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There are many types of natural plants in nature that contain a variety of effective and complex chemical components. These constituents can be categorized as organic acids, volatile oils, coumarins, steroids, glycosides, alkaloids, carbohydrates, phytochromes, etc., all of which play important roles in the fields of pharmaceuticals, food, nutraceuticals, and cosmetics. The study of extraction and chemical composition analysis of natural products is important for the discovery of these active ingredients and their precursors. Therefore, the aim of this article is to review the status of research on the extraction, separation and purification, and structural identification of natural products, to provide a reference for the study of natural products. [ABSTRACT FROM AUTHOR]

Objective. The present study was designed to establish and evaluate an early prediction model of epilepsy after encephalitis in childhood based on electroencephalogram (ECG) and clinical features. Methods. 255 patients with encephalitis were randomly divided into training and verification sets and were divided into postencephalitic epilepsy (PE) and no postencephalitic epilepsy (no-PE) according to whether epilepsy occurred one year after discharge. Univariate and multivariate logistic regression analyses were used to screen the risk factors for PE. The identified risk factors were used to establish and verify a model. Results. This study included 255 patients with encephalitis, including 209 in the non-PE group and 46 in the PE group. Univariate and multiple logistic regression analysis showed that hemoglobin (OR = 0.968, 95% CI = 0.951–0.958), epilepsy frequency (OR = 0.968, 95% CI = 0.951–0.958), and ECG slow wave/fast wave frequency (S/F) in the occipital region were independent influencing factors for PE (P < 0.05).The prediction model is based on the above factors: −0.031 × hemoglobin −2.113 × epilepsy frequency + 7.836 × occipital region S/F + 1.595. In the training set and the validation set, the area under the ROC curve (AUC) of the model for the diagnosis of PE was 0.835 and 0.712, respectively. Conclusion. The peripheral blood hemoglobin, the number of epileptic seizures in the acute stage of encephalitis, and EEG slow wave/fast wave frequencies can be used as predictors of epilepsy after encephalitis. [ABSTRACT FROM AUTHOR]

[Display omitted] • Machine learning is utilized to train a global data set of major-minor elements of Cr-spinels. • Ti, Cr, and Al are critical elements for distinguishing Cr-spinel forming-environments. • The new model is successfully applied to reveal tectonic settings of magmatic sulfide deposits. This study uses the random forest machine learning algorithm to classify and predict Cr-spinel formation environments in mafic–ultramafic rocks. Cr-spinel is an early-crystallized oxide phase in these rocks and exhibits significant compositional variations that provide valuable insights into their formation environments. Traditionally, empirical diagrams have been used to classify the origins of Cr-spinel based on major and trace element compositions; however, overlap exists among spinel from different formation environments. To overcome this limitation, we develop a random forest model using a compiled dataset of Cr-spinel compositions from various tectonic settings, including small intrusions from continental collisional zones, layered intrusions and small intrusions from intra-continental plates (including large igneous provinces and intra-continental rifts), Alaskan-type complexes from oceanic subduction zones, and ophiolites from oceanic spreading centers. The model is trained, validated, and optimized using cross-validation and hyperparameter tuning. The results show high accuracy in predicting the Cr-spinel formation environments, as demonstrated by high precision, recall, and F1 scores. Feature importance analyses reveal that elements, such as Ti, Cr, and Al, play a more significant role in the prediction. Visualization techniques, i.e., the t-distributed stochastic neighbor embedding (TSNE) algorithm, are applied to reduce the dimensionality of the dataset and create decision boundaries for better interpretation. The model is validated using an independent Cr-spinel composition dataset obtained from an area with known geological settings, to confirm the model's reliability. The model is applied successfully to reveal the heterogeneous sources of the rifting-related Daxueshan magmatic Ni-Cu sulfide deposit in the Baoshan block in the eastern part of the Tethyan orogenic belt. The machine learning algorithm can accurately distinguish different Cr-spinel types using large and diverse datasets to provide valuable insights into geological formation conditions. This approach is a powerful tool for understanding Earth's geological processes, improving exploration models of magmatic sulfide deposit and reducing mineral exploration costs. [ABSTRACT FROM AUTHOR]

Objective. We conducted a meta-analysis to evaluate the predictive value of interim 18F-FDG PET/CT in patients with DLBCL treated with R-CHOP chemotherapy. Methods. We searched for articles published in PubMed, ScienceDirect, Wiley, Scopus, and Ovid database from inception to March 2014. Articles related to interim PET/CT in patients with DLBCL treated with R-CHOP chemotherapy were selected. PFS with or without OS was chosen as the endpoint to evaluate the prognostic significance of interim PET/CT. Results. Six studies with a total of 605 cases were included. The sensitivity of interim PET/CT ranged from 21.2% to 89.7%, and the pooled sensitivity was 52.4%. The specificity of interim PET/CT ranged from 37.4% to 90.7%, and the pooled specificity was 67.8%. The pooled positive likelihood ratio and negative likelihood ratio were 1.780 and 0.706, respectively. The explained AUC was 0.6978 and the Q* was 0.6519. Conclusions. The sensitivity and specificity of interim PET/CT in predicting the outcome of DLBCL patients treated with R-CHOP chemotherapy were not satisfactory (52.4% and 67.8%, resp.). To improve this, some more work should be done to unify the response criteria and some more research to assess the prognostic value of interim PET/CT with semiquantitative analysis. [ABSTRACT FROM AUTHOR]

The size uniformity and spatial dispersion of nanoparticles (NPs) formed by ion implantation must be further improved due to the characteristics of the ion implantation method. Therefore, specific swift heavy ion irradiation and thermal annealing are combined in this work to regulate the size and spatial distributions of embedded Au NPs formed within LiTaO3 crystals. Experimental results show that small NPs migrate to deeper depths induced by 656 MeV Xe35+ ion irradiation. During thermal annealing, the growth of large Au NPs is limited due to the reductions in the number of small Au NPs, and the migrated Au NPs aggregate at deeper depths, resulting in a more uniform size distribution and an increased spatial distribution of Au NPs. The present work presents a novel method to modify the size and spatial distributions of embedded NPs. [ABSTRACT FROM AUTHOR]

Explores the prospects of carbon sequestration in the agricultural market. Activities that may enhance the storage of carbon on agricultural soils; Estimation on the potential impact of carbon sequestration on farm income in the United States; Implementation issues surrounding the involvement of agriculture in carbon storage; Merits and pitfalls of policy mechanisms developed for carbon sequestration.

Background: Although the association between ambient temperature and mortality of respiratory diseases was numerously documented, the association between various ambient temperature levels and respiratory emergency department (ED) visits has not been well studied. A recent investigation of the association between respiratory ED visits and various levels of ambient temperature was conducted in Beijing, China. Methods: Daily meteorological data, air pollution data, and respiratory ED visits data from 2017 to 2018 were collected in Beijing. The relationship between ambient temperature and respiratory ED visits was explored using a distributed lagged nonlinear model (DLNM). Then we performed subgroup analysis based on age and gender. Finally, meta-analysis was utilized to aggregate the total influence of ambient temperature on respiratory ED visits across China. Results: The single-day lag risk for extreme cold peaked at a relative risk (RR) of 1.048 [95% confidence interval (CI): 1.009, 1.088] at a lag of 21 days, with a long lag effect. As for the single-day lag risk for extreme hot, a short lag effect was shown at a lag of 7 days with an RR of 1.076 (95% CI: 1.038, 1.114). The cumulative lagged effects of both hot and cold effects peaked at lag 0–21 days, with a cumulative risk of the onset of 3.690 (95% CI: 2.133, 6.382) and 1.641 (95% CI: 1.284, 2.098), respectively, with stronger impact on the hot. Additionally, the elderly were more sensitive to ambient temperature. The males were more susceptible to hot weather than the females. A longer cold temperature lag effect was found in females. Compared with the meta-analysis, a pooled effect of ambient temperature was consistent in general. In the subgroup analysis, a significant difference was found by gender. Conclusions: Temperature level, age-specific, and gender-specific effects between ambient temperature and the number of ED visits provide information on early warning measures for the prevention and control of respiratory diseases. Highlights: 1. Cold weather had a longer lag time and hot weather had a shorter lag time but a stronger effect. 2. Extreme temperatures had a greater effect on emergency room visits for respiratory disease than moderate temperatures. 3. The elderly population were more sensitive to cold and hot weather. [ABSTRACT FROM AUTHOR]

Hydrophilic trioctylammonium triflate ([TOA][OTf]), a protic organic ionic plastic crystal (POIPC), is studied by differential scanning calorimetry (DSC) and broadband dielectric spectroscopy (BDS) in a temperature range from −100°C to 120 °C. Below the melting temperature, ${T}_{m}~\approx ~18 ^{\circ} {\mathrm {C}}$ , [TOA][OTf] shows five solid phases, separated by sharp thermal transitions as detected by DSC. BDS spectra are analyzed using various strategies for data analysis. Phase changes are discernible in temperature-dependent permittivity and dielectric loss data; however, the derivatives ${{\partial \epsilon ^{\prime }}}/ {{\partial }\text {ln}{\omega }}$ and ${{\partial }\text {ln}{\varepsilon ^{\prime }}}/ {{\partial {T}}}$ appear to be much more sensitive to confirm all calorimetric phase transitions consistently. Fitting of ${{\partial \epsilon ^{\prime }}} /{{\partial }\text {ln}{\omega }}$ spectra with symmetric Cole–Cole functions reveals two conductivity relaxation processes, the relaxation time of which (${\tau }_{\text {fast}}$ and ${\tau }_{\mathrm {slow}}$) is separated by about two decades over the whole temperature range. The dc conductivity (${\sigma }_{\mathrm {dc}}$) is computed from ${\varepsilon ^{\prime \prime }}$ spectra for the solid phases I–IV and in the melt. Within all solid phases, ${\sigma }_{\text {dc}}$ shows Arrhenius behavior with typically decreasing activation energy toward higher temperature except for phase III. In the melt, ${\sigma }_{\text {dc}}$ obeys Vogel–Fulcher–Tammann (VFT) behavior as expected favoring a “vehicle” mechanism for ionic charge transport. Surprisingly, the ratio ${\tau }_{\text {fast}}/ {\tau }_{\text {slow}}$ shows an exceptional sensitivity to phase changes, either by stepwise changes or changes in its temperature dependence. From the presence of two distinct conductivity relaxation modes, we conclude that the crossover from subdiffusive to diffusive charge transport proceeds via two characteristic length scales, where the longer one likely relates to apolar aggregates of nanophase-separated cation tails as proposed by various authors. Contact angle measurements support this hypothesis. Finally, we discuss the temperature dependence of ${\sigma \tau {T}}$ and ${\sigma \tau }$ in the framework of the Debye–Stokes–Einstein (DSE) and Barton–Nakajima–Namikawa (BNN) relation. Here, ${\sigma }_{\text {dc}}{\tau }_{\text {slow}}{T}$ exclusively “sees” the transition III $\to $ II, which implies that this transition originates from a reorganization of the nanophase-separated apolar aggregates. [ABSTRACT FROM AUTHOR]

In this article, the authors reflect on the importance of international cooperation in reducing climate risks. They state that it is essential for nations to set of governing rules, particularly on greenhouse gas emissions. They add that a mechanism such as linear compensation (LinC) aids in moving past political impasse and achieve international cooperation.

Positron emission tomography (PET) imaging offers physiological and biological information through thein vivodistribution of PET agents for disease diagnosis, therapy monitoring and prognosis evaluation. Due to the unique structural characteristics allowing for facile modification of targeting ligands and radionuclides, dendrimers can be served as a versatile scaffold to build up various PET imaging agents, and significant breakthroughs have been made in this field over the past decades. This review focuses on the recent advances in dendrimer-based contrast agents for PET imaging of cancer, cardiovascular and other diseases. In particular, radiolabeling strategies for different PET isotopes are described in detail. Several challenges involved in clinical translation of radiolabeled dendrimers are also discussed. [ABSTRACT FROM AUTHOR]

This paper proposes an ex post path choice estimation framework for urban rail systems using an aggregated time-space hypernetwork approach. We aim to infer the actual passenger flow distribution in an urban rail system for any historical day using the observed automated fare collection (AFC) data. By incorporating a schedule-based dynamic transit network loading (SDTNL) model, the framework captures the crowding correlation among stations and the interaction between the path choice and passenger left behind, which is important for the path choice estimation in a "near-capacity" operated urban rail system. The path choice estimation is formulated as an optimization problem, which aims to minimize the difference between the model-derived and observed information with path choice parameters as decision variables. The original problem is intractable because of nonlinear (logit model) and nonanalytical (SDTNL) constraints. A solution procedure is proposed to decompose the original problem into three tractable subproblems, which can be solved efficiently. Solving the decomposed problem is equivalent to finding a fixed point. We prove that the solution to the original problem is the same as the decomposed problem (i.e., the fixed point) when passenger path choices follow the predefined behavior model. If this condition does not hold, the solution of the original problem is proved to be an "almost fixed point" for the decomposed problem. The model is validated using both synthetic and real-world AFC data from a major urban railway system. The analysis with synthetic data validates the model's effectiveness in estimating path choice parameters and left behind probabilities, which outperforms state-of-art simulation-based optimization methods and probabilistic models in both accuracy and efficiency. The analysis using actual data shows that the estimated path shares are more reasonable than the baseline uniform path shares and survey-derived path shares. The model estimation is robust to different initial parameter values and AFC data from various dates. Funding: The project is partially funded by the TRENoP Strategic Research funding at KTH. Supplemental Material: The online appendices are available at https://doi.org/10.1287/trsc.2022.1177. [ABSTRACT FROM AUTHOR]

Objectives: To validate a total-body PET-guided deep progressive learning reconstruction method (DPR) for low-dose 18F-FDG PET imaging. Methods: List-mode data from the retrospective study (n = 26) were rebinned into short-duration scans and reconstructed with DPR. The standard uptake value (SUV) and tumor-to-liver ratio (TLR) in lesions and coefficient of variation (COV) in the liver in the DPR images were compared to the reference (OSEM images with full-duration data). In the prospective study, another 41 patients were injected with 1/3 of the activity based on the retrospective results. The DPR images (DPR_1/3(p)) were generated and compared with the reference (OSEM images with extended acquisition time). The SUV and COV were evaluated in three selected organs: liver, blood pool and muscle. Quantitative analyses were performed with lesion SUV and TLR, furthermore on small lesions (≤ 10 mm in diameter). Additionally, a 5-point Likert scale visual analysis was performed on the following perspectives: contrast, noise and diagnostic confidence. Results: In the retrospective study, the DPR with one-third duration can maintain the image quality as the reference. In the prospective study, good agreement among the SUVs was observed in all selected organs. The quantitative results showed that there was no significant difference in COV between the DPR_1/3(p) group and the reference, while the visual analysis showed no significant differences in image contrast, noise and diagnostic confidence. The lesion SUVs and TLRs in the DPR_1/3(p) group were significantly enhanced compared with the reference, even for small lesions. Conclusions: The proposed DPR method can reduce the administered activity of 18F-FDG by up to 2/3 in a real-world deployment while maintaining image quality. [ABSTRACT FROM AUTHOR]

This study investigates the influence of EGR (exhaust gas recirculation) coupled with injection pressure on the combustion and emission characteristics of an engine fueled with methanol-gasoline blends. Increasing the methanol blending ratio can improve the knocking phenomenon, BTE (brake thermal efficiency) and regulated emissions. As the methanol blending ratio increases, the optimal fuel injection pressure for achieving the optimal combustion process, BTE and CO (carbon monoxide) emissions increases. The optimal EGR rate for achieving the highest BTE also increases. As the methanol blending ratio increases, the optimal injection pressure for achieving the lowest TPN (total particle number) and NPN (nucleation mode particle number) also increases. Increasing the fuel injection pressure leads to a decrease in APN (accumulation mode particle number). Increasing the methanol blending ratio and EGR rate can reduce TPN and NPN. With increasing methanol blending ratio, APN initially increases and then decreases. When using a lower methanol blending ratio, increasing the EGR rate leads to a higher proportion of APN to TPN. However, when using a higher methanol blending ratio, the opposite is true. The optimal engine performance can be achieved by using M100 fuel with a 35 MPa injection pressure and a 30% EGR rate. • Investigation of the effects of EGR dilution and injection pressure on engine performance with a methanol/gasoline blend. • Blending methanol fuel reduces total particles and increases accumulation mode particles. • Increasing EGR reduces total particles and increases accumulation mode particles. • Appropriate increase in injection pressure reduces total particles and accumulation mode particles. • Increasing EGR, injection pressure, and methanol blending ratio reduces knock intensity. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinoma (CCA) is a rare biliary adenocarcinoma related to poor clinical prognosis. Crowberry is an herbal medicine used to control inflammatory diseases and reestablish antioxidant enzyme activity. Although crowberry shows significant therapeutic efficacy in various tumors and diseases, its anticancer effects and specific molecular mechanisms in CCA are poorly understood. Aim of the study: This study was conducted to characterize crowberry effects on CCA cells behavior. Materials and methods: The chemical profiles of crowberry extract was qualitatively analyzed by high-performance liquid chromatography (HPLC) and HPLC–tandem mass spectrometry. MTT, colony formation and EdU assays were performed to measure cell proliferation. The effect of crowberry treatment on CCA cell migration was assessed by wound healing and migration assays. Moreover, Hoechst staining assay and flow cytometry were performed to assess the cell apoptosis rate. Western blotting was used to assess the protein expression levels of key factors associated with apoptosis, the Akt signaling pathway, and the epithelial-mesenchymal transition. A xenograft model was established and immunohistochemical and H&E staining was performed to assess crowberry antitumor effects in vivo. Results: Crowberry clearly inhibited CCA cells proliferation and migration in a dose-dependent manner and induced apoptosis in vitro. Crowberry inactivated the PI3K/Akt signaling pathway by regulating DEK in vitro and significantly inhibited tumor growth by downregulating the DEK expression in xenograft models. Conclusion: Crowberry inhibits CCA cells proliferation and migration through a molecular mechanism that includes inhibition of DEK and Akt signaling pathway inhibition in vitro and in vivo. Highlights: Crowberry alterd expression levels of key mediators in PI3K/Akt signaling pathway. Crowberry alterd expression levels of key mediators in PI3K/Akt signaling pathway. Crowberry suppressed the expression of the proto-oncogene DEK in vivo and in vitro. Crowberry inhibited CCA progression and migration through a molecular mechanism that includes inhibition of DEK and the Akt signaling pathway in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Certain receptors are often overexpressed during tumor occurrence and development and closely correlate with carcinogenesis. Owing to its overexpression on the cell membrane and cytoplasm of various tumors, plectin, which is involved in tumor proliferation, migration, and invasion, has been viewed as a promising target for cancer imaging. Hence, plectin-targeting agents have great potential as imaging probes for tumor diagnosis. In this study, we developed a [99mTc]Tc-labeled plectin-targeted peptide (PTP) as a novel single-photon emission computed tomography (SPECT) probe for tumor imaging and investigated its pharmacokinetics, biodistribution, and targeting ability in several types of tumor-bearing mouse models. The PTP had good biocompatibility and targeting ability to tumor cells in vitro and could be readily labeled with [99mTc]Tc after modification with the bifunctional chelator 6-hydrazino nicotinamide (HYNIC). Furthermore, the prepared [99mTc]Tc-labeled PTP ([99mTc]Tc-HYNIC-PTP) showed high radiochemical purity and excellent stability in vitro. In addition, favorable biodistribution, fast blood clearance, and clear accumulation of [99mTc]Tc-HYNIC-PTP in several types of tumors were observed, with a good correlation between tumor uptake and plectin expression levels. These results indicate the potential of [99mTc]Tc-HYNIC-PTP as a novel SPECT probe for tumor imaging. [ABSTRACT FROM AUTHOR]

Fucan sulfate I (FSI) from the sea cucumber Holothuria fuscopunctata was purified and its structure was clarified based on a bottom-up strategy. The unambiguous structures of a series of oligosaccharides including disaccharides, trisaccharides, and tetrasaccharides, which were released from mild acid hydrolysis of FSI, were identified by one-dimensional (1D)/two-dimensional (2D) nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis. All the glycosidic bonds in these oligosaccharides were presented as α1,3 linkages confirmed by correlated signals from their 1H-1H ROESY and 1H-13C HMBC spectra. The structural sequence of these oligosaccharides formed by Fuc2S4S, Fuc2S, and non-sulfated ones (Fuc0S), along with the general structural information of FSI, indicated that the structure of FSI could be elucidated as: [-L-Fuc2S4S-α1,3-L-Fuc(2S)-α1,3-L-Fuc2S-α1,3-L-Fuc0S-α1,3-1-]n. Moreover, the L-Fuc0S-α1,3-L-Fuc2S4S linkage in FSI was susceptible to be cleaved by mild acid hydrolysis. The antioxidant activity assays in vitro showed that FSI and the depolymerized product (dFSI′) had potent activities for superoxide radical scavenging activity with IC50 of 65.71 and 83.72 μg/mL, respectively, while there was no scavenging effect on DPPH, hydroxyl and ABTS radicals. [ABSTRACT FROM AUTHOR]

Objective: Parkinson's disease (PD), also known as paralysis tremor, is a chronic disease of the central nervous system. It has been reported that hepatocyte nuclear factor 4 alpha (HNF4A) is upregulated in PD, but its specific function has not been well explored. Methods: We established an in vitro PD model in SH‐SY5Y cells stimulated with 1‐methyl‐4‐phenylpyridinium (MPP+). Meanwhile, the effect of HNF4A on MPP+‐treated SH‐SY5Y cell behavior was monitored by functional assays. Mechanism assays were conducted to verify the relationship among LINC00667/miR‐34c‐5p/HNF4A. Rescue experiments validated the regulatory mechanism in PD model. Results: The results revealed that depletion of HNF4A suppressed cell cytotoxicity and apoptosis caused by MPP+. Knockdown of HNF4A recovered MPP+‐stimulated oxidative stress and neuroinflammation. Mechanically, HNF4A was targeted and inhibited by miR‐34c‐5p. Furthermore, we found that LINC00667 positively modulated HNF4A expression via sequestering miR‐34c‐5p in MPP+‐stimulated SH‐SY5Y cells. Interestingly, the data indicated that HNF4A could transcriptionally activate LINC00667 expression. Rescue experiments presented that miR‐34c‐5p interference or HNF4A overexpression could mitigate the effects of LINC00667 knockdown on cell viability, cytotoxicity, cell apoptosis, oxidative stress, and neuroinflammation in MPP+‐treated SH‐SY5Y cells. Conclusion: Our study first proved LINC00667, miR‐34c‐5p, and HNF4A constructed a positive feedback loop in MPP+‐treated SH‐SY5Y cells, enriching our understanding of PD. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the impact of a deep learning (DL)-based denoising method on the image quality and lesion detectability of 18F-FDG positron emission tomography (PET) images. Methods: Fifty-two oncological patients undergoing an 18F-FDG PET/CT imaging with an acquisition of 180 s per bed position were retrospectively included. The list-mode data were rebinned into four datasets: 100% (reference), 75%, 50%, and 33.3% of the total counts, and then reconstructed by OSEM algorithm and post-processed with the DL and Gaussian filter (GS). The image quality was assessed using a 5-point Likert scale, and FDG-avid lesions were counted to measure lesion detectability. Standardized uptake values (SUVs) in livers and lesions, liver signal-to-noise ratio (SNR) and target-to-background ratio (TBR) values were compared between the methods. Subgroup analyses compared TBRs after categorizing lesions based on parameters like lesion diameter, uptake or patient habitus. Results: The DL method showed superior performance regarding image noise and inferior performance regarding lesion contrast in the qualitative assessment. More than 96.8% of the lesions were successfully identified in DL images. Excellent agreements on SUV in livers and lesions were found. The DL method significantly improved the liver SNR for count reduction down to 33.3% (p < 0.001). Lesion TBR was not significantly different between DL and reference images of the 75% dataset; furthermore, there was no significant difference either for lesions of > 10 mm or lesions in BMIs of > 25. For the 50% dataset, there was no significant difference between DL and reference images for TBR of lesion with > 15 mm or higher uptake than liver. Conclusions: The developed DL method improved both liver SNR and lesion TBR indicating better image quality and lesion conspicuousness compared to GS method. Compared with the reference, it showed non-inferior image quality with reduced counts by 25–50% under various conditions. [ABSTRACT FROM AUTHOR]

Recent evidence from laboratory experiments suggests that important disparities exist between willingness to pay (WTP) and compensation demanded for the same good. Because a fundamental postulate in neoclassical theory is that with small income effects and many available substitutes, the willingness to accept (WTA) and WTP measures of value for a commodity should be roughly equivalent, this finding has vast implications in both a positive and normative sense. This study advances, and experimentally tests, a new explanation of the WTP/WTA disparity-a dynamic theory based on the presence of commitment costs. Although to date neoclassical models have not explained the observed data patterns well, we find that the commitment cost theory combined with a simple behavioral anomaly is able to lend insights into the causes and severity of the WTA/WTP disparity. Furthermore, we find that market experience attenuates the behavioral anomaly, consistent with the notion that no value disparity exists for agents with sufficient market experience. [ABSTRACT FROM AUTHOR]

Previous reports suggest that an important characteristic of chemosensitive neurones is an unusually large change of steady-state intracellular pH in response to a change in extracellular pH (ΔpHi/ΔpHo). To determine whether such a correlation exists between neurones from the medullary raphe (a chemosensitive brain region) and hippocampus (a non-chemosensitive region), we used BCECF to monitor pHi in cultured neurones subjected to extracellular acid--base disturbances. In medullary raphe neurones, respiratory acidosis (5% → 9% CO2) caused a rapid fall in pHi (ΔpHi ∼0.2) with no recovery and a large ΔpHi/ΔpHo of 0.71. Hippocampal neurones had a similar response, but with a slightly lower ΔpHi/ΔpHo (0.59). We further investigated a possible link between pHi regulation and chemosensitivity by following the pHi measurements on medullary raphe neurones with an immunocytochemistry for tryptophan hydroxylase (a marker of serotonergicu neurones). We found that the ΔpHi/ΔpHo of 0.69 for serotonergic neurones (which are stimulated by acidosis) was not different from either the ΔpHi/ΔpHo of 0.75 for non-serotonergic neurones (most of which are not chemosensitive), or from the ΔpHi/ΔpHo of hippocampal neurones. For both respiratory alkalosis (5% → 3% CO2) and metabolic alkalosis (22 mM → 35 mM HCO3-), ΔpHi/ΔpHo was 0.42-0.53 for all groups of neurones studied. The only notable difference between medullary raphe and hippocampal neurones was in response to metabolic acidosis (22 mM → 14 mM HCO3-), which caused a large pHi decrease in ∼80% of medullary... [ABSTRACT FROM AUTHOR]

Background: The development of alternative anti-angiogenesis therapy for choroidal neovascularization (CNV) remains a great challenge. Nanoparticle systems have emerged as a new form of drug delivery in ocular diseases. Here, we report the construction and characterization of arginine-glycine-aspartic acid (RGD)-conjugated polyethyleneimine (PEI) as a vehicle to load antioxidant salvianolic acid A (SAA) for targeted anti-angiogenesis therapy of CNV. In this study, PEI was consecutively modified with polyethylene glycol (PEG) conjugated RGD segments, 3-(4′-hydroxyphenyl) propionic acid-Osu (HPAO), and fluorescein isothiocyanate (FI), followed by acetylation of the remaining PEI surface amines to generate the multifunctional PEI vehicle PEI.NHAc-FI-HPAO-(PEG-RGD) (for short, RGD-PEI). The formed RGD-PEI was utilized as an effective vehicle platform to load SAA. Results: We showed that RGD-PEI/SAA complexes displayed desirable water dispersibility, low cytotoxicity, and sustainable release of SAA under different pH conditions. It could be specifically taken up by retinal pigment epithelium (RPE) cells which highly expressed ɑvβ5 integrin receptors in vitro and selectively accumulated in CNV lesions in vivo. Moreover, the complexes displayed specific therapeutic efficacy in a mouse model of laser induced CNV, and the slow elimination of the complexes in the vitreous cavity was verified by SPECT imaging after 131I radiolabeling. The histological examinations further confirmed the biocompatibility of RGD-PEI/SAA. Conclusions: The results suggest that the designed RGD-PEI/SAA complexes may be a potential alternative anti-angiogenesis therapy for posterior ocular neovascular diseases. [ABSTRACT FROM AUTHOR]

Transit network simulation models are often used for performance and retrospective analysis of urban rail systems, taking advantage of the availability of extensive automated fare collection (AFC) and automated vehicle location (AVL) data. Important inputs to such models, in addition to origin-destination flows, include passenger path choices and train capacity. Train capacity, which has often been overlooked in the literature, is an important input that exhibits a lot of variabilities. The paper proposes a simulation-based optimization (SBO) framework to simultaneously calibrate path choices and train capacity for urban rail systems using AFC and AVL data. The calibration is formulated as an optimization problem with a black-box objective function. Seven algorithms from four branches of SBO solving methods are evaluated. The algorithms are evaluated using an experimental design that includes five scenarios, representing different degrees of path choice randomness and crowding sensitivity. Data from the Hong Kong Mass Transit Railway (MTR) system is used as a case study. The data is used to generate synthetic observations used as "ground truth." The results show that the response surface methods (particularly constrained optimization using response surfaces) have consistently good performance under all scenarios. The proposed approach drives large-scale simulation applications for monitoring and planning. [ABSTRACT FROM AUTHOR]

Background: Influenza virus remains a continuous and severe threat to public health worldwide, and its prevention and treatment have always been a major international issue. Because of its ability to evade immune surveillance through rapid antigenic drift and antigenic shift, broad-spectrum vaccines seem increasingly important. Methods: A mAb named 3C12 from an immortalized hybrid cell was generated via immunizing mice with HA2 protein from A/chicken/Anhui/BRI99/2016 (AH/BRI99/16, H9N2) generated by prokaryotic expression. Then, its broad-spectrum activity was analyzed by WB and IFA. Next, the minimal linear epitope was identified via analyzing the reaction of a series of HA truncations with 3C12. Finally, the protective effects of 3C12 were evaluated in vitro and in vivo infection experiments. Results: The mAb could react with the viruses of subtypes H1, H2, H5, H8, H9, H12, H13, H16, and HA protein of H18 in group 1, but failed to react with viruses in group 2. The minimal linear epitope targeted by the mAb was 433NAELLVL439 in full length of HA and localized in the C-helix region of HA2 (residue 95-101, HA2 numbering). What's more, the mAb 3C12 inhibited H1, H2, H5, H8, H9, H12, H13 and H16 virus-replication in vitro and also has shown effectiveness in preventing and treating disease in mice challenged with lethal dose of AH/BRI99/16 (H9N2) virus in vivo. These results suggested that the broadly reactive anti-HA stem mAb 3C12 exhibited prophylactic and therapeutic efficacy. Conclusions: Here, we have demonstrated that the linear epitope identified in this study could be a novel target for developing broad-spectrum influenza diagnostics or vaccine design, and the HA2-based monoclonal antibody is indeed a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses. [ABSTRACT FROM AUTHOR]

The tectonic boundaries and geodynamic evolution of the South China Block are widely debated. While the community largely agrees on the occurrence of the collision between the Yangtze and Cathaysia Blocks, the lack of ultrahigh-pressure metamorphic rocks and obscurity of the boundary lead to inconsistencies among the abundant geological and geophysical data. We present three profiles that reveal the geoelectrical structure of eastern South China. Distinct conductive interfaces oriented NE–SW are identified in the geoelectrical lithosphere, which separate the region into six parts. To interpret our observations and resultant model, we develop and propose a mechanism of "microcontinent interaction". Our new model justifies the prior proposed models of 'block collision' and additionally proposes 'multi-terrane accretion-collision' to address the tectonic evolution. [ABSTRACT FROM AUTHOR]

Background: Glioma is the deadliest brain cancer in adults because the blood–brain-barrier (BBB) prevents the vast majority of therapeutic drugs from entering into the central nervous system. The development of BBB-penetrating drug delivery systems for glioma therapy still remains a great challenge. In this study, we aimed to design and develop a theranostic nanocomplex with enhanced BBB penetrability and tumor-targeting efficiency for glioma single-photon emission computed tomography (SPECT) imaging and anticancer drug delivery. Results: This multifunctional nanocomplex was manufactured using branched polyethylenimine (PEI) as a template to sequentially conjugate with methoxypolyethylene glycol (mPEG), glioma-targeting peptide chlorotoxin (CTX), and diethylenetriaminepentaacetic acid (DTPA) for 99mTc radiolabeling on the surface of PEI. After the acetylation of the remaining PEI surface amines using acetic anhydride (Ac2O), the CTX-modified PEI (mPEI-CTX) was utilized as a carrier to load chemotherapeutic drug doxorubicin (DOX) in its interior cavity. The formed mPEI-CTX/DOX complex had excellent water dispersibility and released DOX in a sustainable and pH-dependent manner; furthermore, it showed targeting specificity and therapeutic effect of DOX toward glioma cells in vitro and in vivo (a subcutaneous tumor mouse model). Owing to the unique biological properties of CTX, the mPEI-CTX/DOX complex was able to cross the BBB and accumulate at the tumor site in an orthotopic rat glioma model. In addition, after efficient radiolabeling of PEI with 99mTc via DTPA, the 99mTc-labeled complex could help to visualize the drug accumulation in tumors of glioma-bearing mice and the drug delivery into the brains of rats through SPECT imaging. Conclusions: These results indicate the potential of the developed PEI-based nanocomplex in facilitating glioma-targeting SPECT imaging and chemotherapy. [ABSTRACT FROM AUTHOR]

PET/CT has been identified as one of the routine methods for the assessment of multiple myeloma (MM) bone marrow infiltration. In the routine method of performing PET/CT, the 18F-Fludeoxyglucose (18F-FDG) uptake in this disease is often used in the assessment of this condition, however CT diagnosis is not currently commonly used. The aim of the present study was to investigate the importance of CT in PET/CT for assessing diffuse infiltration (DI) of bone marrow in MM. MRI was used as a control in the present study, which is the gold standard for assessing DI of bone marrow and is divided into 3 levels: Mild, moderate and severe DI. Subsequently, a total of four combinations of PET and CT results were listed using the enumeration method for the evaluation of DI in the bone marrow. These combinations were respectively compared with the three levels of MR imaging to screen the most consistent method. The concordances of the new method and routine 18F-FDG PET/CT for the assessment of DI with MR imaging were compared using the McNemar test, respectively. The results of the DI assessment from the two methods were verified by performing Durie-Salmon (D-S) PLUS staging. Compared with MR imaging, the results were as follows: PET and CT exhibited negative results, suggesting mild DI; one of them was positive, suggesting moderate DI; and two were positive, suggesting severe DI. The results of concordance between two methods (new and routine) and MR imaging are indicated as follows: For the new method, McNemar test, P=0.513 and Kappa=0.745; for the routine 18F-FDG PET/CT method, McNemar test, P=0.03 and Kappa=0.547. Re-performance of D-S PLUS staging presented the following results: New method, McNemar test, P=0.317 and Kappa=0.93; for the routine method, McNemar test, P=0.223 and Kappa=0.811. These findings indicated that the CT component of PET/CT could improve the concordance with MRI results in the assessment of DI, and the same results were obtained when D-S PLUS staging was performed. The CT in PET/CT can enhance diagnostic accuracy in the assessment of DI by reducing the false negatives when compared with the routine 18F-FDG method. [ABSTRACT FROM AUTHOR]

Epigallocatechin-3-gallate (EGCG), a main active catechin in green tea, was reported to attenuate renal injury and hypertension. However, its effects on salt-induced hypertension and renal injury remain unclear. In the present study, we explored its effects on hypertension and renal damage in Dahl rats with salt-sensitive hypertension. We found that EGCG could lower blood pressure after 6 weeks of oral administration, reduce 24 h urine protein levels and decrease creatinine clearance, and attenuate renal fibrosis, indicating that it could attenuate hypertension by protecting against renal damage. Furthermore, we studied the renal protective mechanisms of EGCG, revealing that it could lower malondialdehyde levels, reduce the numbers of infiltrated macrophages and T cells, and induce the apoptosis of NRK-49F cells. Considering that the 67 kD laminin receptor (67LR) binds to EGCG, its role in EGCG-induced fibroblast apoptosis was also investigated. The results showed that an anti-67LR antibody partially abrogated the apoptosis-inducing effects of EGCG on NRK-49F cells. In summary, EGCG may attenuate renal damage and salt-sensitive hypertension via exerting anti-oxidant, anti-inflammatory, and apoptosis-inducing effects on fibroblasts; the last effect is partially mediated by 67LR, suggesting that EGCG represents a potential strategy for treating salt-sensitive hypertension. [ABSTRACT FROM AUTHOR]

The identification of markers expressed by pathological cells or their microenvironment would help to distinguish such cells from the normal tissues. The strategies derived from this theory can be a promising modality for imaging and treating diseases. LyP-1, a tumor homing peptide, can selectively bind to its receptor p32 protein overexpressed in various tumor-associated cells and atherosclerotic plaque macrophages. During recent decades, multiple types of LyP-1-based imaging probes and drug delivery systems have been designed and developed for diagnostic and therapeutic applications. This review first introduces LyP-1 and its receptor p32, as well as its homing, internalization and proapoptotic properties. Next, we highlight recent studies focusing on the applications of LyP-1-based strategies in the diagnosis and treatment of tumors, metastatic lesions, and atherosclerotic plaques. Finally, several limitations in the clinical translation of LyP-1-based bioconjugates are summarized. [ABSTRACT FROM AUTHOR]

Abstract Air pollution imposes significant environmental and health risks worldwide and is expected to deteriorate in the coming decade as cities expand. Measuring population exposure to air pollution is crucial to quantifying risks to public health. In this work, we introduce a big data analytics framework to model residents' stay and commuters' travel exposure to outdoor PM 2.5 and evaluate their environmental justice, with Beijing as an example. Using mobile phone and census data, we first infer travel demand of the population to derive residents' stay activities in each analysis zone, and then focus on commuters and estimate their travel routes with a traffic assignment model. Based on air quality observations from monitoring stations and a spatial interpolation model, we estimate the outdoor PM 2.5 concentrations at a 500-m grid level and map them to road networks. We then estimate the travel exposure for each road segment by multiplying the PM 2.5 concentration and travel time spent on the road. By combining the estimated PM 2.5 exposure and housing price harnessed from online housing transaction platforms, we discover that in the winter, Beijing commuters with low wealth level are exposed to 13% more PM 2.5 per hour than those with high wealth level when staying at home, but exposed to less PM 2.5 by 5% when commuting the same distance (due to lighter traffic congestion in suburban areas). We also find that the residents from the southern suburbs of Beijing have both lower level of wealth and higher stay- and travel- exposure to PM 2.5 , especially in the winter. These findings inform more equitable environmental mitigation policies for future sustainable development in Beijing. Finally, or the first time in the literature, we compare the results of exposure estimated from passive data with subjective measures of perceived air quality (PAQ) from a survey. The PAQ data was collected via a mobile-app. The comparison confirms consistencies in results and the advantages of the big data for air pollution exposure assessments. Highlights • A data analysis framework is proposed to estimate commuter's exposure to ambient PM 2.5 using mobile phone data. • Urban scale dynamic stay exposure is estimated based on the travel demand. • Travel exposure of commuters is estimated by combining the travel time and the PM 2.5 concentration. • Environmental justice in PM 2.5 exposure is investigated by comparing the exposure with housing price. [ABSTRACT FROM AUTHOR]

Non-invasive imaging of apoptosis in tumors induced by chemotherapy is of great value in the evaluation of therapeutic efficiency. In this study, we report the synthesis, characterization, and utilization of radionuclide technetium-99m (99mTc)-labeled dendrimer-entrapped gold nanoparticles (Au DENPs) for targeted SPECT/CT imaging of chemotherapy-induced tumor apoptosis. Generation five poly(amidoamine) (PAMAM) dendrimers (G5.NH2) were sequentially conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), polyethylene glycol (PEG) modified duramycin, PEG monomethyl ether, and fluorescein isothiocyanate (FI) to form the multifunctional dendrimers, which were then utilized as templates to entrap gold nanoparticles. Followed by acetylation of the remaining dendrimer surface amines and radiolabeling of 99mTc, the SPECT/CT dual mode nanoprobe of tumor apoptosis was constructed. The developed multifunctional Au DENPs before and after 99mTc radiolabeling were well characterized. The results demonstrate that the multifunctional Au DENPs display favorable colloidal stability under different conditions, own good cytocompatibility in the given concentration range, and can be effectively labeled by 99mTc with high radiochemical stability. Furthermore, the multifunctional nanoprobe enables the targeted SPECT/CT imaging of apoptotic cancer cells in vitro and tumor apoptosis after doxorubicin (DOX) treatment in the established subcutaneous tumor model in vivo. The designed duramycin-functionalized Au DENPs might have the potential to be employed as a nanoplatform for the detection of apoptosis and early tumor response to chemotherapy. [ABSTRACT FROM AUTHOR]

Plasma contact system is the initial part of both the intrinsic coagulation pathway and kallikrein–kinin pathway, which mainly involves three proteins: coagulation factor XII (FXII), prekallikrein (PK) and high-molecular weight kininogen. Fucosylated chondroitin sulfate (FCS) is a unique sulfated glycosaminoglycan (GAG) composed of a chondroitin sulfate-like backbone and sulfated fucose branches. The native FCS was preliminary found to cause undesired activation of the plasma contact system. How this unusual GAG functions in this process remains to be clarified. Herein, the relationship between its structure, plasma contact activation and its effects on the PK–FXII reciprocal activation loop were studied. The recalcification time assay indicated that the FCS at high concentration could be procoagulant which may be attributed to its contact activation activity. The structure–activity relationship study indicated that its high molecular weight and distinct fucose side chains are required for contact activation by FCS, although the sulfate substitution types of its side chains have less impact. In human plasma, the native FCSs potently induced FXII-dependent contact activation. However, in purified systems FCS did not significantly activate FXII per se or induce its autoactivation, whereas FCS significantly promoted the activation of PK by factor XIIa. Polysaccharide–protein interaction assays showed that FCS bound to PK with higher affinity than other contact system proteins. These data suggested that potent contact activation by FCS requires the positive feedback loop between PK and FXII. These findings contribute to better understanding of contact activation by complex GAG. [ABSTRACT FROM AUTHOR]

Non-invasive imaging of apoptosis in tumors induced by chemotherapy is of great value in the evaluation of therapeutic efficiency. In this study, we report the synthesis, characterization, and utilization of radionuclide technetium-99m (99mTc)-labeled dendrimer-entrapped gold nanoparticles (Au DENPs) for targeted SPECT/CT imaging of chemotherapy-induced tumor apoptosis. Generation five poly(amidoamine) (PAMAM) dendrimers (G5.NH2) were sequentially conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), polyethylene glycol (PEG) modified duramycin, PEG monomethyl ether, and fluorescein isothiocyanate (FI) to form the multifunctional dendrimers, which were then utilized as templates to entrap gold nanoparticles. Followed by acetylation of the remaining dendrimer surface amines and radiolabeling of 99mTc, the SPECT/CT dual mode nanoprobe of tumor apoptosis was constructed. The developed multifunctional Au DENPs before and after 99mTc radiolabeling were well characterized. The results demonstrate that the multifunctional Au DENPs display favorable colloidal stability under different conditions, own good cytocompatibility in the given concentration range, and can be effectively labeled by 99mTc with high radiochemical stability. Furthermore, the multifunctional nanoprobe enables the targeted SPECT/CT imaging of apoptotic cancer cells in vitro and tumor apoptosis after doxorubicin (DOX) treatment in the established subcutaneous tumor model in vivo. The designed duramycin-functionalized Au DENPs might have the potential to be employed as a nanoplatform for the detection of apoptosis and early tumor response to chemotherapy. [ABSTRACT FROM AUTHOR]

This paper reports the up-conversion emission properties of alumina sol containing only Tm 3+ or both Tm 3+ and Yb 3 + ions under 650 nm pumping using a low power xenon lamp source. Two UV emission bands which centered at 349 nm for the 1 I 6 → 3 F 4 transition of Tm 3+ ion and at 367 nm for the 1 D 2 → 3 H 6 transition of Tm 3+ ion and two blue emission bands which centered at 457 nm for the 1 D 2 → 3 H 4 transition of Tm 3+ ion and at 485 nm for the 1 G 4 → 3 H 6 transition of Tm 3+ ion have been observed. The up-conversion emission follows a two-photon absorption process for both blue bands, and the UV band centered at 367 nm but follows a cross-relaxation process for the UV band centered at 349 nm. The concentration quenching effect is relatively low in this material under 650 nm pumping. Due to the back energy transfer from Yb 3+ to Tm 3+ ions, the intensity of UV emission corresponding to the 1 I 6 → 3 F 4 transition of Tm 3+ ion is stronger in alumina sol samples containing both Tm 3+ and Yb 3+ ions than in which containing only Tm 3+ ions. [ABSTRACT FROM AUTHOR]

Background: We confirmed that the filaggrin gene mutation c.3321delA is associated with atopic dermatitis in our previous genome wide association study of the Chinese Han population. c.3321delA is the most common filaggrin gene mutation in Chinese atopic dermatitis patients but is not present in European populations. Objective: To investigate the genetic model for the c.3321delA mutation and to determine the correlation between c.3321delA and atopic dermatitis clinical phenotypes in the Chinese Han population. Method: The filaggrin gene mutation c.3321delA was sequenced in 1,080 atopic dermatitis patients and 908 controls from the Chinese population. The χ2 test, ANOVA,nonparametric tests and logistic regression were used to investigate the relationship between the c.3321delA genotype and atopic dermatitis clinical phenotypes in the Chinese Han population. Results: Analyses of the genetic model revealed that the additive model best described the c.3321delA mutation (P = 3.09E-11, OR = 3.43, 95%CI = 2.38–4.96). Stratified analyses showed that the c.3321delA allele frequency distribution is significantly associated with concomitant skin xerosis (P = 1.68E-03, OR = 2.13,95%CI = 1.32–3.46), palmar hyperlinearity (P = 3.64E-17, OR = 4.0,95%CI = 2.86–5.70), white dermatographism (P = 4.25E-03, OR = 1.82,95%CI = 1.22–2.71), food intolerance (P = 1.51E-03, OR = 1.76,95%CI = 1.23–2.50) and disease severity ( P = 9.67E-05). Conclusion: Our study indicates that the filaggrin gene mutation c.3321delA is associated with clinical phenotypes of atopic dermatitis in the Chinese Han population, which might help us gain a better understanding on the pathogenesis of atopic dermatitis. [ABSTRACT FROM AUTHOR]

Epithelial cell shape, tubule convolution, and segment boundary position along the kidney nephron unexpectedly involve the migration of fully differentiated epithelial cells against the flow of lumenal fluid. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Background: Malignant glioma is the most common and deadliest brain cancer due to the obstacle from indistinct tumor margins for surgical excision and blood brain barrier (BBB) for chemotherapy. Here, we designed and prepared multifunctional polyethylenimine-entrapped gold nanoparticles (Au PENPs) for targeted SPECT/CT imaging and radionuclide therapy of glioma. Results: Polyethylenimine was selected as a template for sequential modification with polyethylene glycol (PEG), glioma-specific peptide (chlorotoxin, CTX) and 3-(4-hydroxyphenyl)propionic acid-OSu (HPAO), and were then used to entrap gold nanoparticles (Au NPs). After 131I radiolabeling via HPAO, the 131I-labeded CTX-functionalized Au PENPs as a multifunctional glioma-targeting nanoprobe were generated. Before 131I radiolabeling, the CTX-functionalized Au PENPs exhibited a uniform size distribution, favorable X-ray attenuation property, desired water solubility, and cytocompatibility in the given Au concentration range. The 131I-labeled CTX-functionalized Au PENPs showed high radiochemical purity and stability, and could be used as a nanoprobe for the targeted SPECT/CT imaging and radionuclide therapy of glioma cells in vitro and in vivo in a subcutaneous tumor model. Owing to the unique biological properties of CTX, the developed nanoprobe was able to cross the BBB and specifically target glioma cells in a rat intracranial glioma model. Conclusions: Our results indicated that the formed nanosystem had the significant potential to be applied for glioma targeted diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Background: Hand, Foot, and Mouth Disease (HFMD) is most frequently caused by Enterovirus71 (EV-A71) or Coxsackie virus A16 (CV-A16), infants and young children are at greatest risk. Describing the epidemiology of HFMD can help develop and better target interventions, including the use of pediatric EV-A71 vaccination.Methods: We obtained data from the national surveillance system for HFMD cases with onset dates from 2009 to 2015. We defined probable cases as patient with skin papular or vesicular rashes on the hands, feet, mouth, or buttocks and confirmed cases as patients with the above symptoms along with laboratory-based enterovirus detection. We generated overall and age-specific annual incidence rates and described the temporal variability and seasonality of HFMD in Qinghai Province. We identified spatial clustering of HFMD incidence at the county level using the Local Indicator of Spatial Associationand an alpha level of 0.05.Results: During the study period, 14,480 HFMD probable or confirmed cases were reported in Qinghai Province. Of the 2158 (14.9%) with laboratory confirmation, 924 (42.6%) were caused by CV-A16 and 830 (38.2%) were caused by EV-A71. The majority (89%) of all case-patients were ≤ 5 years of age and male (61.5%). The overall mean annual HFMD incidence rate was 36.4 cases per 100,000 populations, while the incidence rate for children ≤5 years of age was 379.5 cases per 100,000. Case reports peaked during the months of May through July. HFMD was predominantly caused by EV-A71, except in 2010 and 2014 when CV-A16 was the predominant causative agent. High incidence rates of HFMD were clustered (Moran's I = 0.59, P < 0.05) in the eastern region of the province.Conclusion: HFMD remains an important cause of childhood disease in Qinghai Province, occurring in an acyclical pattern of increased incidence, primarily due to CV-A16 circulation every three years. Incidence is also seasonal and tends to spatially cluster in the eastern region of the province. Since approximately 40% of confirmed HFMD cases were due to EV-A71, EV-A71 vaccination is likely to have a positive impact on the HFMD disease burden. Routine analysis of local surveillance data is crucial for describing disease occurrence and changes in etiology. [ABSTRACT FROM AUTHOR]