Exploring the Cellular Impact of Size-Segregated Cigarette Aerosols: Insights into Indoor Particulate Matter Toxicity and Potential Therapeutic Interventions.

Exposure to anthropogenic aerosols has been associated with a variety of adverse health effects, increased morbidity, and premature death. Although cigarette smoke poses one of the most significant public health threats, the cellular toxicity of particulate matter contained in cigarette smoke has not been systematically interrogated in a size-segregated manner. In this study, we employed a refined particle size classification to collect cigarette aerosols, enabling a comprehensive assessment and comparison of the impacts exerted by cigarette aerosol extract (CAE) on SH-SY5Y, HEK293T, and A549 cells. Exposure to CAE reduced cell viability in a dose-dependent manner, with organic components having a greater impact and SH-SY5Y cells displaying lower tolerance compared to HEK293T and A549 cells. Moreover, CAE was found to cause increased oxidative stress, mitochondrial dysfunction, and increased levels of apoptosis, pyroptosis, and autophagy, leading to increased cell death. Furthermore, we found that rutin, a phytocompound with antioxidant potential, could reduce intracellular reactive oxygen species and protect against CAE-triggered cell death. These findings underscore the therapeutic potential of antioxidant drugs in mitigating the adverse effects of cigarette aerosol exposure for better public health outcomes.

In Vitro Culture and Biological Characterization of Meniscal Fibrochondrocytes.

Background: Currently, there is a lot of discussion in clinical and scientific research over the best ways to delay meniscal degeneration and speed up its healing. Meniscal injury and degeneration are significant contributors to the development of knee osteoarthritis in a pathological state. Objective: To isolate, culture and characterize rat meniscal fibrochondrocytes in vitro, and to provide a simple and feasible cell culture method for the study of damage repair of rat meniscal fibrochondrocytes. Methods: The rat medial and lateral meniscus of both knees was surgically isolated. Trypsin and type II collagenase were used to remove the cells, and toluidine blue staining and type II collagen immunofluorescence were used to identify the cells. The cells were then routinely cultured in low-sugar DMEM complete culture medium. Results: At different time points, cells showed different physiological shapes, from polygonal or short spindle to spindle shape, and finally to triangle or ellipse, and cell proliferation ability gradually increased with time. The OD values of cells cultured at 48h and 72h were higher than those at 24h. Comparing OD values of cells cultured for 48h and 72h, although OD value of 72h increased. Toluidine blue staining and type I collagen immunofluorescence staining were positive. Conclusion: A more dependable technique for fibrochondrocyte isolation and culture is offered for the study of meniscus in molecular biology and tissue engineering. The cells cultured using this method are morphologically stable, have a strong proliferation ability, and possess the fundamental biological properties of fibrochondrocytes in vivo.

Differential inhibition of sildenafil and macitentan on saxagliptin metabolism.

The development of diabetes mellitus (DM) is generally accompanied by erectile dysfunction (ED) and pulmonary arterial hypertension (PAH), which increases the use of combination drug therapy and the risk of drug-drug interactions. Saxagliptin for the treatment of DM, sildenafil for the treatment of ED and PAH, and macitentan for the treatment of PAH are all substrates of CYP3A4, which indicates their potential involvement in drug-drug interactions. Therefore, we investigated potential pharmacokinetic interactions between saxagliptin and sildenafil/macitentan. We investigated this speculation both in vitro and in vivo, and explored the underlying mechanism using in vitro hepatic metabolic models and molecular docking assays. The results showed that sildenafil substantially inhibited the metabolism of saxagliptin by occupying the catalytic site of CYP3A4 in a competitive manner, leading to the alterations in the pharmacokinetic properties of saxagliptin in terms of increased maximum plasma concentration (Cmax), area under the plasma concentration-time curve from time 0 to 24 h (AUC(0-t)), area under the plasma concentration-time curve from time 0 extrapolated to infinite time (AUC(0-∞)), decreased clearance rate (CLz/F), and prolonged terminal half-life (t1/2). In contrast, a slight inhibition was observed in saxagliptin metabolism when concomitantly used with macitentan, as no pharmacokinetic parameters were altered, except for CLz/F. Thus, dosage adjustment of saxagliptin may be required in combination with sildenafil to achieve safe therapeutic plasma concentrations and reduce the risk of potential toxicity, but it is not necessary for co-administration with macitentan.

Switching action modes of miR408-5p mediates auxin signaling in rice.

MicroRNAs (miRNAs) play fundamental roles in many developmental and physiological processes in eukaryotes. MiRNAs in plants generally regulate their targets via either mRNA cleavage or translation repression; however, which approach plays a major role and whether these two function modes can shift remains elusive. Here, we identify a miRNA, miR408-5p that regulates AUXIN/INDOLE ACETIC ACID 30 (IAA30), a critical repressor in the auxin pathway via switching action modes in rice. We find that miR408-5p usually inhibits IAA30 protein translation, but in a high auxin environment, it promotes the decay of IAA30 mRNA when it is overproduced. We further demonstrate that IDEAL PLANT ARCHITECTURE1 (IPA1), an SPL transcription factor regulated by miR156, mediates leaf inclination through association with miR408-5p precursor promoter. We finally show that the miR156-IPA1-miR408-5p-IAA30 module could be controlled by miR393, which silences auxin receptors. Together, our results define an alternative auxin transduction signaling pathway in rice that involves the switching of function modes by miR408-5p, which contributes to a better understanding of the action machinery as well as the cooperative network of miRNAs in plants.

Simultaneous determination of iguratimod and its metabolite in rat plasma using a UPLC-MS/MS method: Application for drug-drug interaction.

This aim of the work was to establish an acceptable sensitive assay based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for quantitatively analyzing the plasma concentrations of iguratimod (IGR) and its metabolite M2 in rats, and to further investigate the effect of fluconazole on the pharmacokinetics of IGR and M2. The mobile phase consisted of acetonitrile and water with 0.1% formic acid, was used to separate IGR, M2 and internal standard (IS) fedratinib on a UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 µm) with the flow rate of 0.4 mL/min. Positive ion mode and multiple reaction monitoring (MRM) were used to construct the quantitative analysis. The calibration standard of IGR and M2 covered 2-10000 and 1-1000 ng/mL respectively, with the lower limit of quantification (LLOQ) as 2 ng/mL and 1 ng/mL respectively. In addition, selectivity, recovery, accuracy, precision, matrix effect and stability of the method validation program were well accepted in this work. Subsequently, this approach was used to assess the effect of fluconazole on the pharmacokinetics of IGR and M2 in rats. In the presence of 20 mg/kg fluconazole (experimental group), we found the main pharmacokinetic parameters were significantly altered when compared with 2.5 mg/kg IGR alone (control group). Among them, AUC(0-∞) and Cmax of IGR in the experimental group was 1.43 and 1.08 times higher than that of the control group, respectively. Moreover, we also found that the other main pharmacokinetic parameters of M2 had no significant changes, except t1/2z and Tmax. In conclusion, fluconazole significantly altered the main pharmacokinetics of IGR and M2 in rats. It implys that we should pay more attention to the adverse reaction of IGR when the concomitant use of fluconazole and IGR occur in the future clinical practice.

Influence of Cigarette Aerosol in Alpha-Synuclein Oligomerization and Cell Viability in SH-SY5Y: Implications for Parkinson's Disease.

Although cigarette aerosol exposure is associated with various adverse health issues, its impact on Parkinson's disease (PD) remains elusive. Here, we investigated the effect of cigarette aerosol extract (CAE) on SH-SY5Y cells for the first time, both with and without α-synuclein (α-Syn) overexpression. We found that α-Syn aggravates CAE-induced cell death, oxidative stress, and mitochondrial dysfunction. Fluorescence cross-correlation spectroscopy (FCCS) revealed a dual distribution of α-Syn within the cells, with homogeneous regions indicative of monomeric α-Syn and punctated regions, suggesting the formation of oligomers. Moreover, we observed colocalization of α-Syn oligomers with lysosomes along with a reduction in autophagy activity. These findings suggest that α-Syn overexpression exacerbates CAE-induced intracellular cytotoxicity, mitochondrial dysfunction, and autophagy dysregulation, leading to elevated cell mortality. Our findings provide new insights into the pathogenic mechanisms linking exposure to cigarette aerosols with neurodegenerative diseases.

Optical single-channel cryptosystem based on the non-negative matrix factorization and face biometric in cyan-magenta-yellow-black color space.

In this paper, an optical color single-channel asymmetric cryptosystem based on the non-negative matrix factorization (NMF) and a face biometric in cyan-magenta-yellow-black (CMYK) space is proposed. To the best of our knowledge, this is the first time that NMF has been introduced into optical color image encryption. In the proposed cryptosystem, the color image in CMYK space is first decomposed into four color channels: C, M, Y, and K. By performing NMF operations on the four color channels, the four basic and sparse matrices can be obtained, respectively, which achieves asymmetry and saves computational resources. The four basis matrices can be used as private keys, and the four coefficient matrices are synthesized by the inverse discrete wavelet transform for subsequent encryption. Finally, the synthesized image is encoded with double random phase encoding based on phase truncation (PT). Compared with the existing PT-based cryptosystems, our cryptosystem can improve security against a special attack. In addition, the chaotic random phase mask is generated by a face biometric, which is noncontact and unique. Numerical simulation results are shown to verify the feasibility and robustness of our cryptosystem. Further, the proposed cryptosystem can be extended to encrypt multiple images conveniently.

What should be measured and reported in clinical trials for the treatment of patients with acute pancreatitis? A study protocol for establishing a core outcome set.

INTRODUCTION: Acute pancreatitis (AP) is characterised by inflammation of the exocrine pancreas, which potentially leads to local complications and organ failure resulting in significant morbidity and mortality. A long-term follow-up by an experienced team is needed. Currently, a variety of outcome measures are used in clinical trials for patients with AP. However, due to heterogeneous and selective outcome reporting across trials of interventions, it is hard to combine or compare the trial results compromising systematic evaluations of effectiveness and safety. A core outcome set is demanded to standardise reporting for the management of AP in clinical trials, so as to conduct systematic reviews and to improve the quality of the existing evidence base on the management of AP. We designed a study to establish a core outcome set (COS) on what indicators should be measured and reported in clinical trials of patients with AP (COS-AP). METHODS AND ANALYSIS: This study protocol outlines the following five phases: Phase I will be a systematic review of randomised control trials and semistructured interviews with patients to initially establish a preliminary list of potential outcomes. Phase II will be the recruitment of key stakeholders' groups comprising experts in pancreatic disease, clinical researchers, methodologists, journal editors and patients. Phase III will be two rounds of the Delphi surveys with key stakeholder groups. Phase IV will be a consensus on the outcomes that should be included in a final COS-AP. Phase V will be dissemination of COS-AP. ETHICS AND DISSEMINATION: Ethical approval for this study was obtained from the Biomedical Research Ethics Committee (BREC) of West China Hospital of Sichuan University (2020 No.691). The findings will be disseminated in peer-reviewed journals and meetings. TRIAL REGISTRATION: This study was registered with Core Outcome Measures in Effectiveness Trials (COMET) database as study 2573.

The impacts of CYP3A4 genetic polymorphism and drug interactions on the metabolism of lurasidone.

The aim of this study was to investigate the impacts of 24 variants of recombinant human CYP3A4 and drug interactions on the metabolism of lurasidone. In vitro, enzymatic reaction incubation system of CYP3A4 was established to determine the kinetic parameters of lurasidone catalyzed by 24 CYP3A4 variants. Then, we constructed rat liver microsomes (RLM) and human liver microsomes (HLM) incubation system to screen potential anti-tumor drugs that could interact with lurasidone and studied its inhibitory mechanism. In vivo, Sprague-Dawley (SD) rats were applied to study the interaction between lurasidone and olmutinib. The concentrations of the analytes were detected by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). As the results, we found that compared with the wild-type CYP3A4, the relative intrinsic clearances vary from 355.77 % in CYP3A4.15 to 14.11 % in CYP3A4.12. A series of drugs were screened based on the incubation system, and compared to without olmutinib, the amount of ID-14283 (the metabolite of lurasidone) in RLM and HLM were reduced to 7.22 % and 7.59 %, and its IC50 were 18.83 ± 1.06 µM and 16.15 ± 0.81 µM, respectively. At the same time, it exerted inhibitory effects both through a mixed mechanism. When co-administration of lurasidone with olmutinib in rats, the AUC(0-t) and AUC(0-∞) of lurasidone were significantly increased by 73.52 % and 69.68 %, respectively, while CLz/F was observably decreased by 43.83 %. In conclusion, CYP3A4 genetic polymorphism and olmutinib can remarkably affect the metabolism of lurasidone.

Severe pneumonia with empyema caused by Parvimonas micra and Streptococcus constellatus co-infection: a case report.

Empyema is a common complication of pneumonia, caused by the accumulation of purulent exudate due to pathogenic bacteria invading the pleural cavity. Parvimonas micra and Streptococcus constellatus are pathogens that rarely cause pneumonia with empyema. Herein, a case of severe empyema caused by these two pathogens, confirmed by metagenomic next-generation sequencing (mNGS) of pleural effusion cultures, is reported. A male Chinese patient in his late sixties presented with wheezing, cough, sputum expectoration, and fever. Blood and sputum cultures were negative for pathogens, but the pleural effusion culture was positive for S. constellatus, and was also found to contain P. micra, confirmed by mNGS. The patient's symptoms improved after treatment with cefoperazone/sulbactam and moxifloxacin. Pneumonia caused by P. micra and S. constellatus is rare; however, coinfection with these pathogens may cause severe pneumonia, with or without empyema.

Association between disability in activities of daily living and phase angle in hemodialysis patients.

BACKGROUND: Disability in activities of daily living (ADL) significantly increases the risk of mortality among patients undergoing hemodialysis. Malnutrition and decreased exercise capacity are closely correlated with ADL disability. Phase angle (PhA) has been proposed as a measure of nutritional status and exercise capacity. This study aims to investigate the prevalence of ADL disability in hemodialysis patients and its association with PhA. METHODS: A prospective, observational study was conducted, involving hemodialysis patients treated between November 2019 and January 2020 in an affiliated hospital of Chinese university. ADL was measured using both basic ADL (BADL) scales and instrumental ADL (IADL) scales. PhA measurements were obtained using a BIA device while the patients were in the supine position after dialysis. RESULTS: A total of 237 hemodialysis patients with a mean age of 60.01 ± 13.55 years were included in this study. The prevalence of disability in ADL was 43.5%. Multivariable analysis results showed a robust association between low PhA and disability in both BADL and IADL (for each unit decrease in PhA: odds ratio 4.83 [95% CI: 2.56-9.0], and 3.57 [95% CI: 2.14-5.95], respectively). The optimal cut-off values of PhA for disability in BADL and IADL were 4.8 and 5.4, with the area under the ROC curve (AUC) were 0.783 (0.727, 0.835) and 0.799 (0.743, 0.848), respectively. CONCLUSIONS: Low PhA is strongly associated with disability in ADL in hemodialysis patients. These findings suggest that PhA may serve as a potentially objective measure of ADL disability in hemodialysis patients.

Development of a UPLC-MS/MS method for the determination of lacosamide and its metabolite and its application to drug-drug interaction.

Lacosamide, a third-generation novel antiepileptic drug, was first approved in 2008 as an adjunct to partial seizures. In 2014, the U.S. Food and Drug Administration (FDA) approved it as a single agent for partial seizures. Since epilepsy is a chronic condition, most patients need long-term antiepileptic medicinal products, so it is even more important to consider the drug-drug interactions (DDIs). For the purpose of this experiment, an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay with accuracy and simplicity was optimized and fully validated for the simultaneous quantitative determination of lacosamide and O-Desmethyl-lacosamide (ODL), and DDIs between lacosamide and nisoldipine in vivo and in vitro was researched. The protein was precipitated with acetonitrile, the analytes were eluted with acetonitrile and a 0.1% formic acid solution in a gradient program, and lacosamide, ODL, and lamotrigine (Internal Standard, IS) were successfully separated by chromatography. The findings of the biological analysis revealed that the lower limit of quantification (LLOQ) for lacosamide in samples was 2 ng/mL and the linearity ranged from 2 to 10000 ng/mL. The LLOQ for ODL was 1 ng/mL, while the linearity range for this substance was 1-1,000 ng/mL. In rat liver microsomes (RLM), the LLOQ of ODL was 80 ng/mL and the linear range was 80-40000 ng/mL. The selectivity, stability, matrix effect and recovery rate were all satisfied with the need of quantitative analysis of samples. Then, the UPLC-MS/MS assay was employed successfully on the interactions of lacosamide and nisoldipine in vivo and in vitro. The half-maximal inhibitory concentration (IC50) was 3.412 µM in RLM, where nisoldipine inhibited the metabolism of lacosamide with a mixture of inhibition mechanism. In rat pharmacokinetic experiments, it was found that nisoldipine could significantly change the pharmacokinetic characteristics of lacosamide, including AUC(0-t), AUC(0-∞), Tmax, CLz/F and Cmax, but had no significant effect on ODL. In summary, the UPLC-MS/MS method could accurately and sensitively quantify lacosamide and ODL, and could be used for the interaction between nisoldipine and lacosamide in vivo and in vitro.

VERNALIZATION1 represses FLOWERING PROMOTING FACTOR1-LIKE1 in leaves for timely flowering in Brachypodium distachyon.

FLOWERING PROMOTING FACTOR1 (FPF1), a small protein without any known domains, promotes flowering in several plants; however, its functional mechanism remains unknown. Here, we characterized 2 FPF1-like proteins, FPL1 and FPL7, which, in contrast, function as flowering repressors in Brachypodium distachyon. FPL1 and FPL7 interact with the components of the florigen activation complex (FAC) and inhibit FAC activity to restrict expression of its critical target, VERNALIZATION1 (VRN1), in leaves, thereby preventing overaccumulation of FLOWERING LOCUS T1 (FT1) at the juvenile stage. Further, VRN1 can directly bind to the FPL1 promoter and repress FPL1 expression; hence, as VRN1 gradually accumulates during the late vegetative stage, FAC is released. This accurate feedback regulation of FPL1 by VRN1 allows proper FT1 expression in leaves and ensures sufficient FAC formation in shoot apical meristems to trigger timely flowering. Overall, we define a sophisticated modulatory loop for flowering initiation in a temperate grass, providing insights toward resolving the molecular basis underlying fine-tuning flowering time in plants.

Complexity and regulation of age-dependent alternative splicing in Brachypodium distachyon.

Alternative splicing (AS) is a gene regulatory mechanism that generates multiple transcripts of the same gene precursor by the spliceosome complex, promoting messenger RNA complexity, and proteome diversity. Although AS is extensively studied in response to environmental stresses, whether it mediates age-dependent development and how it is adjusted by growth transitions are largely unknown. Here, we comprehensively explored the AS landscape at different developmental stages in the grass model plant Brachypodium (Brachypodium distachyon). We identified abundant coding genes and noncoding transcripts subject to dynamic AS regulation during juvenile, adult, and reproductive transitions. Moreover, we revealed that SC35-LIKE SPLICING FACTOR 33 (SCL33), a serine/arginine-rich splicing factor in spliceosomes, plays a redundant and antagonistic role with its putative paralog, SCL33L, in regulating intron assembly across distinct developmental stages. In addition, we determined global AS variations in microRNA156 (miR156)-overproducing plants, in which growth transitions are delayed, and found that SPLs were regulated by miR156 in intron retention alteration in addition to mRNA clearance and translation inhibition manners. Finally, we demonstrated a complex regulatory process of age-dependent AS events in B. distachyon that was coincidently or separately regulated by miR156 and SCL33/SCL33L. These results illustrate a substantial machinery of AS that mediates phase transitions in plants.

Glutathione metabolism is conserved in response to excessive copper exposure between mice liver and Aurelia coerulea polyps.

BACKGROUND: Copper (Cu) is a trace element that is engaged in various routine physiological processes. Excessive copper exposure can cause damage to organisms; however, it is unknown if the mechanisms underlying the response to Cu2+ among different species are conserved. METHODS: Aurelia coerulea polyps and mice models were exposed to Cu2+ to assess its effects on survival status and organ damage. Transcriptomic sequencing, BLAST, structural analysis, and real-time quantitative PCR were carried out to analyze the similarities and differences in the molecular composition and response mechanisms between two species when exposed to Cu2+. RESULTS: Excessive Cu2+ exposure led to toxic effects on both A. coerulea polyps and mice. The polyps were injured at a Cu2+ concentration of 3.0 mg L-1. In the mice, increasing Cu2+ concentrations were correlated with, the degree of liver damage, which manifested as hepatocyte apoptosis. In the 300 mg L-1 Cu2+ group of mice, livers cell death was primarily triggered by the phagosome and Toll-like signaling pathways. We found the glutathione metabolism was significantly altered in response to copper stress in both A. coerulea polyps and mice. Moreover, the similarity of gene sequences enriched at the two same sites in this pathway was as high as 41.05 %-49.82 % and 43.61 %-45.99 % respectively. Among them, there was a conservative region in the structure of A. coerulea polyps GSTK1 and mice Gsta2, but the overall difference is large. CONCLUSION: Glutathione metabolism is a conserved copper response mechanism in evolutionary distant organisms such as A. coerulea polyps and mice, although mammals have a more complex regulatory network when it comes to copper-induced cell death.

Optical double-image cryptosystem based on generalized singular value decomposition and five-dimensional hyperchaotic maps.

In this paper, we propose an asymmetric optical double-image cryptosystem based on generalized singular value decomposition (GSVD) and five-dimensional (5D) hyperchaotic maps. In the proposed cryptosystem, the two plain images are first decomposed into five components by the GSVD operation. The two unitary matrices obtained by GSVD are encoded as a complex function, which is then modulated by the chaotic random phase masks (CRPMs). The private key and the final encryption result are generated by phase-truncation and amplitude-truncation operations. The GSVD operation can decompose two images at the same time and is used to generate the private key that enables the encryption process to be asymmetric. Compared with the existing phase-truncated-based cryptosystems, our cryptosystem can improve security against a special attack. In addition, the CRPMs are generated by 5D hyperchaotic maps, which have a larger parameter space and better randomness. Numerical simulation results are shown to verify the feasibility and robustness of our cryptosystem. Furthermore, the proposed cryptosystem can be extended to encrypt multiple images conveniently.

Profile of atmospheric VOC over the Yellow Sea, China: A tale of distribution, constraints, and sources.

In the winter of 2018-2019, 75 air samples were collected through four ship-borne measurements in the Yellow Sea (YS) to assess the levels, confinement processes, and source distribution of volatile organic compounds (VOCs). A total of 41 were eventually detected, which mainly were non-methane hydrocarbons (NMHCs), volatile halogenated hydrocarbons (VHCs), oxygenated volatile organic compounds (OVOCs), and volatile organic sulfur compounds (VSCs). Aromatics (31.93 %) and alkenes (11.04 %) in the atmosphere of the YS accounted for a larger proportion of NMHCs compared with the coastal areas. C3-C5 alkanes, propylene, and chloroform exhibited strong latitudinal gradients and opposite latitudinal distributions in the North and South YS, highlighting the strong contribution of regional outflow to YS's atmosphere. The level of Σ41VOCs increased significantly during the heavy pollution period with some chemical monomers detected, which was further enhanced by the emissions from industrial parks near the Liaodong Peninsula and the Shandong Peninsula. Five main VOC sources were identified by the Positive matrix factorization (PMF) model, which were industrial emissions (13.33 %), fuel use and volatilization (6.67 %), Freon R-22 emissions (33.33 %), oil and gas production (20.00 %), and solvent volatilization (26.67 %). These observations revealed the strong causal relationship between coastal air mass transport and the atmosphere in the marginal sea and emphasized that full attention should be paid to the unintentional and unorganized emission of chemical monomers in the industrial process.

Insights into Enhancer RNAs: Biogenesis and Emerging Role in Brain Diseases.

Enhancers are cis-acting elements that control the transcription of target genes and are transcribed into a class of noncoding RNAs (ncRNAs) termed enhancer RNAs (eRNAs). eRNAs have shorter half-lives than mRNAs and long noncoding RNAs; however, the frequency of transcription of eRNAs is close to that of mRNAs. eRNA expression is associated with a high level of histone mark H3K27ac and a low level of H3K27me3. Although eRNAs only account for a small proportion of ncRNAs, their functions are important. eRNAs can not only increase enhancer activity by promoting the formation of enhancer-promoter loops but also regulate transcriptional activation. Increasing numbers of studies have found that eRNAs play an important role in the occurrence and development of brain diseases; however, further research into eRNAs is required. This review discusses the concept, characteristics, classification, function, and potential roles of eRNAs in brain diseases.

Clustering-enhanced stock price prediction using deep learning.

In recent years, artificial intelligence technologies have been successfully applied in time series prediction and analytic tasks. At the same time, a lot of attention has been paid to financial time series prediction, which targets the development of novel deep learning models or optimize the forecasting results. To optimize the accuracy of stock price prediction, in this paper, we propose a clustering-enhanced deep learning framework to predict stock prices with three matured deep learning forecasting models, such as Long Short-Term Memory (LSTM), Recurrent Neural Network (RNN) and Gated Recurrent Unit (GRU). The proposed framework considers the clustering as the forecasting pre-processing, which can improve the quality of the training models. To achieve the effective clustering, we propose a new similarity measure, called Logistic Weighted Dynamic Time Warping (LWDTW), by extending a Weighted Dynamic Time Warping (WDTW) method to capture the relative importance of return observations when calculating distance matrices. Especially, based on the empirical distributions of stock returns, the cost weight function of WDTW is modified with logistic probability density distribution function. In addition, we further implement the clustering-based forecasting framework with the above three deep learning models. Finally, extensive experiments on daily US stock price data sets show that our framework has achieved excellent forecasting performance with overall best results for the combination of Logistic WDTW clustering and LSTM model using 5 different evaluation metrics.

An environmentally sensitive molecular rotor as a NIR fluorescent probe for the detection of islet amyloid polypeptide.

The deposits of human islet amyloid polypeptide (IAPP), also called amylin, in the pancreas have been postulated to be a factor of pancreatic ß-cell dysfunction and is one of the common pathological hallmarks of type II diabetes mellitus (T2DM). Therefore, it is imperative to gain an in-depth understanding of the formation of these aggregates. In this study, we demonstrate a rationally-designed strategy of an environmentally sensitive near-infrared (NIR) molecular rotor utilizing thioflavin T (ThT) as a scaffold for IAPP deposits. We extended the π delocalized system not only to improve the viscosity sensitivity but also to prolong the emission wavelength to the NIR region. A naphthalene moiety was also introduced to adjust the sensitivity of our designed probes to differentiate the binding microenvironment polarity of different targeted proteins. As a result, a novel NIR fluorogenic probe toward IAPP aggregates, namely AmySP-4-Nap-Ene, was first developed. When attached to different protein aggregates, this probe exhibited distinct fluorescence emission profiles. In a comparison with ThT, the fluorescence emission of non-ionic AmySP-4-Nap-Ene exhibits a significant difference between the presence of non-fibrillar and fibrillar IAPP and displays a higher binding affinity toward IAPP fibrils. Further, the AmySP-4-Nap-Ene can be utilized to monitor IAPP accumulating process and image fibrils both in vitro and in living cells.