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PM$$_{2.5}$$ 2.5 prediction plays an important role for governments in establishing policies to control the emission of excessive atmospheric pollutants to protect the health of citizens. However, traditional machine learning methods that use data collected from ground-level monitoring stations have reached their limit with poor model generalization and insufficient data. We propose a composite neural network trained with aerosol optical depth (AOD) and weather data collected from satellites, as well as interpolated ocean wind features. We investigate the model outputs of different components of the composite neural network, concluding that the proposed composite neural network architecture yields significant improvements in overall performance compared to each component and the ensemble model benchmarks. The monthly analysis also demonstrates the superiority of the proposed architecture for stations where land-sea breezes frequently occur in the southern and central Taiwan in the months when land-sea breeze dominates the accumulation of PM$$_{2.5}$$ 2.5 .

In this work, we aim to use the optical amplifiers, directional couplers and phase modulators to build the electro-optical gates. Thanks to the 2-layer-multilayer-perceptron structure, the inversion of matrix is performed to obtain the coupling ratio of the directional couplers and the phase delay of the phase modulators. The electro-optical OR, AND, XOR, NAND, NOR and XNOR gates are demonstrated. Moreover, we not only study the results under the ideal condition of device, but also discuss the imperfect situation with 1% error of fabrication or operation to study the tolerance of this system. Through our simulation results, the visibility of the gate output can be higher than 0.83. The gates can be fabricated in a silicon-based chip to develop the integrated optics computing system.

Acute upper gastrointestinal bleeding (UGIB) in acute coronary syndrome (ACS) patients are not uncommon, particularly under dual antiplatelet therapy (DAPT). The efficiency and safety of early endoscopy (EE) for UGIB in these patients needs to be elucidated. This multicenter randomized controlled trial randomized recent ACS patients presenting acute UGIB to non-EE and EE groups. All eligible patients received intravenous proton pump inhibitor therapy. Those in EE group underwent therapeutic endoscopy within 24 h after bleeding. The data regarding efficacy and safety of EE were analyzed. It was early terminated because the UGIB rate was lower than expected and interim analysis was done. In total, 43 patients were randomized to non-EE (21 patients) and EE (22 patients) groups. The failure rate of control hemorrhage (intention-to-treat [ITT] 4.55% vs. 23.81%, p

Atrial fibrillation (AF) is often asymptomatic and paroxysmal. Screening and monitoring are needed especially for people at high risk. This study sought to use camera-based remote photoplethysmography (rPPG) with a deep convolutional neural network (DCNN) learning model for AF detection. All participants were classified into groups of AF, normal sinus rhythm (NSR) and other abnormality based on 12-lead ECG. They then underwent facial video recording for 10 min with rPPG signals extracted and segmented into 30-s clips as inputs of the training of DCNN models. Using voting algorithm, the participant would be predicted as AF if > 50% of their rPPG segments were determined as AF rhythm by the model. Of the 453 participants (mean age, 69.3 ± 13.0 years, women, 46%), a total of 7320 segments (1969 AF, 1604 NSR & 3747others) were analyzed by DCNN models. The accuracy rate of rPPG with deep learning model for discriminating AF from NSR and other abnormalities was 90.0% and 97.1% in 30-s and 10-min recording, respectively. This contactless, camera-based rPPG technique with a deep-learning model achieved significantly high accuracy to discriminate AF from non-AF and may enable a feasible way for a large-scale screening or monitoring in the future.

Hyperalgesia has become a major problem restricting the clinical application of tooth bleaching. We hypothesized that transient receptor potential ankyrin 1 (TRPA1), a pain conduction tunnel, plays a role in tooth hyperalgesia and inflammation after bleaching. Dental pulp stem cells were seeded on the dentin side of the disc, which was cut from the premolar buccal tissue, with 15% (90 min) or 40% (3 × 15 min) bleaching gel applied on the enamel side, and treated with or without a TRPA1 inhibitor. The bleaching gel stimulated intracellular reactive oxygen species, Ca2+, ATP, and extracellular ATP in a dose-dependent manner, and increased the mRNA and protein levels of hyperalgesia (TRPA1 and PANX1) and inflammation (TNFα and IL6) factors. This increment was adversely affected by TRPA1 inhibitor. In animal study, the protein levels of TRPA1 (P = 0.0006), PANX1 (P 0.0001), and proliferation factors [PCNA (P 0.0001) and Caspase 3 (P = 0.0066)] increased significantly after treated rat incisors with 15% and 40% bleaching gels as detected by immunohistochemistry. These results show that TRPA1 plays a critical role in sensitivity and inflammation after tooth bleaching, providing a solid foundation for further research on reducing the complications of tooth bleaching.

Airway collapse can occur when the forces of inhalation overpower the strength of the nasal lining flap. The authors established an animal model of the reconstructed nasal airway, and examined mechanical properties of tissue composites based on various materials. Twenty-three Sprague-Dawley rats were divided into three experimental groups: control (n = 5), irradiated homologous costal cartilage (IHCC, n = 10), and expanded polytetrafluoroethylene (ePTFE, n = 8). Two dorsal skin flaps represented nasal lining and skin envelope. No framework, an IHCC or ePTFE rim graft was used as framework. At three weeks, changes in the cross-sectional area of the lining flap were measured when negative pressure was applied. En-bloc specimens containing the graft and soft tissue were examined for histological change and tissue ingrowth. Reduction of cross-sectional area with simulated inhalation was 87.74% in the control group, 82.76% (IHCC), and 67.29% (ePTFE). Cross-sectional reduction was significantly less in ePTFE group than control group (p = 0.004) and IHCC group (p = 0.001). The difference was not significant in the control and IHCC groups. There was histologic evidence of tissue ingrowth in the ePTFE group. This novel animal model of nasal airway reconstruction supports the use and potential benefit of using ePTFE for prevention of airway collapse.

Helicobacter pylori infection is associated with high incidence of gastric diseases. The extensive therapy of H. pylori infection with antibiotics has increased its resistance rates worldwide. Ovatodiolide, a pure constituent isolated from Anisomeles indica, has been demonstrated to possess bactericidal activity against H. pylori. In this study, ovatodiolide inhibited the growth of both H. pylori reference strain and clinical multidrug-resistant isolates. Docking analysis revealed that ovatodiolide fits into the hydrophobic pocket of a ribosomal protein, RpsB. Furthermore, ovatodiolide inhibited bacterial growth by reducing levels of RpsB, which plays a crucial role in protein translation. Our results demonstrate that ovatodiolide binds to a ribosomal protein and interferes with protein synthesis. This study provides evidence that ovatodiolide has the potential to be developed into a potent therapeutic agent for treating H. pylori infection.

Refractive index sensors based on surface plasmon resonance (SPR) promise to deliver high sensitivities. However, these sensitivities depend on the derivative of the monitored SPR parameters near resonance, so this dependency leads to a relatively narrow detection range for refractive index changes. Herein, we introduce an idea to improve the detection range refractive index through a high-contrast-index curved waveguide surrounded with an outer gold ring. The proposed detection technique, based on the output power measurement of the curved waveguide, offers a linear response over an ultrabroad range of the refractive index for a surrounding medium from n = 1 to 2.36. Meanwhile, an theoretically ultrahigh refractive index resolution (RIU) of 4.53 × 10−10 could be accessible for such a broad testing range, available for both gas and aqueous chemical sample refractive indices Furthermore, the power detection approach enables an integrated photodetector for a lab-on-chip sensor platform, revealing a high potential for a multifunctional, compact, and highly sensitive sensor-on-chip device.

Two-pore channel 2 (TPC2) resides in endolysosomal membranes but also in lysosome-related organelles such as the melanin producing melanosomes. Gain-of-function polymorphisms in hTPC2 are associated with decreased melanin production and blond hair color. Vice versa genetic ablation of TPC2 increases melanin production. We show here an inverse correlation between melanin production and melanoma proliferation, migration, and invasion due to the dual activity of TPC2 in endolysosomes and melanosomes. Our results are supported by both genetic ablation and pharmacological inhibition of TPC2. Mechanistically, our data show that loss/block of TPC2 results in reduced protein levels of MITF, a major regulator of melanoma progression, but an increased activity of the melanin-generating enzyme tyrosinase. TPC2 inhibition thus provides a twofold benefit in melanoma prevention and treatment by increasing, through interference with tyrosinase activity, the synthesis of UV blocking melanin in melanosomes and by decreasing MITF-driven melanoma progression by increased GSK3β-mediated MITF degradation.

BackgroundOvarian cancer (OC) is one of the most lethal gynecological cancer globally. Serous ovarian cancer (SOC) is most common pathological type of ovarian cancer. Growing evidence suggests that transcription factors (TFs) play vital roles in serous ovarian cancer (SOC). In the present study, we aimed to develop a transcription factors-related prognostic signature to better predict the survival in patients with SOC.Materials and methodsThe TFs mRNA expression profiles of 564 SOC subjects in the TCGA database, and 70 SOC subjects in the GEO database were screened. Lasso cox regression and consensus clustering analysis were utilized to construct a novel TFs related signature and cluster model, respectively. Genomic alternative analysis was used to elaborate on the association between the TFs related prognostic signature and genomic aberrations. GSEA analysis was applied to identify the biological functional difference between high risk-score group and low-risk score group.ResultsA 17-TFs related prognostic signature was constructed using lasso cox regression and validated in the TCGA and GEO cohorts. Consensus clustering analysis was applied to establish a cluster model. The 17-TFs related prognostic signature, risk score, and cluster models were effective at accurately distinguishing the prognosis of SOC. The GSEA assay results suggested that there was a significant difference in the inflammatory and immune response pathways between the high-risk and low-risk score groups. Immune infiltration, immunotherapy, and chemotherapy responses were analyzed due to the significant difference in the regulation of lymphocyte migration and T cell-mediated cytotoxicity between the two groups; indicating that patients with low-risk score were more likely to respond anti-PD-1, etoposide, paclitaxel, and veliparib but not to gemcitabine, doxorubicin, docetaxel, and cisplatin. Also, the prognostic nomogram model revealed that the risk score was a good prognostic indicator for SOC patients.ConclusionsIn conclusion, we explored the prognostic values of TFs in SOC and developed a 17-TFs related prognostic signature to predict the survival of SOC patients.

Older people are subject to an increased risk of falling compared to the young, especially during obstacle negotiation. This study aimed to quantify the effects of long-term Tai-Chi Chuan (TCC) practice on the balance control during obstacle-crossing in older people in terms of the inclination angles (IA) of the body’s centre of mass (COM) relative to the centre of pressure (COP), and the rate of change of IA (RCIA). Fifteen healthy older adults who had practised TCC for at least 13 years and 15 healthy controls without any experience in TCC performed obstacle-crossing in a gait laboratory. The TCC group showed significantly greater leading and trailing toe-obstacle clearances but smaller trailing stride lengths when compared to controls. In the sagittal plane, the TCC group showed significantly smaller average anterior IA when the COM was anterior to the COP but greater average posterior IA when the COM was posterior to the COP, with significantly smaller average and peak RCIA over the crossing cycle. Long-term TCC practitioners showed an obstacle-crossing technique for less risk of tripping and better balance control, as indicated respectively by significantly increased toe-obstacle clearances and more posterior COM position relative to the COP with smaller anterior IA and RCIA during leading crossing and greater posterior IA and frontal RCIA at trailing-toe crossing. These benefits appeared to be related to the main features of TCC movements that emphasized maintaining balance during single-leg support and keeping the body weight on the trailing limb during the slow weight-shifting of double-limb support.

The prevalence of overweight and obesity amongst reproductive women has been increasing worldwide. Our aim was to compare pregnancy outcomes and infant neurocognitive development by different BMI classifications and investigate whether early pregnancy BMI was associated with risks of adverse outcomes in a Southwest Chinese population. We analysed data from 1273 women enrolled in the Complex Lipids in Mothers and Babies (CLIMB) randomized controlled trial in Chongqing, China. Maternal BMI was classified as underweight, normal weight and overweight/obese according to the Chinese, WHO Asian, and WHO European standards. For the adverse pregnancy outcomes, after adjustment for potential confounders, an underweight BMI was associated with increased risk of small for gestational age (SGA) babies, and an overweight/obese BMI was associated with increased risk of maternal gestational diabetes mellitus (GDM), caesarean section (C-section), macrosomia and large for gestational age (LGA) babies. For infant neurocognitive development, 1017 mothers and their children participated; no significant differences were seen in the Mental Development Index (MDI) or the Psychomotor Development Index (PDI) between the three BMI groups. Our findings demonstrate that abnormal early pregnancy BMI were associated with increased risks of adverse pregnancy outcomes in Chinese women, while early pregnancy BMI had no significant influence on the infant neurocognitive development at 12 months of age.

The association between regional economic status and the probability of renal recovery among patients with dialysis-requiring AKI (AKI-D) is unknown. The nationwide prospective multicenter study enrolled critically ill adult patients with AKI-D in four sampled months (October 2014, along with January, April, and July 2015) in Taiwan. The regional economic status was defined by annual disposable income per capita (ADIPC) of the cities the hospitals located. Among the 1,322 enrolled patients (67.1 ± 15.5 years, 36.2% female), 833 patients (63.1%) died, and 306 (23.1%) experienced renal recovery within 90 days following discharge. We categorized all patients into high (n = 992) and low economic status groups (n = 330) by the best cut-point of ADIPC determined by the generalized additive model plot. By using the Fine and Gray competing risk regression model with mortality as a competing risk factor, we found that the independent association between regional economic status and renal recovery persisted from model 1 (no adjustment), model 2 (adjustment to basic variables), to model 3 (adjustment to basic and clinical variables; subdistribution hazard ratio, 1.422; 95% confidence interval, 1.022–1.977; p = 0.037). In conclusion, high regional economic status was an independent factor for renal recovery among critically ill patients with AKI-D.

Nanoporous structures have proven as an effective way for enhanced electrochromic performance by providing a large surface area can get fast ion/electron transfer path, leading to larger optical modulation and fast response time. Herein, for the first time, application of vacuum cathodic arc plasma (CAP) deposition technology to the synthesis of WO3/NiO electrode films on ITO glass for use in fabricating complementary electrochromic devices (ECDs) with a ITO/WO3/LiClO4-Perchlorate solution/NiO/ITO structure. Our objective was to optimize electrochromic performance through the creation of electrodes with a nanoporous structure. We also examined the influence of WO3 film thickness on the electrochemical and optical characteristics in terms of surface charge capacity and diffusion coefficients. The resulting 200-nm-thick WO3 films achieved ion diffusion coefficients of (7.35 × 10−10 (oxidation) and 4.92 × 10−10 cm2/s (reduction)). The complementary charge capacity ratio of WO3 (200 nm thickness)/NiO (60 nm thickness) has impressive reversibility of 98%. A demonstration ECD device (3 × 4 cm2) achieved optical modulation (ΔT) of 46% and switching times of 3.1 sec (coloration) and 4.6 sec (bleaching) at a wavelength of 633 nm. In terms of durability, the proposed ECD achieved ΔT of 43% after 2500 cycles; i.e., 93% of the initial device.

Bowel cleansing is essential for a successful colonoscopy, but the ideal clearing agent and the volume have yet to be determined. A small-volume cleanser is important for patient compliance. This study aimed to compare the bowel cleansing efficacy, safety, tolerability, and acceptability of a 300-mL small-volume sodium picosulfate/magnesium citrate (PSMC) preparation-Bowklean with one 2-L polyethylene glycol (PEG)/bisacodyl-Klean-Prep/Dulcolax preparation under identical dietary recommendations. This multicenter, randomized, parallel-group, pre-specified noninferiority study enrolled 631 outpatients scheduled to undergo colonoscopy (Bowklean = 316 and Klean-Prep/Dulcolax = 315). After bowel preparation, an independent evaluator blinded to the subject’s treatment allocation rated the quality of the colon cleansing. Efficacy was evaluated using the Aronchick Scale and Ottawa Bowel Preparation Scale (OPBS). Safety was assessed by monitoring adverse events. Tolerability and acceptability were measured via a patient questionnaire. Bowklean was non-interior to Klean-Prep/Dulcolax in overall colon cleansing but was associated with significantly better preparation quality. Notably, Bowklean was associated with significantly greater tolerability and acceptability of bowel preparations than Klean-Prep/Dulcolax. Safety profiles did not differ significantly between the groups. Our data indicate that Bowklean is a more effective and better-tolerated bowel cleansing preparation before colonoscopy than Klean-Prep/Dulcolax. Bowklean may therefore increase positive attitudes toward colonoscopies and participation rates.

Severe neurological complications following infective endocarditis remain a major problem with high mortality rate. The long-term neurological consequences following infective endocarditis remain uncertain. Otherwise, neurosurgeries could be performed after these complications; however, few clinical series have reported the results. Therefore, we utilized a large, nationwide database to unveil the long-term mortality and neurosurgical outcome following infective endocarditis. We included patients with a first-time discharge diagnosis of infective endocarditis between January 2001 and December 2013 during hospitalization. Patients were further divided into subgroups consisting of neurological complications under neurosurgical treatment and complications under non-neurosurgical treatment. Long-term result of symptomatic neurological complications after infective endocarditis and all-cause mortality after different kinds of neurosurgeries were analyzed. There were 16,495 patients with infective endocarditis included in this study. Symptomatic neurological complications occurred in 1,035 (6.27%) patients, of which 279 (26.96%) accepted neurosurgical procedures. Annual incidence of neurological complications gradually increased from 3.6% to 7.4% (P P = 0.012, increased from 20% initially to nearly 50% over the 5-year follow-up). However, neurosurgery had no effect on the long-term mortality rate (50.9% vs. 47.6%, P = 0.451). Incidence of neurological complications post-infective endocarditis is increasing, and patients with these complications have higher mortality rates than patients without. Neurosurgery in these populations was not associated with higher long-term mortality. Therefore, it should not be ruled out as an option for those with neurological complications.

Clinical Treatment Score post-5 years (CTS5) is a promising prognostic tool to evaluate late recurrence risk for breast cancer. Our study aimed to validate its prognostic value in large-scale population and explore the impact of menopausal and HER2 status on CTS5 model. We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database. Survival analyses were conducted to assess the prognostic value of CTS5 in different breast cancer subgroups in terms of overall survival (OS) and breast cancer specific survival (BCSS) after five years. A total of 23,168 breast cancer patients with positive hormone receptor (HoR) were enrolled. Postmenopausal and premenopausal patients were 13,686 and 9,482, respectively. Taking CTS5 score as a continuous variable, it had significant positive correlation with poor prognosis beyond five years in both postmenopausal and premenopausal subgroups. Nevertheless, for HER2+ postmenopausal patients, the model has less effective prognostic value on long-term BCSS [HR1.177 (95%CI 0.960–1.443), p = 0.117]. Using CTS5 score as a categorical variable, HER2- patients with high-risk level revealed significant poor survival in terms of both BCSS and OS, irrespective of menopausal status. Our study showed the CTS5 model could be a useful prognostic tool for predict long-term survival in HoR+/HER2- patients. And further large-scale studies are warranted to assess its prognostic value for HER2+ patients and develop novel prediction model for late recurrence risk estimation.

Urinary tract infection (UTI) is caused principally by ascending Escherichia coli infection via an intestine-stool-urethra route. Recent studies found that the strains of E. coli causing UTIs, called extra-intestinal pathogenic E. coli (ExPEC), were distinct from the intestinal pathogenic strains and normal commensal strains. Further analysis found the meat including poultry and pork is the major reservoir for ExPECs. Vegetarians avoid meat and should theoretically have less exposure to ExPEC. However, no study thus far has examined whether vegetarian diets reduce the risk of UTI. Our aim was to examine the association between vegetarian diet and UTI risk in a Taiwanese Buddhist population. We prospectively followed 9724 Buddhists free of UTI from 2005 to 2014. During the 10-year follow-up, 661 incident UTI cases were confirmed. Diet was assessed through a food frequency questionnaire. Cox regression was used to evaluate the prospective association between a vegetarian diet on risk of UTI while adjusting for age, sex, educational level, alcohol-drinking, smoking, hypertension, diabetes mellitus, hyperlipidemia, and disease conditions predisposing to UTIs. Overall, vegetarian diet was associated with 16% lower hazards (hazard ratio [HR]: 0.84, 95% confidence interval [CI]: 0.71–0.99). In subgroup analysis, the protective association between vegetarian diet and UTI is observed mainly in the female (HR: 0.82, 95% CI: 0.69–0.99), never smokers (HR: 0.80, 95% CI: 0.67–0.95), and for uncomplicated UTI (HR: 0.81, 95% CI: 0.68–0.98).

Cardiopulmonary resuscitation (CPR) training and its quality are critical in improving the survival rate of cardiac arrest. This randomized controlled study investigated the efficacy of a newly developed CPR training program for the public in a Taiwanese setting. A total of 832 adults were randomized to either a traditional or blended (18-minute e-learning plus 30-minute hands-on) compression-only CPR training program. The primary outcome was compression depth. Secondary outcomes included CPR knowledge test, practical test, quality of CPR performance, and skill retention. The mean compression depth was 5.21 cm and 5.24 cm in the blended and traditional groups, respectively. The mean difference in compression depth between groups was −0.04 (95% confidence interval −0.13 to infinity), demonstrating that the blended CPR training program was non-inferior to the traditional CPR training program in compression depth after initial training. Secondary outcome results were comparable between groups. Although the mean compression depth and rate were guideline-compliant, only half of the compressions were delivered with adequate depth and rate in both groups. CPR knowledge and skill retained similarly in both groups at 6 and 12 months after training. The blended CPR training program was non-inferior to the traditional CPR training program. However, there is still room for improvement in optimizing initial skill performance as well as skill retention. Clinical Trial Registration: NCT03586752; www.clinicaltrial.gov

In this study, novel ZnS@In2S3 core@shell hollow nanospheres were fabricated by a facile refluxing method for the first time, and the formation mechanism of hollow structure with interior architecture was discussed based on ion-exchange Ostwald ripening. As the photocatalytic material for degradation of gaseous o-Dichlorobenzene (o-DCB), the as-synthesized core@shell hollow nanospheres were found to show significantly enhanced catalytic performance for effective separation of photo-generated charges. Moreover, the mechanisms of enhanced activity were elucidated by band alignment and unique configuration. Such photocatalyst would meet the demands for the control of persistent organic pollutant (POPs) in the atmospheric environment.

Loss of regenerative capacity plays a critical role in age-related autoimmune hepatitis. Evidence implicates SIRT1 and p66shc in cell senescence, apoptosis, oxidative stress, and proliferation. This study investigated the effect of resveratrol on concanavalin A (Con A)-induced hepatitis in aged mice and the roles of SIRT1 and p66shc. Aged mice were administrated resveratrol (30 mg/kg orally) seven times at an interval of 12 h before a single intravenous injection of Con A (20 mg/kg). Results showed that the cytokines, TNF-α, IL-6, IFN-γ, and MCP-1, as well as infiltration of macrophages, neutrophils, and T lymphocytes in liver were dramatically enhanced in the mice given only Con A. The aged mouse livers showed markedly raised oxidative stress and cell apoptosis. This oxidative stress further aggravated regenerative dysfunction as indicated by the decreased levels of Ki67, PCNA, Cyclin D1, and Cdk2. Conversely, these phenomena were attenuated by pretreatment with resveratrol. Moreover, resveratrol suppressed the elevation of p66shc in the liver by reversing Con-A-mediated downregulation of SIRT1. The findings suggest that resveratrol protected against Con A-induced hepatitis in aged mice by attenuating an aberration of immune response and liver regeneration, partially via the mechanism of SIRT1-mediated repression of p66shc expression.

Two rare N-β-D-glucopyranosyl-1H-indole-3-acetic acid conjugates, N-[2-(1-β-D-glucopyranosyl)-1H-indol-3-yl)acetyl]-L-glutamic acid (1) and N-[2-(1-β-D-glucopyranosyl)-1H-indol-3-yl)acetyl]-L-aspartic acid (2) were isolated from Ginkgo biloba. The structures were elucidated by analyses of HRMS and NMR spectroscopic data. In addition, a simplified and efficient synthetic route for compounds 1 and 2 is also disclosed to determine the absolute configurations of them. This concise syntheses of compounds 1 and 2 may facilitate studies of the biology of this type alkaloids. Compounds 1 and 2 were also tested for their cytotoxic and anti-inflammatory activities. The biological evaluation showed that compounds 1 and 2 led to the decrease of interleukin (IL)-6, nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 at mRNA level in lipopolysaccharide (LPS)-stimulated murine macrophage RAW264.7 cells.

Precipitation is useful information for assessing vital water resources, agriculture, ecosystems and hydrology. Data-driven model predictions using deep learning algorithms are promising for these purposes. Echo state network (ESN) and Deep Echo state network (DeepESN), referred to as Reservoir Computing (RC), are effective and speedy algorithms to process a large amount of data. In this study, we used the ESN and the DeepESN algorithms to analyze the meteorological hourly data from 2002 to 2014 at the Tainan Observatory in the southern Taiwan. The results show that the correlation coefficient by using the DeepESN was better than that by using the ESN and commercial neuronal network algorithms (Back-propagation network (BPN) and support vector regression (SVR), MATLAB, The MathWorks co.), and the accuracy of predicted rainfall by using the DeepESN can be significantly improved compared with those by using ESN, the BPN and the SVR. In sum, the DeepESN is a trustworthy and good method to predict rainfall; it could be applied to global climate forecasts which need high-volume data processing.

Severe infection with the re-emerging enterovirus 71 (EV71 or EV-A71) can cause cardiopulmonary failure. However, in patients’ heart and lung, viral protein has not been detected. In mouse models, heart disease has not been reported. EV71-infected brainstem is generally believed to be responsible for the cardiopulmonary collapse. One major limitation in EV71 research is the lack of an efficient oral infection system using non-mouse-adapted clinical isolates. In a robust oral infection NOD/SCID mouse model, we detected EV71 protein at multiple organs, including heart and lung, in 100% of moribund mice with limb paralysis. Infiltrating leukocytes were always detected in heart and muscle, and VP1-positive M2 macrophages were abundant in the lung. Functional dissection on the pathogenesis mechanism revealed severe apoptosis, inflammatory cytokines, and abnormal electrocardiogram (EKG) in orally infected hearts. Therefore, cardiopulmonary disease could be one plausible cause of death in this mouse model. Inoculation of EV71 through an oral route resulted in viral infection in the intestine, viremia, and EV71 appeared to spread to peripheral tissues via blood circulation. Infectious virus was no longer detected in the blood on day 5 post-infection by the plaque formation assay. We demonstrated that both EV71 clinical isolate and cloned virus can target the cardiopulmonary system via a natural infection-like oral route.

We report on evaluations of local heating in Au single-atom chains at room temperature. We performed onsite thermometry of atomic-scale Au junctions under applied sinusoidal voltage of variable amplitudes. The AC approach enabled to preclude electromigration effects for characterizing the influence of energy dissipations on the lifetime. We elucidated nonlinear increase in the effective temperature of the current-carrying single-atom chains with the voltage amplitudes, which was attributed to subtle interplay between electron-phonon scattering and electron-mediated thermal transport in the quasi-ballistic conductor. We also found that only 0.2% of the electric power contributed to local heating while the majority was consumed at the diffusive bank. The present findings can be used for thermal management of future integrated nanoelectronics.

Response surface models (RSMs) were used to predict effects of multiple drugs interactions. Our study was aimed to validate accuracy of the previous published volunteer models during transoesophageal echocardiography (TEE). This is a cross-sectional study with 20 patients scheduled for transesophageal echocardiography in Taipei Veterans General Hospital, Taiwan. Effect-site concentration pairs of alfentanil and propofol were recorded and converted to equivalent remifentanil and propofol effect-site concentrations. Observer’s Assessment of Alertness/Sedation (OAA/S) scores were assessed every 2 minutes. Using these data, previous published models of loss of response (LOR), intolerable ventilatory depression (IVD), and loss of response to esophageal instrumentation (LREI) were then estimated. Accuracy of prediction is assessed by calculating the difference between the true response and the model-predicted probability. Clinical events such as interruption of TEE were recorded. The average procedure time was 11 minutes. Accuracy for prediction of LOR and LREI is 63.6% and 38.5%, respectively. There were four patients experienced desaturation for less than 1 minute, which were not predicted by IVD model, and one interruption of TEE due to involuntary movement. The previous published drug-interaction RSMs predict LOR well but not LREI for TEE sedation. Further studies using response surface methodology are needed to improve quality for TEE sedation and clinical implementation.

In this work, we perform the numerical investigation of the performance of the small optical reservoir computing (RC) systems with four neurons using the commercial software for optical fiber communication system. The small optical RC system consists of the components of the optical fiber communication. The nonlinear function which is required in RC is provided by the erbium-doped optical fiber amplifiers (EDFA). We demonstrate that the EDFA should be operated in the saturated or non-linear regime to obtain a better performance of the small optical RC system. The performance of the small optical RC systems for different topological neuron structures is investigated. The results show that the interconnection between the neurons could offer a better performance than the systems without interconnection between the neurons. Moreover, the input signals with different noise levels are launched into the systems. The results show that the small optical RC system can classify the noisy input optical waveforms even when the signal-to-noise ratio is as low as − 2.55 dB.

The selective intrauterine growth restriction (sIUGR) of monochorionic diamniotic (MCDC) twins causes phenotypic growth discordance, which is correlated with metabolomic pertubations. A global, untargeted identification of the metabolic fingerprint may help elucidate the etiology of sIUGR. Umbilical cord blood and placentas collected from 15 pairs of sIUGR monochorionic twins, 24 pairs of uncomplicated twins, and 14 singletons diagnosed with intrauterine growth restriction (IUGR) were subjected to gas chromatography-mass spectrometry based metabolomic analyses. Supervised multivariate regression analysis and pathway analysis were performed to compare control twins with sIUGR twins. A generalized estimating equation (GEE) model was utilized to explore metabolic differences within sIUGR co-twins. Linear logistic regression was applied to screen metabolites that significantly differed in concentration between control twins and sIUGR twins or IUGR singletons. Umbilical cord blood demonstrated better global metabolomic separation of sIUGR and control twins compared to the placenta. Disrupted amino acid and fatty acid metabolism as well as high levels of exposure to environmental xenobiotics were associated with sIUGR. The metabolic abnormalities in MCDA twins suggested that in utero growth discordance is caused by intrauterine and extrauterine environmental factors, rather than genetics. Thus, this study provides new therapeutic targets and strategies for sIUGR management and prevention.

China produces large amount of cotton stalk (CS) residues as agricultural biomass, which are incinerated on-site, causing air pollution. The high organic content of CS could be utilized for biogas production, but the direct digestion without pretreatment always leads to a low methane yield and biodegradability, due to the complicated structure of lignocellulose. In order to search best fitting pretreatment methods in effective anaerobic digestion (AD) of CS, effects of various pretreatments including KOH, NaOH, Ca(OH)2, alkali hydrogen peroxide (AHP), H2SO4, H3PO4 and steam explosion (SE) were studied. It was seen that all treatments resulted in varying methane yields. Among all the pretreatments, acid pretreatment is not suitable for AD of CS. The results showed that the highest cumulative methane yield (CMY) of 192.4 mL·gVS−1 was obtained after 3% AHP pretreatment of CS, and the methane yield improved by 254.3% than the untreated CS. Therefore, AHP treatment was proven to be an efficient pretreatment technique. XRD and FTIR analyses had shown that pretreated CS had favorable structural changes. This research is beneficial in developing environment friendly and cost-effective pretreatment technologies to utilize CS for methane production in future application.

Emodin is a natural anthraquinone derivative that is present in various herbal preparations. The pharmacological effects of emodin include anticancer, hepatoprotective, anti-inflammatory, antioxidant and even antimicrobial activities. However, emodin also has been reported to induce hepatotoxicity, nephrotoxicity, genotoxicity and reproductive toxicity. The mechanism of emodin’s adverse effects is complicated and currently not well understood. This study aimed to establish a cell metabonomic method to investigate the toxicity of emodin and explore its potential mechanism and relevant targets. In the present study, metabonomic profiles of cell extracts and cell culture media obtained using the 1H NMR technique were used to assess emodin toxicity in HepG2 cells. Multivariate statistical analyses such as partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to characterize the metabolites that differed between the control and emodin groups. The results indicated that emodin resulted in differences in 33 metabolites, including acetate, arginine, aspartate, creatine, isoleucine, leucine and histidine in the cell extract samples and 23 metabolites, including alanine, formate, glutamate, succinate and isoleucine, in the cell culture media samples. Approximately 8 pathways associated with these metabolites were disrupted in the emodin groups. These results demonstrated the potential for using cell metabonomics approaches to clarify the toxicological effects of emodin, the underlying mechanisms and potential biomarkers. Our findings may help with the development of novel strategies to discover targets for drug toxicity, elucidate the changes in regulatory signal networks and explore its potential mechanism of action.

Sarcomeric signaling complexes are important to sustain proper sarcomere structure and function, however, the mechanisms underlying these processes are not fully elucidated. In a gene trap experiment, we found that vascular cell adhesion protein 1 isoform X2 (VCAP1X2) mutant embryos displayed a dilated cardiomyopathy phenotype, including reduced cardiac contractility, enlarged ventricular chamber and thinned ventricular compact layer. Cardiomyocyte and epicardial cell proliferation was decreased in the mutant heart ventricle, as was the expression of pAKT and pERK. Contractile dysfunction in the mutant was caused by sarcomeric disorganization, including sparse myofilament, blurred Z-disc, and decreased gene expression for sarcomere modulators (smyd1b, mypn and fhl2a), sarcomeric proteins (myh6, myh7, vmhcl and tnnt2a) and calcium regulators (ryr2b and slc8a1a). Treatment of PI3K activator restored Z-disc alignment while injection of smyd1b mRNA restored Z-disc alignment, contractile function and cardiomyocyte proliferation in ventricles of VCAP1X2 mutant embryos. Furthermore, injection of VCAP1X2 variant mRNA rescued all phenotypes, so long as two cytosolic tyrosines were left intact. Our results reveal two tyrosine residues located in the VCAP1X2 cytoplasmic domain are essential to regulate cardiac contractility and the proliferation of ventricular cardiomyocytes and epicardial cells through modulating pAKT and pERK expression levels.

Pathological cardiac hypertrophy, a dynamic remodeling process, is a major risk factor for heart failure. Although a number of key regulators and related genes have been identified, how the transcription factors (TFs) dynamically regulate the associated genes and control the morphological and electrophysiological changes during the hypertrophic process are still largely unknown. In this study, we obtained the time-course transcriptomes at five time points in four weeks from male murine hearts subjected to transverse aorta banding surgery. From a series of computational analyses, we identified three major co-expression modules of TF genes that may regulate the gene expression changes during the development of cardiac hypertrophy in mice. After pressure overload, the TF genes in Module 1 were up-regulated before the occurrence of significant morphological changes and one week later were down-regulated gradually, while those in Modules 2 and 3 took over the regulation as the heart size increased. Our analyses revealed that the TF genes up-regulated at the early stages likely initiated the cascading regulation and most of the well-known cardiac miRNAs were up-regulated at later stages for suppression. In addition, the constructed time-dependent regulatory network reveals some TFs including Egr2 as new candidate key regulators of cardiovascular-associated (CV) genes.

Autosomal dominant polycystic kidney disease (ADPKD) is a common kidney disease caused by mutations in PKD1 or PKD2. Metformin reduces cyst growth in mouse models of PKD1. However, metformin has not been studied in animal models of PKD2, and the cellular mechanism underlying its effectiveness is not entirely clear. This study investigated the effects of metformin on cyst formation in a zebrafish model of polycystin-2 deficiency resulting from morpholino knockdown of pkd2. We added metformin (2.5 to 20 mM) to the embryo media between 4 and 48 hours post fertilisation and observed pronephric cyst formation by using the wt1b promoter-driven GFP signal in Tg(wt1b:GFP) pkd2 morphants. Metformin inhibited pronephric cyst formation by 42–61% compared with the untreated controls. Metformin also reduced the number of proliferating cells in the pronephric ducts, the degree of dorsal body curvature, and the infiltration of leukocytes surrounding the pronephros. Moreover, metformin treatment increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and enhanced autophagy in the pronephros. Our data suggest that metformin reduces cyst formation through activation of the AMPK pathway and modulation of defective cellular events such as proliferation and autophagy. These results also imply that metformin could have therapeutic potential for ADPKD treatment.

Previous studies have reported inconsistent results of the associations of alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) with incident type 2 diabetes (diabetes hereafter). We aimed to resolve the controversy by taking nonalcoholic fatty liver disease (NAFLD) into account. The study population comprised 132,377 non-diabetic individuals (64,875 men and 67,502 women) aged 35–79 who had two or more health examinations during 1996–2014. A total of 6,555 incident diabetes (3,734 men and 2,821 women) were identified, on average, over 5.8 years of follow-up. Cox regression was used to calculate the hazard ratio (HR) for incident diabetes, adjusting for classical confounders. The risk of incident diabetes was significantly associated with NAFLD [HR = 2.08 (men) and 2.65 (women)]. Elevated ALT, AST, GGT and ALP were also significantly associated with the increased risk of diabetes, with HRs of 1.27, 1.23, 1.58 and 1.37, respectively, in men, and 1.56, 1.18, 1.48 and 1.44, respectively in women. Our results suggest that NAFLD, ALT, AST, GGT and ALP are independent predictors for incident diabetes in both men and women.

Medicinal herbs belonging to the same genus are always easily confused due to their extremely similar morphology and metabolites. Previously, to differentiate them, inherently specific biomarkers were screened out via intuitive comparison of their metabolite profiles. Unfortunately, the selected biomarkers have worked only partially. Most significant specific biomarkers have been neglected. Herein, a novel method for screening specific biomarkers of medicinal herbs using a metabolomics technique was developed. Firstly, the profiles of a group of easily confused herbs belonging to the same genus were analyzed by ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry to detect all components, including low-response metabolites. Then, all components were compared between the different samples, and specific biomarkers were extracted by the metabolomics techniques of alignment, normalization, defining the sample sets, filtering by frequency and Venn diagram analysis with Mass Profiler Professional (MPP) software. Thirdly, the correlations of these biomarkers were investigated via partial correlational analysis to obtain the most representative specific biomarkers. As an example, selection of specific biomarkers for ginseng (Panax ginseng) was performed, and three specific biomarkers including chikusetsusaponin IVa, ginsenoside Rf and ginsenoside Rc were finally selected and verified as the most representative specific biomarkers of Panax ginseng.

This follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological response (SVR) or nonsustained virological response (NSVR). A total of 4639 patients who received pegylated interferon and ribavirin during 2004–2013 were followed until December 2014. HCC was confirmed through health examinations and data linkage with a national database. A total of 233 HCC cases were reported after 26,163 person-years of follow-up, indicating an incidence of 8.9 per 1000 person-years: 6.9 for SVR and 21.6 for NSVR per 1000 person-years. The associated risk of HCC in patients with SVR was 0.37 (0.22–0.63) for those without cirrhosis and 0.54 (0.31–0.92) for those with cirrhosis compared with their respective counterparts with NSVR. Among patients with SVR, advanced age, male gender, cirrhosis, decreased platelet count, and increased aspartate aminotransferase and α-fetoprotein levels were associated with HCC (p

Diarrhoea lasting longer than 14 days and failing to respond to conventional management is defined as severe and protracted diarrhoea (SD). In this study, we investigated the prevalence, pathogens and prognosis of SD in primary immunodeficiency diseases (PIDs). Among 246 patients with predominantly paediatric-onset PIDs from 2003–2015, 21 [Btk (six), IL2RG (four), WASP, CD40L, gp91 (three each), gp47, RAG2 (one each)] and five [CVID (four), SCID (one)] without identified mutations had SD before prophylactic treatment. Detectable pathogens included pseudomonas, salmonella (six each), E. coli, cytomegalovirus, coxsackie virus and cryptosporidium (one each), all of whom improved after a mean 17 days of antibiotics and/or IVIG treatment. Seven (7/26; 27.0%) patients died [respiratory failure (four), lymphoma, sepsis and intracranial haemorrhage (one each)]. The patients with WAS, CGD and CD40L and SD had a higher mortality rate than those without. Another five males with mutant XIAP, STAT1, FOXP3 (one each) and STAT3 (two) had undetectable-pathogenic refractory diarrhoea (RD) that persisted >21 days despite aggressive antibiotic/steroid treatment and directly resulted in mortality. For the patients with RD without anti-inflammatory optimization, those with mutant XIAP and FOXP3 died of Crohn’s-like colitis and electrolyte exhaustion in awaiting transplantation, while transplantation cured the STAT1 patient.

In this study, novel ZnS@In2S3 core@shell hollow nanospheres were fabricated by a facile refluxing method for the first time, and the formation mechanism of hollow structure with interior architecture was discussed based on ion-exchange Ostwald ripening. As the photocatalytic material for degradation of gaseous o-Dichlorobenzene (o-DCB), the as-synthesized core@shell hollow nanospheres were found to show significantly enhanced catalytic performance for effective separation of photo-generated charges. Moreover, the mechanisms of enhanced activity were elucidated by band alignment and unique configuration. Such photocatalyst would meet the demands for the control of persistent organic pollutant (POPs) in the atmospheric environment.