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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]

This study investigated the differential metabolites after rheumatoid arthritis (RA) rats were treated with Jinteng Qingbi granules. Collagen‐induced arthritis rats were divided into three groups, namely normal group, model group, and Jinteng Qingbi granules group. Serum compounds were identified, annotated, and classified using metabolomics to explain the physicochemical properties and biological functions. The metabolites were screened using univariate and multivariate statistical analyses. There were differences in serum metabolites between RA and normal rats; Jinteng Qingbi granules improved RA and recovered the metabolite levels to normal. Compared to the normal group, 51 differential ions were screened, and 108 ions were changed in the Jinteng Qingbi granules group compared to the RA model. Eight metabolites were upregulated in the RA model group compared to the normal group, whereas 10 metabolites were downregulated. Treatment with Jinteng Qingbi granules increased the levels of 12 metabolites such as cinnamate and decreased the levels of 16 metabolites such as allamandin in the RA model. Differential ion enrichment was mainly related to the histidine metabolic pathway in amino acid metabolism. Jinteng Qingbi granules resulted in improvements in the RA model, which were mainly associated with lipids and lipid‐like molecules, organic acids, and derivatives, providing a new possibility and basis for screening biomarkers for the diagnosis and treatment of RA. [ABSTRACT FROM AUTHOR]

A catalyst‐free electrochemical alkylacetoxylation reaction of terminal alkynes with (thio)xanthenes and carboxylic acids is developed. Treating the addition products with K2CO3 as a base in methanol affords the ketones in moderate to good yields. Preliminary experimental and computational studies indicate that the benzylic cation generated from the (thio)xanthenes triggers the electrophilic addition to alkynes. [ABSTRACT FROM AUTHOR]

Background: The cell endocrine pathway is a critical physiological process composed of the endoplasmic reticulum, Golgi apparatus and associated vesicles. Loss of enzymes or proteins can cause dysfunction of endoplasmic reticulum and Golgi apparatus and affect secretion pathways leading to a variety of human diseases, including cancer. Methods: The single‐cell RNA sequencing and single nucleotide variant principal component analysis data of ovarian cancer were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) datasets. Eighty‐four genes from SECRETORY_PATHWAYs were obtained from the gene set enrichment analysis (GSEA) website. Univariate cox regression analyses and ConsensusClusterPlus were used to identify prognostic genes and molecular subtypes, which were validated using the tumor immune dysfunction and exclusion (i.e. TIDE) analysis and gene mutation analysis. A prognosis model was established by randomForestSRC. Abundant infiltrated immune cells and pathway enrichment analyses were carried out, respectively, through ssGSEA, ESTIMATE, MCP‐counter and GSEA. The drug sensitive analysis was performed using pRRophetic package. Immunotherapy datasets and pan‐carcinoma analysis were used to examine the performance of prognostic model. Results: Eighteen prognostic genes from SECRETORY_PATHWAYs were found in both TCGA and GEO datasets. Next, two clusters (C1 and C2) were determined, for which C1 with a poor prognosis had higher immune infiltration. Tumor‐related pathways, such as PATHWAYS_IN_CANCER and B_CELL_RECEPTOR_SIGNALING_PATHWAY, were enriched in C1. Moreover, C2 was suitable for immunotherapy. A four‐gene (DNAJA1, NDRG3, LUZP1 and ZCCHC24) signature was developed and successfully validated. RiskScore of higher levels were significantly associated with worse prognoses. An enhanced immune infiltration, increased pathways score and inappropriate immunotherapy were observed in the high RiskScore group. The high‐ and low‐RiskScore groups had different drug sensitivities. Immunotherapy datasets and pan‐carcinoma analysis indicated that the low RiskScore group may benefit from immunotherapy. Conclusions: Based on the perspective of the secretory signaling pathway, a robust prognostic signature with great performances was determined, which may provide clues for clinical precision treatment of ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: To describe and conclude the in vitro fertilization (IVF) results of patients with X chromosome abnormality. Methods: A retrospective case series was conducted. According to the number of normal X, patients were allocated into two groups: Group A (patients with only a normal X, while other X has any types of abnormalities) and Group B (patients have two or more normal X chromosomes). Clinical data, including basic information, fertility information, and IVF outcomes, were collected. Results: Fourteen patients with X chromosome abnormality were included, among which 13 patients underwent a total of 29 cycles. Patients in Group B had five successful pregnancies and three live births, while no patient in Group A had a clinical pregnancy. Furthermore, the blastocyst formation rate and incidence of pregnancy were significantly lower in Group A (Z = −3.135, p =.002; Z = −2.946, p =.003, respectively). When controlled covariates, the karyotype of one normal X was also a risk factor for both blastocyst formation rate and success pregnancy (β =.820, 95% confidence interval [CI] = 0.458–1.116, β =.333, 95% CI = 0.017–0.494, respectively). Conclusions: Our results revealed that women with only one normal X might suffer from worse IVF outcomes, mainly blastocyst formation rate, compared with those who had two or more normal X, including mosaic Turner syndrome and 47,XXX. [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]

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]

The objective of this study was to better understand the stressors in families of children with congenital heart disease (CHD) to assist with formulating targeted stress management plans for such families. A descriptive qualitative study was undertaken at a tertiary referral hospital in China. Following purposeful sampling, interviews were conducted with 21 parents of children with CHD regarding the stressors in their families. Following content analysis, 11 themes were generated from the data and categorised into six main domains: the initial stressor and associated hardships, normative transitions, prior strains, the consequences of family efforts to cope, intrafamily and social ambiguity, and sociocultural values. The 11 themes include confusion regarding the disease, hardships encountered during treatment, the heavy financial burden, the unusual growth track of the child due to the disease, normal events becoming abnormal for the family, impaired family functioning, family vulnerability, family resilience, family boundary ambiguity induced by role alteration, a lack of knowledge about community support and family stigma. Various and complex stressors exist for families of children with CHD. Medical personnel should fully evaluate the stressors and take targeted measures before implementing family stress management practices. It is also necessary to focus on the posttraumatic growth of families of children with CHD and strengthen resilience. Moreover, family boundary ambiguity and a lack of knowledge about community support should not be ignored, and further research is needed to explore these variables. Most importantly, policymakers and healthcare providers should adopt a range of strategies to address the stigma of being in a family of a child with CHD. [ABSTRACT FROM AUTHOR]

Kupffer cells (KCs) are liver‐resident macrophages involved in hepatic inflammatory responses, including nonalcoholic fatty liver disease (NAFLD) development. However, the contribution of KC subsets to liver inflammation remains unclear. Here, using high‐dimensional single‐cell RNA sequencing, we characterized murine embryo‐derived KCs and identified two KC populations with different gene expression profiles: KC‐1 and KC‐2. KC‐1 expressed CD170, exhibiting immunoreactivity and immune‐regulatory abilities, while KC‐2 highly expressed lipid metabolism‐associated genes. In a high‐fat diet–induced NAFLD model, KC‐1 cells differentiated into pro‐inflammatory phenotypes and initiated more frequent communications with invariant natural killer T (iNKT) cells. In KC‐1, interleukin (IL)‐10 expression was unaffected by the high‐fat diet but impaired by iNKT cell ablation and upregulated by iNKT cell adoptive transfer in vivo. Moreover, in a cellular co‐culture system, primary hepatic iNKT cells promoted IL‐10 expression in RAW264.7 and primary KC‐1 cells. CD206 signal blocking in KC‐1 or CD206 knockdown in RAW264.7 cells significantly reduced IL‐10 expression. In conclusion, we identified two embryo‐derived KC subpopulations with distinct transcriptional profiles. The CD206‐mediated crosstalk between iNKT and KC‐1 cells maintains IL‐10 expression in KC‐1 cells, affecting hepatic immune balance. Therefore, KC‐based therapeutic strategies must consider cellular heterogeneity and the local immune microenvironment for enhanced specificity and efficiency. [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]

Aim: This study aims to examine the relationship between professional identity and job satisfaction and their impact on intention to stay among clinical nurses in China during the prolonged COVID‐19 pandemic. Methods: A cross‐sectional survey was conducted from April 30 to May 25, 2021, in China. Data were collected using professional identity, job satisfaction, and intention to stay questionnaires from 1425 clinical nurses. A single mediation analysis was utilized to test the interrelationship among the variables, and the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist as a reporting guide. Results: Nurses indicated a medium level of professional identity, job satisfaction, and intention to stay, with mean scores of 3.85, 3.25, and 3.47, respectively. The professional identity displayed positive indirect effect on nurses' intention to stay through job satisfaction (indirect effect = 0.498, 95% CI [0.439, 0.558]). Conclusion: Cultivating professional identity among nurses can increase their job satisfaction and ultimately enhance the intention to stay in the nursing profession. However, this study also suggests paying more attention to job satisfaction to keep nursing retention. These may be helpful to retain the nursing workforce. [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 frequency and severity of extreme weather events are increasing and expected to increase more in the future, together with global change. However, how extreme events and global change factors interactively influence community structures and ecosystem processes is largely unknown. Here, we investigated the responses of the temporal stability and resilience of aboveground net primary productivity (ANPP) of an alpine meadow to an extreme flooding event under different treatments of experimental drought and clipping. We found that ecosystems that were exposed to drought treatments for 3 years significantly decreased the temporal stability of community productivity but increased resilience to flooding, whereas their resistance to or recovery from flooding did not change. Neither clipping nor its interaction with drought altered the responses of these community stability metrics to flooding. Drought treatments significantly decreased plant species richness and asynchrony and dominant species stability, leading to a decrease in temporal stability and an increase in resilience in response to the extreme flooding event. The study also revealed that the change in species asynchrony was the dominant impact pathway determining the responses of resilience and temporal stability to flooding. Our results highlight that alpine grassland that experiences a multiyear drought may aggravate the instability of community productivity to extreme climatic events by reducing species asynchrony. [ABSTRACT FROM AUTHOR]

In Nicotiana tabacum, the degeneration of connective tissue and stomium tissue (the stomium and circular cell cluster [CCC]) is essential for anther dehiscence. Both connective cells and CCC cells are crystal idioblasts, and these cells will undergo degeneration after accumulating calcium oxalate (CaOx) crystals. However, detailed data concerning this process are minimal. Therefore, this study used cellular biological and physiological methods to illustrate this relationship. Results demonstrated that tobacco anther dehiscence is a series of timed programmed cell death (PCD) processes that include the CCC, connective tissue, and stomium. The degenerating crystal idioblasts of the tobacco anther were found to possess two hallmark characteristics that distinguished them from normal PCD cells, namely dynamic changes in CaOx crystals and the appearance of numerous peroxisomes. The accumulation of CaOx and the production of H2O2 occurred simultaneously or successively before PCD. The peak H2O2 content was found to appear after the insoluble oxalate. Further, CeCl3 cytochemistry staining was used to detect subcellular H2O2, and the precipitate of H2O2 was primarily present in peroxisomes and around CaOx crystals. These results show that anther dehiscence in N. tabacum is a PCD process in which crystal idioblasts play a vital role in CaOx degradation and H2O2 production. [ABSTRACT FROM AUTHOR]

In this article, molecular dynamics simulation is used to primarily explore the lattice matching problem of solute atoms in different configurations after entering the Fe lattice at 0 K temperature. It reveals that by changing the initial configurations, metal solute atoms (Cr, Cu, Ti, Al) are more stable in the <110> configuration while C atom tends to stay in the octahedral gap of the BCC lattice. In addition, the matching mechanisms of different solute atoms in BCC Fe lattice in different configurations are elaborated in detail. The relaxation of metal solute atoms in different configurations eventually forms different stable structures while C atoms only exist in the nearest‐neighbor octahedral gap of the BCC Fe lattice in each configuration. [ABSTRACT FROM AUTHOR]

The measurement of protein expression level plays a pivotal role in both biological and medical studies. Housekeeping proteins, generally encoded by housekeeping genes are used as loading control proteins to normalize protein expression. Obviously, proper reference standards are essential for adequate analysis of protein expression. However, our study showed that the widely used normalisation proteins, whose expression levels varied greatly among sperm samples, were unsuitable for data standardisation. To uncover the proteins steadily expressed in sperm, we analysed several published transcriptome data of sperm. Seven proteins whose expression levels were relatively stable (co‐efficient variation values less than 0.35) were selected and further evaluated by quantitative real‐time polymerase chain reaction, Western Blot (WB) and immunocytochemistry. Our results showed that among the classical housekeeping proteins, only β‐tubulin remained constant in sperm samples from 85 individuals. Compared with other classical housekeeping proteins such as glyceraldehyde 3‐phosphate dehydrogenase, actin and histone H3, Cullin‐1 (CUL1) and F‐box only protein 7 (FBXO7) seemed to be more suitable to be used as internal controls for WB in sperm protein studies. Combined with the locations of these proteins, CUL1 and FBXO7 were suggested to be used as a housekeeping protein for total proteins. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are being extensively studied as they function as key metabolic regulators which play a role in the heat stress response. However, the role of miRNAs in heat stress remains uncertain and many new miRNAs have not yet been discovered. In a previous study, we performed high‐throughput sequencing of differentially expressed miRNAs identified on exposing rainbow trout (Oncorhynchus mykiss) to heat stress (18 vs. 24°C), which led to the identification of two novel miRNAs, temporarily named novel miR‐434 and ‐242. The differential expression level of these miRNAs was extremely significant (P < 0.01); we analysed target gene mRNA transcripts by bioinformatics software (miRanda). We found novel miR‐434 and ‐242 were predicted to regulate the transcripts of heat shock 70‐kDa protein 4‐like (HSPA4L) and calreticulin (CRT), respectively, by bioinformatics software. Here our core objective was to validate if HSPA4L and CRT are indeed the target genes of novel miR‐434 and ‐242, respectively, and for this purpose we used the dual‐luciferase reporter assay system. Target gene sequences were synthesized and cloned into a dual‐luciferase vector. To better understand the function of the target genes, we combined the previous sequencing results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We found that novel miR‐434 regulated HSPA4L expression by binding to a putative binding site in the 3′‐UTR of HSPA4L, and luciferase activity inhibition was observed. In contrast, novel miR‐242 was not involved in regulating CRT expression. To conclude, we believe our results should serve as a foundation for future studies aiming to comprehensively understand the mechanisms used by rainbow trout to cope with heat stress. [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]

The electron dynamics in uniform magnetized capacitively coupled plasmas are investigated by using a one‐dimensional particle‐in‐cell simulation with a Monte Carlo collision model. It is found that the nonlinear dynamic behaviors of electrons are slightly modulated at weak magnetic fields, with more electron beams appearing during one sheath expansion. The electron beams are reversed before reaching the opposite electrode at moderate magnetic fields under the effect of Lorentz force. The discharge becomes very localized at very high magnetic fields, as the energetic electrons are confined in the vicinity of the sheath edge. The nonlocal to local transition of discharge characteristics is induced at different magnetic fields for various discharge frequencies. Generally, the discharge transition happens at stronger magnetic fields for high‐discharge frequencies. A quantitative relation between the discharge frequency and cyclotron frequency is given for the discharge transition. [ABSTRACT FROM AUTHOR]

Antimetastatic effect of Metformin has been documented in epithelial ovarian cancer (EOC). Presently, we investigated the regulatory mechanism of Metformin in EOC metastasis. First, Girdin was significantly enhanced in EOC tumorous tissues and cell lines. Seconded, knockdown of Girdin significantly suppressed EOC cell viability, migration, and invasion, while upregulation of Girdin produced the opposite effects in vitro and facilitated lung metastasis in EOC cell xenograft in vivo. In addition, we confirmed that the inhibitory effect of Metformin on Girdin expression. Mechanistically, the oncogenic effects of Girdin could be reversed by LY294002 (an AKT pathway inhibitor) and Metformin. These results suggested that Metformin attenuated EOC metastasis through Girdin and targeting Girdin may be a promising therapeutic strategy for EOC in the future. [ABSTRACT FROM AUTHOR]

Summary: Changes in carbohydrates and organic acids largely determine the palatability of edible tissues of horticulture crops. Elucidating the potential molecular mechanisms involved in the change in carbohydrates and organic acids, and their temporal and spatial crosstalk are key steps in understanding fruit developmental processes. Here, we used apple (Malus domestica Borkh.) as research materials and found that MdbHLH3, a basic helix–loop–helix transcription factor (bHLH TF), modulates the accumulation of malate and carbohydrates. Biochemical analyses demonstrated that MdbHLH3 directly binds to the promoter of MdcyMDH that encodes an apple cytosolic NAD‐dependent malate dehydrogenase, activating its transcriptional expression, thereby promoting malate accumulation in apple fruits. Additionally, MdbHLH3 overexpression increased the photosynthetic capacity and carbohydrate levels in apple leaves and also enhanced the carbohydrate accumulation in fruits by adjusting carbohydrate allocation from sources to sinks. Overall, our findings provide new insights into the mechanism of how the bHLH TF MdbHLH3 modulates the fruit quality. It directly regulates the expression of cytosolic malate dehydrogenase MdcyMDH to coordinate carbohydrate allocation and malate accumulation in apple. [ABSTRACT FROM AUTHOR]

Objectives: To explore the perceptions of patients undergoing percutaneous coronary intervention (PCI) regarding their pre‐operative health education. Methods: A qualitative study using semi‐structured, in‐depth interviews was conducted in one cardiology unit in China from July 2019 to December 2019. Purposeful sampling of 17 patients undergoing PCI was interviewed about their perceptions of pre‐operative health education. Thematic analysis of the transcribed data was then used to identify the themes. Results: Four themes emerged from the data:(a) triple roles of pre‐operative education with the categories of relief (reliving fear); burden (leading to stress); and meaningless (changing nothing); (b) family member involvement with the categories of shared responsibility and family members' duty; (c) facilitators in the process of pre‐operative health education with the categories of emotional support, plain language and individualized pre‐operative education; (d) inhibitors in the process of pre‐operative health education with the categories of contradiction and threatening words. Conclusions: Pre‐operative health education for patients undergoing PCI should be aligned with the individual patients' information‐seeking styles and personal differences, emphasizing individualized patient education. Traditional Chinese philosophy should be considered in the practice of pre‐operative education for patients undergoing PCI, which emphasizes family member involvement; at the same time, patient empowerment and self‐care should also be stressed. In addition, emotional support and plain language from health professionals are important in pre‐operative health education for patients undergoing PCI; contradiction should be avoided, and threatening words should be used with caution and with consideration for cultural variations during pre‐operative education for patients undergoing PCI. [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]

Model‐informed drug development (MIDD) has become an important approach to improving clinical trial efficiency, optimizing drug dosing, and proposing drug labeling in the absence of dedicated clinical trials. For the first time, we developed a physiologically based pharmacokinetic (PBPK) model‐based approach to assess CYP3A‐mediated drug‐drug interaction (DDI) risk for polatuzumab vedotin (Polivy), an anti‐CD79b‐vc‐monomethyl auristatin E (MMAE) antibody‐drug conjugate (ADC). The model was developed and verified using data from the existing clinical DDI study for brentuximab vedotin, a similar vc‐MMAE ADC. Analogous to the brentuximab vedotin clinical study, polatuzumab vedotin at the proposed labeled dose was predicted to have a limited drug interaction potential with strong CYP3A inhibitor and inducer. Polatuzumab vedotin was also predicted to neither inhibit nor induce CYP3A. The present work demonstrated a high‐impact application using a PBPK MIDD approach to predict the CYP3A‐mediated DDI to enable drug labeling in the absence of any dedicated clinical DDI study. The key considerations for the PBPK report included in the Biologics License Application/Marketing Authorization Application submission, as well as the strategy and responses to address some of the critical and challenging questions from the health authorities following the submission are also discussed. Our experience and associated perspective using a PBPK approach to ultimately enable a drug interaction label claim for polatuzumab vedotin in lieu of a dedicated clinical DDI study, as well as the interactions with the regulatory agencies, further provides confidence in applying MIDD to accelerate the registration and approval of new drug therapies. [ABSTRACT FROM AUTHOR]

Background: Prior studies have noted the importance of T cell immunoglobulin and mucin domain containing 4 (TIMD4) in various diseases and its functions on cell malignant behaviors. However, the biological function of TIMD4 in diffuse large B‐cell lymphoma (DLBCL) is unknown. Methods: Relative expression of TIMD4 was analyzed based on the GSE56315 array including 88 cases of human tissues. TIMD4 expression in cells was detected using a quantitative reverse transcriptase‐polymerase chain reaction and western blot experiments. Cell proliferation was measured using the cell counting kit‐8 (CCK‐8) assay and apoptotic properties were assessed through the detection of related proteins by western blotting. The underlying molecular mechanism of TIMD4 in DLBCL was predicted and confirmed using KEGG enrichment analysis and western blotting. Results: The results indicate that TIMD4 is overexpressed in DLBCL tissues and the poor prognosis of DLBCL patients is significantly linked with the higher TIMD4 expression. The loss‐of‐TIMD4 experiment in CYP6D reveals that knockdown of TIMD4 blocks cell growth and accelerates cell apoptosis, whereas the gain‐of‐TIMD4 experiment in Raji cells suggests that up‐regulation of TIMD4 promotes cell proliferation and inhibits cell apoptosis. The activity of the Wnt/β‐catenin pathway is mediated by the TIMD4 expression in DLBCL cells. Conclusions: These findings demonstrate that TIMD4 is up‐regulated in patients with DLBCL and the regulatory effects of TIMD4 on cell proliferation and apoptosis are associated with the Wnt/β‐catenin pathway, posing a novel target for DLBCL therapy. [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]

Converting CO2 into high‐value chemicals has been regarded as an important solution for a sustainable low‐carbon economy. In this work, we have theoretically designed an innovative strategy for the absorption and activation of CO2 by the electride N3Li, that is, 1,3,5(2,6)‐tripyridinacyclohexaphane (N3) intercalated by lithium. DFT computations showed that the interaction of CO2 with N3Li leads to the catalytic complex N3Li(η2‐O2C), which can initiate the radical‐controlled reduction of another CO2 to form organic acids through radical reactions in the gas phase. The CO2 reduction consists of four steps: (1) The formation of N3Li(η2‐O2C) through the combination of N3Li and CO2, (2) hydrogen abstraction from RH (R=H, CH3, and C2H5) by N3Li(η2‐O2C) to form the radical R. and N3Li(η2‐O2C)H, (3) the combination of CO2 and the radical R. to form RCOO. and (4) intermolecular hydrogen transfer from the intermediate N3Li(η2‐O2C)H to RCOO.. In the whole reaction process, the CO2 moiety in the complex N3Li(η2‐O2C) maintains a certain radical character at the carbon atom of CO2 and plays a self‐catalyzing role. This work represents the first example of electride‐sponsored radical‐controlled CO2 reduction, and thus provides an alternative strategy for CO2 conversion. [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]

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]

An efficient silver‐catalyzed stereoselective trans‐addition of 4‐hydroxycoumarins to haloalkynes under ambient air is described, allowing the straightforward synthesis of vinyl halides. The late‐stage nitration of the resulting products with silver nitrate proceeded with retention of configuration, affording a series of nitroalkenes in good yields. Additionally, DFT calculations were employed for mechanistic studies, and a possible mechanism for the Ag(I)‐catalyzed addition was proposed. Two silver medals: An efficient silver‐catalyzed stereoselective trans addition of 4‐hydroxycoumarins to haloalkynes afforded a number of exclusive addition products in high yields. Nitration of the addition products provided an approach to synthesize nitroalkenes. Additionally, based on the results from DFT calculations, a possible mechanism for the Ag(I)‐catalyzed addition was proposed. [ABSTRACT FROM AUTHOR]

GDC‐0810 was under development as an oral anti‐cancer drug for the treatment of estrogen receptor‐positive breast cancer as a single agent or in combination. In vitro data indicated that GDC‐0810 is a potent inhibitor of OATP1B1/1B3. To assess clinical risk, a PBPK model was developed to predict the transporter drug–drug interaction (tDDI) between GDC‐0810 and pravastatin in human. The PBPK model was constructed in Simcyp® by integrating in vitro and in vivo data for GDC‐0810. The prediction of human pharmacokinetics (PK) was verified using GDC‐0810 phase I clinical PK data. The Simcyp transporter DDI model was verified using known OATP1B1/1B3 inhibitors (rifampicin, cyclosporine and gemfibrozil) and substrate (pravastatin), prior to using the model to predict GDC‐0810 tDDI. The effect of GDC‐0810 on pravastatin PK was then predicted based on the proposed clinical scenarios. Sensitivity analysis was conducted on the parameters with uncertainty. The developed PBPK model described the PK profile of GDC‐0810 reasonably well. In the tDDI verification, the model reasonably predicted pravastatin tDDI caused by rifampicin and gemfibrozil OATP1B1/3 inhibition but under‐predicted tDDI caused by cyclosporine. The effect of GDC‐0810 on pravastatin PK was predicted to be low to moderate (pravastatin Cmax ratios 1.01–2.05 and AUC ratio 1.04–2.23). The observed tDDI (Cmax ratio 1.20 and AUC ratio 1.41) was within the range of the predicted values. This work demonstrates an approach using a PBPK model to prospectively assess tDDI caused by a new chemical entity as an OATP1B1/3 uptake transporter inhibitor to assess clinical risk and to support development strategy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cr(VI) is being increasingly used in a variety of fields, including electroplating, metallurgy, pigment synthesis and leather tanning. The possible application of a microbial extracellular polymeric substance (EPS) from Klebsiella sp. J1 with abundant functional groups in remediating Cr(VI) pollution in water system was demonstrated. RESULTS: The maximum biosorption capacity of EPS for Cr(VI) was found to be 53.3 mg g−1 at an EPS dose of 1.5 g L−1, which was better than the majority of reported biosorbents. The adsorption of EPS for Cr(VI) was a spontaneous and endothermic process. The removal mechanism of Cr(VI) in aquatic environments was explored qualitatively and quantitatively by Zeta‐potential meter, X‐ray photoelectron spectrometer (XPS) as well as Fourier transform infrared spectrometer. The superior Cr(VI) removal performance was attributed mainly to Cr(VI) adsorption on EPS via chelation and ion‐exchange sorption, and the efficient reduction (82.3%) of Cr(VI) to Cr(III) by benzenoid amine (–NH–) on EPS, followed by generated Cr(III) immobilization on the surface of EPS via surface physical sorption and chelation, which might control the reaction rate of Cr(VI) removal process. CONCLUSION: The removal of Cr(VI) by EPS from Klebsiella sp. J1 was attributed mainly to simultaneous sorption and reduction of Cr(VI) by EPS. The results demonstrated that EPS from Klebsiella sp. J1 has great potential in treating Cr(VI)‐contaminated water. © 2018 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Abstract: Adsorption of hexavalent uranium (U(VI)) by extracellular polymeric substances (EPS) has been studied, but the possibility of simultaneous U(VI) reduction mediated by EPS has not had experimental confirmation, as the reduction products have not yet been directly proven. Here, we reported the first direct evidence of lower‐valent products of U(VI) immobilization by loosely associated EPS (laEPS) isolated from a fermenter strain of Klebsiella sp. J1 when the laEPS was exposed to H2. During the 120‐min tests for similarly 86% adsorption under O2, N2, and H2, 8% more U was immobilized through a non‐adsorptive pathway by the EPS for H2 than for N2 and O2. A set of solid‐state characterization tools (FT‐IR, XPS, EELS, and TEM‐EDX) confirmed partial reduction of U(VI) to lower‐valence U, with the main reduced form being uraninite (UIVO2) nanoparticles, and the results reinforced the role of the reduction in accelerating U immobilization and shaping the characteristics of immobilized U in terms of valency, size, and crystallization. The laEPS, mostly comprised of carbohydrate and protein, contained non‐cytochrome enzymes and electron carriers that could be responsible for electron transfer to U(VI). Taken together, our results directly confirm that EPS was able to mediate partial U(VI) reduction in the presence of H2 through non‐cytochrome catalysis and that reduction enhanced overall U immobilization. Our study fills in some gaps of the microbe‐mediated U cycle and will be useful to understand and control U removal in engineered reactors and in‐situ bioremediation. [ABSTRACT FROM AUTHOR]

Abstract: The non‐peripherally substituted 1,4,8,11,15,18,22,25‐octa(butoxy)‐phthalocyanine‐involved unsymmetrical heteroleptic bis(phthalocyaninato) terbium double‐decker, Tb(Pc){H[Pc(α‐OC4H9)8]} (Pc=unsubstituted phthalocyanine) (1), was revealed to exhibit typical single ion magnet (SIM) behavior with effective energy barrier, 180 K (125 cm−1), and blocking temperature, 2 K, due to the severe deviation of the terbium coordination polyhedron from square‐antiprismatic geometry. Fabrication of this double‐decker compound into the novel tetrakis(phthalocyaninato) terbium pseudo‐quadruple‐decker Na2{Tb(Pc)[Pc(α‐OC4H9)8]}2 (2) single molecule magnet (SMM) not only optimizes the coordination polyhedron of terbium ion towards the square‐antiprismatic geometry and intensifies the coordination field strength, but more importantly significantly enhances the molecular magnetic anisotropy in the unsymmetrical bis(phthalocyaninato) double‐decker unit, along with the change of the counter cation from H+ of 1 to Na+ of 2, leading to an significantly enhanced magnetic behavior with spin‐reversal energy barrier, 528 K (367 cm−1), and blocking temperature, 25 K. The present result is surely helpful towards developing novel tetrapyrrole lanthanide SMMs through rational design and self‐assembly from bis(tetrapyrrole) lanthanide single ion magnet (SIM) building block. [ABSTRACT FROM AUTHOR]

Metastasis-associated lung adenocarcinoma transcript 1 (malat1) is an oncogenic long non-coding RNA (lncRNA) which has been proven to be associated with various types of tumors. Transcription factor specificity protein 1 (SP1) is overexpressed in many types of cancers. Previously, we observed that malat1 expression level is regulated by SP1 in lung cancer. In the present study, we found that transfection of expression construct of malat1 50 end fragment M5 enhances stability and transcriptional activity of SP1. Various SP1 target genes are also upregulated following overexpression of malat1 M5 in lung adenocarcinoma cells. We also showed that malat1 M5 interacts with the C-terminal domain of SP1 by RNA immunoprecipitation (RIP) assay coupled with UV cross-linking. Malat1-SP1 association results in increase of SP1 stability. In turn, SP1 promotes malat1 transcription, thus forming a positive feedback loop. In conclusion, our data show that in lung adenocarcinoma cells, malat1 interacts with SP1 protein and promotes SP1-mediated transcriptional regulation of SP1 target genes. [ABSTRACT FROM AUTHOR]

Based on the seismic profiles, drilling, tomographic images and other geological data, we use the I2VIS code to program the Mesozoic finite‐difference numerical model in the southern part of the East China Sea Continental Shelf Basin (ECSCSB). We try to model the basin evolutionary process by setting up different boundaries to the 2‐D models. After analysing the simulation results of low‐speed and high‐speed stretching models, we found that under the condition of preliminary tensile value, the magma could not be generated in both rapid and slow stretching cases. This means that the regional extension of the Mesozoic ECSCSB is not the only dominant factor for basin evolution. Based on the analysis of the regional geological features and the modelling results, we suggest that the low‐velocity lithosphere mantle in the study area may be due to the melting of the mantle caused by the subduction and dehydration of the Izawa Nasaki Plate. The evolutionary process of the Mesozoic basins in the ECSCSB is closely related to regional extension and the magma upwelling caused by subduction and dehydration of the Izawa Nasaki Plate during the Mesozoic Era. The magma upwelling led to large‐scale magmatic events. It is likely to act in the Minjiang Sag, which resulted in the further rise of the Minjiang Sag and the formation of the present slope zone. [ABSTRACT FROM AUTHOR]

In this article, foam zero‐valent nickel (FZVN) was put forward as a promising zero‐valent metal for the pretreatment of azo dye wastewater (MO as a model contaminant). The characteristics of FZVN were evaluated by methods of Barrett‐Emmett‐Teller, scanning electron microscopy, X‐ray diffraction, and X‐ray photoelectron spectroscopy. Moreover, influence of key experimental parameters, including oxygen concentration, presence of different acid, pH, and temperature on the MO decolorization were systematically ascertained. Furthermore, possible mechanism of MO removal by FZVN was investigated by using Liquid chromatography‐mass spectrometry (LC‐MS). Results showed that FZVN was a three‐dimensional pore material with a specific surface area of 3 m2 g−1. Moreover, anoxic condition, presence of acetic acid, higher temperatures and acid conditions were beneficial to decolorize MO by FZVN while the decolorization process obeyed the first order kinetic model with an apparent rate constant (kapp) of 0.162 min−1 at pH value of 4 (25°C). The activation energy Ea obtained from the decolorization reaction was 83.1 kJ mol−1. Based on LC‐MS results, the role of FZVN in the decolorization reaction process was suggested as follows: strong reductive, catalysis, and adsorption. © 2017 American Institute of Chemical Engineers Environ Prog, 37: 686–694, 2018 [ABSTRACT FROM AUTHOR]

BACKGROUND The importance of arbuscular mycorrhizal fungi ( AMF) for nutrient uptake and growth in rice has been widely recognized. However, little is known about the distribution of carbon (C) and nitrogen (N) in rice under AMF inoculation, which can affect grain yield and quality. This study was conducted to investigate the distribution of C and N within rice plants under AMF inoculation and the effects on grain yield and quality. RESULTS AMF inoculation significantly increased N accumulation and distribution in vegetative tissues at tillering, and N translocation into seeds from heading to maturity. Consequently, AMF inoculation more strongly impacted the distribution of N than that of C in seeds, with significantly reduced C:N ratios and increased protein content (by 7.4%). Additionally, AMF inoculation significantly increased grain yield by 28.2% through increasing the grain:straw ratio by 18.4%. In addition, the roots of inoculated rice exhibited greater change in C distribution, with significantly higher C concentrations, C accumulations, and C:N ratios at tillering and maturity. CONCLUSION AMF inoculation affected the distribution of N in seeds and C in roots. As such, AMF inoculation may be a potential method for improving grain yield and quality. © 2016 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

The of epoxide and CO2 to synthesize cyclic carbonate catalyzed by VO(IV) porphyrin was achieved under 1.4 MPa at 150°C. The effects of reaction temperature, time, CO2 pressure, co-catalyst and porphyrin framework were investigated. The catalytic results showed that moderate to high yields of cyclic carbonates were obtained under the optimal reaction conditions. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Synthesis of cyclic carbonates from CO2 and terminal epoxides catalyzed by Mg, Ca and In BINOL complexeswas achieved without organic solvents. Effects of temperature, CO2 pressure, reaction time and co-catalyst on the cycloaddition were investigated. Propylene carbonatewas obtained under a CO2 pressure of 1.2MPawithin 10 hours in a yield of 98%catalyzed by Ca-BINOL at 120°C. The order of catalytic activity of the metal center is Ca>In>Mg. [ABSTRACT FROM AUTHOR]

As a kind of ammonia-oxidizing bacteria, Nitrosomonas europaea (N. europaea) was chosen as a research model to study the alteration of cell membrane in the presence of tourmaline and biodegradation of acetochlor. atomic force microscopy images reveal that the presence of tourmaline substantially changes the structure of the outer membrane of the cell responsible for the cell permeability. SEM images show that the introduction of tourmaline makes the cell lose its ability to resist lysozyme owing to the damages. The fluorescence polarization has shown a significant decrease in membrane fluidity and the increase of permeability of cell membrane. Ca2+ and Mg2+ was measured using inductively coupled plasma mass spectrometry and was found in the supernatant from the cells treated by tourmaline. Tourmaline can improve the efficiency of biodegradation of acetochlor for N. europaea. It is proposed that the cell permeability is slightly increased, and the absorbability of nutrition from the medium becomes easier. As a result, N. europaea grows faster in the presence of tourmaline than the native cells. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim To evaluate the reliability of contrast-enhanced ultrasonography ( CEUS) for the detection of renal microvascular blood perfusion in a type 2 diabetic Goto- Kakizaki ( GK) rat model. Methods Male GK and Wistar rats at the age of 4, 12 and 20 weeks ( n = 10, respectively) were used for the study. Real-time and haemodynamic imaging of the renal cortex was performed using CEUS with SonoVue. Outage time-intensity curves ( TICs) were applied for the analysis of basic intensity, slope rates of the ascending ( S1) and descending curves ( S2), time to peak ( TTP), half time of peak descending ( HDT), peak intensity ( PI), and total area under the curve ( AUC). Immunohistochemical staining for endothelial cells ( ECs) was performed using the CD34 monoclonal antibody for the quantification of microvessel density and distribution. Results Images of the renal cortex microvascular beds after injection of Sono Vue in the rats were rapidly and clearly displayed, and it is easy to differentiate the enhanced and faded images of renal perfusion. The TICs of the GK rats were much wider than the controls; however, no significant changes in PI were found in all aged rats. Ultrasonographic quantitative analysis revealed a decrease in S1 and S2, and an increase in TTP, HDT and AUC in the 12- and 20-week-old GK rats compared with the controls ( P < 0.05). Moreover, the 20-week-old GK rats had much lower glomerular density and smaller distribution area of CD34-positive ECs, which was in parallel with more severe proteinuria, GBM thickening, glomerulosclerosis and interstitial vascular damages ( P < 0.05). Interestingly, negative correlations between AUC and glomerular microvessel density or distribution were detected, respectively ( P < 0.05). Conclusions Contrast-enhanced ultrasonography is a valid technique for the real-time and dynamic assessment of renal cortex microvascular perfusion and haemodynamic characterization in GK rats. [ABSTRACT FROM AUTHOR]

Context In light of the call for humanistic caring in the contemporary health care system globally and in China, the issue of improving the caring skills that are essential to student success, high-quality nursing practice and positive patient outcomes is at the forefront of nursing education. Objectives The aim of this mixed-methods quantitative and qualitative study was to investigate baccalaureate nursing students' caring ability in the context of China and to explore the role of clinical practice learning in the development of students' caring skills. Methods A two-phase, descriptive study utilising a mixed methodology consisting of a caring ability survey and focus group interviews was conducted. In the quantitative phase, 598 baccalaureate nursing students at two colleges in Yunnan Province in southwest China were surveyed using the Caring Ability Inventory ( CAI). In the qualitative phase, 16 of the students who had participated in the quantitative phase were interviewed. Results Students obtained lower scores on the CAI than have been reported elsewhere by other researchers. In addition, students in the clinical stage of training scored lower than students in the pre-clinical stage. Three themes concerning facilitation by and three themes concerning the obstructive effects of clinical practice learning in the development of caring ability were identified. Themes pertaining to facilitation were: (i) promoting a sense of professional responsibility and ethics; (ii) providing an arena in which to practise caring, and (iii) learning from positive role models. Themes pertaining to obstruction were: (i) a critical practice learning environment; (ii) encountering inappropriate clinical teachers, and (iii) experiencing shock at the contrast between an idealised and the real environment. Conclusions The key to developing students' ability to care lies in highlighting caring across the entire health care system. By diminishing exposure to negative role models, and adopting appropriate pedagogical ideas about education in caring, such as truth telling and helping students to think in a critical manner, educators can help students to improve their caring ability. [ABSTRACT FROM AUTHOR]