10−4, odds ratio or OR = 11.04), and the finding was confirmed in population 2 (P = 0.03, OR = 3.62). The association remained highly significant in the combined population (P = 3.09 × 10−5, OR = 6.17). Significant association was also identified between p.Gly8Ser and idiopathic VT (P = 1.89 × 10−5, OR = 7.27). Functional analysis with Western blotting showed that both p.Gly8Ser and p.Ala145Ser variants significantly reduced the expression level of Navβ4. Based on 2015 ACMG Standards and Guidelines, p.Gly8Ser and p.Ala145Ser can be classified as the pathogenic and likely pathogenic variant, respectively. Our data suggest that SCN4B is a susceptibility gene for common VT and idiopathic VT and link rare SCN4B variants with large effects (OR = 6.17–7.27) to common VT. [ABSTRACT FROM AUTHOR]

Most biomechanical models that aim to investigate traumatic brain injury consider the corona radiata as a homogeneous structure. To verify this, indentation-relaxation tests using a custom-designed indentation device were performed on the anterior, superior, and posterior region of the corona radiata in the coronal plane of the porcine brain. Using Boltzmann hereditary integral, a linear viscoelastic model with a Prony series approximation was fitted to the time-dependent shear modulus for different regions of the corona radiata, and the fit parameters were generated. The posterior region was the stiffest and the anterior region was the least stiff. A statistical analysis revealed a significant difference in biomedical properties between the anterior and superior regions, as well as between the anterior and posterior regions in the short time scale. However, the results showed that these differences faded away as the tissue approached equilibrium. No significant difference was observed between the superior and posterior regions along the total time history of relaxation. This is the first demonstration of the regional biomechanical heterogeneity of the corona radiata, and these results will improve future biomedical models of the porcine brain. [ABSTRACT FROM AUTHOR]

Collapsin response mediator proteins (CRMPs) family predominantly expressed in the developing nervous system as key molecular components in shaping neural networks. However, knowledge of the evolution of CRMPs is limited. To gain further insight into nervous system evolution in vertebrates, we have performed a comprehensive bioinformatics analysis of CRMPs, including phylogenetic analysis, an examination of positively selected sites and putative biological significance and protein structure analysis. Sequence similarity searches have been performed in genome data to identify homologues of CRMPs in vertebrates. Phylogenetic relationships were constructed to trace the family evolutionary history. Five CRMP members might form through gene duplication. The inferred evolutionary transitions that separate members which belong to different gene clusters correlated with changes in functional properties. To determine the mode of evolution in vertebrates, we used several complementary methods, including site-specific models, branch-specific models and branch-site models to estimated molecular substitution rates and determined the selective force operating at each CRMPs gene cluster. Nineteen positive selection sites and the functional areas were detected in this process. This research gives us a first look at the phylogeny and evolutionary selection pressure of the CRMP family in vertebrates. Additionally, we identified a number of critical amino acid residues likely relevant for the distinct functional properties of the paralogues. In conclusion, the results of this study contribute novel detailed information about the molecular evolution of CRMPs, reveal CRMPs' roles in the pathogenesis of nervous system diseases and provide a new thought of the targeted therapy from the molecular evolution angle. [ABSTRACT FROM AUTHOR]

GATA transcription factors perform conserved and essential roles during animal development, including germ-layer specification, hematopoiesis, and cardiogenesis. The evolutionary history and the changes in selection pressures following duplication of the six GATA family members in vertebrates have not been completely understood. Recently, we explored multiple databases to find GATAs in different vertebrate species. Using these sequences, we have performed molecular phylogenetic analyses using Maximum Likelihood and Bayesian methods, and statistical tests of tree topologies, to ascertain the phylogenetic relationship and selection pressures among GATA proteins. Seventy-one full-length cDNA sequences from 24 vertebrate species were extracted from multiple databases. By phylogenetic analyses, we investigated the origin, conservation, and evolution of the GATAs. Six GATA genes in vertebrates might be formed by gene duplication. The inferred evolutionary transitions that separate members which belong to different gene clusters correlated with changes in functional properties. Selection analysis and protein structure analysis were combined to explain Darwinian selection in GATA sequences and these changes brought putative biological significance. 26 positive selection sites were detected in this process. This study reveals the evolutionary history of vertebrate GATA paralogous and positively selected sites likely relevant for the distinct functional properties of the paralogs. It provides a new perspective for understanding the origin and evolution and biological functions of GATAs, which will help to uncover the GATAs' biological roles, evolution and their relationship with associated diseases; in addition, other complex multidomain families and also larger superfamilies can be investigated in a similar way. [ABSTRACT FROM AUTHOR]

Lacustrine sediments have been widely used to investigate past climatic and environmental changes on millennial to seasonal time scales. Sedimentary archives of lakes in mountainous regions may also record non-climatic events such as earthquakes. We argue herein that a set of 64 annual laminae couplets reconciles a stratigraphically inconsistent accelerator mass spectrometry (AMS) C chronology in a ~4-m-long sediment core from Lake Mengda, in the north-eastern Tibetan Plateau. The laminations suggest the lake was formed by a large landslide, triggered by the 1927 Gulang earthquake ( M = 8.0). The lake sediment sequence can be separated into three units based on lithologic, sedimentary, and isotopic characteristics. Starting from the bottom of the sequence, these are: (1) unweathered, coarse, sandy valley-floor deposits or landslide debris that pre-date the lake, (2) landslide-induced, fine-grained soil or reworked landslide debris with a high organic content, and (3) lacustrine sediments with low organic content and laminations. These annual laminations provide a high-resolution record of anthropogenic and environmental changes during the twentieth century, recording enhanced sediment input associated with two phases of construction activities. The high mean sedimentation rates of up to 4.8 mm year underscore the potential for reconstructing such distinct sediment pulses in remote, forested, and seemingly undisturbed mountain catchments. [ABSTRACT FROM AUTHOR]

Inorganic minerals form a major component of lacustrine sediments and have the potential to reveal detailed information on previous climatic and hydrological conditions. The ability to extract such information however, has been restricted by a limited understanding of the relationships between minerals and the environment. In an attempt to fill in this gap in our knowledge, 146 surface sediment samples have been investigated from 146 lakes on the Tibetan Plateau. The mineral compositions derived from these samples by X-Ray Diffraction (XRD) were used to examine the relationships between mineral compositions and the environmental variables determined for each site. Statistical techniques including Multivariate regression trees (MRT) and Redundancy Analysis (RDA), based on the mineral spectra and environmental variables, reveal that the electrical conductivity (EC) and Mg/Ca ratios of lake water are the most important controls on the composition of endogenic minerals. No endogenic minerals precipitate under hyper-fresh water conditions (EC lower than 0.13 mS/cm), with calcite commonly forming in water with EC values above 0.13 mS/cm. Between EC values of 0.13 and 26 mS/cm the mineral composition of lake sediments can be explained in terms of variations in the Mg/Ca ratio: calcite dominates at Mg/Ca ratios of less than 33, whereas aragonite commonly forms when the ratio is greater than 33. Where EC values are between 26 and 39 mS/cm, monohydrocalcite precipitates together with calcite and aragonite; above 39 mS/cm, gypsum and halite commonly form. Information on the local geological strata indicates that allogenic (detrital) mineral compositions are primarily influenced by the bedrock compositions within the catchment area. By applying these relationships to the late glacial and Holocene mineral record from Chaka Salt Lake, five lake stages have been identified and their associated EC conditions inferred. The lake evolved from a freshwater lake during the late glacial (before 11.4 cal. ka BP) represented by the lowest EC values (<0.13 mS/cm), to a saline lake with EC values slightly higher than 39 mS/cm during the early and mid Holocene (ca. 11.4-5.3 cal. ka BP), and finally to a salt lake (after 5.3 cal. ka BP). These results illustrate the utility of our mineral-environmental model for the quantitative reconstruction of past environmental conditions from lake sediment records. [ABSTRACT FROM AUTHOR]

The chemical weathering intensity and element migration features of the Xiashu loess profile in Zhenjiang are studied in this paper. (1) The Xiashu loess profile underwent moderate chemical weathering. It seems that the precipitation is a more important factor than the temperature in controlling the process of the chemical weathering. (2) The major elements such as Si, K, Na, Ca, Mg, Mn and P were migrated and leached, while the elements Fe and Ti were slightly enriched. The migration features of the major elements reveal that the Xiashu loess finished the primary process of chemical weathering characterized by leaching of Ca and Na, and almost reached the secondary process characterized by leaching of K. Except the elements Sr and Ga, other trace elements such as Th, Ba, Cu, Zn, Co, Ni, Cr and V were enriched. It might be caused by both the biogeochemical process and the adsorption of trace elements by clay mineral and organic materials. (3) The difference of element migration down the Xiashu loess profile reveals that the climate was warm and wet at the early-middle stage of the middle Pleistocene. At the end of the middle Pleistocene, it became dry and cool. At the early stage of the Late Pleistocene, the paleoclimate became warm and wet again. As a whole, the paleoclimate generally became drier and cooler in this region from the beginning of the middle Pleistocene. [ABSTRACT FROM AUTHOR]

The δ18O records of ostracode shells in sediments of core QH-2000 from Qinghai Lake can be used as a better proxy to reflect monsoon changes, Low monsoon precipitation between 17.5 and 11 cal. ka BP is indicated by positive #180 values averaging 2.37‰. A fast shift in #180 from positive at 11 cal, ka BP to negative at 10 cal. ka BP indicates sharp increase of monsoon precipitation. An interval of generally high monsoon precipitation is observed between 10 and 6 cal. ka BP with δ18O values averaging -2,15‰. Decrease of monsoon precipitation between 6 and 2.5 cal. ka BP is indicated by positive δ18O values. δ18O keeps positive values averaging 3.0‰ between 2,5 and 0 cal, ka BP suggesting low high monsoon precipitation. The climatic changes indicated by δ18O records of ostracode shells in sediments of core QH-2000 from Qinghai Lake and our broader regional comparison show that the climate in Qinghai Lake since the late Glacial is probably controlled by southwest monsoon other than southeast monsoon. [ABSTRACT FROM AUTHOR]

Authors would like to correct the error in in their original publication of the article. [ABSTRACT FROM AUTHOR]

Background: Decreased heart rate variability (HRV) is a predictor of autonomic system dysfunction, and is considered as a potential mechanism of increased risk of cardiovascular disease (CVD) induced by exposure to particulate matter less than 2.5 μm in diameter (PM2.5). Previous studies have suggested that exposure to PM2.5 may lead to decreased HRV levels, but the results remain inconsistent. Methods: An updated systematic review and meta-analysis of panel studies till November 1, 2019 was conducted to evaluate the acute effect of exposure to ambient PM2.5 on HRV. We searched electronic databases (PubMed, Web of Science, and Embase) to identify panel studies reporting the associations between exposure to PM2.5 and the four indicators of HRV (standard deviation of all normal-to-normal intervals (SDNN), root mean square of successive differences in adjacent normal-to-normal intervals (rMSSD), high frequency power (HF), and low frequency power (LF)). Random-effects model was used to calculate the pooled effect estimates. Results: A total of 33 panel studies were included in our meta-analysis, with 16 studies conducted in North America, 12 studies in Asia, and 5 studies in Europe. The pooled results showed a 10 μg/m3 increase in PM2.5 exposure which was significantly associated with a − 0.92% change in SDNN (95% confidence intervals (95%CI) − 1.26%, − 0.59%), − 1.47% change in rMSSD (95%CI − 2.17%, − 0.77%), − 2.17% change in HF (95%CI − 3.24%, − 1.10%), and − 1.52% change in LF (95%CI − 2.50%, − 0.54%), respectively. Overall, subgroup analysis suggested that short-term exposure to PM2.5 was associated with lower HRV levels in Asians, healthy population, and those aged ≥ 40 years. Conclusion: Short-term exposure to PM2.5 was associated with decreased HRV levels. Future studies are warranted to clarity the exact mechanism of exposure to PM2.5 on the cardiovascular system through disturbance of autonomic nervous function. [ABSTRACT FROM AUTHOR]

Proxy-based reconstructions and modeling of Holocene spatiotemporal precipitation patterns for China and Mongolia have hitherto yielded contradictory results indicating that the basic mechanisms behind the East Asian Summer Monsoon and its interaction with the westerly jet stream remain poorly understood. We present quantitative reconstructions of Holocene precipitation derived from 101 fossil pollen records and analyse them with the help of a minimal empirical model. We show that the westerly jet-stream axis shifted gradually southward and became less tilted since the middle Holocene. This was tracked by the summer monsoon rain band resulting in an early-Holocene precipitation maximum over most of western China, a mid-Holocene maximum in north-central and northeastern China, and a late-Holocene maximum in southeastern China. Our results suggest that a correct simulation of the orientation and position of the westerly jet stream is crucial to the reliable prediction of precipitation patterns in China and Mongolia. The basic mechanisms behind the East Asian Summer Monsoon remain poorly understood. Using proxy-based reconstructions and simulations, here the authors show that changes in the orientation and position of the westerly jet stream resulted in regionally asynchronous Holocene precipitation maxima. [ABSTRACT FROM AUTHOR]

A ratiometric fluorescent nanoprobe is described for the detection of H2O2. It is based on the use of a mixture of green-emitting CdTe quantum dots (GQDs) and red-emitting CdTe QDs (RQDs). The two kinds of QDs have different size and different fluorescence response towards H2O2. The ratio of the emission intensities at 606 and 510 nm (under 365 nm photoexcitation) can be used as the analytical information. Even without any chemical modification of the surface of the QDs, the probe display high sensitivity and selectivity for H2O2. The fluorescence of small QDs is more effectively quenched by H2O2. Stern-Volmer analysis showed both static and dynamic quenching to occur. The probe works well in the 10~125 μM H2O2 concentration range and has a 0.3 μM detection limit (3σ/slope). [ABSTRACT FROM AUTHOR]

RBM10 is an RNA splicing regulator that is frequently mutated in lung adenocarcinoma (LUAD) and has recently been proposed to be a cancer gene. How RBM10 mutations observed in LUAD affect its normal functions, however, remains largely unknown. Here integrative analysis of RBM10 mutation and RNA expression data revealed that LUAD-associated RBM10 mutations exhibit a mutational spectrum similar to that of tumor suppressor genes. In addition, this analysis showed that RBM10 mutations identified in LUAD patients lacking canonical oncogenes are associated with significantly reduced RBM10 expression. To systematically investigate RBM10 mutations, we developed an experimental pipeline for elucidating their functional effects. Among six representative LUAD-associated RBM10 mutations, one nonsense and one frameshift mutation caused loss-of-function as expected, whereas four missense mutations differentially affected RBM10-mediated splicing. Importantly, changes in proliferation rates of LUAD-derived cells caused by these RBM10 missense mutants correlated with alterations in RNA splicing of RBM10 target genes. Together, our data implies that RBM10 mutations contribute to LUAD pathogenesis, at least in large part, by deregulating splicing. The methods described in this study should be useful for analyzing mutations in additional cancer-associated RNA splicing regulators. [ABSTRACT FROM AUTHOR]