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Maternal anaemia is a major public health problem. Developing maternal anaemia prevention and control policies is an important prerequisite for carrying out evidence‐based interventions. This article reviews maternal anaemia prevention and control policies in China, identifies gaps, and provides references for other countries. We examined policies concerning maternal nutrition and other related literature in China, identified through key databases and government websites, and conducted a narrative review of the relevant documentations guided by the Smith Policy‐Implementing‐Process framework. A total of 65 articles and documents were identified for analysis. We found that Chinese government has committed to reducing maternal anaemia at the policy level, with established objectives and a clear time frame. However, most of policies were not accompanied by operational guidelines, standardized interventions, and vigorous monitoring and evaluation mechanisms, and 85% of the policies don't have quantifiable objectives on anaemia. Maternal anaemia prevention and control services offered in clinical settings were primarily nutrition education and anaemia screening. Population‐based interventions such as iron fortification have yet to be scaled up. Furthermore, medical insurance schemes in some regions do not cover anaemia prevention and treatment, and in other regions that offer coverage, the reimbursement rate is low. The number and capacity of health professionals is also limited. Policy changes should focus on the integration of evidence‐based interventions into routine antenatal care services and public health service packages, standardization of dosages and provision of iron supplementation, streamline of reimbursement for outpatient expenses, and capacity building of health professionals. Key messages: The Government of China has established targets with a clear time frame for maternal anaemia prevention and control and identified several interventions at the national level.There are still gaps in policy‐binding forces, prevention strategies, reimbursement regulations of medical insurance schemes, and human resource.Policy changes should focus on the integration of evidence‐based interventions into routine antenatal care services and public health service packages, standardization of dosages and provision of iron supplementation, streamline of reimbursement for outpatient expenses, and capacity building of health professionals. [ABSTRACT FROM AUTHOR]

Video transformers achieve superior performance in video recognition. Despite the recent advances in video transformers, they still require substantial computation and memory resources. To cater for the computation efficiency, a kernel‐based video transformer is proposed, including: (1) a new formulation of the video transformer via the kernel learning is presented to better understand the individual components of it; (2) a lightweight Kernel‐based spatial–temporal multi‐head self‐attention block is explored to learn the compact joint spatial–temporal video feature; (3) an adaptive‐score position embedding method is conducted to promote the flexibility of video transformer. Experimental results on several action recognition datasets demonstrate the effectiveness of the proposed method. Only pretrained on ImageNet‐1K, the method achieves the preferable balance between computation and accuracy, while requiring 7×$\times$ fewer parameters and 13×$\times$ fewer floating point operations than other comparable methods. [ABSTRACT FROM AUTHOR]

Purpose: Vancomycin-resistant enterococci (VRE) have recently become a major cause of nosocomial infections and a global public health concern. Tedizolid exhibits powerful antibacterial activity against VRE in vitro, but its pharmacokinetic/pharmacodynamic (PK/PD) parameters remain unclear. Therefore, we aimed to determine the PK/PD indices of tedizolid action on VRE and the mechanisms underlying the PK/PD indices differences of tedizolid against VRE and methicillin-resistant Staphylococcus aureus (MRSA). Methods: Optimal PK/PD target values of tedizolid were determined in vitro, based on time-kill curves and post-antibiotic effects (PAEs), and in vivo, using mouse models of thigh infection with VRE and MRSA strains. Results: The tedizolid bactericidal activity on VRE and MRSA was time-dependent. Correlations were closest between fAUC24/MIC and the tedizolid PK/PD index against MRSA and VRE. To achieve 1 log10 kill tedizolid fAUC24/MIC in neutropenic mouse models of thigh infection with VRE and MRSA should be 14.2 and 138.5, respectively. The PAEs of tedizolid against VRE and MRSA were 2.39 and 0.99 h, respectively. Conclusion: Tedizolid showed bactericidal effects against VRE even in neutropenic mice unlike MRSA, which could be attributed to its longer PAE against VRE. Hence, we hypothesize that tedizolid treatment against VRE infections is promising for achieving therapeutic success in clinical. [ABSTRACT FROM AUTHOR]

Fruit ripening is usually accompanied by anthocyanin accumulation. Ethylene is key in ripening-induced anthocyanin production in many fruits. However, the effects of fruit ripening and ethylene on anthocyanin biosynthesis in purple tomato fruits are unclear. This study shows that bagged fruits of the purple tomato cultivar 'Indigo Rose' failed to produce anthocyanins at the red ripening stage after bag removal. In contrast, the bagged immature fruits accumulated a significant amount of anthocyanins after removing the bags. The transcriptomic analyses between immature and red ripening fruit before and after bag removal revealed that anthocyanin-related genes, including the key positive R2R3-MYB regulator SlAN2-like, were repressed in the red ripening fruit. The 86 identified transcription factors, including 13 AP2/ERF, 7 bZIP, 8 bHLH and 6 MYB, showed significantly different expressions between immature and red ripening fruits. Moreover, subjecting bagged immature fruits to exogenous ethylene treatment significantly inhibited anthocyanin accumulation and the expression of anthocyanin-related genes, including the anthocyanin structure genes and SlAN2-like. Thus, ethylene inhibits anthocyanin biosynthesis by repressing the transcription of SlAN2-like and other anthocyanin-related genes. These findings provide new insights into anthocyanin regulation in purple tomato fruit. [ABSTRACT FROM AUTHOR]

The informatization of cities has been further promoted, and the construction of smart cities supported by technological innovation has been upgraded. The financial industry and data are closely related. Whether the financial industry can make good use of new information technology is the key to its successful transformation. The development of smart cities has a significant effect on the development of people's livelihood, the process of urbanization, the use of technology, the solution of urban problems, and the improvement of economic levels. This also provides a good choice for the development of cities in each country. For better development, it needs technical support. Therefore, it is very important to improve the technical level. This research mainly discusses the risk assessment and regulation algorithms of financial technology platforms in smart cities. This study divides the risk decision channels into two paths based on the smart city theory, considers the internal risk factors and external risk factors of the robo-advisory service platform from the three perspectives of platform characteristics, corporate characteristics, and investor characteristics and exploring the construction of a robo-advisory service platform risk prediction model based on the machine learning perspective. The design and implementation of a personalized financial investment prototype system, a Python-based web development framework Django, and a variety of toolkits have realized a B/S architecture robo-advisor. Among them, the function of buying and selling ETF and the trend recording function after buying are realized by simulating the transaction data collected by the data collection module. The study found that the key potential characteristics that constitute platform risks are mainly the listing year of the background company, the age of the platform, the investment threshold, and the search index. To a certain extent, this provides data support for investors and regulatory authorities to evaluate platform capabilities and platform selection. Investors should comprehensively consider platform qualifications when making platform decisions and pay attention to information such as the age of listing of companies with platform background, platform age, and investment thresholds. Only when the quality of people is improved, the quality of the population of this city improves, so that the development of the city has a broad room for growth. The accuracy of the similar formula calculation method in the big data proposed in this study reached 88%. This research provides new ideas for perfecting the black box regulatory system of robo-advisory algorithms. [ABSTRACT FROM AUTHOR]

Crabs in mangroves could enhance the transfer of organic carbon (OC) from leaf litter to soils, whose variation with the difference in crab size is, however, not well known. A 32-day laboratory feeding experiment was conducted to explore the effects of different sizes of the crabs Parasesarma plicatum foraging on leaf litter of Kandelia obovata on OC accumulation in mangrove soils. Mean rates of soil OC accumulation due to leaf foraging by large, medium, and small crabs were 21.11, 16.11, and 0.77 mg C ind−1 d−1, corresponding to the rates of OC removal from leaf litter of 62.60%, 51.37%, and 2.19%, respectively. Large and medium crabs ingested larger amounts of leaf litter, and soil OC accumulation rates resulting from leaf foraging by large and medium crabs were approximately 8 times higher than those by leaf litter decomposition and triple those by non-leaf foraging. Small crabs ingested the smallest amount of leaf litter, which was almost used for their growth and metabolism. These results underline the key ecological roles of leaf foraging by crabs, especially those with large and medium sizes, in OC accumulation in mangrove soils, which is conducive to estimating carbon sequestration in mangrove soils. • We divided the herbivorous crabs into large, medium and small sizes. • Large and medium crabs significantly increased soil OC accumulation. • Small crabs had little impact on soil OC accumulation. • The transformation rate of leaf litter decay to soil OC was 6.63%. • The transformation rates of large, medium and small crabs to soil OC were 62.60%, 51.37% and 2.19%. [ABSTRACT FROM AUTHOR]

Sepsis-induced acute kidney injury (AKI) continues to be associated with poor outcomes in critical care patients. Previous research has revealed that tetrahydrocurcumin (THC) exerts renoprotective effects in multiple nephritic disorders by modulating inflammation and oxidative stress. However, the effects of THC on sepsis-induced AKI and the underlying mechanisms remain unclear. In this study, a mouse model of sepsis-induced AKI, generated by cecal ligation and puncture operation, was used to investigate the protective effects of THC and the role of SIRT1. Histological manifestation and TUNEL analysis were observed to determine the severity of kidney damage. Levels of BUN, SCr, KIM-1, and UAlb/Cr were calculated to assess the renal function. Expressions of IL-1β, IL-6, and TNF-α were measured to evaluate the inflammatory response. MDA content, SOD, GSH, CAT, and GPx activities and DHE staining were analyzed to estimate the degree of oxidative stress. Protein expressions of SIRT1, Ac-p65, and Ac-foxo1 were detected to explore the underlying mechanisms. We observed that THC not only increased the survival rate, improved the kidney function and ameliorated the renal histological damage of septic mice, but also inhibited inflammatory response, prohibited oxidative stress, and prevented cell apoptosis in renal tissues in septic mice. Mechanistically, THC remarkably increased the expression of SIRT1, accompanied by decreased expressions of downstream molecules Ac-p65 and Ac-foxo1. Meanwhile, the beneficial effects of THC were clearly abolished by the SIRT1-specific inhibitor EX527. These results delineate that THC prevents sepsis-induced AKI by suppressing inflammation and oxidative stress through activating the SIRT1 signaling. Abbreviation: Ac-p65: acetylated p65; Ac-foxo 1: acetylated forkhead box O1; AKI: acute kidney injury; BUN: blood urea nitrogen; CAT: catalase; DHE: dihydroethidium; GPx: glutathione peroxidase; GSH: reduced glutathione; IL-1β: Interleukin-1 beta; IL-6: Interleukin-6; KIM-1: kidney injury molecule 1; MDA: malondialdehyde; SCr: serum creatinine; SIRT1: silent information regulator 1; SOD: superoxide dismutase; THC: tetrahydrocurcumin; TNF-α: tumor necrosis factor-alpha; TUNEL: TdT-mediated dUTP Nick-End Labeling; UAlb/Cr: urine micro albumin/creatinine. [ABSTRACT FROM AUTHOR]

Deubiquitinating enzymes (DUBs) are a largely understudied and untapped resource in the toolkit of protein degradation functionalities. They comprise a large repertoire of enzymes that remove ubiquitin from substrates in a variety of cellular and pathophysiological contexts, and have enormous potential for research and clinical use. It is only within the last 5 years that potent, selective, and well-characterized small-molecule inhibitors of DUBs have been described. These compounds are now being used to study the biological roles of DUBs. Here, we describe downstream applications of small-molecule inhibitors for studying DUBs and provide a framework for future studies. We highlight recent examples of using these inhibitors to confirm and explore the role of these enzymes in both normal and pathological contexts. These studies represent the first steps in the burgeoning field of pharmacological and chemoproteomic studies of DUBs, which will be critical for the continued advancement of DUB field. [Display omitted] Magin et al. review the development of small-molecule inhibitors of deubiquitinating enzymes (DUBs), and their application in studying DUB function and therapeutic potential. Examples of well-validated inhibitors are given and future perspectives for this growing field are discussed. [ABSTRACT FROM AUTHOR]

Background: Hispidin (HIP) and its derivatives, a class of natural fungal metabolites, possess complex chemical structures with extensive pharmacological activities. Phellinus igniarius, the most common source of HIP, can be used as both medicine and food. However, the biosynthetic pathway of HIP in P. igniarius remains unclear and we have a limited understanding of the regulatory mechanisms related to HIP. In this work, we sought to illustrate a biosynthesis system for hispidin and its derivatives at the protein level. Results: We found that tricetolatone (TL) is a key biosynthetic precursor in the biosynthetic pathway of hispidin and that its addition led to increased production of hispidin and various hispidin derivatives. Based on the changes in the concentrations of precursors and intermediates, key timepoints in the biosynthetic process were identified. We used isobaric tags for relative and absolute quantification (iTRAQ) to study dynamic changes of related proteins in vitro. The 270 differentially expressed proteins were determined by GO enrichment analysis to be primarily related to energy metabolism, oxidative phosphorylation, and environmental stress responses after TL supplementation. The differentially expressed proteins were related to ATP synthase, NAD binding protein, oxidoreductase, and other elements associated with electron transfer and dehydrogenation reactions during the biosynthesis of hispidin and its derivatives. Multiple reaction monitoring (MRM) technology was used to selectively verify the iTRAQ results, leading us to screen 11 proteins that were predicted to be related to the biosynthesis pathways. Conclution: These findings help to clarify the molecular mechanism of biosynthesis of hispidin and its derivatives and may serve as a foundation for future strategies to identify new hispidin derivatives. [ABSTRACT FROM AUTHOR]

Spirulina platensis can synthesize a large amount of phycocyanin, which had been developed as a health food. At the same time, Spirulina can absorb the nitrogen and phosphorus in wastewater and provide for its own growth. Here, we studied the optimal nitrogen and phosphorus supply for the Spirulina production process. For the first time, 405 nm portable Raman spectrometer was used to estimate phycocyanin content for real-time industrial applications. We obtained three Raman characteristic peaks of phycocyanin through density functional theory combined with home-built Raman spectrometer, which were 1272, 1337, and 1432 cm − 1 . There was a good linear correlation between the sum of the three peak intensities and the PCL concentration (y = 18.887x + 833.530, R 2 = 0.890). The least squares support vector machine model based on the characteristic peaks was used to estimate the concentration of phycocyanin and obtained good results with a correlation coefficient of prediction of 0.907 and residual predictive deviation of 3.357. The results can provide decision-making for integration of Spirulina effluent treatment and phycocyanin production and provide references for real-time Spirulina-based biorefinery applications. [ABSTRACT FROM AUTHOR]

We quantify the effect of exchange rate fluctuations on firm leverage. When home currency appreciates, firms who hold foreign currency debt and local currency assets observe higher net worth as appreciation lowers the value of their foreign currency debt. These firms can borrow more as a result and increase their leverage. When home currency depreciates, the reverse happens as firms have to de-lever with a negative shock to their balance sheets. Using firm-level data for leverage from 10 emerging market economies during the period from 2002 to 2015, we show that firms operating in countries whose non-financial sectors hold more of the debt in foreign currency, increase (decrease) their leverage relatively more after home currency appreciations (depreciations). Combining the leverage data with firm-level FX debt data for 4 emerging market countries, we further show that our results hold at the most granular level. Our quantitative results are asymmetric: the effects of depreciations, that are generally associated with sudden stops, are quantitatively larger than those of appreciations, which take place at a slower pace over time during capital inflow episodes. As our exercise compares depreciations and appreciations of similar size, these results are suggestive of financial frictions being more binding during depreciations than a possible relaxation of such frictions during appreciations. [ABSTRACT FROM AUTHOR]

Motivation The interaction between proteins and nucleic acids plays a crucial role in gene regulation and cell function. Determining the binding preferences of nucleic acid-binding proteins (NBPs), namely RNA-binding proteins (RBPs) and transcription factors (TFs), is the key to decipher the protein–nucleic acids interaction code. Today, available NBP binding data from in vivo or in vitro experiments are still limited, which leaves a large portion of NBPs uncovered. Unfortunately, existing computational methods that model the NBP binding preferences are mostly protein specific: they need the experimental data for a specific protein in interest, and thus only focus on experimentally characterized NBPs. The binding preferences of experimentally unexplored NBPs remain largely unknown. Results Here, we introduce ProbeRating, a nucleic acid recommender system that utilizes techniques from deep learning and word embeddings of natural language processing. ProbeRating is developed to predict binding profiles for unexplored or poorly studied NBPs by exploiting their homologs NBPs which currently have available binding data. Requiring only sequence information as input, ProbeRating adapts FastText from Facebook AI Research to extract biological features. It then builds a neural network-based recommender system. We evaluate the performance of ProbeRating on two different tasks: one for RBP and one for TF. As a result, ProbeRating outperforms previous methods on both tasks. The results show that ProbeRating can be a useful tool to study the binding mechanism for the many NBPs that lack direct experimental evidence. and implementation Availability and implementation The source code is freely available at < https://github.com/syang11/ProbeRating >. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Sequences homologous to human herpesvirus 6 (HHV-6) are integrated within the nuclear genome of about 1% of humans, but it is not clear how this came about. It is also uncertain whether integrated HHV-6 can reactive into an infectious virus. HHV-6 integrates into telomeres, and this has recently been associated with polymorphisms affecting MOV10L1. MOV10L1 is located on the subtelomere of chromosome 22q (chr22q) and is required to make PIWI-interacting RNAs (piRNAs). As piRNAs block germline integration of transposons, piRNA-mediated repression of HHV-6 integration has been proposed to explain this association. In vitro, recombination of the HHV-6 genome along its terminal direct repeats (DRs) leads to excision from the telomere and viral reactivation, but the expected "solo-DR scar" has not been described in vivo. Here we screened for integrated HHV-6 in 7,485 Japanese subjects using whole-genome sequencing (WGS). Integrated HHV-6 was associated with polymorphisms on chr22q. However, in contrast to prior work, we find that the reported MOV10L1 polymorphism is physically linked to an ancient endogenous HHV-6A variant integrated into the telomere of chr22q in East Asians. Unexpectedly, an HHV-6B variant has also endogenized in chr22q; two endogenous HHV-6 variants at this locus thus account for 72% of all integrated HHV-6 in Japan. We also report human genomes carrying only one portion of the HHV-6B genome, a solo-DR, supporting in vivo excision and possible viral reactivation. Together these results explain the recently-reported association between integrated HHV-6 and MOV10L1/piRNAs, suggest potential exaptation of HHV-6 in its coevolution with human chr22q, and clarify the evolution and risk of reactivation of the only intact (non-retro)viral genome known to be present in human germlines. Author summary: Human herpesvirus 6 (HHV-6) infects most people during childhood and can reactivate later in life to contribute to diseases. The HHV-6 genome is also inherited by about 1% of people, included in the end "cap" of one of their 46 chromosomes. Little is known about how HHV-6 genomes entered human genomes, whether or not they still do, and the risk this poses for virus reactivation. We looked for HHV-6 in genome sequences from ~7,500 Japanese people. Most integrated HHV-6 variants have been co-evolving with human chromosomes for many generations. Surprisingly, in almost three-fourths of Japanese people with HHV-6 in their genome, HHV-6 is integrated in the same end of the same chromosome– 22q. Persistence of the HHV-6 genome within the short "cap" that preserves the end of chromosome 22q raises the question of whether the integrated viral sequence has taken on a useful function for this chromosome. Some human genomes harbor only one part of the HHV-6 genome–the same part that remains after experimental HHV-6 reactivation, during which most of the virus is cut out of the genome. This suggests that integration of HHV-6 into inherited human genomes is not irreversible, and possibly leads to production of infectious virus. [ABSTRACT FROM AUTHOR]

Key message: Combining phenotype and gene expression analysis of the CRISPR/Cas9-induced SlAN2 mutants, we revealed that SlAN2 specifically regulated anthocyanin accumulation in vegetative tissues in purple tomato cultivar 'Indigo Rose.' Anthocyanins play an important role in plant development and also exhibit human health benefits. The tomato genome contains four highly homologous anthocyanin-related R2R3-MYB transcription factors: SlAN2, SlANT1, SlANT1-like, and SlAN2-like/Aft. SlAN2-like/Aft regulates anthocyanin accumulation in the fruit; however, the genetic function of the other three factors remains unclear. To better understand the function of R2R3-MYB transcription factors, we conducted targeted mutagenesis of SlAN2 in the purple tomato cultivar 'Indigo Rose' using clustered regularly interspersed short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9). The SlAN2 mutants had a fruit color and anthocyanin content similar to cv. 'Indigo Rose,' while the anthocyanin content and the relative expression levels of several anthocyanin-related genes in vegetative tissues were significantly lower in the SlAN2 mutant relative to cv. Indigo Rose. Furthermore, we found that anthocyanin biosynthesis is controlled by different regulators between tomato hypocotyls and cotyledons. In addition, SlAN2 mutants were shorter, with smaller and lighter fruits than cv. 'Indigo Rose.' Our findings further our understanding of anthocyanin production in tomato and other plant species. [ABSTRACT FROM AUTHOR]

A new coordination polymer, namely, [Co2(L)2(H2O)4]n·nH2O (1) (H2L = 5-(1H-1,2,4-triazol-1-yl)-1,3-benzenedicarboxylic acid), was synthesized via the reaction of H2L and Co(NO3)2·6H2O at pH value of 3.6 under the hydrothermal conditions. In addition, a technique of green hand grinding was carried out to decrease complex 1's particle size, resulting in the formation of nanoscale 1 (denoted as nano 1 hereafter) with ball-like morphology. Furthermore, the prevention and treatment ability of the compound on the Alzheimer's disease (AD) was evaluated and the related mechanism was discussed. First, the animal model AD of was established within mice, then brain weight along with volume was measured after compound treatment. Besides, the content of the Amyloid (Aβ) was detected to reveal the mechanism and the target of the compound. [ABSTRACT FROM AUTHOR]

PUPOSE: We investigated the prevalence and spectrum of pathogenic germline variants in patients with early-onset colorectal cancer (CRC), breast cancer (BC), and prostate cancer (PCA) in the Japanese population. We also identified pathogenic variants in other cancer risk genes, giving consideration to future multigene testing panels for this population. METHODS: We performed whole-genome sequencing for 1,037 Japanese individuals, including patients with early-onset CRC (n = 196), BC (n = 237), and PCA (n = 215) and controls (n = 389). We screened for pathogenic variants, including single nucleotide variants and copy number variants, among well-established first-tier cancer genes for each cancer type and examined an expended second-tier panel including cancer-predisposing genes from the Cancer Gene Census. RESULTS: Proportions of patients with germline pathogenic variants differed by cancer subgroup, with the highest in BC (14.8%), followed by CRC (9.2%), and PCA (3.7%). In contrast, 2 of 389 control subjects (0.5%) carried a germline pathogenic variant. In comparison with controls, the proportion of patients with pathogenic variants in the second-tier panel was increased significantly for PCA (3.7% to 11.6%, P = 2.96 × 10−4), but not for CRC or BC, after multitesting adjustment. In patients with PCA, DNA repair pathway genes in the extended panel often contained pathogenic variants (P =.011). CONCLUSION: Our analyses support the clinical usefulness of established cancer gene panels in the Japanese population for 3 major cancer types. Additional genes, especially those involved in DNA repair, might be considered for developing multipanel testing in Japanese patients with early-onset PCA. [ABSTRACT FROM AUTHOR]

Ubiquitin specific peptidase 7 (USP7) is a deubiquitinating enzyme (DUB) that removes ubiquitin tags from specific protein substrates in order to alter their degradation rate and sub-cellular localization. USP7 has been proposed as a therapeutic target in several cancers because it has many reported substrates with a role in cancer progression, including FOXO4, MDM2, N-Myc, and PTEN. The multi-substrate nature of USP7, combined with the modest potency and selectivity of early generation USP7 inhibitors, has presented a challenge in defining predictors of response to USP7 and potential patient populations that would benefit most from USP7-targeted drugs. Here, we describe the structure-guided development of XL177A, which irreversibly inhibits USP7 with sub-nM potency and selectivity across the human proteome. Evaluation of the cellular effects of XL177A reveals that selective USP7 inhibition suppresses cancer cell growth predominantly through a p53-dependent mechanism: XL177A specifically upregulates p53 transcriptional targets transcriptome-wide, hotspot mutations in TP53 but not any other genes predict response to XL177A across a panel of ~500 cancer cell lines, and TP53 knockout rescues XL177A-mediated growth suppression of TP53 wild-type (WT) cells. Together, these findings suggest TP53 mutational status as a biomarker for response to USP7 inhibition. We find that Ewing sarcoma and malignant rhabdoid tumor (MRT), two pediatric cancers that are sensitive to other p53-dependent cytotoxic drugs, also display increased sensitivity to XL177A. [ABSTRACT FROM AUTHOR]

Chemical ionization mass spectrometry (CIMS) techniques have become prominent methods for sampling trace gases of relatively low volatility. Such gases are often referred to as being "sticky", i.e., having measurement artifacts due to interactions between analyte molecules and instrument walls, given their tendency to interact with wall surfaces via absorption or adsorption processes. These surface interactions can impact the precision, accuracy, and detection limits of the measurements. We introduce a low-pressure ion–molecule reaction (IMR) region primarily built for performing iodide-adduct ionization, though other adduct ionization schemes could be employed. The design goals were to improve upon previous low-pressure IMR versions by reducing impacts of wall interactions at low pressure while maintaining sufficient ion–molecule reaction times. Chamber measurements demonstrate that the IMR delay times (i.e., magnitude of wall interactions) for a range of organic molecules spanning 5 orders of magnitude in volatility are 3 to 10 times lower in the new IMR compared to previous versions. Despite these improvements, wall interactions are still present and need to be understood. To that end, we also introduce a conceptual framework for considering instrument wall interactions and a measurement protocol to accurately capture the time dependence of analyte concentrations. This protocol uses short-duration, high-frequency measurements of the total background (i.e., fast zeros) during ambient measurements as well as during calibration factor determinations. This framework and associated terminology applies to any instrument and ionization technique that samples compounds susceptible to wall interactions. [ABSTRACT FROM AUTHOR]

AR‐67 is a lipophilic camptothecin analog currently under clinical investigation using a Cremophor EL based formulation. However, as potential toxicity limitations exist in the clinical use of Cremophor, an alternative cyclodextrin (SBE‐β‐CD) based formulation has been proposed. Pharmacokinetic (PK) studies were conducted in mice and the SBE‐β‐CD based formulation was compared with the Cremophor EL formulation. PK studies were conducted following intravenous or oral administration of AR‐67 in either Cremophor or SBE‐β‐CD formulation in mice. Noncompartmental analysis was used to determine the plasma and tissue drug distribution. A non‐linear mixed effects (population) PK model was developed to fit both the oral and intravenous data and to estimate key PK parameters. The effect of formulation was explored as a covariate in the PK model. AR‐67 in the SBE‐β‐CD formulation had similar plasma PK and biodistribution to that in the Cremophor EL formulation. The proposed two‐compartment model described the plasma PK of AR‐67 in both formulations adequately. AR‐67 in the SBE‐β‐CD formulation exhibited dose linearity following both oral and intravenous administration. Our studies indicate that SBE‐β‐CD is a viable alternative to Cremophor EL as a pharmaceutical excipient for formulating AR‐67. [ABSTRACT FROM AUTHOR]

[Display omitted] • 13C-bicarbonate is a crucial measure of pyruvate oxidation and TCA cycle flux. • Signal of 13C-bicarbonate can be increased with a bSSFP sequence. • Bicarbonate MS-bSSFP requires specialized RF pulse, optimized TR and 3D encoding. • Bicarbonate MS-bSSFP shows SNR improvements in preclinical, human brain and human kidney studies Metabolite-specific bSSFP sequence has the potential to estimate T 2 of HP 13 C metabolites. 13C-bicarbonate is a crucial measure of pyruvate oxidation and TCA cycle flux, but is challenging to measure due to its relatively low concentration and thus will greatly benefit from improved signal-to-noise ratio (SNR). To address this, we developed and investigated the feasibility of a 3D stack-of-spirals metabolite-specific balanced steady-state free precession (MS-bSSFP) sequence for improving the SNR and spatial resolution of dynamic 13C-bicarbonate imaging in hyperpolarized [1-13C]pyruvate studies. The bicarbonate MS-bSSFP sequence was evaluated by simulations, phantoms studies, preclinical studies on five rats, brain studies on two healthy volunteers and renal study on one renal cell carcinoma patient. The simulations and phantom results showed that the bicarbonate-specific pulse had minimal perturbation of other metabolites (<1%). In the animal studies, the MS-bSSFP sequence provided an approximately 2.6–3 × improvement in 13C-bicarbonate SNR compared to a metabolite-specific gradient echo (MS-GRE) sequence without altering the bicarbonate or pyruvate kinetics, and the shorter spiral readout in the MS-bSSFP approach reduced blurring. Using the SNR ratio between MS-bSSFP and MS-GRE, the T 2 values of bicarbonate and lactate in the rat kidneys were estimated as 0.5 s and 1.1 s, respectively. The in-vivo feasibility of bicarbonate MS-bSSFP sequence was demonstrated in two human brain studies and one renal study. These studies demonstrate the potential of the sequence for in-vivo applications, laying the foundation for future studies to observe this relatively low concentration metabolite with high-quality images and improve measurements of pyruvate oxidation. [ABSTRACT FROM AUTHOR]

Provides information on a study which reported the preparation, microstructure, magnetic properties and the temperature dependence of lanthanum-zinc substituted strontium ferrite thin films. Experimental procedures; Results and discussions.

Recent work has quantified the delay times in measurements of volatile organic compounds (VOCs) caused by the partitioning between the gas phase and the surfaces of the inlet tubing and instrument itself. In this study we quantify wall partitioning effects on time responses and transmission of multifunctional, semivolatile, and intermediate-volatility organic compounds (S/IVOCs) with saturation concentrations (C∗) between 10 0 and 10 4 µgm-3. The instrument delays of several chemical ionization mass spectrometer (CIMS) instruments increase with decreasing C∗ , ranging from seconds to tens of minutes, except for the NO3- CIMS where it is always on the order of seconds. Six different tubing materials were tested. Teflon, including PFA, FEP, and conductive PFA, performs better than metals and Nafion in terms of both delay time and transmission efficiency. Analogous to instrument responses, tubing delays increase as C∗ decreases, from less than a minute to >100 min. The delays caused by Teflon tubing vs. C∗ can be modeled using the simple chromatography model of Pagonis et al. (2017). The model can be used to estimate the equivalent absorbing mass concentration (Cw) of each material, and to estimate delays under different flow rates and tubing dimensions. We also include time delay measurements from a series of small polar organic and inorganic analytes in PFA tubing measured by CIMS. Small polar molecules behave differently than larger organic ones, with their delays being predicted by their Henry's law constants instead of their C∗ , suggesting the dominance of partitioning to small amounts of water on sampling surfaces as a result of their polarity and acidity properties. PFA tubing has the best performance for gas-only sampling, while conductive PFA appears very promising for sampling S/IVOCs and particles simultaneously. The observed delays and low transmission both affect the quality of gas quantification, especially when no direct calibration is available. Improvements in sampling and instrument response are needed for fast atmospheric measurements of a wide range of S/IVOCs (e.g., by aircraft or for eddy covariance). These methods and results are also useful for more general characterization of surface–gas interactions. [ABSTRACT FROM AUTHOR]

Puerarin, baicalin and berberine hydrochloride are the main components of Gegen Qinlian Decoction, which has been used to treat diarrhoea in China for hundreds of years, yet the biological function and molecular mechanism of these components are not clear. To investigate the effects of puerarin, baicalin, and berberine hydrochloride on the regulation of porcine intestinal epithelial cells (IPEC-J2 cells) infected with enterotoxigenic Escherichia coli (ETEC). IPEC-J2 cells were pretreated with puerarin (200 μg/mL), baicalin (1 μg/mL), and berberine hydrochloride (100 μg/mL) at 37°C for 3 h and then coincubated with the F4ac ETEC bacterial strain 200 at 37°C for 3 h. ETEC infection damaged the structure of IPEC-J2 cells, upregulated mucin 4 (P < 0.01) and mucin 13 mRNA (P < 0.05) expression, increased the apoptosis rate (P < 0.05), and promoted inflammatory responses (IL-6 and CXCL-2 mRNA expression) in IPEC-J2 cells by activating the nuclear factor-κB (NF-κB) signaling pathway. Pretreatment with puerarin, baicalin, and berberine hydrochloride improved the structure and morphology of IPEC-J2 cells and inhibited ETEC adhesion by downregulating specific adhesion molecules. Pretreatment with baicalin decreased the inflammatory response; pretreatment with baicalin and berberine hydrochloride decreased the inflammatory response mediated by the NF-κB signaling pathway. Pretreatment with puerarin, baicalin, and berberine hydrochloride protected IPEC-J2 cells from ETEC infection by inhibiting bacterial adhesion and inflammatory responses. [ABSTRACT FROM AUTHOR]

Abstract Source apportionment studies have been performed on online receptor datasets in recent years (called online source apportionment), including mass spectra and online chemical dataset. Single particle aerosol mass spectrometry (SPAMS), an important online technique, has the ability to analyze mass spectrum (MS) and particular size information of a single particle in real time. Clustering methods have been widely applied to MS dataset to investigate the sources of particles, although the receptor models are the common tools to probe the particle sources based on the receptor dataset. This work developed a new method (SPAMS-RM) that employed the receptor model (RM) on an MS dataset from SPAMS to identify particle sources. Particles were measured by SPAMS from July 14 to August 15, 2015, at an urban site in Tianjin, China. Multilinear Engine-2 (ME2) and adaptive resonance theory-based neural networks-2a (ART-2a) were separately used to analyze the single particle MS dataset. This work also evaluated the performance of SPAMS-RM method. Concentrations of chemical components of PM 2.5 (particulate matter with an aerodynamic diameter of less than 2.5 μm) and gaseous pollutants were measured by independent online instruments (1 h resolution). Source apportionment was separately conducted using two receptor models, Positive Matrix Factorization (PMF) and ME2, based on the 1 h resolution chemical dataset. This method was called online chemical source apportionment (OCSA-RM). ART-2a obtained 19 clusters that merged into five major classes: carbon species, rich-K, sea salt, crustal dust, and industrial metals. SPAMS-RM identified eight sources by interpreting the MS characteristic of factors and investigating the relationship of the temporal trends of factor contributions, chemical species, gaseous pollutants, and particle clusters. OCSA-ME2 and OCSA-PMF both identified seven factors. Source apportionment results between SPAMS-RM and OCSA-ME2/PMF were compared. Each method identified coal combustion, biomass burning, sea salt, nitrate source, sulfate source, vehicle emission, and crustal dust. The SPAMS-RM results showed that nitrate source was the most significant contributor (34%) to the PM followed by sulfate source (17%), coal combustion (14%), crustal dust (11%), vehicle emission (10%), biomass burning-OCEC (7%), and industrial activities & sea salt (4%). Some differences between SPAMS-RM and OCSA-ME2/PMF results existed and might be due to chemical analysis methods and sampling methods. ME2 was used for the first time to identify the PM sources based on the MS dataset from SPAMS and demonstrated its capability when coupled with MS dataset from SPAMS to apportion the source of PM. Highlights • A new method that employed ME2 on SPAMS dataset was developed to infer PM sources. • PMF and ME2 were employed on the 1 h resolution chemical dataset. • ART-2a was employed on the SPAMS dataset to qualitatively identify the PM sources. [ABSTRACT FROM AUTHOR]

A major challenge in population pharmacokinetic modeling is handling data with missing or potentially incorrect dosing records. Leaving such records untreated or "commented out" will cause bias in parameter estimates. Several approaches were previously developed to address this challenge. Published in 2004, the missing dose method (MDM) demonstrated its robustness in handling missing dosing history in pharmacokinetic (PK) modeling. In this study, we presented two new extensions: a modified MDM method (MDM2) and a compartment initialization method (CIM). Their performance was examined with a large batch of simulated PK studies. For each method, 8,000 models were run, including different model structures, dosing routes, and missing dosing record scenarios. Both MDM2 and CIM exhibited robust performance and improved parameter estimation results. Specifically, CIM consistently outperformed other methods in fixed‐effect and random‐effect PK parameter estimation. The new methods demonstrate great potential in addressing missing dosing records challenges in PK analysis. [ABSTRACT FROM AUTHOR]

Background: The heart has metabolic flexibility, which is influenced by fed/fasting states, and pathologies such as myocardial ischemia and hypertrophic cardiomyopathy (HCM). Hyperpolarized (HP) 13C-pyruvate MRI is a promising new tool for non-invasive quantification of myocardial glycolytic and Krebs cycle flux. However, human studies of HP 13C-MRI have yet to demonstrate regional quantification of metabolism, which is important in regional ischemia and HCM patients with asymmetric septal/apical hypertrophy. Methods: We developed and applied methods for whole-heart imaging of 13C-pyruvate, 13C-lactate and 13C-bicarbonate, following intravenous administration of [1-13C]-pyruvate. The image acquisition used an autonomous scanning method including bolus tracking, real-time magnetic field calibrations and metabolite-specific imaging. For quantification of metabolism, we evaluated 13C metabolite images, ratio metrics, and pharmacokinetic modeling to provide measurements of myocardial lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) mediated metabolic conversion in 5 healthy volunteers (fasting & 30 min following oral glucose load). Results: We demonstrate whole heart coverage for dynamic measurement of pyruvate-to-lactate conversion via LDH and pyruvate-to-bicarbonate conversion via PDH at a resolution of 6 × 6 × 21 mm3 (13C-pyruvate) and 12 × 12 × 21 mm3 (13C-lactate, 13C-bicarbonate). 13C-pyruvate and 13C-lactate were detected simultaneously in the RV blood pool, immediately after intravenous injection, reflecting LDH activity in blood. In healthy volunteers, myocardial 13C-pyruvate-SNR, 13C-lactate-SNR, 13C-bicarbonate-SNR, 13C-lactate/pyruvate ratio, 13C-pyruvate-to-lactate conversion rate, kPL, and 13C-pyruvate-to-bicarbonate conversion rate, kPB, all had statistically significant increases following oral glucose challenge. kPB, reflecting PDH activity and pyruvate entering the Krebs Cycle, had the highest correlation with blood glucose levels and was statistically significant. Conclusions: We demonstrate first-in-human regional quantifications of cardiac metabolism by HP 13C-pyruvate MRI that aims to reflect LDH and PDH activity. [ABSTRACT FROM AUTHOR]

This study sought to examine grouped and right-censored (GRC) counts of adolescent marijuana use and estimate its temporal trajectories and sociodemographic disparities over almost half a century. After compiling 46 waves of nationally representative data from the Monitoring the Future (MTF) study from 1976 to 2021 (sample size = 491,348), we utilized an innovative modified Poisson (mixture) approach to analyze past-year marijuana use quantified by GRC counts. The overall reduction in incidence rates of marijuana use was attributable to an almost 40% reduction in the risk of marijuana use (with the proportion of at-risk adolescents at 51.36% in 1979 and 31.53% in 2021). Despite substantial changes over the study period, the recent incidence rates for at-risk individuals were similar to those in the early 1980s. Living in an intact family was a protective factor against adolescent marijuana use over time. The incidence rates of marijuana use among at-risk students, especially those from disadvantaged families, remained high over the study period. The modified Poisson (mixture) approach serves as the preferred tool for modeling GRC responses. It is essential to distinguish among risk, at-risk incidence, and overall incidence when assessing substance use and other risky behaviors. [ABSTRACT FROM AUTHOR]

An ultrathin MgO/Fe seed layer was introduced to manipulate the crystal orientation and crystallinity of Fe/MgO/Fe trilayers. The crystallographic properties and magnetic properties of the trilayer are investigated. It is concluded that the texture of the MgO layer is strongly dependent on the texture of the Fe layer. (001) oriented Fe layer can assist the growth of (001) oriented MgO barrier upon annealing. A 0.5 nm MgO seed layer can introduce (001) orientation in the following Fe layer. It is also found that the crystal orientation of the Fe/MgO/Fe trilayer is independent of the initial Fe seed layer thickness. However, the crystallinity of both the Fe layer and the MgO layer is dependent on the initial Fe seed layer. [ABSTRACT FROM AUTHOR]

The crystallographic and magnetic properties of sub-10-nm Nd2Fe14B films have been investigated. It is found that the magnetization reversal mechanism is changed in Nd–Fe–B films with the decrease of film thickness. Films with thickness greater than 10 nm show domain-wall-motion type of behavior. Strong exchange coupling between the grains makes the magnetic domain wall easily propagate in the films. Films with thickness of 4 nm show the Stoner-Wohlfarth particle behavior. The initial magnetization process is magnetization rotation. This is also verified by angular dependence of the coercivity. [ABSTRACT FROM AUTHOR]

The magnetic properties of multilayer composed of Fe65Co35 and thin layers of Co (less than 5 nm) have been investigated. It is found that the microstructure, crystallographic texture, and magnetic softness of the multilayers depended on the initial layer. Multilayers with saturation magnetic induction higher than 23 kG and hard axis coercivity smaller than 2 Oe have been successfully prepared by using Co as the initial layer. Furthermore, the structure provided an effective process to tailor the in-plane magnetic anisotropy field without deteriorating the magnetic softness of the multilayers. [ABSTRACT FROM AUTHOR]

The history of processing tomato industry in China is short and the major variety being used in production to date is still Riegel 87-5, a variety released in 1996. To investigate the genetic and fruit trait differences between Chinese elite lines/varieties and American varieties, 51 including 24 recently developed Chinese elite lines, four Chinese varieties, and 23 American varieties were subjected to genotypic analysis using 547 InDel markers. The range of Nei’s genetic distance was wider in Chinese elite lines (0.209–0.383) than in Chinese varieties (0.126–0.214) and American varieties (0.223–0.342). Cluster analysis indicated that the 51 varieties/lines could be classified into three groups without specific relationship between group and country. This was further supported by population structure analysis using the software STRUCTURE2.3.4. Fruit traits were collected from 51 tomato varieties/lines grown in 2013 and 2014. The average soluble solid content was lower, while the average fruit weight was larger, and the average color was relatively poorer in both Chinese elite lines and varieties than in the American varieties. However, some elite lines such as 9508-h and their progenies had relatively good fruit traits, and thus could be superior sources for processing tomato improvement. The experience of developing processing tomato industry in China could be of value to countries with similar situations. [ABSTRACT FROM AUTHOR]

In 2014 and 2015, the Research Center for Chinese Frontier Archaeology at Jilin University and the Jilin Province Archaeological Research Institute jointly conducted two excavations at the Yinjiawopu Site, in Da’an City, Jilin Province, Northeast China. One burial, two canals, five leaching pits, two house-foundations, four hearths, 103 pits, two ditches, and over 800 pieces of artifacts dated from the 12th to the 13th centuriesa.d.(the Liao-Jin period) were found. Analysis shows that these features belong to a salt production workshop. This study marks the first discovery of a salt production site in Northeast China. The archaeological, ethnographic, and historical materials from the site allow a reconstruction of thechaîne opératoireof salt-making by the inhabitants of the Northeast China Plain during this period. This study sheds light on the exchange and control of salt, on the activities and daily life of the inhabitants of the region, and on their relationship with the environment. [ABSTRACT FROM PUBLISHER]

Molecular chlorine (Cl2) and nitryl chloride (ClNO2) concentrations were measured using chemical ionization mass spectrometry at a rural site over the North China Plain during June 2014. High levels of daytime Cl2 up to ∼450 pptv were observed. The average diurnal Cl2 mixing ratios showed a maximum around noon at ∼100 pptv. ClNO2 exhibited a strong diurnal variation with early morning maxima reaching ppbv levels and afternoon minima sustained above 60 pptv. A moderate correlation (R2 = 0.31) between Cl2 and sulfur dioxide was observed, perhaps indicating a role for power plant emissions in the generation of the observed chlorine. We also observed a strong correlation (R2 = 0.83) between daytime (10:00-20:00) Cl2 and ClNO2, which implies that both of them were formed from a similar mechanism. In addition, Cl2 production is likely associated with a photochemical mechanism as Cl2 concentrations varied with ozone (O3) levels. The impact of Cl2 and ClNO2 as Cl atom sources is investigated using a photochemical box model. We estimated that the produced Cl atoms oxidized slightly more alkanes than OH radicals and enhanced the daily concentrations of peroxy radicals by 15% and the O3 production rate by 19%. [ABSTRACT FROM AUTHOR]

We have successfully prepared Sr-ferrite dot arrays with perpendicular magnetic anisotropy by electron beam lithography. Virgin magnetic configurations detected by magnetic force microscopy (MFM) show single domain configuration for a 0.5 μm dot, while multidomain configurations are found for larger dots. The magnetization reversal mechanism in dots larger than 0.5 μm is found to be domain wall motion. While the magnetization reversal mechanism in 0.5 μm dots is found to be magnetization rotation. A normalized dc demagnetization remanence curve (DCD) measured by a superconducting quantum interference device (SQUID) indicates that with a decrease of dot size, the DCD curve is approaching the curve predicted by the coherent rotation model. Both MFM and SQUID results indicate that the single-domain dots reversed individually free from interdot magnetostatic coupling. [ABSTRACT FROM AUTHOR]

La–Zn substituted Sr-ferrite thin films were prepared by rf diode sputtering. The magnetic and crystallographic properties of the films were investigated by vibrating sample magnetometry and x-ray diffractometry. It is found that the texture of the films sensitively depends on the amount of substitution. Both the saturation magnetization M[sub s] and coercivity H[sub c] increase with the increase of La–Zn substitution. The increase of H[sub c] is caused, in part, by the increase of K[sub 1] due to the substitution. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Purpose: Nacubactam (NAC) is a novel diazabicyclooctane β-lactamase inhibitor used in combination with cefepime (CFPM). In this study, we aimed to determine the target pharmacokinetics (PK) and pharmacodynamics (PD) values of CFPM/NAC in mice infected with β-lactamase-producing Enterobacterales, such as the carbapenemase-producing Enterobacterales. Methods: Three strains of β-lactamase-producing Enterobacterales, Klebsiella pneumoniae MSC 21444, Escherichia coli MSC 20662, and K. pneumoniae ATCC BAA-1898, were used for checkerboard assays and fractionation studies and dose-range studies. A PK study was performed in neutropenic mice. Additionally, PK/PD analysis was performed based on the instantaneous minimum inhibitory concentration (MICi) concept. Results: Checkerboard measurements revealed that higher NAC concentrations decreased the CFPM MIC in a concentration-dependent manner. In all tested strains, fT > MICi calculated from the PK experiments showed a high correlation with the mean change in the bacterial count of thigh-infected mice in the in vivo PD study, suggesting that fT > MICi is an optimal PK/PD parameter for monitoring the CFPM/NAC combination. The target fT > MICi values for CFPM/NAC to achieve a bacteriostatic effect, 1-log10-kill, and 2-log10-kill values were 30, 49, and 94%, respectively. Conclusions: Our results indicate that fT > MICi is a PK/PD parameter is suitable for monitoring the CFPM/NAC combination. The minimum target value for achieving a static effect against β-lactamase-producing Enterobacterales is 30%. [ABSTRACT FROM AUTHOR]

Purpose: Intravenous (IV) magnesium sulfate (MgSO) is used as adjunct therapy to treat acute asthma exacerbations. Despite its clinical use, there is a limited understanding of the disposition of magnesium in children. Methods: To explore the pharmacokinetics (PK) of IV MgSO in this population, we collected retrospective data from 54 children who received IV MgSO for treatment of an acute asthma exacerbation at Primary Children's Hospital in Salt Lake City, UT. These data were analyzed using population PK modeling techniques in NONMEM® to determine sources of variability affecting the disposition of magnesium, as well as to predict the dose of IV MgSO needed to achieve clinical benefit. Results: The covariate analysis found that only weight was a significant predictor of magnesium concentrations in children. Estimated model parameters suggested that magnesium exhibits a short serum half-life (2.7 h) in children. The average endogenous magnesium concentration (prior to administration of IV MgSO) was estimated to be 21 mg/L. Simulated data suggested that doses between 50 and 75 mg/kg are required to achieve concentration-time profiles within a hypothesized target therapeutic range between 25 and 40 mg/L. Conclusions: These results provide new insight into the disposition of IV MgSO in children and provide dosing guidelines for future prospective studies of IV MgSO in children with acute asthma. [ABSTRACT FROM AUTHOR]

Aims Caffeine concentrations in preterm infants are usually measured in the blood. However, salivary assays may provide a valid and practical alternative. The present study explored the validity and clinical utility of salivary caffeine concentrations as an alternative to blood concentrations and developed a novel plasma/salivary caffeine distribution model. Methods Paired salivary and plasma samples were obtained in 29 infants. Salivary samples were obtained using a commercially available salivary collection system. Caffeine concentrations in the saliva and plasma were determined using high-performance liquid chromatography. A population pharmacokinetic (PK) model was developed using NONMEM 7.3. Results The mean (± standard deviation) gestational age (GA) at birth and birth weight were 27.9 ± 2.1 weeks and 1171.6 ± 384.9 g, respectively. Paired samples were obtained at a mean postmenstrual age (PMA) of 35.5 ± 1.1 weeks. The range of plasma caffeine concentrations was 9.5-54.1 μg ml−1, with a mean difference (95% confidence interval) between plasma and salivary concentrations of −0.18 μg ml−1 (−1.90, 1.54). Salivary and plasma caffeine concentrations were strongly correlated (Pearson's correlation coefficient = 0.87, P < 0.001). Caffeine PK in plasma and saliva was simultaneously described by a three-compartment recirculation model. Current body weight, birth weight, GA, PMA and postnatal age were not significantly correlated with any PK parameter. Conclusions Salivary sampling provides an easy, non-invasive method for measuring caffeine concentrations. Salivary concentrations correlate highly with plasma concentrations. Caffeine PK in saliva and plasma are well described by a three-compartment recirculation model. [ABSTRACT FROM AUTHOR]

PurposePatchouli alcohol (PA) is used to treat gastrointestinal dysfunction. The purpose of this study was to ascertain the function of PA in the regulated process of oxidative stress in rat intestinal epithelial cells (IEC-6).Materials and methodsOxidative stress was stimulated by exposing IEC-6 cells to heat shock (42 °C for 3 h). IEC-6 cells in treatment groups were pretreated with various concentrations of PA (10, 40, and 80 ng/mL) for 3 h before heat shock.ResultsHeat shock caused damage to the morphology of IEC-6 cells, and increased reactive oxygen species (ROS) level and malondialdehyde (MDA) content. Moreover, mRNA and protein expression by target genes related to oxidative stress in heat shock were also altered. Specifically, the mRNA expression byHSP70,HSP90, GSH-px,NRF2ndHO-1were all increased, and Nrf2 and Keap1 protein expression were increased after heat shock. However, pretreatment with PA weakened the level of damage to the cellular morphology, and decreased the MDA content caused by heat shock, indicating PA had cytoprotective activities. Pretreatment with PA at high dose significantly increased generation of intracellular ROS. Compared with the heat shock group alone, PA pretreatment significantly decreased the mRNA expression byHSP70,HSP90,SOD,CAT,GSH-px,KEAP1andHO-1. Furthermore, the high dose of PA significantly increased Nrf2 protein expression, while both the intermediate and high dose of PA significantly increased HO-1 protein expression.ConclusionHeat-shock-induced oxidative stress in IEC-6 cells, and PA could alleviate the Nrf2-Keap1 cellular oxidative stress responses. [ABSTRACT FROM PUBLISHER]

Investigates the effect of underlayer for Ba-ferrite sputtered films on c-axis orientation. Improvement of crystallinity for hexagonal M phase; Preparation of the BaM films on the amorphous underlayer.

Tedizolid (TZD) is an oxazolidinone anti-methicillin-resistant Staphylococcus aureus (MRSA) drug. Linezolid (LZD), another oxazolidinone, has been shown to have an anti-inflammatory effect. TZD has been shown to exhibit an anti-inflammatory effect in a murine model of hematogenous pulmonary infection. In this study, we further investigated the anti-inflammatory effect of TZDs using a carrageenan-induced rat footpad edema model. TZD was administered at 0, 10, 20, and 40 mg/kg to the carrageenan-induced rat footpad edema model, and the edema rate was measured over time up to 9 h later. The area under the time curve of the edema rate profile (AUC edema0→9) decreased in a TZD dose-dependent manner. In addition, the correlation between AUC edema0→9 and the area under the time curve of free TZD plasma concentration (f AUC blood) obtained from the pharmacokinetic study of TZD in the carrageenan-induced rat footpad edema model was examined. f AUC blood and AUC edema0→9 showed a good negative correlation. These results indicate that TZD suppresses carrageenan-induced footpad edema and that TZD exerts its anti-inflammatory effects in a plasma concentration-dependent manner. [ABSTRACT FROM AUTHOR]

Co-ferrite thin film with spinel structure is attractive for spintronics and multifunctional devices. So far, single-crystal substrates are necessary to introduce perpendicular magnetic anisotropy in co-ferrite films. In this paper, a unique process has been developed to deposit co-ferrite thin films onto thermally oxidized silicon wafer with perpendicular magnetic anisotropy. We have successfully prepared co-ferrite films with (00l) orientation. Those films show perpendicular coercivities as large as 12.8 kOe. X-ray diffractometry results revealed that compressive strain, which is introduced by the postannealing process rather than deposition process, is as large as 1.3% in films with (00l) orientation. The large coercivity and perpendicular magnetic anisotropy can be quantitatively explained by the magnetoelastic effect. This silicon-compatible fabrication process is useful to further extending the applications of co-ferrite films. [ABSTRACT FROM AUTHOR]

Chirality-assisted synthesis (CAS) is a general approach to control the shapes of large molecular strips. CAS is based on enantiomerically pure building blocks that are designed to strictly couple in a single geometric orientation. Fully shape-persistent structures can thus be created, even in the form of linear chains. With CAS, selective recognition between large host and guest molecules can reliably be designed de novo. To demonstrate this concept, three C-shaped strips that can embrace a pillar[5]arene macrocycle were synthesized. The pillar[5]arene bound to the strips was a better host for electron-deficient guests than the free macrocycle. Experimental and computational evidence is provided for these unique cooperative interactions to illustrate how CAS could open the door towards the precise positioning of functional groups for regulated supramolecular recognition and catalysis. [ABSTRACT FROM AUTHOR]

Chirality-assisted synthesis (CAS) is a general approach to control the shapes of large molecular strips. CAS is based on enantiomerically pure building blocks that are designed to strictly couple in a single geometric orientation. Fully shape-persistent structures can thus be created, even in the form of linear chains. With CAS, selective recognition between large host and guest molecules can reliably be designed de novo. To demonstrate this concept, three C-shaped strips that can embrace a pillar[5]arene macrocycle were synthesized. The pillar[5]arene bound to the strips was a better host for electron-deficient guests than the free macrocycle. Experimental and computational evidence is provided for these unique cooperative interactions to illustrate how CAS could open the door towards the precise positioning of functional groups for regulated supramolecular recognition and catalysis. [ABSTRACT FROM AUTHOR]

Xie,Y.; Liu, X.; Tang, J., and Wu, R., 2015. Research on berthing capability and working property of pontoon bases. This paper proposes an integrated computing theory of the berthing capacity of port bases for the first time. By analyzing working conditions the base required, main influencing factors, berthing capability and working properties of the anchor-chain system, a method to calculate the berthing capability of the basis proposed. The work-energy theory is used to compute the impact force when berthing. This theory overcomes the defect of the method based on experience. The upper limit condition is determined. The research results fit the in-situ mooring test well, and have a greater significance for the analogous projects in the future. [ABSTRACT FROM AUTHOR]

ATP-binding cassette transporter D2 (D2) is an ABC half transporter that is thought to promote the transport of very long-chain fatty acyl-CoAs into peroxisomes. Both D2 and peroxisomes increase during adipogenesis. Although peroxisomes are essential to both catabolic and anabolic lipid metabolism, their function, and that of D2, in adipose tissues remain largely unknown. Here, we investigated the D2 localization and the proteome of D2-containing organelles, in adipose tissue. Centrifugation of mouse adipose homogenates generated a fraction enriched with D2, but deficient in peroxisome markers including catalase, PEX19, and ABCD3 (D3). Electron microscopic imaging of this fraction confirmed the presence of D2 protein on an organelle with a dense matrix and a diameter of ∼200 nm, the typical structure and size of a microperoxisome. D2 and PEX19 antibodies recognized distinct structures in mouse adipose. Immunoisolation of the D2-containing compartment confirmed the scarcity of PEX19 and proteomic profiling revealed the presence of proteins associated with peroxisome, endoplasmic reticulum (ER), and mitochondria. D2 is localized to a distinct class of peroxisomes that lack many peroxisome proteins, and may associate physically with mitochondria and the ER. [ABSTRACT FROM AUTHOR]

The first examplesof azomethine ylides derived from allylic amineand glyoxal precursors are reported. The condensation of primary allylicand α-aryl amines with glyoxylates or α-aryl glyoxalsaffords conjugated azomethine ylides that undergo facile [3 2] cycloaddition,providing 5-alkenyl pyrrolidine cycloadducts that cannot be accessedthrough the classical use of amino esters as ylide precursors. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate immune-related gene expression in rat small intestine after heat stress. Materials and methods: Twelve Sprague Dawley (SD) rats were randomly divided into control and heat-stressed groups. Rats in both groups were housed at 25 °C with 60% relative humidity. The heat-stressed group was subjected to 40 °C for 2 h/day for 3 days. After heat stress, the mRNA expression profile of small intestine epithelial tissue was evaluated by microarray analysis. Results: A total of 23 genes related to immune responses were significantly altered, of which 12 genes were up-regulated and 11 genes were down-regulated. Conclusions: Microarray analysis demonstrated the JAK-STAT pathway had a potentially important role in the regulation of inflammation in the small intestine, and changes in antigen presentation might reduce intestinal immune responses after heat stress. [ABSTRACT FROM AUTHOR]