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The frog-in-the-pan (FIP) phenomenon suggests that investors are more sensitive to abrupt price changes than gradual price changes in the stock market. Based on the cognitive-evolutionary model of surprise and the reinforcement learning model, this paper provides a new explanation for the FIP phenomenon in that this phenomenon could be explained by the elicitation of surprise emotion. We predict that when a change substantially and abruptly occurs, the significant prediction error triggers participants’ surprise, which makes participants more sensitive to the change. To ascertain these hypotheses, we recruited 109 participants and compared participants’ learning rates and surprise responses under different contexts. We observed that participants’ learning rate soared when the prediction error was large enough to trigger surprise emotion under abruptly changed conditions and confirmed that the FIP phenomenon could be explained by the elicitation of surprise emotion. In a word, this research demonstrates the significant role of surprise emotion in the decision-making process.

The present study aimed to investigate the effect of dietary astaxanthin (Ast) from Phaffia rhodozyma on growth performance, survival, carotenoid content, the activity of antioxidant and immune-related enzymes, intestinal microbiota comparison, and disease resistance against Vibrio parahaemolyticus in Penaeus monodon. Juveniles (average weight 3.15 ± 0.12 g) were fed with six experimental diets supplemented with 0 (Control), 20.5, 41, 61.5, 82, and 102.5 mg/kg of Ast (defined as diet A–D) in triplicate for 56 days. The results indicated that shrimp fed with Ast supplementation significantly (p < 0.05) improved growth performance compared with the control. Furthermore, significantly (p < 0.05) increased survival and decreased feed conversion ratio (FCR) demonstrated the beneficial effects of dietary Ast on enhancing nutrient utilization and ultimately improving the growth and survival of shrimp. Furthermore, shrimp fed with Ast including diet developed a deeper red color than the control, consistent with the significantly (p < 0.05) increased Ast deposition in the shrimp shell. Hemolymph-immunological parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (AKP)] and hepatopancreatic antioxidant status [total antioxidant capacity (T-AOC), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)] were significantly (p < 0.05) affected by dietary Ast supplementation. Dietary increasing Ast levels significantly (p < 0.05) increased shrimp resistance performance to V. parahaemolyticus according to the LT50 results in the current study, which may be caused by increased total carotenoid contents in shrimp tissues from all the Ast-supplemented treatments. Conversely, intestinal microbiota biodiversity and richness were not affected by dietary Ast. The best performances of growth, antioxidant status, immunological response, and carotenoid deposition were observed in diets E and F among all the Ast-supplemented treatments. Overall, all the data suggested that dietary P. rhodozyma Ast played a critical role in improving growth performance, achieving the desired coloration, increasing carotenoid content, and keeping better health status of shrimp. Based on these positive performances, P. rhodozyma Ast could gain the trust of the consumers as a natural source and provide a potential alternative for synthetic Ast using in the Penaeus monodon culture industry.

BackgroundHepatocellular carcinoma (HCC) and hepatic iflammatory pseudotumor (IPT) share similar symptoms and imaging features, which makes it challenging to distinguish from each other in clinical practice. This study aims to develop a predictive model based on contrast-enhanced ultrasound (CEUS) and clinical features to discriminate HCC from IPT.MethodsSixty-two IPT and 146 HCC patients were enrolled in this study, where pathological diagnosis served as the reference standard for diagnosis. Clinical and ultrasound imaging data including CEUS features: enhancement degree during arterial phase, portal phase and delayed phase, enhancement pattern, early washout within 60 s, feeding artery, peritumoral vessels, peritumoral enhancement, and margin of nonenhanced area were retrospectively collected. Imaging data were reviewed by two experienced ultrasound doctors. Patients were randomly assigned to training and validation sets. Chi-squared test followed by LASSO regression was performed on ultrasonographic features in the training set to identify the most valuable features that distinguish HCC from IPT, based on which the sonographic score formula was generated. With the significant clinical and ultrasonographic indicators, a nomogram was developed. The performance of the nomogram was verified by ROC curve and decision curve analysis (DCA) with the comparison with sonographic score and the ultrasound doctor’s diagnosis.ResultsThe most valuable ultrasonographic features that distinguish between HCC and IPT were enhancement degree during arterial phase, early washout, peritumoral vessels, peritumoral enhancement, and liver background. The sonographic score based on these features was verified to be an independent factor that predicts the diagnosis (p = 0.003). Among the clinical indicators, AFP (p = 0.009) and viral hepatitis infection (p = 0.004) were significant. Sonographic score, AFP, and viral hepatitis were used to construct a predictive nomogram. The AUC of the nomogram was 0.989 and 0.984 in training and validation sets, respectively, which were higher than those of sonographic score alone (0.938 and 0.958) or the ultrasound doctor’s diagnosis (0.794 and 0.832). DCA showed the nomogram provided the greatest clinical usefulness.ConclusionA predictive nomogram based on a sonographic signature improved the diagnostic performance in distinguishing HCC and IPT, which may help with individualized diagnosis and treatment in clinical practice.

Background: With the discovery of more and more drug–resistant bacterial strains, there is an urgent need for safer and more effective alternative treatments. In this study, antibacterial peptides and probiotic microcapsules were combined to treat gastrointestinal inflammation caused by Vibrio parahaemolyticus infection. Methods: To improve the stability of probiotics in the gastrointestinal tract, two types of mixed natural anionic polysaccharides and chitosan were used as carriers to embed the probiotics. Taking Lacticaseibacillus casei CGMCC1.8727 microcapsules with good performance as the research object, the in vitro characteristics of the microcapsules were studied via acid resistance test and intestinal release test. The microcapsules were then tested for in vivo treatment in combination with the antibacterial peptide, bomidin, and the therapeutic effects were compared among microencapsulated probiotics, free probiotics, and probiotics in combination with bomidin. Results: Microencapsulation was successfully manufactured under suitable processing parameters, with the product particle size being 2.04 ± 0.2743 mm. Compared with free probiotics, microencapsulation significantly improved the activity and preservation stability of the probiotics under simulated gastrointestinal conditions. Microencapsulated probiotics showed better therapeutic effects than free probiotics in vivo. Microcapsules combined with antimicrobial peptides accelerated the elimination of bacteria in vivo. This study provides a reference for anti–inflammatory treatment, especially for the treatment of gastrointestinal diseases.

BACKGROUND We aimed to examine the associations of voltage-dependent calcium-channel genes CACNA1A and CACNA1C with blood pressure (BP) changes and hypertension incidence in a longitudinal family study. METHODS A total of 1,768 Han Chinese participants from the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) follow-up study were eligible for the current study. Nine BP measurements were obtained at baseline and each follow-up visit using a random-zero sphygmomanometer. Mixed-effect models were used to assess additive associations of 176 tag single-nucleotide polymorphisms (SNPs) in CACNA1A and CACNA1C with longitudinal BP changes and hypertension incidence. The truncated product method was used for gene-based analysis. The Bonferroni correction was used for adjustment of multiple testing. RESULTS During an average of 7.2 years of follow-up, 512 (32.1%) participants developed hypertension. CACNA1A SNP rs8182538 was significantly associated with longitudinal diastolic BP (DBP) change after Bonferroni correction (Pinteraction = 9.90×10−5), with mean DBP increases of 0.85, 1.03, and 1.19mm Hg per year for participants with genotypes C/C, C/T, and T/T, respectively. A similar trend was observed for the association of rs8182538 with systolic BP (SBP) change. In the gene-based analysis, CACNA1A and CACNA1C were significantly associated with DBP change (P = 2.0×10−5) and SBP change (P = 1.4×10−4) after Bonferroni correction, respectively. The gene-based associations remained significant after removing rs8182538 within CACNA1A and rs758116 within CACNA1C in sensitivity analysis. CONCLUSIONS Our findings indicated that CACNA1A and CACNA1C might contribute to BP changes over time in Han Chinese population. Further replication of these findings is warranted. [ABSTRACT FROM AUTHOR]

Titanium dioxide nanoparticles (nano-TiO2) are widely used in consumer products. Nano-TiO2 dispersion could, however, interact with metals and modify their behavior and bioavailability in aquatic environments. In this study, we characterized and examined arsenate (As(V)) accumulation, distribution, and toxicity in Daphnia magna in the presence of nano-TiO2. Nano-TiO2 acts as a positive carrier, significantly facilitating D. magna's ability to uptake As(V). As nano-TiO2 concentrations increased from 2 to 20 mg-Ti/L, total As increased by a factor of 2.3 to 9.8 compared to the uptake from the dissolved phase. This is also supported by significant correlations between arsenic (As) and titanium (Ti) signal intensities at concentrations of 2.0 mg-Ti/L nano-TiO2 (R = 0.676, P < 0.01) and 20.0 mg-Ti/L nano-TiO2 (R = 0.776, P < 0.01), as determined by LA-ICP-MS. Even though As accumulation increased with increasing nano-TiO2 concentrations in D. magna, As(V) toxicity associated with nano-TiO2 exhibited a dual effect. Compared to the control, the increased As was mainly distributed in BDM (biologically detoxified metal), but Ti was mainly distributed in MSF (metal-sensitive fractions) with increasing nano-TiO2 levels. Differences in subcellular distribution demonstrated that adsorbed As(V) carried by nano-TiO2 could dissociate itself and be transported separately, which results in increased toxicity at higher nano-TiO2 concentrations. Decreased As(V) toxicity associated with lower nano-TiO2 concentrations results from unaffected As levels in MSFs (when compared to the control), where several As components continued to be adsorbed by nano-TiO2. Therefore, more attention should be paid to the potential influence of nano-TiO2 on bioavailability and toxicity of cocontaminants. [ABSTRACT FROM AUTHOR]

Abstract Background College life represents a key transitional period in the life of young adults that is marked by increased social engagement; living habits acquired during this period have implications on the future life of college students. Therefore, investigation of the determinants of health status of college students is a key imperative; however, there is limited evidence on the study of concomitant effects of physical activity (PA), sedentary time (ST), and sleep duration on the health-related quality of life (HRQOL) of college students. Methods This cross-sectional survey was conducted at a medical university in Shenyang in Northeast China in 2017. The study group comprised 926 undergraduate students. Data were collected by a self-administered questionnaire. PA, ST, sleep duration, and HRQOL were measured using the international physical activity questionnaire (IPAQ)-Long Form and the Chinese version of the 12-Item Short-Form Health Survey (SF-12). The association of PA, ST, and sleep duration with the HRQOL was examined using independent t-test, Pearson Chi-squared test, and multivariate linear regression analysis. Results After adjusting for potential confounding factors, students who reported high PA had significantly higher physical component summary (PCS) score in the total study population and among female students than those who reported low PA, whereas students who reported moderate PA had significantly higher PCS score only among female students (P

Fermentation is one of the most economical and safe methods to improve the nutritional value, sensory quality and functional characteristics of raw materials, and it is also an important method for cereal processing. This paper reviews the effects of microbial fermentation on cereals, focusing on their nutritional value and health benefits, including the effects of fermentation on the protein, starch, phenolic compounds contents, and other nutrient components of cereals. The bioactive compounds produced by fermented cereals have positive effects on health regulation. Finally, the future market development of fermented cereal products is summarized and prospected.

The human brain grows the most dramatically during the perinatal and early post-natal periods, during which pre-term birth or perinatal injury that may alter brain structure and lead to developmental anomalies. Thus, characterizing cortical thickness of developing brains remains an important goal. However, this task is often complicated by inaccurate cortical surface extraction due to small-size brains. Here, we propose a novel complex framework for the reconstruction of neonatal WM and pial surfaces, accounting for large partial volumes due to small-size brains. The proposed approach relies only on T1-weighted images unlike previous T2-weighted image-based approaches while only T1-weighted images are sometimes available under the different clinical/research setting. Deep neural networks are first introduced to the neonatal magnetic resonance imaging (MRI) pipeline to address the mis-segmentation of brain tissues. Furthermore, this pipeline enhances cortical boundary delineation using combined models of the cerebrospinal fluid (CSF)/GM boundary detection with edge gradient information and a new skeletonization of sulcal folding where no CSF voxels are seen due to the limited resolution. We also proposed a systematic evaluation using three independent datasets comprising 736 pre-term and 97 term neonates. Qualitative assessment for reconstructed cortical surfaces shows that 86.9% are rated as accurate across the three site datasets. In addition, our landmark-based evaluation shows that the mean displacement of the cortical surfaces from the true boundaries was less than a voxel size (0.532 ± 0.035 mm). Evaluating the proposed pipeline (namely NEOCIVET 2.0) shows the robustness and reproducibility across different sites and different age-groups. The mean cortical thickness measured positively correlated with post-menstrual age (PMA) at scan (p < 0.0001); Cingulate cortical areas grew the most rapidly whereas the inferior temporal cortex grew the least rapidly. The range of the cortical thickness measured was biologically congruent (1.3 mm at 28 weeks of PMA to 1.8 mm at term equivalent). Cortical thickness measured on T1 MRI using NEOCIVET 2.0 was compared with that on T2 using the established dHCP pipeline. It was difficult to conclude that either T1 or T2 imaging is more ideal to construct cortical surfaces. NEOCIVET 2.0 has been open to the public through CBRAIN (https://mcin-cnim.ca/technology/cbrain/), a web-based platform for processing brain imaging data.

In our previous in vitro study, we found that chlorogenic acid (CGA) inhibited adipocyte differentiation and triglyceride (TG) accumulation, but the underlying mechanism is still unclear. Accumulative genetic evidence supports that canonical Wnt signaling is a key modulator on adipogenesis. Methods. In this study, 3T3-L1 cells were induced adipogenic differentiation and then treated with CGA. We investigate the effect of CGA in inhibiting adipogenesis and evaluate its role in modulating Wnt10b (wingless integration1 10b), β-catenin, glycogen synthase kinase-3β (GSK-3β), and peroxisome proliferator-activated receptor γ (PPAR-γ) involved in the Wnt (wingless integration1)/β-catenin signaling pathway. Results. The result showed that after CGA treatment, lipid accumulation and TG level decreased significantly in 3T3-L1 cells, indicating that CGA could inhibit adipogenesis. In addition, CGA repressed the induction of adipocyte differentiation biomarkers as PPAR-γ, adipocyte protein 2 (aP2), fatty acid synthase (FAS), and lipoprotein lipase (LPL), and the secretion of GSK-3β in a dose-dependent manner upregulated the expression of β-catenin and Wnt10b both in gene and protein levels. Moreover, CGA induced phosphorylation of GSK-3β and promoted the accumulation of free cytosolic β-catenin in 3T3-L1 adipocytes. Conclusion. Overall, these findings gave us the implications that CGA inhibits adipogenesis via the canonical Wnt signaling pathway.

Recent studies have demonstrated structural and functional alterations in Parkinson’s disease (PD) with mild cognitive impairment (MCI). However, the topological patterns of functional brain networks in newly diagnosed PD patients with MCI are unclear so far. In this study, we used functional magnetic resonance imaging (fMRI) and graph theory approaches to explore the functional brain network in 45 PD patients with MCI (PD-MCI), 22 PD patients without MCI (PD-nMCI), and 18 healthy controls (HC). We found that the PD-MCI, PD-nMCI, and HC groups exhibited a small-world architecture in the functional brain network. However, early-stage PD-MCI patients had decreased clustering coefficient, increased characteristic path length, and changed nodal centrality in the default mode network (DMN), control network (CN), somatomotor network (SMN), and visual network (VN), which might contribute to factors for MCI symptoms in PD patients. Our results demonstrated that PD-MCI patients were associated with disrupted topological organization in the functional network, thus providing a topological network insight into the role of information exchange in the underlying development of MCI symptoms in PD patients.

As one of the abundant and inexpensive metals on the earth, copper has demonstrated broad applications in synthetic chemistry and catalysis. Among these copper-catalyzed advances, copper carbenes are versatile and reactive intermediates that can mediate a variety of transformations, which have attracted much attention in the past decades. The present review summarizes two different reaction models that take place between a copper carbene intermediate and alkyne species, including the cross-coupling reaction of copper carbene intermediate with terminal alkyne, and the addition of copper carbene intermediate onto the C–C triple bond. This article will cover the profile from 2010 to 2021 by placing emphasis on the detailed catalytic models and highlighting the synthetic applications offered by these practical and mild methods.

Advanced oxidation processes (AOPs) have become a favored approach in wastewater treatment due to the high efficiency and diverse catalyzed ways. Iron-based materials were the commonly used catalyst due to their environmental friendliness and sustainability in the environment. We collected the published papers relative to the application of the modified iron-based materials in AOPs between 1999 and 2020 to comprehensively understand the related mechanism of modified materials to improve the catalytic performance of iron-based materials in AOPs. Related data of iron-based materials, modification types, target pollutants, final removal efficiencies, and rate constants were extracted to reveal the critical process of improving the catalytic efficiency of iron-based materials in AOPs. Our results indicated that the modified materials through various mechanisms to enhance the catalytic performance of iron-based materials. The principal aim of iron-based materials modification in AOPs is to increase the content of available Fe2+ and enhance the stability of Fe2+ in the system. The available Fe2+ is elevated by the following mechanisms: (1) modified materials accelerate the electron transfer to promote the Fe3+/Fe2+ reaction cycle in the system; (2) modified materials form chelates with iron ions and bond with iron ions to avoid Fe3+ precipitation. We further analyzed the effect of different modifying materials in improving these two mechanisms. Combining the advantages of different modified materials to develop iron-based materials with composite modification methods can enhance the catalytic performance of iron-based materials in AOPs for further application in wastewater treatment.

Background: The CheckMate 227 trial has indicated that nivolumab plus ipilimumab compared with chemotherapy significantly increases long-term survival in the first-line setting of advanced non-small-cell lung cancer (NSCLC).Methods: A Markov model was built to estimate the cost and effectiveness of nivolumab plus ipilimumab vs. chemotherapy as the first-line therapy in patients with advanced NSCLC based on outcomes data from the CheckMate 227 trial. We calculated the cost and health outcomes at a willingness-to-pay (WTP) threshold of $150,000 per quality adjusted life year (QALY) in populations with different programmed death ligand 1 (PD-L1) expression levels (≥50, ≥1, and

Metabolic reprogramming is closely related to melanoma. However, the prognostic role of metabolism-related genes (MRGs) remains to be elucidated. We aimed to establish a nomogram by combining MRGs signature and clinicopathological factors to predict melanoma prognosis. Eighteen prognostic MRGs between melanoma and normal samples were identified using The Cancer Genome Atlas (TCGA) and GSE15605. WARS (HR = 0.881, 95% CI = 0.788–0.984, P = 0.025) and MGST1 (HR = 1.124, 95% CI = 1.007–1.255, P = 0.037) were ultimately identified as independent prognostic MRGs with LASSO regression and multivariate Cox regression. The MRGs signature was established according to these two genes and externally validated in the Gene Expression Omnibus (GEO) dataset. Kaplan-Meier survival analysis indicated that patients in the high-risk group had significantly poorer overall survival (OS) than those in the low-risk group. Furthermore, the MRGs signature was identified as an independent prognostic factor for melanoma survival. An MRGs nomogram based on the MRGs signature and clinicopathological factors was developed in TCGA cohort and validated in the GEO dataset. Calibration plots showed good consistency between the prediction of nomogram and actual observation. The receiver operating characteristic curve and decision curve analysis indicated that MRGs nomogram had better OS prediction and clinical net benefit than the stage system. To our knowledge, we are the first to develop a prognostic nomogram based on MRGs signature with better predictive power than the current staging system, which could assist individualized prognosis prediction and improve treatment.

Six previously undescribed ophiobolin-type sesterterpenes, namely, bipolatoxins A–F (1–6); and one previously undescribed pimarane-type diterpene, namely, 1β-hydroxy momilactone A (7); together with three known compounds, namely, 25-hydroxyophiobolin I (8), ophiobolin I (9), and ophiobolin A lactone (10); were isolated and identified from the endophytic fungus Bipolaris species TJ403-B1. Their structures with absolute configurations were elucidated on the basis of extensive spectroscopic analyses (including 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectroscopy data), single-crystal X-ray diffraction analyses, and comparison of experimental circular dichroism data. All compounds (except for 5) were evaluated for antimicrobial potential, which indicated that bipolatoxin D (4) showed significant inhibitory activity against Enterococcus faecalis with a minimum inhibitory concentration (MIC) value of 8 μg/mL, and ophiobolin A lactone (10) showed significant inhibitory activity against Acinetobacter baumannii and E. faecalis with MIC values of 8 and 8 μg/mL, respectively.

Objective This study investigated whether hypercapnia influenced the inflammatory response of hypoxic blood. Methods Human whole blood was cultured with 0.2% oxygen (O 2 ) and treated with 5%, 7%, or 10% carbon dioxide (CO 2 ). Interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 were evaluated in whole blood cultures. Reactive oxygen species (ROS) production and expression levels of caspase-1 and IL-1β were evaluated in THP-1 monocytic cells. Results IL-1β, TNF-α, and IL-6 levels were higher in the hypoxia + 7% CO 2 group than in the hypoxia + 5% CO 2 group. The hypoxia + 10% CO 2 group had the highest IL-1β, TNF-α, and IL-6 levels, compared with the hypoxia + 7% CO 2 and hypoxia + 5% CO 2 groups. Expression levels of IL-1β, TNF-α, and IL-6 were significantly negatively correlated with pH levels in the cell culture medium. Treatment with 7% and 10% CO 2 increased the production of ROS and the expression of caspase-1 and IL-1β in hypoxia-activated THP-1 cells. Conclusions High levels of CO 2 treatment increased expression levels of IL-1β, TNF-α, and IL-6 in hypoxic whole blood cultures. High levels of CO 2 -induced ROS overproduction and NLRP3 inflammasome activation in monocytes may comprise a target to mitigate the inflammatory response of hypoxic blood.

Abstract In bone implants, antibacterial biomaterials with nonleaching surfaces are superior to ones based on abrupt release because systemic side effects arising from the latter can be avoided. In this work, a nonleaching antibacterial concept is demonstrated by fabricating 2D nanoflakes in situ on magnesium (Mg). Different from the conventional antibacterial mechanisms that depend on Mg2+ release and pH increase, the nanoflakes exert mechanical tension onto the bacteria membranes to destroy microorganisms on contact and produce intracellular stress via physical interactions, which is also revealed by computational simulations. Moreover, the nanoflake layer decelerates the corrosion process resulting in mitigated Mg2+ release, weaker alkalinity in the vicinity, and less hydrogen evolution, in turn inducing less inflammatory reactions and ensuring the biocompatibility as confirmed by the in vivo study. In this way, bacteria are killed by a mechanical process causing very little side effects. This work provides information and insights pertaining to the design of multifunctional biomaterials.

Background/Aims: Liver damage is a typical manifestation of nonalcoholic fatty liver disease (NAFLD). It originates from excessive fat accumulation, leading to hepatocyte death, inflammation, and fibrosis. Nonalcoholic steatohepatitis (NASH) is a type of NAFLD with a prevalence of 49% in morbidly obese patients. Pyroptosis plays an important role in the development of NASH; thus, it is important to elucidate the effect of lipid accumulation on pyroptosis. Genipin (GNP), a natural water-soluble cross-linking agent, has hepatoprotective effects and decreases lipid accumulation in the liver; however, the mechanisms underlying these effects are unknown. Methods: In this study, qPCR and Western blot were used to examine pyroptotic gene expression in high-fat diet (HFD) induced obese mice and free fatty acids (FFAs) treated hepatocytes. At the same time, relative lactate dehydrogenase (LDH) release and Hoechst & propidium iodide (PI) staining were done to verify cell death. To explore the molecular mechanism, cell transfection were constructed with siRNA or plasmid to obtain knockdown or overexpression hepatocytes. Results: We found that HFD-fed mice and FFAs-treated hepatocytes had obvious pyroptosis, and addition of GNP reversed liver damage and inhibited pyroptosis both in vitro and in vivo. Besides, UCP2 knockdown cells showed suppressed FFAs-mediated pyroptosis, as determined by decreased pyroptotic gene expression, reduced lactate dehydrogenase (LDH) release, and reduced cell death. Consistent with this, cells transfected with UCP2 had upregulated pyroptotic gene expression, increased LDH release, and increased cell death. Conclusion: GNP reverses HFD-induced liver damage and inhibits UCP2-mediated pyroptosis. Thus, GNP may serve as a potential therapeutic candidate for NAFLD.

Based on network pharmacological analysis and molecular docking techniques, the main components of M. cordata for the treatment of bovine relevant active compounds in M. cordata were searched for through previous research bases and literature databases, and then screened to identify candidate compounds based on physicochemical properties, pharmacokinetic parameters, bioavailability, and drug-like criteria. Target genes associated with hoof disease were obtained from the GeneCards database. Compound−target, compound−target−pathway−disease visualization networks, and protein−protein interaction (PPI) networks were constructed by Cytoscape. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed in R language. Molecular docking analysis was done using AutoDockTools. The visual network analysis showed that four active compounds, sanguinarine, chelerythrine, allocryptopine and protopine, were associated with the 10 target genes/proteins (SRC, MAPK3, MTOR, ESR1, PIK3CA, BCL2L1, JAK2, GSK3B, MAPK1, and AR) obtained from the screen. The enrichment analysis indicated that the cAMP, PI3K-Akt, and ErbB signaling pathways may be key signaling pathways in network pharmacology. The molecular docking results showed that sanguinarine, chelerythrine, allocryptopine, and protopine bound well to MAPK3 and JAK2. A comprehensive bioinformatics-based network topology strategy and molecular docking study has elucidated the multi-component synergistic mechanism of action of M. cordata in the treatment of bovine hoof disease, offering the possibility of developing M. cordata as a new source of drugs for hoof disease treatment.

Bopu powder® and Sangrovit® were developed from Macleayacordata and are widely used in agriculture and animal husbandry, but their impurities have been rarely reported in the literature. Impurity analysis is of great importance to the quality and safety of veterinary drugs. In this study, high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS) combined with a screening method was used to screen and characterize the impurities in Bopu powder® and Sangrovit®. A total of 58 impurities were screened from Bopu powder® and Sangrovit® using the screening strategies, of which 39 were identified by their accurate m/z value, characteristic MS/MS data, and fragmentation pathways of references. This established method was used for impurity analysis for the first time and proved to be a useful and rapid tool to screen and identify the impurities of Bopu powder® and Sangrovit®, especially for those at trace levels in a complex sample. In addition, this study marks the first comprehensive research into impurities in these two products and has great significance for the systematic detection of impurities in other plant-derived drugs.

A novel network of spindle-like carbon nanofibers was fabricated via a simplified synthesis involving electrospinning followed by preoxidation in air and postcarbonization in Ar. Not only was the as-obtained carbon network comprised of beads of spindle-like nanofibers but the cubic MnO phase and N elements were successfully anchored into the amorphous carbon matrix. When directly used as a binder-free anode for lithium-ion batteries, the network showed excellent electrochemical performance with high capacity, good rate capacity and reliable cycling stability. Under a current density of 0.2 A g−1, it delivered a high reversible capacity of 875.5 mAh g−1 after 200 cycles and 1005.5 mAh g−1 after 250 cycles with a significant coulombic efficiency of 99.5%.

Using antibiotics as feed additives have been successively banned worldwide from 1986; therefore, it is an urgent task to finding safe and effective alternatives. As natural products of plant origin, essential oils (EOs) are an outstanding option due to their reported bioactivity. In this research, ten EOs of Labiatae species were extracted by steam distillation and its chemical constituents were identified by gas chromatography-mass spectrometry (GC-MS). A total of 123 chemical compounds, including alkenes, phenols, aldehydes and ketones, were identified. The results of antioxidant activity carried out through DPPH free radical scavenging (DPPH) and ferric reducing antioxidant power (FRAP), showing that EOs of Ocimum basilicum Linn. (ObEO), Thymus mongolicus Ronn. (TmEO), Origanum vulgare Linn. (OvEO) and Mosla chinensis Maxim. (McEO) have strong antioxidant activities. Their 50%-inhibitory concentration (IC50) value was Staphylococcus aureus (S. aureus) and their minimal inhibitory concentrations (MIC) value was 1 μL/mL, 2 μL/mL, and 2 μL/mL, respectively. In conclusion, the results in this work demonstrate the possibility for development and application of EOs as potential feed additives.

Agricultural infrastructure is a typical public good, and it plays an important role in rural development. The “participation of beneficiary groups (PBG)” system is encouraged by government to supply village level public goods in China. Based on micro survey data from the village level in Jiangsu Province, this study analyzes the status of agricultural infrastructure construction and the promotion of PBG model and quantitatively analyzes the impact of different factors using an econometric model. The results found that the PBG model of agricultural infrastructure construction only accounted for 22.8% of projects, and the bottleneck was the challenge in raising funds at the village level; the total number of projects and the number of projects in the PBG model significantly increased with collective irrigation, and the farmland lease was found to hinder the promotion of the PBG model. The government should take measures to enhance farmers’ awareness of social trust, continuously improve the governance capacity of the village collectives, improve the role of village self-governance and social forces in agricultural infrastructure construction, and actively guide farmers and private enterprises to participate in agricultural infrastructure construction so that farmers can obtain more practical benefits.

Colorectal cancer is often accompanied by multiple organ metastasis. Anaerobic Bifidobacterium Infantis (BI) bacterial can selectively grow in hypoxic colorectal tumor microenvironment (TME), to own the natural advantage of preferentially colorectal tumor targeting. Herein, a self-guidance biological hybrid drug delivery system (BI-ES-FeAlg/DOX) based on BI was constructed to inhibit the proliferation and metastasis of colon cancer. Results demonstrated that BI-ES-FeAlg/DOX could overcome physical barriers to target and accumulate in colon tumor tissues. Then DOX was released to kill tumor cells along with the phase transition (solid to liquid) of FeAlg hydrogel, due to Fe3+ was reduced to Fe 2 + by intracellular GSH. Meanwhile, BI-ES selectively colonized into tumors and expressed endostatin (ES) protein to down-regulate VEGF and bFGF expression, exerting anti-angiogenic effect. Moreover, FeAlg catalyzed H2O2 in the local tumor to generate cytotoxic ·OH, further enhancing the antitumor effect. The pharmacodynamic result in AOM/DSS model proved that BI-ES-FeAlg/DOX had the best therapeutic effect, with the final V/V0 of 2.19 ±0.57, which was significantly lower than the other groups. Meanwhile, on CT-26 tumor-bearing model, it also showed an outstanding anti-tumor effect with inhibition rate of 82.12% ± 3.08%. In addition, lung metastases decreased significantly in tumor metastasis model after BI-ES-FeAlg/DOX treatment. [ABSTRACT FROM AUTHOR]

Nine novel butenolide derivatives, including four pairs of enantiomers, named (±)-asperteretones A–D (1a/1b–4a/4b), and a racemate, named asperteretone E (5), were isolated and identified from the coral-associated fungus Aspergillus terreus. All the structures were established based on extensive spectroscopic analyses, including HRESIMS and NMR data. The chiral chromatography analyses allowed the separation of (±)-asperteretones A–D, whose absolute configurations were further confirmed by experimental and calculated electronic circular dichroism (ECD) analysis. Structurally, compounds 2–5 represented the first examples of prenylated γ-butenolides bearing 2-phenyl-3-benzyl-4H-furan-1-one motifs, and their crucial biogenetically related metabolite, compound 1, was uniquely defined by an unexpected cleavage of oxygen bridge between C-1 and C-4. Importantly, (±)-asperteretal D and (4S)-4-decarboxylflavipesolide C were revised to (±)-asperteretones B (2a/2b) and D (4), respectively. Additionally, compounds 1a/1b–4a/4b and 5 were evaluated for the α-glucosidase inhibitory activity, and all these compounds exhibited potent inhibitory potency against α-glucosidase, with IC50 values ranging from 15.7 ± 1.1 to 53.1 ± 1.4 μM, which was much lower than that of the positive control acarbose (IC50 = 154.7 ± 8.1 μM), endowing them as promising leading molecules for the discovery of new α-glucosidase inhibitors for type-2 diabetes mellitus treatment.

Considering the complexity and the criticality of the stacker equipment, in order to solve the problem that the stop accuracy of the stacker reduces or even fails to work due to abrasion of the running rail, this paper proposes a cooperative detection method based on Pulse Coupling Neural Network (PCNN) and wavelet transform theory to detect the abnormal points of the stacker running rail in industrial environment by analyzing the variation signals. First of all, considering the fact that the data is mixed up with noises because of the environment at the site and the possibility of the data acquisition equipment breaking down, a noise reduction method for the vibration signal data of stacker is constructed based on PCNN. Then, the basic theory of wavelet transform is introduced and then the rules of judging anomaly points on stackers’ running tracks are discussed based on wavelet transform. In addition, a cooperative detection method based on PCNN and wavelet transform theory is carried out based on the space-time distribution feature of the vibration of the stacker orbits in the industrial environment. Then the rationality of the proposed algorithm is verified by simulation through data provided by State Grid Measuring Center of China. This paper constructs a model of the abnormal point detection of the stackers in an industrial environment. The experimental simulation and example simulation show that the cooperative detection method based on PCNN and wavelet transform theory can effectively detect and locate the anomaly points of the stacker running tracks. The expansibility in engineering applications is promising. Lastly, some conclusions are discussed.

Corydalis Rhizoma, named YuanHu in China, is the dried tuber of Corydalis yanhusuo W.T. Wang which is used in Traditional Chinese Medicine for pain relief and blood activation. Previous pharmacological studies showed that apart from analgesics, the alkaloids from YuanHu may be useful in the therapy of depression by acting on the GABA, dopamine and benzodiazepine receptors. In this study, the antidepressive effect of the total alkaloid of YuanHu (YHTA) was investigated in a chronic unpredictable mild stress (CUMS) rat model using 1H-NMR-based metabonomics. Plasma metabolic profiles were analyzed and multivariate data analysis was applied to discover the metabolic biomarkers in CUMS rats. Thirteen biomarkers of CUMS-introduced depression were identified, which are myo-inositol, glycerol, glycine, creatine, glutamine, glutamate, β-glucose, α-glucose, acetoacetate, 3-hydroxybutyrate, leucine and unsaturated lipids (L7, L9). Moreover, a metabolic network of the potential biomarkers in plasma perturbed by CUMS was detected. After YHTA treatment, clear separation between the model group and YHTA-treated group was achieved. The levels of all the abnormal metabolites mentioned above showed a tendency of restoration to normal levels. The results demonstrated the therapeutic efficacy of YHTA against depression and suggested that NMR-based metabolomics can provide a simple and easy tool for the evaluation of herbal therapeutics.

OBJECTIVE:The prognostic significance of CD147 expression in esophageal cancer patients remains controversial. Using a meta-analysis, we investigated the prognostic and clinicopathologic characteristics of CD147 in esophageal cancer. METHODS:A comprehensive literature search of the PubMed (1966-2016), EMBASE (1980-2016), Cochrane Library (1996-2016), Web of Science (1945-2016), China National Knowledge Infrastructure (1982-2016), and Wanfang databases (1988-2016) was performed to identify studies of all esophageal cancer subtypes. Correlations between CD147 expression and survival outcomes and clinicopathological features were analyzed using meta-analysis methods. RESULTS:Seventeen studies were included. High CD147 expression reduced the 3-year survival rate (OR = 3.26, 95% CI = (1.53, 6.93), p = 0.02) and 5-year survival rate(OR = 4.35, 95% CI = (2.13, 8.90), p < 0.0001). High CD147 expression reduced overall survival in esophageal cancer (HR = 1.60, 95% CI = (1.19, 2.15), p = 0.02). Additionally, higher CD147 expression was detected in esophageal cancer tissues than noncancerous tissues (OR = 9.45, 95% CI = (5.39, 16.59), p < 0.00001), normal tissues (OR = 12.73, 95% CI = (3.49, 46.46), p = 0.0001), para-carcinoma tissues (OR = 12.80, 95% CI = (6.57, 24.92), p < 0.00001), and hyperplastic tissues (OR = 3.27, 95% CI = (1.47, 7.29), p = 0.004). CD147 expression was associated with TNM stage (OR = 3.66, 95% CI = (2.20, 6.09), p < 0.00001), tumor depth (OR = 7.97, 95% CI = (4.13, 15.38), p < 0.00001), and lymph node status (OR = 5.14, 95% CI = (2.03,13.01), p = 0.0005), but not with tumor differentiation, age, or sex. CONCLUSION:Our meta-analysis suggests that CD147 is an efficient prognostic factor in esophageal cancer. High CD147 expression in patients with esophageal cancer was associated with worse survival outcomes and common clinicopathological indicators of poor prognosis.

The effect of tropical cyclones on the turbulent flow over 2D continuous rolling hills was numerically investigated based on a field test analysis of the coastal region of Southeast China. A computational fluid dynamics (CFD) method was first developed and verified using previously published experimental results. Then two typical beneficial and destructive cyclone cases were studied above different locations of the hills. Results showed that the continuous hilly flow was much more drastic and variable than previously reported normal wind; the mean and turbulent magnitudes became the strongest around the hill top, with the maximum speed-up ratio, turbulence intensity and gust-speed ratio of 1.1, 0.32 and 1.6; the flow over lower hill was greatly affected by the nearby higher hills; the mean and fluctuating quantities were mostly smaller than the corresponding single hill case. These phenomena were considered to be related with the rather strong detachment and attachment of the cyclone flow around the two hills. In addition, the mean and fluctuating wind velocities were found to be underestimated by at least 20% if the widely accepted IEC standard equations were utilized, suggesting the necessity to supplement the field test analysis in the standard for more reasonable wind resource evaluation within the Southeast China coastal area.

Mycophenolic acid (MPA) is a potent inosine-5′-monophosphate dehydrogenase (IMPDH) inhibitor for immunosuppressive chemotherapy. Most importantly, as the 2-morpholinoethyl ester prodrug of MPA, mycophenolate mofetil (MMF) is a well-known immunosuppressant used to prevent rejection in organ transplantations. Nevertheless, due to its frequently occurred side effects, searching for new therapeutic agents is ongoing. In our current work, by virtue of efficient bioassay-guided fractionation and purification, eleven mycophenolic acid derivatives, including five previously unreported metabolites (3–7) and six known compounds (1, 2, and 8–11), were obtained from the coral-derived fungus Penicillium bialowiezense. Their structures were elucidated by means of extensive spectroscopic analyses (including 1D and 2D NMR and HRESIMS data) and comparison of the NMR and other physical data with those reported in the literature in the case of the known compounds. All the isolates 1–11 were evaluated for the immunosuppressive activity, and 1–3 showed potent IMPDH2 inhibitory potency with IC50 values of 0.84–0.95 μM, which were comparable to that of MPA (the positive control), while 4–10 showed significant inhibitory potency with IC50 values of 3.27–24.68 μM. All the MPA derivatives showed promising immunosuppressive activity, endowing them as potential drug leads for organ transplantations and autoimmune related diseases.

Patchouli ("Guanghuoxiang") or scientifically known as Pogostemon cablin Benth, belonging to the family Lamiaceae, has been used in traditional Chinse medicine (TCM) since the time of the Eastern Han dynasty. In TCM theory, patchouli can treat colds, nausea, fever, headache, and diarrhea. Various bioactive compounds have been identified in patchouli, including terpenoids, phytosterols, flavonoids, organic acids, lignins, glycosides, alcohols, pyrone, and aldehydes. Among the numerous compounds, patchouli alcohol, β-patchoulene, patchoulene epoxide, pogostone, and pachypodol are of great importance. The pharmacological impacts of these compounds include anti-peptic ulcer effect, antimicrobial effect, anti-oxidative effect, anti-inflammatory effect, effect on ischemia/reperfusion injury, analgesic effect, antitumor effect, antidiabetic effect, anti-hypertensive effect, immunoregulatory effect, and others.For this review, we examined publications from the previous five years collected from PubMed, Web of Science, Springer, and the Chinese National Knowledge Infrastructure databases. This review summarizes the recent progress in phytochemistry, pharmacology, and mechanisms of action and provides a reference for future studies focused on clinical applications of this important plant extract. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the association of neighborhood segregation and socioeconomic status (NSES) with cognitive functioning among older Chinese immigrants. Topics discussed include characteristics of the Population Study of Chinese Elderly (PINE) sample and stratification by Index of Concentrations at the Extremes (ICE) quartile, neighborhood-level language use, and statistical analysis.

A thermo-sensitive film composed of polycaprolactone and poly(N-isopropylacrylamide) was fabricated via electrospinning, with ketoconazole as the model drug. The morphology, elemental composition, and surface hydrophilicity of the nanofibres were characterized, and the results showed that nanofibres switched from a hydrophilic to a hydrophobic state as the temperature increased from 25 °C to 37 °C. The drug release profiles of the films suggested that sustained drug release behavior was achieved, and a lower temperature induced a faster delivery. Therefore, the prepared nanofibres could be highly applicable as wound dressings for on-demand and sustained drug release systems based on their temperature-responsive properties. [ABSTRACT FROM AUTHOR]

In this paper, a hydraulic fracturing operation in the tight gas reservoir LZN in the North Germany Basin was numerically investigated to find out the reason for the weak productivity after the fracturing operation. For the investigation, a self-developed numerical model was used, in which rock formation, pore and fracture systems are coupled together. The hydro-mechanical coupling effect, the proppant transport and settling as well as their influences on the fracture closure and contact were fully considered. In the numerical modeling of the in situ operation, the whole process of the data and the main fracturing including fracture propagation, closure, contact and proppant transport were simulated. The modeling was based on the history matching of the derived bottom hole pressure (BHP) from the measured treating pressure. According to the final placement of the proppant and the width distribution after 1500 min, it was found that the middle part of the fracture around the perforation was fully closed after shut in. It indicates that the operation is unsuccessful for the production enhancement; because the connection between the borehole and the created fracture is weak. If the perforation would have been set 15 m lower, then a successful operation with a better connectivity between the borehole and the propped fracture would have been achieved. The precondition to move down the perforation is that the lower fracture barrier must be thick and has a much higher minimum horizontal stress to prevent the fracture going through it. This requirement is also fulfilled in the case study. [ABSTRACT FROM AUTHOR]

Potentially inappropriate prescribing (PIP), including potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs), is a major risk factor for adverse drug reactions (ADRs). Establishing a risk warning model for PIP to screen high-risk patients and implementing targeted interventions would significantly reduce the occurrence of PIP and adverse drug events. Elderly patients with cardiovascular disease hospitalized at the Sichuan Provincial People's Hospital were included in the study. Information about PIP, PIM, and PPO was obtained by reviewing patient prescriptions according to the STOPP/START criteria (2nd edition). Data were divided into a training set and test set at a ratio of 8:2. Five sampling methods, three feature screening methods, and eighteen machine learning algorithms were used to handle data and establish risk warning models. A 10-fold cross-validation method was employed for internal validation in the training set, and the bootstrap method was used for external validation in the test set. The performances were assessed by area under the receiver operating characteristic curve (AUC), and the risk warning platform was developed based on the best models. The contributions of features were interpreted using SHapley Additive ExPlanation (SHAP). A total of 404 patients were included in the study (318 [78.7%] with PIP; 112 [27.7%] with PIM; and 273 [67.6%] with PPO). After data sampling and feature selection, 15 datasets were obtained and 270 risk warning models were built based on them to predict PIP, PPO, and PIM, respectively. External validation showed that the AUCs of the best model for PIP, PPO, and PIM were 0.8341, 0.7007, and 0.7061, respectively. The results suggested that angina, number of medications, number of diseases, and age were the key factors in the PIP risk warning model. The risk warning platform was established to predict PIP, PIM, and PPO, which has acceptable accuracy, prediction performance, and potential clinical application perspective., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xingwei, Huan, Mengting, Lv, Jiaying, Enwu, Jiuqun and Rongsheng.)

Objective: This study investigated the effects of hydroxyapatite (HA)/chitosan (CS)-transforming growth factor-β1 (TGF-β1) composite coatings on titanium surfaces, as well as on the attachment and proliferation of osteoblasts., Methods: HA/CS-TGF-β1 composite coatings were prepared on titanium surfaces by physical, chemical, and biological modifications. Scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FTIR), and other methods were employed to analyze the chemical composition and surface topography of the composite coatings. CCK-8 and immunofluorescence assays were used to analyze the effects of the coatings on the attachment and proliferation of osteoblasts., Results: HA/CS-TGF-β1 composite coatings were successfully prepared. Their contact angle was almost zero. These composite coatings were applied in vitro, with a drug released early and a burst release effect. The growth of osteoblasts was not inhibited on it and it had obvious promoting effect on the adhesion and early proliferation of osteoblasts., Conclusion: The composite coatings significantly promote the adhesion and early proliferation of osteoblasts in vitro. This finding shows that the proposed method demonstrates a good prospective application in surface modification of titanium.