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The pathological features of Alzheimer's disease are the formation of amyloid plaques and entanglement of nerve fibers. Studies have shown that Cu may be involved in the formation of amyloid plaques. However, their role has been controversial. The aim of this study was to explore the role of Cu in AD. We applied the "R" software for our differential analysis. Differentially expressed genes were screened using the limma package. Copper metabolism-related genes and the intersection set of differential genes with GSE5281 were searched; functional annotation was performed. The protein–protein interaction network was constructed using several modules to analyse the most significant hub genes. The hub genes were then qualified, and a database was used to screen for small-molecule AD drugs. We identified 87 DEGs. gene ontology analysis focused on homeostatic processes, response to toxic substances, positive regulation of transport, and secretion. The enriched molecular functions are mainly related to copper ion binding, molecular function regulators, protein-containing complex binding, identical protein binding and signalling receptor binding. The KEGG database is mainly involved in central carbon metabolism in various cancers, Parkinson's disease and melanoma. We identified five hub genes, FGF2, B2M, PTPRC, CD44 and SPP1, and identified the corresponding small molecule drugs. Our study identified key genes possibly related to energy metabolism in the pathological mechanism of AD and explored potential targets for AD treatment by establishing interaction networks. [ABSTRACT FROM AUTHOR]

Intestinal-type gastric adenocarcinoma (IGA) is a common phenotype of gastric cancer. Currently, few studies have constructed nomograms that may predict overall (OS) and cancer-specific survival (CSS) probability after surgery. This study is to establish novel nomograms for predicting the survival of IGA patients who received surgery. A total of 1814 IGA patients who received surgery between 2000 and 2018 were selected from Surveillance, Epidemiology, and End Results database and randomly assigned to the training and validating sets at a ratio of 7:3. Then univariate and multivariate cox regression analyses were performed to screen significant indictors for the construction of nomograms. The calibration curve, the area under the receiver operating characteristic (receiver operating characteristic, ROC) curve (the area under curve, AUC), C-index, net reclassification index (NRI), integrated discrimination improvement (IDI) and decision curve analysis (DCA) curves were applied to assess the performance of the model. The significant outcomes of multivariate analysis revealed that ten variables (age, sex, race, surgery type, summary stage, grade, AJCC TNM stage, radiotherapy, number of regional nodes examined, number of regional nodes positive) were demonstrated to construct the nomogram for OS and ten variables (age, sex, race, surgery type, summary stage, grade, AJCC TNM stage, chemotherapy, number of regional nodes examined, number of regional nodes positive) for CSS. The calibration and AUC uncovered their favorable predictive performance. Subsequently, C-index, NRI, IDI and DCA curves further validated the predicative superiority of nomograms over 7th AJCC Stage System. The validated nomogram provides more reliable OS and CSS predictions for postoperative IGA patients with good accuracy, which can help surgeons in treatment decision-making and prognosis evaluation. [ABSTRACT FROM AUTHOR]

The pathological features of Alzheimer's disease are the formation of amyloid plaques and entanglement of nerve fibers. Studies have shown that Cu may be involved in the formation of amyloid plaques. However, their role has been controversial. The aim of this study was to explore the role of Cu in AD. We applied the "R" software for our differential analysis. Differentially expressed genes were screened using the limma package. Copper metabolism-related genes and the intersection set of differential genes with GSE5281 were searched; functional annotation was performed. The protein–protein interaction network was constructed using several modules to analyse the most significant hub genes. The hub genes were then qualified, and a database was used to screen for small-molecule AD drugs. We identified 87 DEGs. gene ontology analysis focused on homeostatic processes, response to toxic substances, positive regulation of transport, and secretion. The enriched molecular functions are mainly related to copper ion binding, molecular function regulators, protein-containing complex binding, identical protein binding and signalling receptor binding. The KEGG database is mainly involved in central carbon metabolism in various cancers, Parkinson's disease and melanoma. We identified five hub genes, FGF2, B2M, PTPRC, CD44 and SPP1, and identified the corresponding small molecule drugs. Our study identified key genes possibly related to energy metabolism in the pathological mechanism of AD and explored potential targets for AD treatment by establishing interaction networks. [ABSTRACT FROM AUTHOR]

Intestinal-type gastric adenocarcinoma (IGA) is a common phenotype of gastric cancer. Currently, few studies have constructed nomograms that may predict overall (OS) and cancer-specific survival (CSS) probability after surgery. This study is to establish novel nomograms for predicting the survival of IGA patients who received surgery. A total of 1814 IGA patients who received surgery between 2000 and 2018 were selected from Surveillance, Epidemiology, and End Results database and randomly assigned to the training and validating sets at a ratio of 7:3. Then univariate and multivariate cox regression analyses were performed to screen significant indictors for the construction of nomograms. The calibration curve, the area under the receiver operating characteristic (receiver operating characteristic, ROC) curve (the area under curve, AUC), C-index, net reclassification index (NRI), integrated discrimination improvement (IDI) and decision curve analysis (DCA) curves were applied to assess the performance of the model. The significant outcomes of multivariate analysis revealed that ten variables (age, sex, race, surgery type, summary stage, grade, AJCC TNM stage, radiotherapy, number of regional nodes examined, number of regional nodes positive) were demonstrated to construct the nomogram for OS and ten variables (age, sex, race, surgery type, summary stage, grade, AJCC TNM stage, chemotherapy, number of regional nodes examined, number of regional nodes positive) for CSS. The calibration and AUC uncovered their favorable predictive performance. Subsequently, C-index, NRI, IDI and DCA curves further validated the predicative superiority of nomograms over 7th AJCC Stage System. The validated nomogram provides more reliable OS and CSS predictions for postoperative IGA patients with good accuracy, which can help surgeons in treatment decision-making and prognosis evaluation. [ABSTRACT FROM AUTHOR]

Falls are a serious public health problem in the aging population because of the associated clinical and socioeconomic impact. Although previous studies have investigated fall-risk-increasing drugs (FRIDs), few studies have focused on dosage among adult inpatients. This study aimed to evaluate associations between fall risk and dosage of different FRIDs classes in hospital inpatients. Inpatients who experienced falls at medical or surgical wards of Changhua Christian Hospital from January 2017 to December 2021 were identified and matched by age, sex, and hospital ward to randomly selected controls (four per case). Anonymous patient data were extracted from the hospital medical data repository, including demographic characteristics, comorbidities, fall-risk scores, and drug prescriptions. Medication dosages were computed using the anatomical therapeutic chemical classification and the defined daily dose system of the World Health Organization. A total of 852 cases and 3408 controls were identified as eligible. Reducing the use of CNS-active medications, administering lower doses of sedative-hypnotics, prescribing sufficient dopaminergic anti-Parkinson agents, and using NSAIDs instead of opioids are imperative in preventing falls among hospitalized patients according to the findings in the study. [ABSTRACT FROM AUTHOR]

The level of fibrinogen in patients with lower extremity atherosclerosis (LEAD) has been widely identified as a risk factor contributing to adverse outcomes. However, some knowledge gaps remain regarding fibrinogen levels and downstream adverse outcomes, such as length of stay (LOS). We conducted this study to examine the association between fibrinogen level and LOS in LEAD patients. The retrospective cohort study included 1428 LEAD patients between January 2014 and November 2021 in China. Several generalized linear models with a negative binomial link function were used to evaluate the association between fibrinogen level and LOS. The area under the curve (AUC) was used to evaluate the predicting effect of fibrinogen level on a LOS greater than 10 days (median LOS). The median age of the patients was 70 years old, and 1153 (80.74%) were males. Fibrinogen level was positively associated with LOS (β = 1.14; 95% CI, 0.42–1.86; p = 0.002) in LEAD patients after controlling for age, gender, number of historical hospitalizations, surgical history, vascular disease history, drinking history, smoking history, insurance type, surgical approach, lesion site, weight loss, Fontaine classification, age-adjusted Charlson comorbidity index, urea, total protein, activated partial thromboplastin time, thrombin time, prothrombin time-international normalized ratio, calcium, triglyceride, albumin/globulin ratio, phosphorus, and D-dimer. The fibrinogen-added prediction model demonstrated good discrimination and calibration, with an AUC value of 0.807. Fibrinogen level was positively associated with LOS in LEAD patients. The fibrinogen level is a widely available and easy-to-measure biochemical indicator, and it could be used as a suitable indicator for the prognosis and prophylaxis of prolonged LOS in patients with LEAD during hospitalization. [ABSTRACT FROM AUTHOR]

The relationship between strain and elastic energy is simplified by introducing a stress state parameter based on the generalised Hooke's law. It is assumed that the micro-element strengths satisfy the Weibull distribution and a new model for the non-linear evolution of energy is developed by introducing the concept of rock micro-element strengths. A sensitivity analysis of the model parameters is carried out on this basis. The results show that the model agrees well with the experimental data. The model is close to the deformation and damage laws of the rock and is able to reflect the relationship between the elastic energy and strain of the rock. By comparing with other model curves, the model of this paper is more suitable for the experimental curve. They show that the improved model could better describe the stress–strain relationship of rock. Finally, according to the analysis of the influence of the distribution parameter on the variation pattern of the elastic energy of the rock, the magnitude of the distribution parameter can directly reflect the peak energy of the rock. [ABSTRACT FROM AUTHOR]

The transcription factor BarH-like homeobox 2 (BARX2), a member of the Bar-like homeobox gene family, is involved in cell proliferation, differentiation, immune responses and tumorigenesis. However, the potential role of BARX2 in the development of liver hepatocellular carcinoma (LIHC) remains unclear. Therefore, we aimed to study the biological role of BARX2 in hepatocellular carcinoma. Through the UALCAN, GTEx PORTAL, TIMER 2.0, LinkedOmics, SMART, MethSurv, Metascape, GSEA and STRING public databases, the BARX2 mRNA level, prognostic value, coexpressed genes, associated differentially expressed genes, DNA methylation and functional enrichment of LIHC patients were studied. The relationships between BARX2 expression and various clinical or genetic parameters of LIHC patients were determined using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and BEAT LIHC databases. In addition, the biological function of BARX2 in LIHC was studied in vitro. Through large-scale data mining, our study showed that BARX2 was differentially expressed between different normal and tumour tissues.BARX2 expression in LIHC tissues was significantly lower than that in corresponding controls, especially in patients with T2-4 stage disease. In patients with LIHC, overexpression of BARX2 was an independent poor prognostic factor associated with poor cytogenetic risk and gene mutations. Genomic hypermethylation of the BARX2 gene was associated with upregulated BARX2 expression and poor overall survival (OS) in LIHC. Functional enrichment analysis showed that BARX2 had an immunomodulatory role and was involved in the inflammatory response in LIHC occurrence. In conclusion, the oncogene BARX2 may serve as a new biomarker and prognostic factor for patients with LIHC. The immunomodulatory function of BARX2 deserves further validation in LIHC. [ABSTRACT FROM AUTHOR]

Different stress creep tests are conducted on the sandstone in this study to better describe the creep properties of rocks under different stress states. A model that describes the rock creep process is established. The various stages of creep can be described by combining the creep properties of the creep elements of the model. A new method for determining creep parameters is proposed by using the special point on the creep curve and the definition of creep deformation. The relationship between the creep parameters, stress, and time is analyzed. An improved creep model that considers the effects of stress state and time on the creep parameters is developed. This model is verified using experimental data and calculation results. Results shows that the improved creep model better describes the creep properties of rocks and provides a new method for determining future model parameters. The shear modulus of elastic model controls the instantaneous deformation. The shear modulus of viscoelastic model governs the limit of viscoelastic deformation. The shear viscoelastic coefficient of viscoelastic model increases with the increase in stress. The coefficient of viscoplastic model controls the viscoplastic creep rate. The coefficient of a nonlinear Newtonian dashpot mainly controls the accelerated creep deformation of rock. The calculation results of the proposed model agree well with the experimental data under the action of different stress levels. This model accurately reflects the creep characteristics of the primary and steady-state creep stages, and overcomes the shortcomings of the traditional Nishihara model in describing accelerated creep. [ABSTRACT FROM AUTHOR]

A large number of adverse drug reaction (ADR) reports are collected yearly through the spontaneous report system (SRS). However, experienced experts from ADR monitoring centers (ADR experts, hereafter) reviewed only a few reports based on current policies. Moreover, the causality assessment of ADR reports was conducted according to the official approach based on the WHO-UMC system, a knowledge- and labor-intensive task that highly relies on an individual's expertise. Our objective is to devise a method to automatically assess ADR reports and support the efficient exploration of ADRs interactively. Our method could improve the capability to assess and explore a large volume of ADR reports and aid reporters in self-improvement. We proposed a workflow for assisting the assessment of ADR reports by combining an automatic assessment prediction model and a human-centered interactive visualization method. Our automatic causality assessment model (ACA model)—an ordinal logistic regression model—automatically assesses ADR reports under the current causality category. Based on the results of the ACA model, we designed a warning signal to indicate the degree of the anomaly of ADR reports. An interactive visualization technique was used for exploring and examining reports extended by automatic assessment of the ACA model and the warning signal. We applied our method to the SRS report dataset of the year 2019, collected in Guangdong province, China. Our method is evaluated by comparing automatic assessments by the ACA model to ADR reports labeled by ADR experts, i.e., the ground truth results from the multinomial logistic regression and the decision tree. The ACA model achieves an accuracy of 85.99%, a multiclass macro-averaged area under the curve (AUC) of 0.9572, while the multinomial logistics regression and decision tree yield 80.82%, 0.8603, and 85.39%, 0.9440, respectively, on the testing set. The new warning signal is able to assist ADR experts to quickly focus on reports of interest with our interactive visualzation tool. Reports of interest that are selected with high scores of the warning signal are analyzed in details by an ADR expert. The usefulness of the overall method is further evaluated through the interactive analysis of the data by ADR expert. Our ACA model achieves good performance and is superior to the multinomial logistics and the decision tree. The warning signal we designed allows efficient filtering of the full ADR reports down to much fewer reports showing anomalies. The usefulness of our interactive visualization is demonstrated by examples of unusual reports that are quickly identified. Our overall method could potentially improve the capability of analyzing ADR reports and reduce human labor and the chance of missing critical reports. [ABSTRACT FROM AUTHOR]

Shennongjia is one of the most important ecological function areas and ecologically vulnerable zones in the world. With the rapid development of social economies, especially tourism, the ecological environment of Shennongjia has experienced profound changes. Exploring the characteristics and changing trends of ecological environment in Shennongjia will help to analyze the causes of the damage to the ecological environment, and build a vulnerability analysis framework with multi-scale, multi-element, multi-flow, and multi-circulation characteristics, which provides an effective research paradigm and analysis tool for the study of regional ecological vulnerability. With the support of RS and GIS technology, this study uses spatial principal component analysis (SPCA) and the vulnerability scoring diagram (VSD) model to comprehensively and quantitatively analyze the spatial and temporal evolution characteristics and driving forces of ecological vulnerability in Shennongjia from 1996 to 2018. The VSD model was selected to decompose the vulnerability into three components of "exposure-sensitivity-adaptation", and 16 indicators were selected to construct an ecological vulnerability evaluation system in Shennongjia, and the evaluation data were organized in a progressive and detailed way. (1) During the study period, the overall ecological vulnerability of Shennongjia is in a mild vulnerability level, exhibiting differentiation characteristics of high in the northeast and low in the southwest. High vulnerability zones are mainly distributed in the main towns and roads. (2) The risk of ecological vulnerability of the entire region presents the characteristics of continuous decline. (3) Land-use types, population density, and vegetation coverage are the main factors driving the evolution of ecological vulnerability. (4) A high level of coupling coordination exists between ecological vulnerability and landscape patterns. Analyses of the ecological vulnerability of Shennongjia shows that the entire region is in a mild vulnerability level. The extreme vulnerability risk of the ecological environment shows polarization. The evolution of ecological environment in Shennongjia is the result of the interaction between human activities and natural environment. This study offers an effective way to assess ecological vulnerability and provides some strategies and guidance for improving ecological security. [ABSTRACT FROM AUTHOR]

The association between bladder antimuscarinic use and dementia development is unclear. We used data from the Taiwan National Health Insurance Research Database to determine the association between the exposure dose and duration of bladder antimuscarinics and the subsequent dementia risk. We enrolled participants aged 55 years or more and defined a dementia cohort (International Classification of Diseases, Ninth Revision, Clinical Modification codes 290, 294.1, and 331.0). We used a propensity score matching method, and randomly enrolled two controls without dementia. We evaluated dementia risk with respect to the exposure dose and duration of treatment with seven bladder antimuscarinics (oxybutynin, propiverine, tolterodine, solifenacin, trospium, darifenacin, and fesoterodine) used for at least 1 year before the index date, after adjusting for age, sex, comorbidities, and medications. The dementia risk was 2.46-fold (95% confidence interval: 2.22–2.73) higher in Taiwanese patients who used bladder antimuscarinics for ≥ 1 year than in those who were not exposed to this treatment. The risk proportionally increased with increasing doses of antimuscarinics for less than 4 years. Taiwanese patients aged 55 years or more on bladder antimuscarinics exhibited a higher risk of dementia. Additional studies in other countries are required to determine whether this result is valid worldwide. [ABSTRACT FROM AUTHOR]

Motor imagery (MI) is the only way for disabled subjects to robustly use a robot arm with a brain-machine interface. There are two main types of MI. Kinesthetic motor imagery (KMI) is proprioceptive (OR somato-) sensory imagination and Visual motor imagery (VMI) represents a visualization of the corresponding movement incorporating the visual network. Because these imagery tactics may use different networks, we hypothesized that the connectivity measures could characterize the two imageries better than the local activity. Electroencephalography data were recorded. Subjects performed different conditions, including motor execution (ME), KMI, VMI, and visual observation (VO). We tried to classify the KMI and VMI by conventional power analysis and by the connectivity measures. The mean accuracies of the classification of the KMI and VMI were 98.5% and 99.29% by connectivity measures (alpha and beta, respectively), which were higher than those by the normalized power (p < 0.01, Wilcoxon paired rank test). Additionally, the connectivity patterns were correlated between the ME-KMI and between the VO-VMI. The degree centrality (DC) was significantly higher in the left-S1 at the alpha-band in the KMI than in the VMI. The MI could be well classified because the KMI recruits a similar network to the ME. These findings could contribute to MI training methods. [ABSTRACT FROM AUTHOR]

Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-023-44671-w, published online 13 October 2023 The original version of this Article contained an error in the order of the author names, which was incorrectly given as Yu-Shen Yang, Chu-Yun Liu, Kai Ye and He-fan He. These authors contributed equally: Chu-Yun Liu and Yu-Shen Yang. [Extracted from the article]

Heavy metals content in tires affects the safety of soil and agricultural products. The digestion method is a pretreatment for determining heavy metals in tire samples, and will affect the efficiency and accuracy of the heavy metal determination. The microwave digestion process and reagents for tire samples are not currently standardized. Therefore, this study attempts to provide an appropriate method of resolution for scholars. All digestion processes were performed in Mars One. We tested 15 different acid mixtures to determine the best reagent type and dose and then investigated the effect of maximum temperature, holding time, and sample grams on the degree of digestion. In summary, the best condition to digest the tire sample was a mixture of 3 ml HNO3 and 7 ml H2SO4, taking 0.1 (± 0.0005) g tire sample, at the maximum digestion temperature of 220 °C for 25 min. The experimental conclusion will provide a reliable experimental method for scientists using MARS One to study heavy metals in tires. At the same time, researchers using the MARS series can also find valuable references in this paper. [ABSTRACT FROM AUTHOR]

Experiencing a social threat, such as social exclusion, is a painful event. In contrast to previous studies providing insight into the processing of a single short-termed threat, we exposed healthy individuals to the simultaneous onset of different social threats. This approach allowed us to track whether these threats are processed independently—or whether they interact in a common system. Using a virtual ball-throwing game (Cyberball), electrophysiological (event-related brain potentials, ERPs) and behavioral (self-reports) responses were collected. We assigned undergraduates to three experimental groups: single threat exclusion (n = 24), single threat loss of control (n = 26), and joint onset of both threats (dual-threat, n = 25). Self-reports indicated an increase in threats (i.e., in perceived exclusion and loss-of-control) in the latter group. The ERPs disentangled the neural responses to each threat: In the dual-threat group, the amplitudes of the P3 responses to exclusionary and intervention events were enhanced. This indicates that individuals are sensitized to each of the threats when the other threat is present simultaneously. Our findings support the theoretical notion of a common cognitive system responding to violations in subjective expectations. [ABSTRACT FROM AUTHOR]

Climate change and disease threaten shrimp farming. Here, we studied the beneficial properties of a phytogenic formulation, Shrimp Best (SB), in whiteleg shrimp. Functional studies showed that SB dose-dependently increased shrimp body weight and decreased feed conversion ratio. We found that SB protected against Vibrio parahaemolyticus as evidenced by survival rate, bacterial load, and hepatopancreatic pathology in shrimp. Finally, we explored the likely mechanism by which SB affects growth performance and vibriosis in shrimp. The 16S rRNA sequencing data showed that SB increased 6 probiotic genera and decreased 6 genera of pathogenic bacteria in shrimp. Among these, SB increased the proportion of Lactobacillus johnsonii and decreased that of V. parahaemolyticus in shrimp guts. To dissect the relationship among SB, Lactobacillus and Vibrio, we investigated the in vitro regulation of Lactobacillus and Vibrio by SB. SB at ≥ 0.25 μg/mL promoted L. johnsonii growth. Additionally, L. johnsonii and its supernatant could inhibit V. parahaemolyticus. Furthermore, SB could up-regulate five anti-Vibrio metabolites of L. johnsonii, which caused bacterial membrane destruction. In parallel, we identified 3 fatty acids as active compounds from SB. Overall, this work demonstrated that SB improved growth performance and vibriosis protection in shrimp via the regulation of gut microbiota. [ABSTRACT FROM AUTHOR]

Understanding human mobility is of great significance for sustainable transportation planning. Long-term travel delay change is a key metric to measure human mobility evolution in cities. However, it is challenging to quantify the long-term travel delay because it happens in different modalities, e.g., subway, taxi, bus, and personal cars, with implicated coupling. More importantly, the data for long-term multi-modal delay modeling is challenging to obtain in practice. As a result, the existing travel delay measurements mainly focus on either single-modal system or short-term mobility patterns, which cannot reveal the long-term travel dynamics and the impact among multi-modal systems. In this paper, we perform a travel delay measurement study to quantify and understand long-term multi-modal travel delay. Our measurement study utilizes a 5-year dataset of 8 million residents from 2013 to 2017 including a subway system with 3 million daily passengers, a 15 thousand taxi system, a 10 thousand personal car system, and a 13 thousand bus system in the Chinese city Shenzhen. We share new observations as follows: (1) the aboveground system has a higher delay increase overall than that of the underground system but the increase of it is slow down; (2) the underground system infrastructure upgrades decreases the aboveground system travel delay increase in contrast to the increase the underground system travel delay caused by the aboveground system infrastructure upgrades; (3) the travel delays of the underground system decreases in the higher population region and during the peak hours. [ABSTRACT FROM AUTHOR]

Glutathione peroxidase 3 (GPx3) is a glycosylated member of GPx family and can catalyze the reaction of different types of peroxides with GSH to form their corresponding alcohols in vitro. The active center of GPx3 is selenocysteine (Sec), which is incorporated into proteins by a specific mechanism. In this study, we prepared a recombinant human GPx3 (rhGPx3) mutant with all Cys changed to Ser from a Cys auxotrophic strain of E. coli, BL21(DE3)cys. Although lacking post-translational modification, rhGPx3 mutant still retained the ability to reduce H2O2 and PLPC-OOH. Study on the quaternary structure suggested that rhGPx3 mutant existed as a monomer in solution, which is different from native tetrameric GPx3. Loss of the catalytic activity was considered to be attributed to both the absence of glycosylation and the failure of the tetramer. Further analysis was performed to compare the structures of rhGPx3 and GPx4 mutant, which were quite similar except for oligomerization loop. The differences of amino acid composition and electrostatic potentials on the oligomerization loop may affect the binding of large substrates to rhGPx3 mutant. This research provides an important foundation for biosynthesis of functionally selenium-containing GPx3 mutant in E.coli. [ABSTRACT FROM AUTHOR]

When subjected to constant static load, after a period of damage accumulation and crack development, the rock will fail under a load lower than its compressive strength. The transform of loading rate may have a certain influence on the mechanical properties of rock. In order to investigate the effect of loading rate on mechanical properties of red sandstone, the propagation form of internal cracks in the subcritical propagation stage in rock under static loading is defined as tensile. Based on Maxwell model, the expression of effective tensile stress for crack extension in rock is deduced, which explains the phenomenon of rock tensile failure. Based on the uniaxial compression test of red sandstone under different loading rates, and the surface deformation field of specimens is analysed with the method of digital image correlation, and the corresponding relationship between the loading rate effect and the change of mechanical properties as well as the energy accumulation and release characteristics is analysed, the phenomenon of rock tensile failure is further verified. This research can be effectively applied to geotechnical engineering disaster warning. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) participate in diverse biological pathways and may act as oncogenes or tumor suppressors. Single nucleotide polymorphisms (SNPs) in miRNAs (MirSNPs) might promote carcinogenesis by affecting miRNA function and/or maturation; however, the association between MirSNPs reported and cancer risk remain inconsistent. Here, we investigated the association between nine common MirSNPs and cancer risk using data from large scale case-control studies. Eight precursor-miRNA (pre-miRNA) SNPs (rs2043556/miR-605, rs3746444/miR-499a/b, rs4919510/miR-608, rs2910164/ miR-146a, rs11614913/miR-196a2, rs895819/miR-27a, rs2292832/miR-149, rs6505162/miR-423) and one primary-miRNA (pri-miRNA) SNP (rs1834306/miR-100) were analyzed in 16399 cases and 21779 controls from seven published studies in eight common cancers. With a novel statistic, Cross phenotype meta-analysis (CPMA) of the association of MirSNPs with multiple phenotypes indicated rs2910164 C (P 5 1.11E-03), rs2043556 C (P 5 0.0165), rs6505162 C (P 5 2.05E-03) and rs895819 (P 5 0.0284) were associated with a significant overall risk of cancer. In conclusion, MirSNPs might affect an individual's susceptibility to various types of cancer. [ABSTRACT FROM AUTHOR]

The World Health Organization determined cardiovascular disease to be the leading cause of death globally; atherosclerosis is the primary cause of the high morbidity and mortality rates. Regular physical activity is an effective strategy for maintaining endothelial health and function to prevent the development of atherosclerosis. Obesity is also a crucial risk factor for atherosclerotic progression in combination with various complications and systemic inflammation. Physiological homeostasis is modulated by the intestinal microbiota, but the mechanisms through which exercise attenuates atherosclerosis through the microbiota have not been elucidated. Therefore, we investigated the effects of endurance exercise on atherosclerosis induced by a Western diet (WD) and apolipoprotein E (ApoE) knockout in terms of microbiota parameters and metabolites. Genetically modified ApoE knockout mice (C57BL/6-Apoeem1Narl/Narl, ApoEKO) and wild-type mice (C57BL6/J) were divided into the following four groups (n = 6), namely, wild-type mice fed a chow diet (WT CD), ApoEKO mice fed a chow diet (ApoE CD), ApoEKO mice fed a WD (ApoE WD), and ApoEKO mice fed a WD and performing endurance exercise (ApoE WD EX), for a 12-week intervention. The WD significantly induced obesity and atherosclerotic syndrome in the ApoE WD group. Severe atherosclerotic lesions and arterial thickness were significantly elevated and accompanied by increases in VCAM-1, MCP-1, TNF-α, and IL-1β for immune cell chemotaxis and inflammation during atherosclerotic pathogenesis in the ApoE WD group. In addition, dysbiosis in the ApoE WD group resulted in the lowest short-chain fatty acid (SCFA) production. Endurance exercise intervention (ApoE WD EX) significantly alleviated atherosclerotic syndrome by reducing obesity, significantly inhibiting VCAM-1, MCP-1, TNF-α, and IL-1β expression, and increasing the production of SCFAs. Modulation of the microbiota associated with inflammation, such as Desulfovibrio, Tyzzerella, and Lachnospiraceae_ge, and increased SCFA production, particularly through an abundance of Rikenellaceae and Dubosiella, were also observed after exercise intervention. Endurance exercise can alleviate WD-induced atherosclerosis through the amelioration of obesity, inflammation, and chemotaxis signaling, which are modulated by the microbiota and derived SCFAs. [ABSTRACT FROM AUTHOR]

Ethylene (ET) is one of the many important signaling hormones that functions in regulating defense responses in plants. Gene expression profiling was conducted under exogenous ET application in the high late blight resistant potato genotype SD20 and the specific transcriptional responses to exogenous ET in SD20 were revealed. Analysis of differentially expressed genes (DEGs) generated a total of 1226 ET-specific DEGs, among which transcription factors, kinases, defense enzymes and disease resistance-related genes were significantly differentially expressed. GO enrichment and KEGG metabolic pathway analysis also revealed that numerous defense regulation-related genes and defense pathways were significantly enriched. These results were consistent with the interaction of SD20 and Phytophthora infestans in our previous study, indicating that exogenous ET stimulated the defense response and initiated a similar defense pathway compared to pathogen infection in SD20. Moreover, multiple signaling pathways including ET, salicylic acid, jasmonic acid, abscisic acid, auxin, cytokinin and gibberellin were involved in the response to exogenous ET, which indicates that many plant hormones work together to form a complex network to resist external stimuli in SD20. ET-induced gene expression profiling provides insights into the ET signaling transduction pathway and its potential mechanisms in disease defense systems in potato. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor 2 (HER2) gene amplification helps identify breast cancer patients who may respond to targeted anti-HER2 therapy. This study aims to develop an automated method for quantifying HER2 fluorescence in situ hybridization (FISH) signals and improve the working efficiency of pathologists. An Aitrox artificial intelligence (AI) model based on deep learning was constructed, and a comparison between the AI model and traditional manual counting was performed. In total, 918 FISH images from 320 consecutive invasive breast cancers were analysed and automatically classified into 5 groups according to the 2018 ASCO/CAP guidelines. The overall classification accuracy was 85.33% (157/184) with a mean average precision of 0.735. In Group 5, the most common group, the consistency was as high as 95.90% (117/122), while the consistency was low in the other groups due to the limited number of cases. The causes of this inconsistency, including clustered HER2 signals, coarse CEP17 signals and some section quality problems, were analysed. The developed AI model is a reliable tool for evaluating HER2 amplification statuses, especially for breast cancer in Group 5; additional cases from multiple centres could further improve the accuracy achieved for other groups. [ABSTRACT FROM AUTHOR]

Few studies investigated the respiratory outcomes of metformin use in patients with coexistent type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD). We want to compare the long-term respiratory endpoints of metformin use and nonuse in patients with T2DM and COPD. This retrospective cohort study enrolled patients with T2DM and COPD from Taiwan's National Health Insurance Program between January 1, 2000, and December 31, 2012. Main outcomes were hospitalized bacterial pneumonia, hospitalization for COPD, noninvasive positive pressure ventilation (NIPPV), invasive mechanical ventilation (IMV), and lung cancer. In total, 20,644 propensity score-matched metformin users and nonusers were assessed. The adjusted hazard ratios (95% confidence intervals) of metformin use relative to nonuse for bacterial pneumonia, hospitalization for COPD, NIPPV, IMV, and lung cancer were 1.17 (1.11–1.23), 1.34 (1.26–1.43), 0.99 (0.89–1.10), 1.10 (1.03–1.17), and 1.12 (0.96–1.30). Metformin use also exhibited significant dose–response relationship with respect to the risks of bacterial pneumonia, hospitalization for COPD and IMV. Consistent results were found in the sensitivity test. This nationwide cohort study demonstrated that in patients with T2DM and COPD, metformin use was associated with higher risks of pneumonia, hospitalization for COPD, and IMV. If patients with COPD use metformin, vigilance with regard to their pulmonary condition may be required. [ABSTRACT FROM AUTHOR]

In this work, we experimentally demonstrate that a thin rectangle dielectric-metal structure can have a function of a flat focusing mirror based on photonic jet effect in reflection mode. Using polydimethylsiloxane (PDMS) rectangle with size length of 10 μm and wavelength-scale thickness of 1 μm on the top of a silicon wafer, we have built a flat mirror which focuses an incident beam at the focal length changing from 1.38 μm to 11.67 μm upon tuning the beam incidence angle from 30° to 75°. The focusing properties of such a mirror persist in the wavelength range of 405 nm to 671 nm. Our approach can be extended to realize other optical functionalities by properly controlling rectangle dimensions and materials. This flat focusing mirror is able to guide the incident beam in free space without perceptible diffraction at the distance equal to the photonic jet length and suitable for small-scale photonic circuits. [ABSTRACT FROM AUTHOR]

There are limited studies on the association between systemic autoimmune rheumatic diseases (SARDs) and leptospirosis. Therefore, this study aims to identify the effects of leptospirosis on the risks of developing SARDs with a nationwide retrospective cohort study. Patients with leptospirosis who did not have a diagnosis of SARDs before the index date were enrolled from the Taiwan National Health Insurance Research Database between 2000 and 2010, as the leptospirosis cohort. For each patient with leptospirosis, one control without a history of leptospirosis and SARDs was randomly selected (non-leptospirosis cohort). Cox proportional hazards regression models were used to analyze the risk of SARDs according to sex, age, and comorbidities. Among the 23 million people in the cohort, 3,393 patients with leptospirosis (68.91% men, mean age 52.65 years) and 33,930 controls were followed for 18,778 and 232,999 person-years, respectively. The incidence of SARDs was higher in the leptospirosis cohort than in the non-leptospirosis cohort (1.38 vs 0.33 per 1000 person-years), with a hazard ratio (HR) of 4.42 (95% confidence interval [CI] = 2.82–6.92). The risk of developing SARDs was highest for leptospirosis patients aged ≥65 years (HR = 2.81% CI = 1.07–7.36) compared with patients aged ≤39 years. Patients with leptospirosis have a 4.42-fold higher risk of SARDs than that in the general population. Further research is warranted to investigate the mechanism underlying this association. [ABSTRACT FROM AUTHOR]

Poly (p-phenylene benzobisoxazole) (PBO) fibers were functionalized by 3-Glycidoxypropyltrimethoxysilane (KH-560) and then coated with 1 H, 1 H, 2 H, 2H-Perfluorodecyltrimethoxysilane (HFTES) and UV absorber (UV-328) to improve hydrophobicity and UV aging resistance. The chemical compositions of PBO fibers before and after modification were analyzed by XPS and surface morphologies were observed by SEM. The hydrophobicity of PBO fibers was evaluated by the measurement of contact angle for water and the UV aging resistance was evaluated by the tensile strength retention ratio of PBO fibers. The results showed that KH-560 was successfully introduced onto the PBO fiber surface. The contact angle for water was increased by 128% from 51.7° to 127°, suggesting a huge improvement of hydrophobicity. The UV aging resistance of PBO fibers was also greatly improved. After 400 h UV exposure, the tensile strength retention ratio was increased to 53%, which was much higher than that of 21.4% for pristine PBO fibers. And the results of variable coating times demonstrated that the optimal UV aging resistance was obtained by coating three times. [ABSTRACT FROM AUTHOR]

The identification of novel drug-target interactions (DTI) is critical to drug discovery and drug repurposing to address contemporary medical and public health challenges presented by emergent diseases. Historically, computational methods have framed DTI prediction as a binary classification problem (indicating whether or not a drug physically interacts with a given protein target); however, framing the problem instead as a regression-based prediction of the physiochemical binding affinity is more meaningful. With growing databases of experimentally derived drug-target interactions (e.g. Davis, Binding-DB, and Kiba), deep learning-based DTI predictors can be effectively leveraged to achieve state-of-the-art (SOTA) performance. In this work, we formulated a DTI competition as part of the coursework for a senior undergraduate machine learning course and challenged students to generate component DTI models that might surpass SOTA models and effectively combine these component models as part of a meta-model using the Reciprocal Perspective (RP) multi-view learning framework. Following 6 weeks of concerted effort, 28 student-produced component deep-learning DTI models were leveraged in this work to produce a new SOTA RP-DTI model, denoted the Meta Undergraduate Student DTI (MUSDTI) model. Through a series of experiments we demonstrate that (1) RP can considerably improve SOTA DTI prediction, (2) our new double-cold experimental design is more appropriate for emergent DTI challenges, (3) that our novel MUSDTI meta-model outperforms SOTA models, (4) that RP can improve upon individual models as an ensembling method, and finally, (5) RP can be utilized for low computation transfer learning. This work introduces a number of important revelations for the field of DTI prediction and sequence-based, pairwise prediction in general. [ABSTRACT FROM AUTHOR]

The identification of novel drug-target interactions (DTI) is critical to drug discovery and drug repurposing to address contemporary medical and public health challenges presented by emergent diseases. Historically, computational methods have framed DTI prediction as a binary classification problem (indicating whether or not a drug physically interacts with a given protein target); however, framing the problem instead as a regression-based prediction of the physiochemical binding affinity is more meaningful. With growing databases of experimentally derived drug-target interactions (e.g. Davis, Binding-DB, and Kiba), deep learning-based DTI predictors can be effectively leveraged to achieve state-of-the-art (SOTA) performance. In this work, we formulated a DTI competition as part of the coursework for a senior undergraduate machine learning course and challenged students to generate component DTI models that might surpass SOTA models and effectively combine these component models as part of a meta-model using the Reciprocal Perspective (RP) multi-view learning framework. Following 6 weeks of concerted effort, 28 student-produced component deep-learning DTI models were leveraged in this work to produce a new SOTA RP-DTI model, denoted the Meta Undergraduate Student DTI (MUSDTI) model. Through a series of experiments we demonstrate that (1) RP can considerably improve SOTA DTI prediction, (2) our new double-cold experimental design is more appropriate for emergent DTI challenges, (3) that our novel MUSDTI meta-model outperforms SOTA models, (4) that RP can improve upon individual models as an ensembling method, and finally, (5) RP can be utilized for low computation transfer learning. This work introduces a number of important revelations for the field of DTI prediction and sequence-based, pairwise prediction in general. [ABSTRACT FROM AUTHOR]

To evaluate the diagnostic performance of a new two-dimensional shear wave speed (SWS) imaging (i.e. Toshiba shear wave elastography, T-SWE) in differential diagnosis of breast lesions. 225 pathologically confirmed breast lesions in 218 patients were subject to conventional ultrasound and T-SWE examinations. The mean, standard deviation and ratio of SWS values (m/s) and elastic modulus (KPa) on T-SWE were computed. Besides, the 2D elastic images were classified into four color patterns. The area under the receiver operating characteristic (AUROC) curve analysis was performed to evaluate the diagnostic performance of T-SWE in differentiation of breast lesions. Compared with other quantitative T-SWE parameters, mean value expressed in KPa had the highest AUROC value (AUROC = 0.943), with corresponding cut-off value of 36.1 KPa, sensitivity of 85.1%, specificity of 96.6%, accuracy of 94.2%, PPV of 87.0%, and NPV of 96.1%. The AUROC of qualitative color patterns in this study obtained the best performance (AUROC = 0.957), while the differences were not significant except for that of Eratio expressed in m/s (AUROC = 0.863) (P = 0.03). In summary, qualitative color patterns of T-SWE obtained the best performance in all parameters, while mean stiffness (36.05 KPa) provided the best diagnostic performance in the quantitative parameters. [ABSTRACT FROM AUTHOR]

Haze has reached epidemic levels in many Chinese cities in recent years. Few studies have explored the determinants and heterogeneity of PM2.5. This paper investigates the spatiotemporal characteristics of PM2.5 through spatial analytical methods based on aerosol optical depth data from the Yangtze River Economic Belt (YREB) between 2000 and 2017. Geographically weighted regression and geodetector models were applied to assess the heterogeneity of key factors influencing PM2.5. The results indicate that the annual concentrations of PM2.5 in the YREB were 23.49–37.37 μg/m3, with an initial increase and a later decrease. PM2.5 pollution showed a diagonal high spatial distribution pattern in the northeast and a low spatial distribution in the southwest, as well as a noticeable spatial convergence. The spatial variability of PM2.5 was enlarged, and its main fractal dimension was in the northeast-southwest direction. There were clear spatiotemporal variations in the impacts of natural and anthropogenic factors on PM2.5. Our findings contribute to a better understanding of the impact mechanisms of PM2.5 and the geographic factors that form persistent and highly polluted areas and imply that more specific coping strategies need to be implemented in various areas toward successful particulate pollution prevention and control. [ABSTRACT FROM AUTHOR]

Analyses of cell-free fetal DNA (cff-DNA) from maternal plasma using massively parallel sequencing enable the noninvasive detection of feto-placental chromosome aneuploidy; this technique has been widely used in clinics worldwide. Noninvasive prenatal tests (NIPT) based on cff-DNA have achieved very high accuracy; however, they suffer from maternal copy-number variations (CNV) that may cause false positives and false negatives. In this study, we developed an algorithm to exclude the effect of maternal CNV and refined the Z-score that is used to determine fetal aneuploidy. The simulation results showed that the algorithm is robust against variations of fetal concentration and maternal CNV size. We also introduced a method based on the discrepancy between feto-placental concentrations to help reduce the false-positive ratio. A total of 6615 pregnant women were enrolled in a prospective study to validate the accuracy of our method. All 106 fetuses with T21, 20 with T18, and three with T13 were tested using our method, with sensitivity of 100% and specificity of 99.97%. In the results, two cases with maternal duplications in chromosome 21, which were falsely predicted as T21 by the previous NIPT method, were correctly classified as normal by our algorithm, which demonstrated the effectiveness of our approach. [ABSTRACT FROM AUTHOR]

Three-dimensional visualization of cellular and subcellular-structures in histological-tissues is essential for understanding the complexities of biological-phenomena, especially with regards structural and spatial relationships and pathologlical-diagnosis. Recent advancements in tissue-clearing technology, such as Magnified Analysis of Proteome (MAP), have significantly improved our ability to study biological-structures in three-dimensional space; however, their wide applicability to a variety of tissues is limited by long incubation-times and a need for advanced imaging-systems that are not readily available in most-laboratories. Here, we present optimized MAP-based method for paper-thin samples, Paper-MAP, which allow for rapid clearing and subsequent imaging of three-dimensional sections derived from various tissues using conventional confocal-microscopy. Paper-MAP successfully clear tissues within 1-day, compared to the original-MAP, without significant differences in achieved optical-transparency. As a proof-of-concept, we investigated the vasculature and neuronal-networks of a variety of human and rodent tissues processed via Paper-MAP, in both healthy and diseased contexts, including Alzheimer's disease and glioma. [ABSTRACT FROM AUTHOR]

Acanthamoeba spp. are opportunistic human pathogens that cause granulomatous amoebic encephalitis and keratitis, and their accurate detection and enumeration in environmental samples is a challenge. In addition, information regarding the genotyping of Acanthamoeba spp. using various PCR methods is equally critical. Therefore, considering the diverse niches of habitats, it is necessary to develop an even more efficient genotyping method for Acanthamoeba spp. detection. This study improved the sensitivity of detection to avoid underestimation of Acanthamoeba spp. occurrence in aquatic environmental samples, and to accurately define the pathogenic risk by developing an efficient PCR method. In this study, a new nested genotyping method was established and compared with various PCR-based methods using in silico, lab, and empirical tests. The in silico test showed that many PCR-based methods could not successfully align specific genotypes of Acanthamoeba, except for the newly designed nested PCR and real-time PCR method. Furthermore, 52 water samples from rivers, reservoirs, and a river basin in Taiwan were analysed by six different PCR methods and compared for genotyping and detection efficiency of Acanthamoeba. The newly developed nested-PCR-based method of genotyping was found to be significantly sensitive as it could effectively detect the occurrence of Acanthamoeba spp., which was underestimated by the JDP-PCR method. Additionally, the present results are consistent with previous studies indicating that the high prevalence of Acanthamoeba in the aquatic environment of Taiwan is attributed to the commonly found T4 genotype. Ultimately, we report the development of a small volume procedure, which is a combination of recent genotyping PCR and conventional real-time PCR for enumeration of aquatic Acanthamoeba and acquirement of biologically meaningful genotyping information. We anticipate that the newly developed detection method will contribute to the precise estimation, evaluation, and reduction of the contamination risk of pathogenic Acanthamoeba spp., which is regularly found in the water resources utilised for domestic purposes. [ABSTRACT FROM AUTHOR]

The human microbiome has a role in the development of multiple diseases. Individual microbiome profiles are highly personalized, though many species are shared. Understanding the relationship between the human microbiome and disease may inform future individualized treatments. We hypothesize the blood microbiome signature may be a surrogate for some lung microbial characteristics. We sought associations between the blood microbiome signature and lung-relevant host factors. Based on reads not mapped to the human genome, we detected microbial nucleic acids through secondary use of peripheral blood RNA-sequencing from 2,590 current and former smokers with and without chronic obstructive pulmonary disease (COPD) from the COPDGene study. We used the Genome Analysis Toolkit (GATK) microbial pipeline PathSeq to infer microbial profiles. We tested associations between the inferred profiles and lung disease relevant phenotypes and examined links to host gene expression pathways. We replicated our analyses using a second independent set of blood RNA-seq data from 1,065 COPDGene study subjects and performed a meta-analysis across the two studies. The four phyla with highest abundance across all subjects were Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. In our meta-analysis, we observed associations (q-value < 0.05) between Acinetobacter, Serratia, Streptococcus and Bacillus inferred abundances and Modified Medical Research Council (mMRC) dyspnea score. Current smoking status was associated (q < 0.05) with Acinetobacter, Serratia and Cutibacterium abundance. All 12 taxa investigated were associated with at least one white blood cell distribution variable. Abundance for nine of the 12 taxa was associated with sex, and seven of the 12 taxa were associated with race. Host-microbiome interaction analysis revealed clustering of genera associated with mMRC dyspnea score and smoking status, through shared links to several host pathways. This study is the first to identify a bacterial microbiome signature in the peripheral blood of current and former smokers. Understanding the relationships between systemic microbial signatures and lung-related phenotypes may inform novel interventions and aid understanding of the systemic effects of smoking. [ABSTRACT FROM AUTHOR]

Stabilization of organic matter in soil is important for natural ecosystem to sequestrate carbon and mitigate greenhouse gas emission. It is largely unknown what factors govern the preservation of organic carbon in soil, casting shadow on predicting the response of soil to climate change. Iron oxide was suggested as an important mineral preserving soil organic carbon. However, ferric minerals are subject to reduction, potentially releasing iron and decreasing the stability of iron-bound organic carbon. Information about the stability of iron-bound organic carbon in the redox reaction is limited. Herein, we investigated the sorptive interactions of organic matter with hematite and reductive release of hematite-bound organic matter. Impacts of organic matter composition and conformation on its sorption by hematite and release during the reduction reaction were analyzed. We found that hematite-bound aliphatic carbon was more resistant to reduction release, although hematite preferred to sorb more aromatic carbon. Resistance to reductive release represents a new mechanism that aliphatic soil organic matter was stabilized by association with iron oxide. Selective stabilization of aliphatic over aromatic carbon can greatly contribute to the widely observed accumulation of aliphatic carbon in soil, which cannot be explained by sorptive interactions between minerals and organic matter. [ABSTRACT FROM AUTHOR]

Uncovering complex oil-water flow structure represents a challenge in diverse scientific disciplines. This challenge stimulates us to develop a new distributed conductance sensor for measuring local flow signals at different positions and then propose a novel approach based on multi-frequency complex network to uncover the flow structures from experimental multivariate measurements. In particular, based on the Fast Fourier transform, we demonstrate how to derive multi-frequency complex network from multivariate time series. We construct complex networks at different frequencies and then detect community structures. Our results indicate that the community structures faithfully represent the structural features of oil-water flow patterns. Furthermore, we investigate the network statistic at different frequencies for each derived network and find that the frequency clustering coefficient enables to uncover the evolution of flow patterns and yield deep insights into the formation of flow structures. Current results present a first step towards a network visualization of complex flow patterns from a community structure perspective. [ABSTRACT FROM AUTHOR]

Quantum computation has achieved a tremendous success during the last decades. In this paper, we investigate the potential application of a famous quantum computation model, i.e., quantum walks (QW) in image encryption. It is found that QW can serve as an excellent key generator thanks to its inherent nonlinear chaotic dynamic behavior. Furthermore, we construct a novel QW-based image encryption algorithm. Simulations and performance comparisons show that the proposal is secure enough for image encryption and outperforms prior works. It also opens the door towards introducing quantum computation into image encryption and promotes the convergence between quantum computation and image processing. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) and age-related macular degeneration (AMD) are both common diseases of the elderly people. COPD induced systemic inflammation and hypoxia may have an impact on the development of AMD. This study investigated the possible association between COPD and subsequent risk of AMD. A retrospective cohort study was conducted based on the data from the National Health Insurance Research Database in Taiwan. The COPD cohort comprised 24,625 adult patients newly diagnosed during 2000–2012, whereas age-, gender-, and the year of diagnosis-matched non-COPD cohort comprised 49,250 individuals. Incident AMD was monitored to the end of 2013. A Cox proportional hazards model was applied to evaluate the risk of AMD. The COPD cohort showed 1.25 times higher AMD incidence than the non-COPD cohort (4.80 versus 3.83 per 1000 person-years, adjusted hazard ratio (HR) = 1.20 [95% confident interval (CI) = 1.10–1.32]). Stratified analyses for age, gender, and presence of comorbidity resulted in significant adjusted HRs in most subgroups. Further analysis revealed that the COPD group had an increased risk of both the exudative and non-exudative types of AMD (adjusted HRs = 1.49 [95% CI = 1.13–1.96] and 1.15 [95% CI = 1.05–1.26], respectively). COPD patients have an increased risk for AMD development. Clinicians should provide adequate care for the ocular health to these patients. [ABSTRACT FROM AUTHOR]

Phenomena of nonlinear light-matter interaction that occur during the propagation of intense ultrashort laser pulses in continuous media have been extensively studied in ultrafast optical science. In this vibrant research field, conversion of the input laser beam into optical filament(s) is commonly encountered. Here, we demonstrate generation of distinctive single or double super-luminescent optical jet beams as a result of strong spatial-temporal nonlinear interaction between focused 50 fs millijoule laser pulses and their induced micro air plasma. Such jet-like optical beams, being slightly divergent and coexisting with severely distorted conical emission of colored speckles, are largely different from optical filaments, and obtainable when the focal lens of proper f-number is slightly tilted or shifted. Once being collimated, the jet beams can propagate over a long distance in air. These beams not only reveal a potentially useful approach to coherent optical wave generation, but also may find applications in remote sensing. [ABSTRACT FROM AUTHOR]

The RAF kinase family is essential in mediating signal transduction from RAS to ERK. BRAF constitutively active mutations correlate with human cancer development. However, the precise molecular regulation of BRAF activation is not fully understood. Here we report that BRAF is modified by Lys63-linked polyubiquitination at lysine 578 within its kinase domain once it is activated by gain of constitutively active mutation or epidermal growth factor (EGF) stimulation. Substitution of BRAF lysine 578 with arginine (K578R) inhibited BRAF-mediated ERK activation. Furthermore, ectopic expression of BRAF K578R mutant inhibited anchorage-independent colony formation of MCF7 breast cancer cell line. Our studies have identified a previously unrecognized regulatory role of Lys63-linked polyubiquitination in BRAF-mediated normal and oncogenic signalings. [ABSTRACT FROM AUTHOR]

ER stress and apoptosis contribute to the loss of pancreatic β-cells under pro-diabetic conditions of glucolipotoxicity. Although activation of canonical intrinsic apoptosis is known to require pro-apoptotic Bcl-2 family proteins Bax and Bak, their individual and combined involvement in glucolipotoxic β-cell death are not known. It has also remained an open question if Bax and Bak in β-cells have non-apoptotic roles in mitochondrial function and ER stress signaling, as suggested in other cell types. Using mice with individual or combined β-cell deletion of Bax and Bak, we demonstrated that glucolipotoxic β-cell death in vitro occurs by both non-apoptotic and apoptotic mechanisms, and the apoptosis could be triggered by either Bax or Bak alone. In contrast, they had non-redundant roles in mediating staurosporine-induced apoptosis. We further established that Bax and Bak do not affect normal glucose-stimulated β-cell Ca2+ responses, insulin secretion, or in vivo glucose tolerance. Finally, our experiments revealed that combined deletion of Bax and Bak amplified the unfolded protein response in islets during the early stages of chemical- or glucolipotoxicity-induced ER stress. These findings shed new light on roles of the core apoptosis machinery in β-cell survival and stress signals of importance for the pathobiology of diabetes. [ABSTRACT FROM AUTHOR]