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Objective To investigate the role of lncRNA SNHG1 in homocysteine-induced pyroptosis of podocyte. Methods Cbs*+ mice were randomly divided into two groups : a normal diet group (ND) and a high methionine diet group (HMD). Western blotting was used to detect the protein expression levels of Caspase-1, Cleaved Caspase-1, and NLRP3. Mouse renal glomerular podocytes were cultured in vitro, and then assigned into a control group (Control, 0 imol/L Hcy) and a homocysteine intervention group (Hcy, 80 imol/L Hcy). Western blotting was used to detect the protein expression levels of Caspase-1, Cleaved Caspase-1, and NLRP3. Mouse renal glomerular podocyion group (OE-NC + Hey) and the lncSNHGl overexpression + homocysteine intervention group (OE-SNHG1 + Hcy) were also established.After 48 hours of intervention, Real-time fluorescence quantitative PCR was used to detect the expression of lncSNHGl in podocytes after Hcy intervention. Western blot was used to detect the expressions of Caspase-1, Cleaved Caspase-3 and NLRP3. Immunofluorescence was used to detect the expression levels of GSDMD and GSDMD-N. ELISA was used to detect the contents of IL-1p and IL-18. Results (l)ln the animal experiments, the expression levels of pyroptosis-related proteins Caspase-1, Cleaved Caspase-1, NLRP3, GSDMD, and GSDMD-N were all increased in the HMD group compared with the ND group. (2) In the cellular experiments, the expression levels of Caspase-1, Cleaved Caspase-1, NLRP3, GSDMD, and GSDMD-N were all increased in the Hcy group compared with the Control group, and the contents of pyroptosis-mediated inflammatory factors IL-1p and IL-18 were increased as well. (3) In the cellular experiments, the expression of lncSNHG1 was increased in the Hcy group compared with the control group. After transduction with lnc-SNHG1 lentivirus, the expression of lncSNHG1 was increased in the OE-SNHG1 group, compared with the control group and the OE-NC group. ( 4) In the cellular experiments, the expressions of pyroptosis-related proteins Cas-pase-1, Cleaved Caspase-1, NLRP3, GSDMD, and GSDMD-N were increased compared with the OE-NC+Hcy group, and the contents of pyroptosis-mediated inflammatory factors IL-1p and IL-18 were increased in the OE-SNHG1+Hcy group. Conclusion These results indicate that lncSNHG1 may play a role in promoting Hcy induced podocytepyroptosis. [ABSTRACT FROM AUTHOR]

Sirtuins, which are NAD+-dependent class III histone deacetylases, are involved in various biological processes, including DNA damage repair, immune inflammation, oxidative stress, mitochondrial homeostasis, autophagy, and apoptosis. Sirtuins are essential regulators of cellular function and organismal health. Increasing evidence suggests that the development of age-related diseases, including kidney diseases, is associated with aberrant expression of sirtuins, and that regulation of sirtuins expression and activity can effectively improve kidney function and delay the progression of kidney disease. In this review, we summarise current studies highlighting the role of sirtuins in renal diseases. First, we discuss sirtuin family members and their main mechanisms of action. We then outline the possible roles of sirtuins in various cell types in kidney diseases. Finally, we summarise the compounds that activate or inhibit sirtuin activity and that consequently ameliorate renal diseases. In conclusion, targeted modulation of sirtuins is a potential therapeutic strategy for kidney diseases. -hdQDqtRY6tUdDXwmirmiR Video Abstract [ABSTRACT FROM AUTHOR]

Mosunetuzumab is a CD3/CD20 bispecific antibody. As an on‐target effect, transient elevation of interleukin‐6 (IL‐6) occurs in early treatment cycles. A physiologically‐based pharmacokinetic (PBPK) model was developed to assess potential drug interaction caused by IL‐6 enzyme suppression on cytochrome P450 3A (CYP3A) during mosunetuzumab treatment. The model's performance in predicting IL‐6 CYP3A suppression and subsequent drug–drug interactions (DDIs) was verified using existing clinical data of DDIs caused by chronic and transient IL‐6 elevation. Sensitivity analyses were performed for a complete DDI risk assessment. The IL‐6 concentration‐ and time‐dependent CYP3A suppression during mosunetuzumab treatment was simulated using PBPK model with incorporation of in vitro IL‐6 inhibition data. At clinically approved doses/regimens, the DDI at maximum CYP3A suppression was predicted to be a midazolam maximum drug concentration in plasma (Cmax) and area under the plasma drug concentration–time curve (AUC) ratio of 1.17 and 1.37, respectively. At the 95th percentile of IL‐6 concentration level or when gut CYP3A suppression was considered, the predicted DDI risk for mosunetuzumab remained low (<2‐fold). The PBPK‐based DDI predictions informed the mosunetuzumab product label to monitor, in early cycles, the concentrations and toxicities for sensitive CYP3A substrates with narrow therapeutic windows. [ABSTRACT FROM AUTHOR]

A two-dimensional implicit electrostatic particle-in-cell model is applied for the simulation of non-uniformly magnetized capacitively coupled plasmas. In the absence of a magnetic field, the plasma density is concentrated at the center of the reactor, under the studied parameters. This leads to the formation of a radial density gradient and subsequently generates a radial electric field that causes the deflection of incident ions toward the bottom electrode. Minimizing ion deflection is imperative in order to prevent detrimental effects on plasma processing. In pursuit of this objective, a static magnetic field is applied to the capacitively coupled plasmas by installing direct current coils on the upper section of the reactor. This arrangement has been observed to considerably alter the radial distributions of plasma density and the incident angle of ion bombardment on the bottom electrode. [ABSTRACT FROM AUTHOR]

The dried roots of the perennial herb Angelica sinensis (Oliv.) Diels (AS) are commonly used as medicinal and edible resources. In commercial planting, early bolting and flowering (EB) of ca. 60% in the medicine formation period reduces root yield and quality, becoming a significant bottleneck in agricultural production. In the cultivation process, summer bolting (SB) occurs from June to July, and autumn bolting (AB) occurs in September. The AB root is often mistaken for the AS root due to its similar morphological characteristics. Few studies have involved whether the root of AB could be used as herbal medicine. This study explored and compared the accumulation dynamics of primary and secondary metabolites in AS and EB roots during the vegetative growth stage (from May to September) by light microscopy, ultraviolet spectrometry, and HPLC methods. Under a microscope, the amount of free starch granules and oil chamber in the AS root increased. On the contrary, they decreased further from EB-Jul to EB-Sep. By comparison, the wall of the xylem vessel was slightly thickened and stacked, and the cell walls of parenchyma and root cortex tissue were thickened in the EB root. Early underground bolting reduces soluble sugar, soluble protein, free amino acids, total C element, total N element, ferulic acid, and ligustilide accumulation, accompanied by the lignification of the root during the vegetative growth stage. Furthermore, a total of 55 root samples from different bolting types of AS root (29 samples), SB root (14 samples), and AB root (12 samples) were collected from Gansu Province during the harvesting period (October). The later the bolting occurred, the less difference there was between unbolted and bolted roots in terms of morphological appearance and efficacy components. Fourier transform infrared spectroscopy with the attenuated total reflection mode (ATR-FTIR) provides a "holistic" spectroscopic fingerprinting of all compositions in the tested sample. The ATR-FTIR spectrum of the AB root was similar to that of the AS root. However, the number and location of absorption peaks in the spectra of SB were different, and only one strong absorption peak at 1021 cm−1 was regarded as the characteristic peak of C-O stretching vibration in lignin. The ATR-FTIR spectra can be effectively differentiated based on their various characteristics using orthogonal partial least squares discrimination analysis (OPLS-DA). Results were assessed using multiple statistical techniques, including Spearman's correlation, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and OPLS-DA. Among these methods, the ATR-FTIR data demonstrated the most effective outcomes in differentiating between viable and non-viable roots for their application in herbal medicine. Essential substances are ferulic acid and flavonoid, which are much more abundant in the AB root. It provides a material basis for the pharmacological action of the AB roots and a theoretical basis for improving their availability. [ABSTRACT FROM AUTHOR]

Egl-9 family hypoxia-inducible factor (egln), an oxygen-sensing enzyme family, has been thoroughly characterized in mammals and certain fishes, but there is few research on its involvement in reproductive development and hypoxic stress in rainbow trout. In this study, we investigated the gene structure, physicochemical properties, and evolutionary connection of the egln gene family. The expression profile of egln gene family and their regulatory mechanism were explored using bioinformatics analysis and hypoxia treatment experiments. Five egln genes were discovered in the rainbow trout genome in this investigation (egln1, egln2a, egln2b, egln3a, and egln3b). Domain prediction revealed that all egln proteins have p4hc conserved domains, and phylogenetic analysis revealed that rainbow trout egln2 and egln3 were closely related to Atlantic salmon. The results of real-time quantitative PCR (RT-qPCR) showed that egln genes were generally expressed in all detected tissues, and higher in the ovary, testis, and brain in normoxia. Under hypoxia, the expression level of eglns was significantly down-regulated in most tissues except the liver. Our research contributes to future research on the functional properties of egln genes, as well as the evolution of teleosts and the impact of hypoxia on biological immunity. [ABSTRACT FROM AUTHOR]

The quantitative prediction of human pharmacokinetics (PK) including the PK profile and key PK parameters are critical for early drug development decisions, successful phase I clinical trials, and the establishment of a range of doses to enable phase II clinical dose selection. Here, we describe an approach employing physiologically based pharmacokinetic (PBPK) modeling (Simcyp) to predict human PK and to validate its performance through retrospective analysis of 18 Genentech compounds for which clinical data are available. In short, physicochemical parameters and in vitro data for preclinical species were integrated using PBPK modeling to predict the in vivo PK observed in mouse, rat, dog, and cynomolgus monkey. Through this process, the in vitro to in vivo extrapolation (IVIVE) was determined and then incorporated into PBPK modeling in order to predict human PK. Overall, the prediction obtained using this PBPK‐IVIVE approach captured the observed human PK profiles of the compounds from the dataset well. The predicted Cmax was within 2‐fold of the observed Cmax for 94% of the compounds while the predicted area under the curve (AUC) was within 2‐fold of the observed AUC for 72% of the compounds. Additionally, important IVIVE trends were revealed through this investigation, including application of scaling factors determined from preclinical IVIVE to human PK prediction for each molecule. Based upon the analysis, this PBPK‐based approach now serves as a practical strategy for human PK prediction at the candidate selection stage at Genentech. [ABSTRACT FROM AUTHOR]

The surface charging effect of positive ions at the trench bottom during the etching of dielectric materials has become a severe problem with the shrinkage of electronic feature dimensions. Pulsed plasmas have been widely used to overcome surface charging issues during plasma etching in industry. In this work, synchronized dual-level radio frequency pulsed modulation on capacitively coupled plasmas is investigated based on 1D3V particle-in-cell/Monte Carlo collision simulations. It is found that the plasma always remains a certain initial density during the dual-level pulse modulation, as the high frequency (HF) source still presents during pulse off time (with a reduced voltage amplitude), which may facilitate high processing efficiency. Meanwhile, many HF sheath oscillations are simulated at the initial stage of a pulse period, which induces vast high energy electrons to strike the electrode. When the HF voltage is maintained at a very low value during the pulse off (i.e. 0.1 V HF ), more electrons with higher energy bombard the bottom of the trench, effectively alleviating the charging effect. Furthermore, the nonlinear behavior of sheath oscillations is proved to be very sensitive to dual-frequency voltage amplitudes and pulse ramp-up times. [ABSTRACT FROM AUTHOR]

The plant 14‐3‐3 proteins are essential for many biological processes and responses to abiotic stress. We performed genome‐wide identification and analysis of the 14‐3‐3 family genes in tomato. To explore the properties of the thirteen Sl14‐3‐3 found in the tomato genome, their chromosomal location, phylogenetic, and syntenic relationships were analyzed. The Sl14‐3‐3 promoters were found to have a number of growth‐, hormone‐, and stress‐responsive cis‐regulatory elements. Moreover, the qRT‐PCR assay revealed that Sl14‐3‐3 genes are responsive to heat and osmotic stress. Subcellular localization experiments evidenced that the SlTFT3/6/10 proteins occur in the nucleus and cytoplasm Additional analysis on Sl14‐3‐3 putative interactor proteins revealed a number of prospective clients that potentially participate in stress reactions and developmental processes. Furthermore, overexpression of an Sl14‐3‐3 family gene, SlTFT6, improved tomato plants thermotolerance. Taken together, the study provides basic information on tomato 14‐3‐3 family genes in plant growth and abiotic stress response (high temperature stress), which can be helpful to further study the underlying molecular mechanisms. [ABSTRACT FROM AUTHOR]

Predicting the brain penetration of drugs has been notoriously difficult; however, recently, permeability‐limited brain models have been constructed. Lead optimization for central nervous system compounds often focuses on compounds that have low transporter efflux, where passive permeability could be a main driver in determining cerebrospinal fluid (CSF)/brain concentrations. The main objective of this study was to evaluate the translatability of passive permeability data generated from different in vitro systems and its impact on the prediction of human CSF/brain concentrations using physiologically‐based pharmacokinetic (PBPK) modeling. In vitro data were generated using gMDCK and parallel artificial membrane permeability assay‐blood–brain barrier for comparison and predictions using a quantitative structure‐activity relationship model were also evaluated. PBPK modeling was then performed for seven compounds with moderate‐high permeability and a range of efflux in vitro, and the CSF/brain mass concentrations and Kpuu were reasonably predicted. This work provides the first step of a promising approach using bottom‐up PBPK modeling for CSF/brain penetration prediction to support lead optimization and clinical candidate selection. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of fructo-oligosaccharide (FOS) supplementation intake of Taiping chickens (Gallus gallus domesticus) and its stimulating effects on ileum. 120 healthy chickens were randomly divided into two groups; control group (CT) and fructo-oligosaccharides group (FOS). At the 60th day of age, ileum mucosa of three chickens per group were collected and performed transcriptome profiling of Taiping chicken ileum mucosa using the Hiseq™ 2500 sequencing platform. Compared with CT group, 50 genes were differentially expressed in the FOS group. Ten of the differently expressed genes were further validated by RT-qPCR. In addition, gene ontology and Kyoto encyclopedia of genes and genomes analyses revealed that these differentially expressed genes were mainly enriched to drug metabolism-cytochrome P450, metabolism of xenobiotics by cytochrome P450, retinol metabolism, fat digestion and absorption, herpes simplex infection and valine, leucine and isoleucine biosynthesis. The results of this study provided the help to our understanding application of fructo-oligosaccharides in indigenous chicken production and provide a theoretical basis for the genetic development of indigenous chickens. [ABSTRACT FROM AUTHOR]

Purpose: To explore perceptions of antipsychotics associated side-effects among family caregivers of patients with schizophrenia. Patients and Methods: A descriptive qualitative study was applied in a tertiary referral hospital in China. Purposeful sampling of 18 family caregivers of patients with schizophrenia were interviewed about their perceptions towards antipsychotics related side effects. Results: According to content analysis, three themes emerged from the data: (a) nightmare in the treatment with the categories of sleep disturbances; physical impairment; appearance impairment; (b) opposite attitudes toward side-effect with the categories of being vigilant; do not care; (c) diverse ways of coping side-effects with the categories of asking for help from professionals; self-determined; try any quack's prescription. Conclusion: The side effects of antipsychotics not only damage the health of patients, but also increase the burden and stress of caregivers. However, caregivers have different attitudes and coping styles about the side effects of antipsychotics. Health professionals should be aware of the influence of individual background and cultural factors on caregivers' attitudes towards drug side effects. Furthermore, health professionals should also provide caregivers with knowledge about drug side effects, coping skills, and appropriate management strategies to promote health outcomes for people with schizophrenia. [ABSTRACT FROM AUTHOR]

The characterization of structure of organic salts in complex mixtures has been a difficult problem in analytical chemistry. In the analysis of Scutellariae Radix (SR), the pharmacopoeia of many countries stipulates that the quality control component is baicalin (≥9% by high performance liquid chromatography (HPLC)). The component with highest response in SR was also baicalin detected by liquid chromatography-mass spectrometry (LC-MS). However, in the attenuated total reflection Fourier transform infrared spectroscopy, the carbonyl peak of glucuronic acid of baicalin did not appear in SR. The results of element analysis, time of flight secondary ion mass spectrometry, matrix assisted laser desorption ionization mass spectrometry and solid-state nuclear magnetic resonance all supported the existence of baicalin magnesium salt. Based on this, this study proposes an analysis strategy guided by infrared spectroscopy and combined with multi-spectroscopy techniques to analyze the structure of organic salt components in medicinal plant. It is meaningful for the research of mechanisms, development of new drugs, and quality control. [Display omitted] • Baicalin was verified to exist in the form of magnesium salt in Scutellaria Radix through multi-spectroscopic characterization. • Taken medicinal plant as an example, we propose an identification strategy for organic salts in complex mixture systems. • It is suggested that the structure elucidation can be comprehensively determined by FT-IR as a guide and combined with other techniques. • Nonseparation analysis methods are indispensable in the structural analysis of organic salts in medicinal plant. [ABSTRACT FROM AUTHOR]

Combination administration is becoming a popular strategy in current cancer immunotherapy to enhance tumor response to ICIs. Recently, a peptide drug, a protein–protein interaction inhibitor (PPI), that disrupts the β-catenin/Bcl9 interaction in the tumoral Wnt/β-catenin pathway has become a promising candidate drug for immune enhancement and tumor growth inhibition. However, the peptide usually suffers from poor cell membrane permeability and proteolytic degradation, limiting its adequate accumulation in tumors and ultimately leading to side effects. Herein, a gadolinium–gold-based core/shell nanostructure drug delivery system was established, where Bcl9 was incorporated into a gadolinium–gold core–shell nanostructure and formed GdOFBAu via mercaptogenic self-assembly. After construction, GdOFBAu, when combined with anti-PD1 antibodies, could effectively inhibit tumor growth and enhance the response to immune therapy in MC38 tumor-bearing mice; it not only induced the apoptosis of cancer cells, but also promoted the tumor infiltration of Teff cells (CD8+) and decreased Treg cells (CD25+). More importantly, GdOFBAu maintained good biosafety and biocompatibility during treatment. Taken together, this study may offer a promising opportunity for sensitizing cancer immunotherapy via metal–peptide self-assembling nanostructured material with high effectiveness and safety. [ABSTRACT FROM AUTHOR]

In this study, we explore the subtle temporal structure of environmental data using symbolic information-theory approach. The newly developed multivariate multiscale permutation entropy and complexity-entropy causality plane methodology are applied to the six pollutants data recorded in Beijing during 2013–2016, which is a powerful tool to discriminate nonlinear deterministic and stochastic dynamics. The obtained results showed that pollutant series exhibit significant randomness and a lower level of predictability in spring and summer, and more temporal correlations in winter and fall. In addition, surrogate analysis is implemented to avoid biased conclusion. We also define the relative complexity measure of multivariate series to reflect the complexity of a system. The highest relative complexity in winter is in line with the physical behavior of the pollution phenomenon. [ABSTRACT FROM AUTHOR]

Objective. To explore the changes of entropy index and cerebral oxygen metabolism in the maintenance of remifentanil anesthesia and the predictive value of postoperative hyperalgesia. Methods. A total of 266 patients undergoing general anesthesia in our hospital from January 2020 to October 2021 were selected, and remifentanil was used to maintain anesthesia. The state entropy, reaction entropy, and cerebral oxygen metabolism indexes (cerebral oxygen uptake rate (CERO2), arterial-venous blood oxygen difference (Da-jvO2)) of patients before induction of anesthesia, 15 minutes during the operation, and at the end of the operation were compared. The influencing factors of postoperative hyperalgesia were analyzed. The logistic regression model of postoperative hyperalgesia was established, and the value of entropy index and cerebral oxygen metabolism in predicting postoperative hyperalgesia was evaluated by drawing the receiver operating characteristic curve (ROC). Results. The state entropy, response entropy, and CERO2 at 30 min during the operation and at the end of the operation were lower than those before the induction of anesthesia, and Da-jvO2 was higher than that before the induction of anesthesia (P < 0.001). At the end of the operation, the state entropy, reaction entropy, and CERO2 were higher than 30 minutes during the operation, and Da-jvO2 was lower than 30 minutes during the operation (P < 0.001). The dosage of remifentanil, reaction entropy, and CERO2 at the end of the operation entered the logistic model. The AUC value of the reaction entropy and CERO2 combined to predict postoperative hyperalgesia at the end of the operation was 0.851 greater than the reaction entropy at the end of the operation ( χ 2 = 3.847 , P = 0.036), CERO2 ( χ 2 = 2.589 , P = 0.010) single index predictive value. Conclusion. The entropy index and cerebral oxygen metabolism in general anesthesia patients change with the progress and discontinuation of remifentanil maintenance anesthesia, and the combination of the two has a high predictive power in postoperative hyperalgesia risk assessment. When the reaction entropy > 54.23 , CER O 2 > 34.14 % , or the total dosage of remifentanil ≥ 30 μ g / kg at the end of the operation, we should be highly vigilant of the occurrence of postoperative hyperalgesia and postoperative analgesia management should be strengthened. [ABSTRACT FROM AUTHOR]

Aim: The metabolic markers and differentially expressed genes (DEGs) related to fructo‐oligosaccharide (FOS) were screened, and the response of FOS to the ileum metabolic pathway of Taiping chickens was analysed. Methods and Results: Prebiotic are widely used in agricultural breeding for care and maintenance of animal health, especially FOS. Metabonomics evaluation of ileum of Taiping chicken ultra‐performance liquid chromatography‐quadruple time of‐flight high‐sensitivity mass spectrometry showed that 93 differentially altered metabolites were identified and divided into eight categories, of which organic acids and derivatives was the most important one. Transcriptomic analysis showed that DEGs were mainly enriched in drug metabolism‐cytochrome p450, metabolism of xenobiotics by cytochrome p450, retinol metabolism and fat digestion and absorption. Integrated analysis of metabolite profiles and gene expression revealed that the significantly up‐regulated GSTT1 was significantly correlated with most of the different lipid metabolites, suggesting that GSTT1 may play an important role in FOS regulation of lipid metabolism. Conclusions: The results of this study suggest that supplementation of FOS can have a positive effect on gut metabolites, which may contribute to the overall health with indigenous chickens. Significance and Impact of the Study: Insight into the responses of intestinal prebiotics of Taiping chicken is helpful to understand the role of prebiotics in maintaining intestinal microflora balance and improving immune response and productivity of poultry from the molecular and metabolic levels. [ABSTRACT FROM AUTHOR]

With the continuous advancement in bearing speed, bearing assembly clearance (pocket, radial, and guide clearances) has a particularly significant impact on dynamic characteristics of bearing. In order to improve its performance, it is necessary to generate an optimized design for assembly clearance based on dynamic analysis. In this paper, a dynamic model of cylindrical roller bearing has been put forth based on the variable step fourth-order Runge–Kutta method, while the simulation results have been verified by a high-speed bearing cage motion testing machine. Considering pocket, radial, and guide clearances as independent variables and maximum impact force, whirl deviation ratio, and minimum power loss as the objectives, a multiobjective optimized model of cylindrical roller bearing has been developed using central composite experimental design (CCD) and response surface method. After optimization, the maximum impact force was reduced by 9.26%, the whirl deviation ratio was reduced by 2.87%, and power loss was reduced by 1.45%. [ABSTRACT FROM AUTHOR]

Heat shock proteins (Hsps) are highly conserved proteins whose expression can be induced by high temperature and play an important role in a variety of biological processes. However, systematic identification of the Hsp60/10 and small Hsp (sHsp) gene family in rainbow trout has not yet been reported, and there is little available information about its roles in evolution in rainbow trout, a typical economical cold-water fish. In this study, we performed a comprehensive analysis of the rainbow trout Hsp60/10 and sHsp gene family and to investigate their expression profiles. A total of one Hsp60 gene, one Hsp10 gene, and ten sHsp genes were identified. According to RNA-seq analysis of rainbow trout liver and head kidney under heat stress, a total of six out of ten sHsp genes were significantly upregulated in liver and head kidney. Real-time RT-PCR (RT-qPCR) was used to quantitatively analyze the expression levels of these genes in different tissues of rainbow trout. Results showed that the expression of hspe1 and hspd1 was lowest in liver and gill, respectively, and highest in brain. In sHsp gene family, all genes are highly expressed in the liver and head kidney, but relatively low in the heart, spleen, brain, gills, and muscles. This systematic analysis provided valuable information about the diverse roles of Hsp60/10 and sHsp in the evolution of teleost fish, which will contribute to the functional characterization of Hsp60/10 and sHsp genes in further research. [ABSTRACT FROM AUTHOR]

Background: Aberrant DNA methylation may offer opportunities in revolutionizing cancer screening and diagnosis. We sought to identify a non-invasive DNA methylation-based screening approach using cell-free DNA (cfDNA) for early detection of hepatocellular carcinoma (HCC).Methods: Differentially, DNA methylation blocks were determined by comparing methylation profiles of biopsy-proven HCC, liver cirrhosis, and normal tissue samples with high throughput DNA bisulfite sequencing. A multi-layer HCC screening model was subsequently constructed based on tissue-derived differentially methylated blocks (DMBs). This model was tested in a cohort consisting of 120 HCC, 92 liver cirrhotic, and 290 healthy plasma samples including 65 hepatitis B surface antigen-seropositive (HBsAg+) samples, independently validated in a cohort consisting of 67 HCC, 111 liver cirrhotic, and 242 healthy plasma samples including 56 HBsAg+ samples.Results: Based on methylation profiling of tissue samples, 2321 DMBs were identified, which were subsequently used to construct a cfDNA-based HCC screening model, achieved a sensitivity of 86% and specificity of 98% in the training cohort and a sensitivity of 84% and specificity of 96% in the independent validation cohort. This model obtained a sensitivity of 76% in 37 early-stage HCC (Barcelona clinical liver cancer [BCLC] stage 0-A) patients. The screening model can effectively discriminate HCC patients from non-HCC controls, including liver cirrhotic patients, asymptomatic HBsAg+ and healthy individuals, achieving an AUC of 0.957(95% CI 0.939-0.975), whereas serum α-fetoprotein (AFP) only achieved an AUC of 0.803 (95% CI 0.758-0.847). Besides detecting patients with early-stage HCC from non-HCC controls, this model showed high capacity for distinguishing early-stage HCC from a high risk population (AUC=0.934; 95% CI 0.905-0.963), also significantly outperforming AFP. Furthermore, our model also showed superior performance in distinguishing HCC with normal AFP (< 20ng ml-1) from high risk population (AUC=0.93; 95% CI 0.892-0.969).Conclusions: We have developed a sensitive blood-based non-invasive HCC screening model which can effectively distinguish early-stage HCC patients from high risk population and demonstrated its performance through an independent validation cohort.Trial Registration: The study was approved by the ethic committee of The Second Xiangya Hospital of Central South University (KYLL2018072) and Chongqing University Cancer Hospital (2019167). The study is registered at ClinicalTrials.gov(# NCT04383353 ). [ABSTRACT FROM AUTHOR]

Background: Aberrant DNA methylation may offer opportunities in revolutionizing cancer screening and diagnosis. We sought to identify a non-invasive DNA methylation-based screening approach using cell-free DNA (cfDNA) for early detection of hepatocellular carcinoma (HCC). Methods: Differentially, DNA methylation blocks were determined by comparing methylation profiles of biopsy-proven HCC, liver cirrhosis, and normal tissue samples with high throughput DNA bisulfite sequencing. A multi-layer HCC screening model was subsequently constructed based on tissue-derived differentially methylated blocks (DMBs). This model was tested in a cohort consisting of 120 HCC, 92 liver cirrhotic, and 290 healthy plasma samples including 65 hepatitis B surface antigen-seropositive (HBsAg+) samples, independently validated in a cohort consisting of 67 HCC, 111 liver cirrhotic, and 242 healthy plasma samples including 56 HBsAg+ samples. Results: Based on methylation profiling of tissue samples, 2321 DMBs were identified, which were subsequently used to construct a cfDNA-based HCC screening model, achieved a sensitivity of 86% and specificity of 98% in the training cohort and a sensitivity of 84% and specificity of 96% in the independent validation cohort. This model obtained a sensitivity of 76% in 37 early-stage HCC (Barcelona clinical liver cancer [BCLC] stage 0-A) patients. The screening model can effectively discriminate HCC patients from non-HCC controls, including liver cirrhotic patients, asymptomatic HBsAg+ and healthy individuals, achieving an AUC of 0.957(95% CI 0.939–0.975), whereas serum α-fetoprotein (AFP) only achieved an AUC of 0.803 (95% CI 0.758–0.847). Besides detecting patients with early-stage HCC from non-HCC controls, this model showed high capacity for distinguishing early-stage HCC from a high risk population (AUC=0.934; 95% CI 0.905–0.963), also significantly outperforming AFP. Furthermore, our model also showed superior performance in distinguishing HCC with normal AFP (< 20ng ml−1) from high risk population (AUC=0.93; 95% CI 0.892–0.969). Conclusions: We have developed a sensitive blood-based non-invasive HCC screening model which can effectively distinguish early-stage HCC patients from high risk population and demonstrated its performance through an independent validation cohort. Trial registration: The study was approved by the ethic committee of The Second Xiangya Hospital of Central South University (KYLL2018072) and Chongqing University Cancer Hospital (2019167). The study is registered at ClinicalTrials.gov(#NCT04383353). [ABSTRACT FROM AUTHOR]

Atherosclerosis is a serious age‐related disease, which has a tremendous impact on health care globally. Macrophage inflammation is crucial for the initiation and progression of atherosclerosis, and microRNAs (miRNAs) recently have emerged as potent modulators of inflammation, while the underlying mechanisms of its involvement in homocysteine (Hcy)‐mediated macrophage inflammation of atherosclerosis remain largely unknown. Here, we demonstrated that elevated Hcy inhibits the expression of miR‐195‐3p, which in turn enhances IL‐31 expression and thereby causes the secretion of macrophages pro‐inflammatory factors IL‐1β, IL‐6 and TNF‐α and accelerate atherosclerosis. Furthermore, we identified that Hcy can induce DNA hypermethylation and H3K9 deacetylation of miR‐195‐3p promoter due to the increased the binding of DNMT3a and HDAC11 at its promoter. More importantly, Sp1 interacts with DNMT3a suppressed the binding of HDAC11 at miR‐195‐3p promoter and promoted its transcription. In summary, our results revealed a novel mechanism that transcriptional and epigenetic regulation of miR‐195‐3p inhibits macrophage inflammation through targeting IL‐31, which provides a candidate diagnostic marker and novel therapeutic target in cardiovascular diseases induced by Hcy. [ABSTRACT FROM AUTHOR]

[Display omitted] • Excessive intake of salt is associated with several negative health effects. • The use of natural substances to replace salt in food is a growing trend. • Reduced salt in processed meat products affects quality and shelf life. • Umami substances can lower NaCl in meat products without quality loss. • Natural umami substances can increase the water-holding capacity and reduce lipid oxidation of meat products. Sodium is one of the essential additives in meat processing, but excessive sodium intake may increase risk of hypertension and cardiovascular disease. However, reducing salt content while preserving its preservative effect, organoleptic properties, and technological characteristics poses challenges. In this review, the mechanism of salt reduction of umami substances was introduced from the perspective of gustation-taste interaction, and the effects of the addition of traditional umami substances (amino acids, nucleotides, organic acids(OAs)) and natural umami ingredients (mushrooms, seaweeds, tomatoes, soybeans, tea, grains) on the sensory properties of the meat with reduced-salt contents were summarized. In addition, the impacts of taste enhancers on eating quality (color, sensory, textural characteristics, and water-holding capacity (WHC)), and processing quality (lipid oxidation, pH) of meat products (MP) and their related mechanisms were also discussed. Among them, natural umami ingredients exhibit distinct advantages over traditional umami substances in terms of enhancing quality and nutritional value. On the basis of salt reduction, natural umami ingredients improve the flavor, texture, WHC and antioxidant capacity. This comprehensive review may provide the food industry with a theoretical foundation for mitigating salt consumption through the utilization of umami substances and natural ingredients. [ABSTRACT FROM AUTHOR]

[Display omitted] • We prepared sodium ligninsulfonate derived CDs via solvent-free reaction method. • The CDs show excellent fluorescent response to FA with a LOD of 79 nM. • The CDs exhibit color change under sunlight and UV light in the detection of FA. • A droplet detection system is developed for indoor actual detection of FA gas. • The device achieves on-site, convenient and visual detection of indoor FA gas. Formaldehyde (FA), as a widespread toxic pollutant in cars, furniture and construction materials, has been implicated in hazardous health effects on the human body. This paper presents a green and large-scale preparation of carbon dots (CDs) using sodium ligninsulfonate and o-phenylenediamine through a solvent-free reaction method. The prepared CDs exhibit a synthetic yield of 43 % and show green fluorescence. In addition, the CDs can be employed as an ideal fluorescent FA probe, exhibiting excellent linearity within the range of 0–50 μM (R2 = 0.998, limit of detection (LOD) = 79 nM). By taking advantage of the obvious color changes in detection, the droplet detection system is investigated for on-site visual detection of indoor FA gas. This work not only contributes to the efficient utilization of agricultural waste but also represents a significant process in the development of FA on-site detection. [ABSTRACT FROM AUTHOR]

• Zygotic quiescence prolongation is the main reason for the long reproductive cycle of Berchemia. sinica. • The young fruits of Berchemia. sinica entered dormancy in the form of "overwintering complex", and it is the result of convergent evolution. • Androdioecy in Berchemia is reported for the first time. More than two-thirds of the species in Berchemia exhibit remarkable reproductive phenology, characterized by prolonged fruit ripening and the occurrence of overlapping fruit ripening and flowering. However, the underlying reasons for these phenomena remain unknown. Therefore, this study employed routine paraffin section technology, histochemical technique and scanning electron microscopy to investigate embryo sac development, differences between male and hermaphroditic flowers, as well as the overwintering strategy in Berchemia sinica. The findings of this study revealed a significant reduction in pollen viability and the number of pollen grains per flower in hermaphroditic compared to male flowers. Following fertilization, the ovary of hermaphroditic flowers does not undergo significant enlargement but gradually enters the state of zygotic quiescence. Zygotic quiescence prolongation is the main reason for the long reproductive cycle of B. sinica , and it takes approximately 14 months for the entire cycle from flower bud differentiation to fruit ripening to complete. Long reproductive cycle and complex overwintering mechanism exhibited by B. sinica resemble those seen in species belonging to Betulaceae, Fagaceae, Tapisciaceae, and Theaceae, suggesting convergent evolution during Earth's glacial period resulted in similar adaptive structures among these groups delayed fruit ripening leads to overlap between current year's flowers with previous year's fruits. The trade-off between flower and fruit for reproductive resources may have driven evolutionary transition from ancestral hermaphroditism towards androdioecy in Berchemia. [ABSTRACT FROM AUTHOR]

This paper took the bar space in Hongling area of Shenzhen as the research object, analyzed the relationship between the distribution of bars and urban commercial buildings, traffi c stations, residential areas, hotels and guesthouses. It also analyzed the impact of bars on urban residents in terms of noise, crime and traffi c congestion. The study found that the location of bars was closely related to urban commercial centers, traffi c stations, residential areas, hotels and guesthouses, the occurrence of noise and criminal cases was also highly related to bars; and the distribution of bars had an impact on traffi c congestion to a certain extent. [ABSTRACT FROM AUTHOR]

The connectivity of a graph is the minimum number of nodes, whose removal will cause the graph disconnected. It is one of the basic and important properties of the graph, and can be used as a metric of the graph's robustness. Since the connectivity of a graph is upper-bounded by its minimal node-degree, which can be small, the notion of conditional connectivity has been proposed in the past to more realistically reflect a graph's robustness. The extra connectivity is such a conditional connectivity. In this paper, we introduce a new approach to finding the extra connectivity of the hypercube , a well-known regular graph model for networks of parallel computers. We will show that the results on the isoperimetric inequalities for hypercubes can be used to obtain their extra connectivity. That is, using isoperimetric inequalities, for an n -dimensional hypercube Q n with n ≥ 5 , the h -extra connectivity is equal to its minimum (h + 1) -vertex boundary number for 1 ≤ h ≤ n − 4 and n + 1 ≤ h ≤ 2 n − 4. For n − 3 ≤ h ≤ n , the h -extra connectivity of hypercube equals its minimum (n − 2) -vertex boundary number. The paper's result for the first time establishes a relationship between the isoperimetric inequalities and the extra connectivity of graphs. [ABSTRACT FROM AUTHOR]

Background: Preoperative visit-care for transcatheter aortic valve replacement (TAVR) plays a crucial role in improving the quality of care and patient safety. However, preoperative care for TAVR patients is still in its early stages in China, with the care often being experience-based. The application of relevant evidence in nursing practice is necessary. Little is known regarding the facilitators and barriers to apply and compliance to the evidences about preoperative visit-care for TAVR in nursing. Methods: The Nurse's Compliance Checklist was used to investigate the evidence-based compliance of nurses (n = 21) who worked in the TAVR team in the evidence-based implementation setting. Meanwhile, an Evidence-Based Practice Beliefs Scale, and Influencing Factors Checklist were used to investigate all nurses (n = 66) who work in the same setting. Stakeholders (Middle and senior-level nursing administrators, frontline clinical nurses, and patients) interview was carried out to further disclose the barriers and facilitators in the process of evidence-based practice. Results: The results of this study showed that only 1 evidence implemented fully (100%) by nurses, 3 evidences with 0% implementation rate, and implementation rate of the other evidences were 9.5∼71.4%. The overall score of nurses' evidence-based nursing belief level was (3.52 ± 0.82). Three domains of barriers were identified: the Context Domain included lack of nursing procedures, inadequate health education materials, insufficient training; the Practitioner Domain included insufficient attention, lack of relevant knowledge, high work pressure and uncertainty of expected results, and Patient Domain included lack of relational knowledge. Facilitating factors included leadership support, nurse' high evidence-based nursing belief, high executive ability and enthusiasm for learning. Conclusion: The study indicated that the nurses' compliance of evidence-based practice in preoperative visit-care for TAVR was in lower level. There were some factors influencing the application of the evidences. The study revealed potential modifiable barriers to the successful implementation of evidence-based preoperative visit-care, including a lack of preoperative visit- care routine, related knowledge and training. Leadership support and nurse training should be considered to improve nurses' compliance with evidence-based practice. [ABSTRACT FROM AUTHOR]

Studies indicate that the lysine‐specific demethylase 4A (KDM4A), acts as a key player in neuropathic pain, driving the process through its involvement in promoting neuroinflammation. Emerging evidence reveals that C‐C Motif Chemokine Ligand 2 (CCL2) participates in neuroinflammation, which plays an important role in the development and maintenance of neuropathic pain. However, it remains unclear if KDM4A plays a role in regulating CCL2 in neuropathic pain. This study found that following spinal nerve transection (SNT) of the lumbar 5 nerve root in rats, the expression of KDM4A and CCL2 increased in the ipsilateral L4/5 dorsal root ganglia (DRG). Injecting KDM4A siRNA into the DRGs of rats post‐SNT resulted in a higher paw withdrawal threshold (PWT) and paw‐withdrawal latency (PWL) compared to the KDM4A scRNA group. In addition, prior microinjection of AAV‐EGFP‐KDM4A shRNA also alleviates the decrease in PWT and PWL caused by SNT. Correspondingly, microinjection of AAV‐EGFP‐KDM4A shRNA subsequent to SNT reduced the established mechanical and thermal hyperalgesia. Furthermore, AAV‐EGFP‐KDM4A shRNA injection decreased the expression of CCL2 in DRGs. ChIP‐PCR analysis revealed that increased binding of p‐STAT1 with the CCL2 promoter induced by SNT was inhibited by AAV‐EGFP‐KDM4A shRNA treatment. These findings suggest that KDM4A potentially influences neuropathic pain by regulating CCL2 expression in DRGs. [ABSTRACT FROM AUTHOR]

Dynamic in vitro absorption systems and mechanistic absorption modeling via PBPK have both shown promise in predicting human oral absorption, although these efforts have been largely separate; this work aimed to integrate knowledge from these approaches to investigate the oral absorption of a RET inhibitor, pralsetinib, with BCS Class II properties. Tiny-TIM (TIM B.V., Weteringbrug​, The Netherlands) is a dynamic in vitro model with close simulation of the successive physiological conditions of the human stomach and small intestine. Tiny-TIM runs with pralsetinib were performed at doses of 200 mg and 400 mg under fasting conditions. Mechanistic modeling of absorption was performed in Simcyp V21 (Certara, Manchester, UK). Pralsetinib fasted bioaccessibility in the Tiny-TIM system was 63% at 200 mg and 53% at 400 mg; a 16% reduction at 400 mg was observed under elevated gastric pH. Maximum pralsetinib solubility from the small intestinal compartment in Tiny-TIM directly informed the supersaturation/precipitation model parameters. The PBPK model predicted a similar fraction absorbed at 200 mg and 400 mg, consistent with the dose proportional increases in observed pralsetinib exposure. Integrating dynamic in vitro systems with mechanistic absorption modeling provides a promising approach for understanding and predicting human absorption with challenging low solubility compounds. [ABSTRACT FROM AUTHOR]

Physiologically‐based pharmacokinetic (PBPK) modeling is increasingly used to predict drug disposition and drug–drug interactions (DDIs). However, accurately predicting the pharmacokinetics of transporter substrates and transporter‐mediated DDIs (tDDIs) is still challenging. Rosuvastatin is a commonly used substrate probe in DDI risk assessment for new molecular entities (NMEs) that are potential organic anion transporting polypeptide 1B or breast cancer resistance protein transporter inhibitors, and as such, several rosuvastatin PBPK models have been developed to try to predict the clinical DDI and support NME drug labeling. In this review, we examine five representative PBPK rosuvastatin models, discuss common challenges that the models have come across, and note remaining gaps. These shared learnings will help with the continuing efforts of rosuvastatin model validation, provide more information to understand transporter‐mediated drug disposition, and increase confidence in tDDI prediction. [ABSTRACT FROM AUTHOR]

Background: Non-small cell lung cancer (NSCLC) remains a huge health burden for human health and life worldwide. Our study here was to illuminate the relevance of microRNA-130a-5p (miR-130a-5p) on growth and epithelial mesenchymal transition (EMT) in NSCLC cells along with metastasis in vivo, and to explore the underlying mechanism.Methods: RT-qPCR was carried out for miR-130a-5p expression determination in NSCLC cells and tissue samples. Dual-luciferase reporter gene assay, RT-qPCR and western blot were carried out to study the potential targets of miR-130a-5p. Effects of miR-130a-5p, runt-related transcription factor 2 (RUNX2) and encoding serine/threonine kinase 32A (STK32A) on NSCLC proliferation, migration, invasion as well as EMT processes were assessed by cell counting kits-8, colony formation, Transwell and western blot assays.Results: miR-130a-5p was diminished in NSCLC tissues and cells versus their counterparts. miR-130a-5p exerted its repressive role in NSCLC by curtailing cell viability, migration, invasion as well as EMT, while facilitating apoptosis. miR-130a-5p directly targeted RUNX2, a transcription factor, and conversely regulated its expression. RUNX2 was found to interact with STK32A to promote its expression. Following the validation of the supporting role of STK32A in NSCLC cells and NF-κB p65 phosphorylation, RUNX2 overexpression was monitored to reverse miR-130a-5p-inhibited NSCLC tumor volume and weight through enhancing STK32A expression in vivo.Conclusions: miR-130a-5p diminished the growth and EMT of NSCLC cells by regulating the RUNX2/STK32A/NF-κB p65 axis, offering possible targets for the treatment for NSCLC. [ABSTRACT FROM AUTHOR]

Fenebrutinib is a CYP3A substrate and time‐dependent inhibitor, as well as a BCRP and OATP1B transporter inhibitor in vitro. Physiologically‐based pharmacokinetic (PBPK) modeling strategies with the ultimate goal of understanding complex drug‐drug interactions (DDIs) and proposing doses for untested scenarios were developed. The consistency in the results of two independent approaches, PBPK simulation and endogenous biomarker measurement, supported that the observed transporter DDI is primarily due to fenebrutinib inhibition of intestinal BCRP, rather than hepatic OATP1B. A mechanistic‐absorption model accounting for the effects of excipient complexation with fenebrutinib was used to rationalize the unexpected observation of itraconazole‐fenebrutinib DDI (maximum plasma concentration (Cmax) decreased, and area under the curve (AUC) increased). The totality of the evidence from sensitivity analysis and clinical and nonclinical data suggested that fenebrutinib is likely a sensitive CYP3A substrate. This advanced PBPK application allowed the use of model‐informed approach to facilitate the development of concomitant medication recommendations for fenebrutinib without requiring additional clinical DDI studies. [ABSTRACT FROM AUTHOR]

In this study, we analyzed the gene structure, chemical characterizations, chromosome locations, evolutionary relationship, and expression profile of hsp90 genes with online database. In addition, the expression levels of hsp90s were also investigated under heat stress by quantitative real-time (qRT)-PCR. A total of eight hsp90 genes were identified from the rainbow trout genome. They were all distributed on chromosomes 2, 4, 8, and 13. The molecular weight ranged from 78.93 to 91.39 kDa, and the isoelectric point ranged from 4.84 to 4.96. The eight hsp90 genes were clustered into six subfamilies (A, B, C, D, E, and F). Genetic structure and conserved domain analysis revealed that all eight hsp90 genes had only one exon, and motif 1–motif 10 was shared by most genes. According to RNA-seq analysis of rainbow trout liver and head kidney, a total of seven out of eight genes were significantly upregulated under heat stress, and qRT-PCR was carried out on these seven genes; the expression levels of these genes were significantly upregulated under heat stress. The significantly regulated expressions of hsp90 genes under heat stress indicated that hsp90 genes are involved in heat stress response in rainbow trout. This study provides a theoretical basis for further study on the role of hsp90 in the heat stress tolerance of rainbow trout. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are an important part of non-specific immunity and play a key role in the cellular host defense against pathogens and tissue injury infections. We investigated the effects of AMP supplementation on the antioxidant capacity, non-specific immunity, and gut microbiota of tsinling lenok trout. 240 fish were fed diets (CT, A120, A240 and A480) containing different amounts of AMP peptides (0, 120 mg kg−1, 240 mg kg−1, 480 mg kg−1) for 8 weeks. Our results showed that the activity of total antioxidant capacity (T-SOD) and glutathione peroxidase (GSH-Px), lysozyme (LZM), catalase (CAT) and acid phosphatase (ACP) in the A240 and A480 group were higher than that in the CT group (P < 0.05). The content of malondialdehyde (MDA) in AMP group was significantly lower than that in CT group (P < 0.05). Furthermore, we harvested the mid-gut and applied next-generation sequencing of 16S rDNA. The results showed that the abundance of Halomonas in AMP group was significantly lower than that in CT group. Functional analysis showed that the abundance of chloroalkane and chloroalkene degradation pathway increased significantly in AMP group. In conclusion, AMP enhanced the antioxidant capacity, non-specific immunity, and intestinal health of tsinling lenok trout. [ABSTRACT FROM AUTHOR]

Pralsetinib, a potent and selective inhibitor of oncogenic RET fusion and RET mutant proteins, is a substrate of the drug metabolizing enzyme CYP3A4 and a substrate of the efflux transporter P‐gp based on in vitro data. Therefore, its pharmacokinetics (PKs) may be affected by co‐administration of potent CYP3A4 inhibitors and inducers, P‐gp inhibitors, and combined CYP3A4 and P‐gp inhibitors. With the frequent overlap between CYP3A4 and P‐gp substrates/inhibitors, pralsetinib is a challenging and representative example of the need to more quantitatively characterize transporter‐enzyme interplay. A physiologically‐based PK (PBPK) model for pralsetinib was developed to understand the victim drug–drug interaction (DDI) risk for pralsetinib. The key parameters driving the magnitude of pralsetinib DDIs, the P‐gp intrinsic clearance and the fraction metabolized by CYP3A4, were determined from PBPK simulations that best captured observed DDIs from three clinical studies. Sensitivity analyses and scenario simulations were also conducted to ensure these key parameters were determined with sound mechanistic rationale based on current knowledge, including the worst‐case scenarios. The verified pralsetinib PBPK model was then applied to predict the effect of other inhibitors and inducers on the PKs of pralsetinib. This work highlights the challenges in understanding DDIs when enzyme‐transporter interplay occurs, and demonstrates an important strategy for differentiating enzyme/transporter contributions to enable PBPK predictions for untested scenarios and to inform labeling. [ABSTRACT FROM AUTHOR]

This paper proposes a hybrid pretreating method in the support vector regression (SVR) machines to enhance the extrapolated performance of the traditional method based on particle swarm optimization (PSO)-SVR. This method is introduced into a novel domain wherein the friction coefficient (COF) is extrapolated between the aircraft tire and the runway surface. It includes two parts: the normalized data and the extrapolated method for COF. The first part develops a novel data normalized method, which allows the experiment data to follow sine distribution (SN) instead of traditional linear distribution. For the second part, the SVR with the training set initially extrapolates a COF, and the COF is subsequently added into the original training set to build a new training sample. This process is repeated until the extrapolation is finished. This method is named step-wise (SW) extrapolation. PSO is used to optimize the regularization constant C, the parameter gamma γ, and epsilon parameter ε in SVR. Finally, this study indicates that the proposed method (SN-SW-PSO-SVR) is more suitable for the extrapolation of the COF between the airplane tire and the runway surface than other extrapolated methods. [ABSTRACT FROM AUTHOR]

Recently, the research of animal microRNAs (miRNAs) has attracted wide attention for its regulatory effect in the development process and the response to abiotic stresses. Rainbow trout is a commercially and cold water fish species, and usually encounters heat stress, which affects its growth and leads to a huge economic loss. But there were few investigations about the roles of miRNAs in heat stress in rainbow trout. In this study, miRNAs of rainbow trout which were involved in heat stress were identified by high-throughput sequencing of six small RNA libraries from head kidney tissues under control (18 °C) and heat-treated (24 °C) conditions. A total of 392 conserved miRNAs and 989 novel miRNAs were identified, of which 78 miRNAs were expressed in different response to heat stress. Ten of these miRNAs were further validated by quantitative real–time PCR. In addition to, including 393 negative correlation miRNA-target gene pairs, several important regulatory pathways were involved in heat stress of the potential target genes, including protein processing in endoplasmic reticulum, NOD-like receptor signaling pathway, and phagosome. Our data significantly advance understanding of heat stress regulatory mechanism of miRNA in the head kidney of rainbow trout, which provide a useful resource for the cultivation of rainbow trout. [ABSTRACT FROM AUTHOR]

We assessed the expression stability of several messenger (m)RNAs and micro (mi)RNAs from liver and head kidney of rainbow trout Oncorhynchus mykiss using high‐throughput RNA sequencing (RNA‐seq) and miRNA‐seq data. Additionally, four commonly used reference genes and one small non‐coding RNA (u6) were also selected to identify ideal reference mRNAs and miRNAs for quantitative real‐time (qrt)‐PCR analysis of heat stress responses. GeNorm, NormFinder, BestKeeper and comparative ΔCt were employed for analysis of qrt‐PCR data to systematically assess the expression stability of candidate mRNAs and miRNAs and stability was ranked using geometric means. β‐actin and ef1‐α were the most stably expressed reference mRNAs in liver and head kidney, respectively and ssa‐mir‐26a‐5p and ssa‐mir‐462b‐5p were the most stably expressed miRNAs in these tissues. This is the first identification of appropriate reference mRNAs and miRNAs for qrt‐PCR analysis of O. mykiss under heat stress. [ABSTRACT FROM AUTHOR]

An efficient photoinduced strategy for the hydrogenation and arylsulfonylation of alkenes has been developed. The reaction afforded a range of hydrogenated products and sulfonated oxindoles in high yields under external photocatalyst‐free, oxidant‐ and reductant‐free conditions. Mechanistic investigations suggested this transformation is driven by the photochemical activity of hydrogen bond donor‐acceptor complex, generated from the substrates of arylsulfinic acids and C6‐(vinyl sulfone)phenanthridines or N‐arylacrylamides via hydrogen bond interaction. [ABSTRACT FROM AUTHOR]

Abstract The concept of air resource management originated in the United States and subsequently became the foundation of most air quality control programs in developed countries. However, little is known about its validity and quantitative assessment methods in regional atmospheric environment management. The aim of this study was to construct an air resource endowment (ARE) index and apply it in a case study for assessing the distribution of ARE across mainland China from 2013 to 2017. The quantification of the ARE index includes two terms: the atmospheric diffusion coefficient (A value) and self-purification ability (B value), which can be calculated via Weather Research and Forecasting modeling (WRF-CALMET). The results indicated that about 15% of China's land area enjoys high ARE , around 20–25% of China's land area was considered to have relatively high or relatively low ARE indices, and ARE in the rest of China's land area (40%) was considered to be low. Further, a complex network correlation model was created and used to demarcate highly inter-correlated regions based on the data mining of the ARE index. Six key Joint Prevention and Control of Atmospheric Pollution (JPCAP) regions with strong synchronicity in the ARE index were identified, which suggests that JPCAP could be implemented separately within each of these demarcated regions. The concepts and analysis methods proposed in this study for determining ARE and regional divisions can have broad significance for JPCAP implementation in China. Graphical abstract In general, the air resource endowment (ARE) is richer in western and southern regions than eastern and northern regions and richer in coastal plains than inland areas in China. Six key Joint Prevention and Control of Atmospheric Pollution (JPCAP) regions with strong synchronicity in ARE index were defined. Spatial distribution of gridded ARE index in China and six key JPCAP regions with strong synchronicity in ARE index. Unlabelled Image Highlights • The concept of air resource endowment (ARE) and its assessment methods were proposed and applied in a case study in China. • Spatial and temporal trends of ARE across China from 2013 to 2017 were studied. • Six major regions with similar trends in ARE index were identified. • The results can be used to support future improvement in air quality in China. [ABSTRACT FROM AUTHOR]

A D2h symmetrical ABAB‐phthalocyanine, 1,4,15,18‐tetrapentyloxy‐9,10,23,24‐tetrachlorophthalocyanine (TPTCPc), has been employed in the construction of sandwich‐type bis(phthalocyaninato) terbium double‐decker, resulting in the isolation and identification of a reduced form TbH(TPTCPc)2 (1). Single crystal structure analysis of 1 demonstrates the approximate square‐antiprismatic (SAP) coordination geometry around the TbIII ion along with a twist angle of 42.19°. However, the introduction of strong electron‐withdrawing chloride groups and electron‐donating pentyloxy groups on the peripheral and non‐peripheral positions, respectively, of ABAB‐phthalocyanine significantly perturbs the crystal field D4d symmetry of sandwich‐type bis(phthalcyaninato) lanthanide compound and affords a new crystal field with approximate D2 symmetry. Such perturbation has been clearly evidenced by theoretical calculations, which, instead of the protonation nature, exerts a negative effect in single‐molecule magnet (SMM) performance, further supporting the predominant advantage of crystal field D4d symmetry in SMM behaviors of sandwich‐type lanthanide compounds. A bis(phthalocyaninato) terbium single‐ion magnet (SIM) bearing electron‐donating and electron‐withdrawing substituents has been developed, which exhibits the approximate D2 symmetrical crystal field, revealing the significant electronic structure effect of these substituents on SIM performance. [ABSTRACT FROM AUTHOR]

Background and Objectives: To analyze the potential of fatty liver index (FLI) and several obesity indices and to explore which index is best for predicting nonalcoholic fatty liver disease (NAFLD) in Chinese postmenopausal women.Methods and Study Design: A cross-sectional study was conducted in 680 Chinese postmenopausal women. NAFLD was defined as a hepatic steatosis observed on liver ultrasonography in the absence of a second cause. Odds ratio and corresponding 95% confidence interval (CI) between hepatic steatosis and FLI as well as different obesity indices were evaluated by Binary Logistic regression model. Receiver operating characteristic curve and area under curve (AUC) were used to compare the ability of predicting hepatic steatosis between FLI and obesity indices.Results: The upper values of all indices were significantly associated with the presence of hepatic steatosis (all p<0.01) after the adjustment for potential confounders. The largest AUC [0.85 (0.82-0.88), 95% CI, p<0.01] was observed for FLI, followed by the frequently used obesity indices.Conclusions: FLI is closely associated with the presence of hepatic steatosis in Chinese postmenopausal women. Compared to the obesity indices frequently used, FLI is a better surrogate marker for predicting the presence of hepatic steatosis in Chinese postmenopausal women. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Ultrasonication was successfully used to prepare the composite PVDF/GO membranes. • Largely enhanced hydrophilicity was achieved for the composite membranes. • The composite membrane exhibited excellent adsorption ability toward MB. • The composite membrane showed good regeneration ability and adsorption stability. Abstract In this work, ultrasonication-assisted deposition technology was used to prepare the composite poly(vinylidene fluoride) (PVDF)/graphene oxide (GO) membrane with regarding to organic dyes removal. The electrospun PVDF fibrous membrane, which was first obtained through electrospinning technology, was immersed into the GO aqueous solution, and then the mixture was ultrasonically treated at power of 100 W for different time. Microstructure characterizations and hydrophilicity measurements confirmed that many GO platelets were incorporated into the PVDF membrane. The adsorption ability toward methylene blue (MB) by the composite PVDF/GO membrane was then systematically investigated. The results showed that the ultrasonication time and the concentration of GO in the aqueous solution determined the content of GO in the composite membrane, which also determined the adsorption capacity of the composite membrane. Studies on adsorption kinetics and adsorption isotherms showed that the adsorption behavior of the composite PVDF/GO membrane could be well described by the pseudo second-order model, and the maximum adsorption capacity of MB was 621.1 mg g−1. Furthermore, the composite PVDF/GO membrane exhibited excellent regeneration ability. This work demonstrates that the composite PVDF/GO membrane may be a promising adsorbent to remove organic dyes from wastewater. [ABSTRACT FROM AUTHOR]

Aspergillus flavus is a significant fungus that poses a threat to food safety by producing mycotoxins in various crops. In this study, A. flavus isolates were obtained from storage rice collected from seven provinces in southern China, and their AFB 1 production, biosynthesis genes presence, and diversity were detected. Results showed that 56 out of the 81 A. flavus isolates produced detectable levels of AFB 1 , and 71 isolates (87.6 %) possessed aflR gene in their AF synthesis gene cluster, while only 41 isolates (50.6 %) had the ver-1 gene present. Genetic diversity analysis using inter-simple sequence repeats (ISSR) markers revealed seven main clusters among the isolates and the genetic similarity coefficients of 81 A. flavus isolates ranged from 0.53 to 1.00. Additionally, coculture assays were conducted using two toxigenic and two atoxigenic isolates from the same grain depot to investigate the effect of intraspecific inhibition on AFB 1 production and to assess the AFB 1 contamination risk of storage rice. The in situ results demonstrated that the atoxigenic isolates effectively inhibited the AFB 1 contamination of toxigenic isolates. These findings provide insight into the genetic diversity of A. flavus isolates populations and highlight the potential food safety hazards of them in stored rice grain in China. • Environment affects phenotypes and AFB 1 production of A. flavus isolates from southern China. • Atoxigenic A. flavus isolates have deletions in regions of the AFB 1 biosynthesis gene cluster. • ISSR molecular markers successfully demonstrate genetic diversity among A. flavus isolates. • Atoxigenic A. flavus suppresses toxigenic A. flavus growth and AFB 1 contamination via competition. [ABSTRACT FROM AUTHOR]

Tsinling lenok trout (Brachymystax lenok tsinlingensis) is a typical cold water fish. High temperature has been shown to damage the liver of fish. However, few studies have investigated the liver apoptosis induced by high temperature stress in fish from the perspective of gene expression and metabolic function. Therefore, we investigated the changes caused by high temperature stress (24 °C) on the liver tissue structure, antioxidant capacity, liver gene expression, and the metabolome of tsinling lenok trout. The transcriptomic results showed that genes associated with apoptosis, such as CASP8 , CASP3 , PERK , Bcl-6 and TRAIL , were upregulated under high temperature stress. Metabolomic analysis showed that the metabolic pathway of nucleotide synthesis was significantly downregulated, while that of oxygen radical synthesis was significantly upregulated. Integrated analysis showed that after high temperature stress, immune-related signaling pathways in trout were activated and their apoptosis level increased, which might be related to hepatopancreas injury. In addition, abnormalities in the tricarboxylic acid cycle and mitochondrial function were observed, suggesting that functional hypoxia caused by high temperature might be involved fish cell apoptosis. These results provide new insights into the process of cell apoptosis in fish under high temperature stress. [ABSTRACT FROM AUTHOR]

Biosurfactants from Pseudomonas spp. have been reported to exhibit antibacterial and anti-adhesive properties, but their role during meat spoilage remains unclear. In this study, the biosurfactant was isolated from an isolate of Pseudomonas fragi with strong spoilage potential, and its surface tension and emulsification ability were determined. The chemical and microbial characteristics of the biosurfactant-treated meat samples were periodically analyzed. The results demonstrated that the biosurfactant produced by P. fragi could reduce surface tension and showed good emulsification properties. For the in situ spoilage trials, biosurfactant from P. fragi changed the microbial diversity on meat, helping Pseudomonas establish a dominant position in the population. However, biosurfactant treatment caused chicken meat to exhibit a weaker spoilage state, as indicated by the growth of psychrophilic microorganisms, total volatile basic nitrogen (TVBN) and meat color. These results provide practical information for understanding the role of P. fragi biosurfactant during chilled meat storage. • Biosurfactant was isolated from a strain of meat-borne Pseudomonas fragi. • Biosurfactant can reduce the surface tension and exhibit good emulsification ability. • Biosurfactant can promote the dominance of Pseudomonas in the bacterial community. • Biosurfactant-treatment weakened the spoilage state of chilled meat. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • PPy particles were deposited on electrospun PVDF fibers with the aid of PDA. • The composite fibers showed bidirectional removal ability toward cation/anion dyes. • The composite fibers showed excellent removal ability toward Cr(VI). Abstract In this work, novel composite nanofibers which exhibited 'core–shell'-like structure were fabricated through the deposition of polypyrrole (PPy) particles on the electrospun poly(vinylidene fluoride) (PVDF) nanofibers with the aid of polydopamine (PDA). First, the PVDF/DA electrospun nanofibers were prepared. Then, the self-polymerization of PDA was triggered in a Tris–HCl buffer solution. After that, the pyrrole monomer was added into the distilled water containing the PVDF/PDA fibrous membrane and the chemical oxidation polymerization of PPy was triggered by adding FeCl 3. Morphological characterization confirmed that the electrospun PVDF/PDA nanofibers were homogenously coated by PPy particles. Largely enhanced hydrophilicity of the fibrous membrane surface was achieved due to the presence of many nitrogen-containing groups and the increased surface roughness of nanofibers. The adsorption abilities of the composite nanofibers were investigated using Methylene Blue (MB) and Congo Red (CR) as the probe dyes. The results showed that the composite nanofibers exhibited excellent adsorption abilities toward cation and anion dyes simultaneously, and the maximum adsorption capacities were 370.4 and 384.6 mg/g for MB and CR adsorption, respectively. The adsorption behaviors toward the two dyes could be well described by the pseudo second-order adsorption model and the Langmuir adsorption model. Further results showed that the adsorption abilities of the composite nanofibers were greatly dependent upon the pH values of the solution. Furthermore, the composite nanofibers exhibited good regeneration ability. The removal ability toward Cr(VI) was also measured and the experimental adsorption capacity was 126.7 mg/g. The excellent adsorption abilities toward cation/anion dyes and heavy metal ions endow the composite nanofibers with great potential application in wastewater treatment. [ABSTRACT FROM AUTHOR]

Modified atmosphere packaging (MAP) is considered an effective method for extending the shelf life of meat. The use of optimal mixture of gases (CO 2 and N 2 ) in food packaging containers has been proved to effectively inhibit the growth of microorganisms in poultry meat. In general, a minimum CO 2 concentration range of 20%–30% is required for the inhibitory effect. The aim of this study was to investigate the mechanism by which MAP (CO 2 /N 2 30%/70%) inhibits Pseudomonas fragi , a dominant spoilage microorganism in aerobically stored chilled meat. The cell physiological changes were determined by measuring membrane integrity, membrane potential, ATP level, and extracellular proteolytic activity. The results showed that samples stored under MA retained cell membrane integrity, but lost significant membrane potential and ATP synthesis activity. Furthermore, the peptides issued from 2 structural proteins (myosin and actin) were mainly identified in air samples, indicating that these fragments result from bacterial proteolytic activity while MAP inhibited this activity. Overall, the study found that cell metabolism and extracellular protease activity decreased under MAP conditions. This study showed that MAP is an effective food preservation strategy and revealed mechanisms by which MAP inhibits spoilage. [ABSTRACT FROM AUTHOR]

Abstract The promulgation and implementation of the Air Pollution Prevention and Control Action Plan (APPCAP) have greatly accelerated air quality improvements in China. In this study, these improvements were assessed and analyzed using arithmetic mean and percentile methods. Air quality status and trends were illustrated meticulously. Air pollution risks remaining since the implementation of the APPCAP were also identified. In addition, a complex network correlation model was created and used to demarcate highly inter-correlated regions within China, which were identified using long-term PM 2.5 concentration data. The results indicate that the annual mean PM 2.5 concentration decreased by more than 30% throughout the country since the implementation of the APPCAP. However, more than 1 billion people were still exposed to polluted air containing PM 2.5 concentrations exceeding the WHO Interim Target-1 (WHO IT-1). Cities with populations of more than 10 million were generally among the most polluted regions in China, while PM 2.5 concentrations in locations with populations of less than 1 million met WHO IT-1 standards. Moreover, PM 2.5 network correlation analysis defined 7 key Joint Prevention and Control of Atmospheric Pollution (JPCAP) regions with strong synchronicity in PM 2.5 mass concentrations; these results suggest that JPCAP could be implemented separately with in each of these demarcated regions. The atmospheric pollution control concepts and methods proposed herein are also broadly applicable for the implementation of JPCAP policies in other regions worldwide. Graphical abstract A complex network correlation model was established and used to demarcate highly inter-correlated regions within China based on long-term and massive data mining of PM 2.5 concentration, and seven major regions, including Beijing–Tianjin–Hebei and surrounding areas, Yangtze River Delta, Chengdu–Chongqing, Lanzhou–Xining urban agglomeration, South China, Central China, and Northeast China, were identified. These results provide a scientific basis for formulating long-term, stable, and unified JPCAP strategies for China and implementation of JPCAP measures that focus on the specific problems of each region. Network diagram of the PM 2.5 correlation coefficients for the 31 provinces in China. (a): P ≥ 0; (b): P ≥ 0.6; (c): P ≥ 0.7; (d): P ≥ 0.75. Image Highlights • Spatial and temporal trends of PM2.5 across China from 2013 to 2017 were studied. • The promulgation and implementation of APPCAP improved air quality of China. • Seven major regions with similar trends in air quality were identified. • The results can be used to support future improvement in air quality in China. [ABSTRACT FROM AUTHOR]