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Background: Preeclampsia is a pregnancy-specific disease leading to maternal and perinatal morbidity. Hypertension and inflammation are the main characteristics of preeclampsia. Many factors can lead to hypertension and inflammation, including gut microbiota which plays an important role in hypertension and inflammation in humans. However, alterations to the gut microbiome and fecal metabolome, and their relationships in severe preeclampsia are not well known. This study aims to identify biomarkers significantly associated with severe preeclampsia and provide a knowledge base for treatments regulating the gut microbiome. Methods: In this study, fecal samples were collected from individuals with severe preeclampsia and healthy controls for shotgun metagenomic sequencing to evaluate changes in gut microbiota composition. Quantitative polymerase chain reaction analysis was used to validate the reliability of our shotgun metagenomic sequencing results. Additionally, untargeted metabolomics analysis was performed to measure fecal metabolome concentrations. Results: We identified several Lactobacillaceae that were significantly enriched in the gut of healthy controls, including Limosilactobacillus fermentum, the key biomarker distinguishing severe preeclampsia from healthy controls. Limosilactobacillus fermentum was significantly associated with shifts in KEGG Orthology (KO) genes and KEGG pathways of the gut microbiome in severe preeclampsia, such as flagellar assembly. Untargeted fecal metabolome analysis found that severe preeclampsia had higher concentrations of Phenylpropanoate and Agmatine. Increased concentrations of Phenylpropanoate and Agmatine were associated with the abundance of Limosilactobacillus fermentum. Furthermore, all metabolites with higher abundances in healthy controls were enriched in the arginine and proline metabolism pathway. Conclusion: Our research indicates that changes in metabolites, possibly due to the gut microbe Limosilactobacillus fermentum, can contribute to the development of severe preeclampsia. This study provides insights into the interaction between gut microbiome and fecal metabolites and offers a basis for improving severe preeclampsia by modulating the gut microbiome. [ABSTRACT FROM AUTHOR]

Introduction:The ability to access telepsychiatry through audio–video technology versus audio-only (telephone) technology potentially leads to inequitable outcomes. This study examines the characteristics of patients who relied on the telephone to complete outpatient telepsychiatry visits in a large health system. Methods:This is a retrospective analysis of all telepsychiatry outpatient visits conducted from May 1, 2020, to December 31, 2021. Demographic, clinical, and socioeconomic factors were extracted from the electronic health record. Two-sample t tests were used for continuous variables and χ2 tests for categorical variables for bivariate analyses. Multiple logistic regression was used to examine the association between only telephone visits and all input variables. Results:Eight hundred ninety-four (8.9%) patients completed all visits only by telephone during the study period. In bivariate analyses, factors associated with telephone-only visits included male sex, non-English primary language, Black race, unmarried status, non-Hispanic ethnicity, older age, Medicare enrollment, uninsured status, and higher social vulnerability index (SVI). Psychiatric diagnoses associated with only telephone visits included substance use disorders and psychotic disorders. In multivariate analyses, factors associated with higher odds of only telephone visits included older age, inactive patient portal, comorbid diabetes, higher SVI, and higher broadband adoption. Psychiatric diagnoses associated with higher odds of completing only telephone visits included psychotic disorders, substance use disorders, or intellectual/developmental disabilities. Conclusions:Several patient-level factors are associated with a reliance on the telephone to complete telepsychiatry appointments. [ABSTRACT FROM AUTHOR]

Studies of the effects of COVID-19 on youth suggest a worsening in mental health globally. We performed a retrospective analysis of data from January 2019-November 2021 for all outpatient referrals, as well as outpatient, inpatient, and emergency department (ED) encounters for behavioral health (BH) reasons in children aged < 18 in a large academic health system in the United States. Mean weekly rates of outpatient psychiatry referrals, outpatient psychiatry visits, ED visits, and inpatient admissions for BH reasons were compared between pre-pandemic and pandemic periods. The average weekly rate of ambulatory referrals (8.0 ± 0.33 to 9.4 ± 0.31) and completed appointments (194.2 ± 0.72 to 213.1 ± 0.71) significantly increased during the pandemic, driven largely by teenagers. The weekly average of ED pediatric encounters for BH did not increase during the pandemic, although the percentage of all pediatric ED encounters that were for BH did increase from 2.6 to 4.1% (p < 0.001). Length of stay for pediatric BH ED patients increased from 1.59 ± 0.09 days pre-pandemic to 1.91 ± 0.11 days post-pandemic (p < 0.0001). Inpatient admissions for BH reasons overall decreased during the pandemic, due to a decrease in inpatient psychiatric bed capacity. However, the weekly percentage of inpatient hospitalizations for BH reasons that occurred on medical units increased during the pandemic (15.2% ± 2.8–24.6% ± 4.1% (p = 0.0006)). Taken together, our data suggest the COVID-19 pandemic had varying degrees of impact, depending on the setting of care. [ABSTRACT FROM AUTHOR]

Transition-metal-catalyzed cross-coupling has emerged as one of the most powerful and useful tools for the formation of C–C and C–heteroatom bonds. Given the shortage of resources of precious metals on Earth, the use of Earth-abundant metals as catalysts in developing cost-effective strategies for cross-coupling is a current trend in synthetic chemistry. Compared with the achievements made using first-row nickel, iron, cobalt, and even manganese catalysts, the group 6 metal chromium has rarely been used to promote cross-coupling. This perspective covers recent advances in chromium-catalyzed cross-coupling reactions in transformations of chemically inert C(aryl)–O, C(aryl)–N, and C(aryl)–H bonds, offering selective strategies for molecule construction. The ability of low-valent Cr with a high-spin state to participate in two-electron oxidative addition is highlighted; this is different from the mechanism involving single-electron transfer that is usually assigned to chromium-mediated transformations. 1 Introduction 2 Chromium-Catalyzed Kumada Coupling of Nonactivated C(aryl)–O and C(aryl)–N Bonds 3 Chromium-Catalyzed Reductive Cross-Coupling of Two Nonactivated C(aryl)–Heteroatom Bonds 4 Chromium-Catalyzed Functionalization of Nonactivated C(aryl)–H Bonds 5 Conclusions and Outlook [ABSTRACT FROM AUTHOR]

The use of simple and low-cost chromium chloride salts as catalysts or precatalysts for the development of cost-effective methods is of significant synthetic and mechanistic interest. Here, recent advances in chromium-catalyzed organic transformations are highlighted. 1 Introduction 2 Arylmagnesiation of Alkynes 3 Catalytic Functionalization of C(aryl)–O Bonds 4 Catalytic Functionalization of C(aryl)–N Bonds 5 Catalytic Functionalization of C(aryl)–H Bonds 6 NHK-Type Reactions 7 Hydrogenation 8 Conclusions [ABSTRACT FROM AUTHOR]

Abstract In this paper, we suppress prepulses by introducing a temporal pulse cleaner based on a self-diffraction process to an ultraintense and ultrashort chirped-pulse amplification laser facility. The main characteristics of the pulse cleaner are investigated. By optimizing the time delay between two incident pulses and the input energy, the energy of 130 μJ has been achieved for the first-order self-diffraction seed pulse with the maximum conversion efficiency of ∼11%. The spatial beam quality is improved after the pulse cleaner. The first-order self-diffraction seed pulse is stretched, amplified and recompressed by the chirped-pulse amplification technique. The measurement results show that the temporal contrast is improved by more than five orders of magnitude to at least 3 × 1010 for the recompressed first-order self-diffraction pulse when the incident temporal contrast is 1.5 × 105. This enables the laser facility to generate petawatt-class pulses with a nanosecond temporal contrast of higher than 1010. [ABSTRACT FROM AUTHOR]

A method for the ruthenium-catalyzed ortho-alkynylation of benzoic acids was developed. The reaction was found to be directed by a weakly coordinating carboxyl group and offers a facile route for the synthesis of ortho-alkynylated derivatives. A rare example of a bis(alkynylation) reaction of C-H bonds was described. [ABSTRACT FROM AUTHOR]

Aniron-catalyzed, 8-amido-enabled regiodivergent C–H allylationof quinolines is described. This reaction represents a rare exampleof chelation-induced geometrically inaccessible C–H functionalization,allowing for the highly regio- and stereoselective preparation ofeither the C5- or the C4-allylated quinoline scaffolds regiocontrolledby the catalytic systems. [ABSTRACT FROM AUTHOR]

Abstract: New bounds on the magnitudes of the first- and second-order partial derivatives of rational triangular Bézier surfaces are presented. Theoretical analysis shows that the proposed bounds are tighter than the existing ones. The superiority of the proposed new bounds is also illustrated by numerical tests. [Copyright &y& Elsevier]

Abstract: 1-Substituted benzo[b][1,4]diazepines which are difficult to synthesize by traditional methods have been prepared by an Au(I)–N-heterocyclic carbene complex-catalyzed tandem hydroamination/cyclization process. This protocol features the one-pot formation of a seven-membered N-heterocycle via atom-economic hydroamination/cyclization reactions of readily available N-substituted o-phenylenediamines and terminal alkynes. Based on this strategy, fused tricyclic benzo[b][1,4]diazepines have been accessed for the first time. [Copyright &y& Elsevier]

Anefficient aminocyanation by the direct addition of aryl cyanamidesto arynes is described, enabling incorporation of highly useful aminoand cyano groups synchronously via cleavage of inert N–CN bonds,affording synthetically useful 1,2-bifunctional aminobenzonitriles.The postsynthetic functionalization of the aminocyanation productsallows diverse formation of synthetically important derivatives suchas drug molecule Ponstan and fused heterocycles. [ABSTRACT FROM AUTHOR]

Abstract: A novel polymer-supported N-heterocylic carbene (NHC)–rhodium complex was prepared from chloromethyl polystyrene (CM PS) resin using a simple procedure. This polymer-supported NHC–rhodium complex was used as a catalyst for the addition of arylboronic acids to aldehydes affording arylmethanols in excellent yields. [Copyright &y& Elsevier]

Focuses on the application of genetic algorithm to solve the problem of collision avoidance in ship navigation. Representation of the solution of problems as a finite-length string; Construction of single gene with the position and speed of the ship.

The defluoroborylation of fluoroarenes by chromium-catalyzed cleavage of unactivated C–F bonds is described. The reaction uses HBpin as the boron source, low-cost and commercially available chromium salt as the precatalyst, and terpyridine as a crucial ligand, providing a protocol with atom-efficient benefits and a wide range of applicable substrates for the functionalization of aryl C–F bonds. Preliminary mechanistic studies indicate that an unprecedented Cr-catalyzed magnesiation of the unactivated C–F bond occurred. The generated arylmagnesium intermediates then participated in the subsequent borylation reaction. The application of the strategy in the preparation of valuable derivatives is demonstrated by the late-stage functionalization of boronate ester groups. [ABSTRACT FROM AUTHOR]

Objectives: Preeclampsia (PE) and fetal growth restriction (FGR) have abnormal placental implantation and endothelial dysfunction in common. However, their etiologies are not well understood. Both heat shock protein 70 (Hsp70) and nitric oxide (NO) are suggested to play a major role in the regulation of maternal and fetoplacental hemodynamics. In this study, the association of PE with FGR and Hsp70 or NO was analyzed.Methods: A total of 30 cases of PE, 25 cases of PE complicated with FGR and 50 cases of normal pregnant women were chose, and PE and normal animal models were constructed. Subsequently, the levels of Hsp70 and NO in serum and placental tissues of humans and animals were measured and compared. Further, rats were injected with pLV-NC-shRNA, pLV-Hsp70-shRNA, pLV-EFIa-NC, and pLV-EFIa-Hsp70, respectively, the weight of each conceptus, number of pups, fetal crown to tail length, total weight of the placenta/fetus unit, and the content of NO were analyzed.Results: The expression of Hsp70 in serum and placental tissues of PE complicated with or without FGR group was increased, whereas the content of NO was decreased compared to the normal group. The fetal weight (FW) of the Hsp70 targeted suppression group was higher than the other two groups, whereas the placental weight (PW) was reversed. Also, NO synthase (NOS) expression was decreased in the Hsp70 over-expression group.Conclusions: We speculated that the enhancement of Hsp70 might be related to the development of PE combined with FGR through inhibiting the synthesis of NOS. [ABSTRACT FROM AUTHOR]

Terminal alkynes react with aromatic sulfonyl chlorides in the presence of an iron(II) catalyst and a phosphine ligand to give (E)-β-chlorovinylsulfones with 100% regio- and stereoselectivity. Various functional groups, such as chloride, bromide, iodide, nitro, ketone, and aldehyde, are tolerated under the reaction conditions. Addition of tosyl chloride to a 1,6-enyne followed by radical 5-exo-trigcyclization gave an exocyclic alkenylsulfone. [ABSTRACT FROM AUTHOR]

Geminal cross couplings using multiple components enable the formation of several different bonds at one site in the building of tertiary and quaternary alkanes. Nevertheless, there are remaining issues of concern—cleavage of two geminal bonds and control of selectivity present challenges. We report here the geminal cross couplings of three components by reactions of dihaloalkanes with organomagnesium and chlorosilanes or alkyl tosylates by Cr catalysis, affording the formation of geminal C−C/C−Si or C−C/C−C bonds in the creation of tertiary and quaternary alkanes. The geminal couplings are catalyzed by low‐cost CrCl2, enabling the sluggishness of competitive Kumada‐type side couplings and homocouplings of Grignard reagents, in achieving high chemoselectivity. Experimental and theoretical studies indicate that two geminal C‐halide bonds are continuously cleaved by Cr to afford a metal carbene intermediate, which couples with a Grignard reagent, followed by silylation, in the formation of geminal C−C and C−Si bonds via a novel inner‐sphere radical coupling mechanism. These three‐component geminal cross couplings are value‐addition to the synthesis of commercial drugs and bioactive molecules in medicinal chemistry. [ABSTRACT FROM AUTHOR]

Geminal cross couplings using multiple components enable the formation of several different bonds at one site in the building of tertiary and quaternary alkanes. Nevertheless, there are remaining issues of concern—cleavage of two geminal bonds and control of selectivity present challenges. We report here the geminal cross couplings of three components by reactions of dihaloalkanes with organomagnesium and chlorosilanes or alkyl tosylates by Cr catalysis, affording the formation of geminal C−C/C−Si or C−C/C−C bonds in the creation of tertiary and quaternary alkanes. The geminal couplings are catalyzed by low‐cost CrCl2, enabling the sluggishness of competitive Kumada‐type side couplings and homocouplings of Grignard reagents, in achieving high chemoselectivity. Experimental and theoretical studies indicate that two geminal C‐halide bonds are continuously cleaved by Cr to afford a metal carbene intermediate, which couples with a Grignard reagent, followed by silylation, in the formation of geminal C−C and C−Si bonds via a novel inner‐sphere radical coupling mechanism. These three‐component geminal cross couplings are value‐addition to the synthesis of commercial drugs and bioactive molecules in medicinal chemistry. [ABSTRACT FROM AUTHOR]

Described here is a chromium-catalyzed alkylative cross-coupling of benzamide derivatives with aliphatic electrophiles under mild conditions. This reaction was promoted by a low-cost and air-stable chromium(iii) chloride salt combined with an N-heterocyclic carbene ligand and phenylmagnesium bromide as a reductant, and probably occurred with low-valent chromium involved in the catalytic cleavage of the ortho-C–H bonds of the benzamide, followed by coupling with the alkyl bromide through a radical-involving mechanism. [ABSTRACT FROM AUTHOR]

Review: [24 refs. [ABSTRACT FROM AUTHOR]

Background: Data-independent acquisition (DIA) is one of the most powerful and reproducible proteomic technologies for large-scale digital qualitative and quantitative research. The aim of this study was to use proteomic methodologies for the identification of biomarkers that are over or underexpressed in women with intrahepatic cholestasis of pregnancy (ICP) compared with controls and discover a potential biomarker panel for ICP detection. Methods: The participants included 11 ICP patients and 11 healthy pregnant women as controls. The clinical characteristic data and the laboratory biochemical data were collected at the time of recruitment. Then, a data-independent acquisition (DIA)-based proteomics approach was used to identify differentially expressed proteins (DEPs) in serum exosomes between ICP patients and controls. Finally, bioinformatics analysis was used to identify the relevant processes in which these DEPs were involved. Results: The proteomics results showed that there were 162 DEPs in serum exosomes between pregnant women with ICP and healthy pregnant women, of which 106 were upregulated and 56 were downregulated in ICP. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the identified proteins were functionally related to specific cell processes including apoptosis, lipid metabolism, immune response and cell proliferation, and metabolic disorders, suggesting that these may be primary causative factors in ICP pathogenesis. Meanwhile, complement and coagulation cascades may be closely related to the development of ICP. Receiver operating characteristic curve (ROC) analysis showed that the area under the curve values of Elongation factor 1-alpha 1, Beta-2-glycoprotein I, Zinc finger protein 238, CP protein and Ficolin-3 were all approximately 0.9, indicating the promising diagnostic value of these proteins. Conclusions: This preliminary work provides a better understanding of the proteomic alterations in the serum exosomes of pregnant women with ICP. [ABSTRACT FROM AUTHOR]

Review: 53 refs. [ABSTRACT FROM AUTHOR]

The article presents chemical equations related to the article "Iron-Catalyzed, Chelation-Induced Remote C?H Allylation of Quinolines via 8-Amido Assistance" by Xuefeng Cong and Xiaoming Zeng, published in "Organic Letters" in 2014.

A novel Clostridium sp. strain WST isolated from mangrove sediments demonstrated its unique characteristics of producing high titer of biobutanol from low concentration of substrates via anaerobic fermentation. The strain is able to convert glucose and galactose to high amount of biobutanol up to 16.62 and 12.11 g/L, respectively, and the yields of 0.54 and 0.55 g/g were determined to be much higher than those from the previous reports on Clostridial batch fermentation. Moreover, the inherent strong regulatory system of strain WST also prompts itself to perform the fermentation process without any requirement of pH control. In addition to tolerance of high butanol concentration and negligible production of by-products (e.g., ethanol or acids), this strain has immense potential for the sustainable industry-scale production of biobutanol. [ABSTRACT FROM AUTHOR]

A simple procedure is developed to synthesize benzo[b][1,4]diazepines from o-phenylenediamine derivatives and terminal alkynes using a Au(I)-NHC-complex-catalyzed hydroamination/cyclization process. [ABSTRACT FROM AUTHOR]

The article presents chemical equations related to the article "Aminocyanation by the Addition of N—CN Bonds to Arynes: Chemoselective Synthesis of 1,2-Bifunctional Aminobenzonitriles" by B. Rao and colleagues, published in the "Organic Letters" in 2014.

Review: 456 refs. [ABSTRACT FROM AUTHOR]

Objective: To explore the cytochrome P450 family 27 subfamily A member 1 (CYP27A1) gene mutations in Chinese women with intrahepatic cholestasis of pregnancy (ICP) and the correlation between CYP27A gene mutations and BA (bile acid) level changes.Methods: In this study, the entire coding region of the CYP27A1 gene was sequenced in 151 Han Chinese women with ICP and 1029 matched samples, and the pathogenicity of identified CYP27A1 gene mutations was judged through evolutionary conservation analysis, computational analysis and protein structure modeling. Finally, we verified the relationship between gene mutations and total serum bile acid (TBA) and cholesterol (CHOL) levels through experiments in cell culture.Results: We identified five heterozygous CYP27A1 missense mutations in five ICP samples. Three online tools, Polyphen-2, MutationTaster and SIFT, predicted that the five CYP27A1 mutations were pathogenic. Furthermore, all five mutations caused marked protein structural changes. Experiments in cells showed that the intracellular and medium levels of TBA in the mutant groups were lower than those in the wild-type group, while the CHOL levels were higher in all mutants except for the R158H mutant.Conclusions: CYP27A1 mutations are associated with the levels of TBA and CHOL, suggesting that CYP27A1 mutations contribute to abnormal total cholesterol and BA levels, which leads to ICP. [ABSTRACT FROM AUTHOR]

Binders are required to dissipate huge mechanical stress and enhance the lithium‐ion diffusion kinetics of silicon anodes during cycling. Herein, a stress‐distribution binder with high ionic conductivity (GG‐g‐PAM) is constructed by grating polyacrylamide (PAM) onto ion‐conductive guar gum (GG) backbone. The mechanical stress distribution toward the grafted PAM chain enables the effective stress dissipation of the GG‐g‐PAM binder, and thus maintains a stable electrode‐electrolyte interface during cycling. The stress dissipation ability of the GG‐g‐PAM binder is confirmed by PeakForce atomic force microscopy experiments and finite element simulations. In addition, lithium complexation sites provided by oxygen heteroatoms in GG of the GG‐g‐PAM binder construct the Li‐ion pathways for facilitating Li ionic diffusion in the Si anodes. The good cyclabilities of Ah‐level pouch cells based on Si nanoparticle anodes strongly confirm GG‐g‐PAM as a desirable binder for practical Si anodes. [ABSTRACT FROM AUTHOR]

Cyclic (amino)(aryl)carbenes (CAArCs) result from the replacement of the alkyl substituent of cyclic (alkyl)- (amino) carbenes (CAACs) by an aryl group. This structural modification leads to enhanced electrophilicity of the carbene center with retention of the high nucleophilicity of CAACs, and therefore CAArCs feature a small singlet-triplet gap. The isoindolium precursors are readily prepared in good yields, and deprotonation at low temperature, in the presence of [RhCl(cod)]2 and [(Me2S)AuCl] lead to air-stable rhodium and gold CAArC-supported complexes, respectively. The rhodium complexes promote the [3+2] cycloaddition of diphenylcyclopropenone with ethyl phenylpropiolate, and induce the addition of 2-vinylpyridine to alkenes by CH activation. The gold complexes allow for the catalytic threecomponent preparation of 1,2-dihydroquinolines from aniline and phenyl acetylene. These preliminary results illustrate the potential of CAArC ligands in transition-metal catalysis. [ABSTRACT FROM AUTHOR]

Cyclic (amino)(aryl)carbenes (CAArCs) result from the replacement of the alkyl substituent of cyclic (alkyl)(amino) carbenes (CAACs) by an aryl group. This structural modification leads to enhanced electrophilicity of the carbene center with retention of the high nucleophilicity of CAACs, and therefore CAArCs feature a small singlet-triplet gap. The isoindolium precursors are readily prepared in good yields, and deprotonation at low temperature, in the presence of [RhCl(cod)]2 and [(Me2S)AuCl] lead to air-stable rhodium and gold CAArC-supported complexes, respectively. The rhodium complexes promote the [3+2] cycloaddition of diphenylcyclopropenone with ethyl phenylpropiolate, and induce the addition of 2-vinylpyridine to alkenes by CH activation. The gold complexes allow for the catalytic three-component preparation of 1,2-dihydroquinolines from aniline and phenyl acetylene. These preliminary results illustrate the potential of CAArC ligands in transition-metal catalysis. [ABSTRACT FROM AUTHOR]

Described here is the chromium-catalyzed cleavage of C(aryl)–SMe bonds leading to coupling with organomagnesium to give functionalized benzaldehydes under mild conditions. This reaction was promoted specifically by a low-cost and simple CrCl2 salt used as a precatalyst, enabling synchronous activations of ortho-C(aryl)–SMe and ortho′-C(aryl)–H bonds to achieve difunctionalization of benzaldimines. This work provided a strategy for accessing arylated, alkylated, and diarylated benzaldehyde derivatives as a result of the couplings of C(aryl)–SMe and C(aryl)–SMe/C(aryl)–H bonds promoted with cost-effective Cr catalysis. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholestasis of pregnancy (ICP) can cause adverse pregnancy outcomes, such as spontaneous preterm delivery and stillbirth. It is a complex disease influenced by multiple factors, including genetics and the environment. Previous studies have reported that functioning nuclear receptor subfamily 1 group H member 4 (NR1H4) plays an essential role in bile acid (BA) homeostasis. However, some novel variants and their pathogenesis have not been fully elucidated. Therefore, this research aimed to investigate the genetic characteristics of the NR1H4 gene in ICP. Methods: In this study, we sequenced the entire coding region of NR1H4 in 197 pregnant women with ICP disease. SIFT and PolyPhen2 were used to predict protein changes. Protein structure modelling and comparisons between NR1H4 reference and modified protein structures were performed by SWISS-MODEL and Chimera 1.14rc, respectively. T-tests were used to analyse the potential significant differences between NR1H4 mutations and wild types for 29 clinical features. Fisher's test was conducted to test the significance of differences in mutation frequencies between ICP and the three databases. Results: We identified four mutations: two novel missense mutations, p.S145F and p.M185L; rs180957965 (A230S); and rs147030757 (N275N). The two novel missense mutations were absent in 1029 controls and three databases, including the 1000 Genomes Project (1000G_ALL), Exome Aggregation Consortium (ExAC) and ChinaMAP. Two web-available tools, SIFT and PolyPhen2, predicted that these mutations are harmful to the function of the protein. Moreover, compared to the wild-type protein structure, the NR1H4 p.S145F and p.M185L protein structure showed a slight change in the chemical bond in two zinc finger structures. Combined clinical data indicate that the mutation group had higher levels of total bile acid (TBA) than the wild-type group. Therefore, we hypothesized that these two mutations altered the protein structure of NR1H4, which impaired the function of NR1H4 itself and its target gene and caused an increase in TBA. Conclusions: To our knowledge, this is the first study to identify the novel p.S145F and p.M185L mutations in 197 ICP patients. Our present study provides new insights into the genetic architecture of ICP involving the two novel NR1H4 mutations. [ABSTRACT FROM AUTHOR]

Websites were retrospectively analysed to study the effects that technological advances in web design have had on accessibility for persons with disabilities. A random sample of general websites and a convenience sample of US government websites were studied and compared for the years 1997 – 2002. Web accessibility barrier (WAB) and complexity scores were calculated. Analysis of Variance (ANOVA) and Tukey's HSD were used to determine differences among years for general sites. Repeated measures of ANOVA were used to analyse trends in US government sites, and Pearson's correlation coefficient (r) was computed to evaluate the relationship between accessibility and complexity. Random websites become progressively inaccessible as complexity increases. US government websites remain accessible while increasing in complexity. Increasing complexity, often caused by adding complex components to a Webpage, doesn't have to contribute to increasing barriers to accessibility: US government websites remain accessible despite increasing complexity by limiting the number of scripts used in Webpage design. [ABSTRACT FROM AUTHOR]

Reductive cleavage of aromatic and benzylic C–O bonds by chromium catalysis is reported. This deoxygenative reaction was promoted by low-cost CrCl2 precatalyst combined with poly(methyl hydrogen siloxane) as the mild reducing agent, providing a strategy in forming reduced motifs by cleavage of unactivated C–O bonds. A range of functional groups such as bromide, chloride, fluoride, hydroxyl, amino, and alkoxycarbonyl can be retained in the reduction. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholestasis of pregnancy (ICP) can cause premature delivery and stillbirth. Previous studies have reported that mutations in ABC transporter genes strongly influence the transport of bile salts. However, to date, their effects are still largely elusive.Methods: A whole-exome sequencing (WES) approach was used to detect novel variants. Rare novel exonic variants (minor allele frequencies: MAF < 1%) were analyzed. Three web-available tools, namely, SIFT, Mutation Taster and FATHMM, were used to predict protein damage. Protein structure modeling and comparisons between reference and modified protein structures were performed by SWISS-MODEL and Chimera 1.14rc, respectively.Results: We detected a total of 2953 mutations in 44 ABC family transporter genes. When the MAF of loci was controlled in all databases at less than 0.01, 320 mutations were reserved for further analysis. Among these mutations, 42 were novel. We classified these loci into four groups (the damaging, probably damaging, possibly damaging, and neutral groups) according to the prediction results, of which 7 novel possible pathogenic mutations were identified that were located in known functional genes, including ABCB4 (Trp708Ter, Gly527Glu and Lys386Glu), ABCB11 (Gln1194Ter, Gln605Pro and Leu589Met) and ABCC2 (Ser1342Tyr), in the damaging group. New mutations in the first two genes were reported in our recent article. In addition, compared to the wild-type protein structure, the ABCC2 Ser1342Tyr-modified protein structure showed a slight change in the chemical bond lengths of ATP ligand-binding amino acid side chains. In placental tissue, the expression level of the ABCC2 gene in patients with ICP was significantly higher (P < 0.05) than that in healthy pregnant women. In particular, the patients with two mutations in ABC family genes had higher average values of total bile acids (TBA), aspartate transaminase (AST), direct bilirubin (DBIL), total cholesterol (CHOL), triglycerides (TG) and high-density lipoprotein (HDL) than the patients who had one mutation, no mutation in ABC genes and local controls.Conclusions: Our present study provide new insight into the genetic architecture of ICP and will benefit the final identification of the underlying mutations. [ABSTRACT FROM AUTHOR]

This article presents a method for improving the amplification performance of strong-coupling stimulated Brillouin scattering by adding an external static magnetic field longitudinal to the laser propagation direction. Simulation results show that when the laser intensity is low, the output seed intensity can be increased by applying an external magnetic field and a right-hand circularly polarized laser pulse. When the seed intensity is higher, the amplification enters the regime of relativistic electron nonlinearity, the amplification oscillates, and the portion of the seed that is amplified moves from the first peak to the second and then the third. Under these circumstances, a reversed magnetic field helps to obtain a higher output intensity and a smoother output pulse profile. Adjusting the magnetic field dynamically, such as by using a double-pass scheme, combines these two advantages and maximizes the intensity enlarging and profile smoothing of the output pulse. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus and cholestasis in late pregnancy and results in adverse pregnancy outcomes, including preterm delivery and birth weight, which are affected by the genetic and environmental background. However, until now, the genetic architecture of ICP has remained largely unclear.Methods: Twenty-six clinical data points were recorded for 151 Chinese ICP patients. The data generated from whole-exome sequencing (WES) using the BGISEQ-500 platform were further analyzed by Burrows-Wheeler Aligner (BWA) software, Genome Analysis Toolkit (GATK), ANNOVAR tool, etc. R packages were used to conduct t-test, Fisher's test and receiver operating characteristic (ROC) curve analyses.Results: We identified eighteen possible pathogenic loci associated with ICP disease in known genes, covering ABCB4, ABCB11, ATP8B1 and TJP2. The loci Lys386Gln, Gly527Gln and Trp708Ter in ABCB4, Leu589Met, Gln605Pro and Gln1194Ter in ABCB11, and Arg189Ser in TJP2 were novel discoveries. In addition, WES analysis indicated that the gene ANO8 involved in the transport of bile salts is newly identified as associated with ICP. The functional network of the ANO8 gene confirmed this finding. ANO8 contained 8 rare missense mutations that were found in eight patients among the 151 cases and were absent from 1029 controls. Out of the eight SNPs, 3 were known, and the remaining five are newly identified. These variants have a low frequency, ranging from 0.000008 to 0.00001 in the ExAC, gnomAD - Genomes and TOPMED databases. Bioinformatics analysis showed that the sites and their corresponding amino acids were both highly conserved among vertebrates. Moreover, the influences of all the mutations on protein function were predicted to be damaging by the SIFT tool. Combining clinical data, it was found that the mutation group (93.36 µmol/L) had significantly (P = 0.038) higher total bile acid (TBA) levels than the wild-type group (40.81 µmol/L).Conclusions: To the best of our knowledge, this is the first study to employ WES technology to detect genetic loci for ICP. Our results provide new insights into the genetic basis of ICP and will benefit the final identification of the underlying mutations. [ABSTRACT FROM AUTHOR]

Reported here is a straightforward process in which a cyclic (alkyl)(amino)carbene/Rh catalyst system facilitates the preferential addition of hydrogen to the substitution sites of difluoromethylated and trifluoromethylated arenes and heteroarenes, leading to dearomative reduction. This strategy enables the diastereoselective synthesis of cis‐difluoromethylated and cis‐trifluoromethylated cycloalkanes and saturated heterocycles, and even allows formation of all‐cis multi‐trifluoromethylated cyclic products with a defined equatorial orientation of the di‐ and trifluoromethyl groups. Deuterium‐labeling studies indicate that hydrogen preferentially attacks the substitution sites of planar arenes, resulting in dearomatization, possibly with heterogeneous Rh as the reactive species, followed by either reversible or irreversible hydrogen addition to the nonsubstitution sites. [ABSTRACT FROM AUTHOR]

Reported here is a straightforward process in which a cyclic (alkyl)(amino)carbene/Rh catalyst system facilitates the preferential addition of hydrogen to the substitution sites of difluoromethylated and trifluoromethylated arenes and heteroarenes, leading to dearomative reduction. This strategy enables the diastereoselective synthesis of cis‐difluoromethylated and cis‐trifluoromethylated cycloalkanes and saturated heterocycles, and even allows formation of all‐cis multi‐trifluoromethylated cyclic products with a defined equatorial orientation of the di‐ and trifluoromethyl groups. Deuterium‐labeling studies indicate that hydrogen preferentially attacks the substitution sites of planar arenes, resulting in dearomatization, possibly with heterogeneous Rh as the reactive species, followed by either reversible or irreversible hydrogen addition to the nonsubstitution sites. [ABSTRACT FROM AUTHOR]

A mild, scalable, high yielding, and rapid route to access diverse nitriles from aldehyde oxime esters enabled by iron(III) and phenol co‐catalysis has been developed. The reaction was performed at room temperature to give nitriles in excellent yield within minutes. Mechanistic studies show that the reaction may proceed through a radical process in which benzoyl aldehyde oxime is not only a substrate, but also an ancillary ligand to support iron salt in the promotion of the transformation. [ABSTRACT FROM AUTHOR]

We herein report the hydrogenation of substituted aryl‐ and heteroaryl boronate esters for the selective synthesis of cis‐substituted borylated cycloalkanes and saturated heterocycles. A cyclic (alkyl)(amino)carbene‐ligated rhodium complex with two dimethyl groups at the ortho‐alkyl scaffold of the carbene showed high reactivity in promoting the hydrogenation, thereby enabling the hydrogenation of (hetero)arenes with retention of the synthetically valuable boronate group. This process constitutes a clean, atom‐economic, as well as chemo‐ and stereoselective route for the generation of cis‐configured, diversely substituted borylated cycloalkanes and saturated heterocycles that are usually elusive and difficult to prepare. [ABSTRACT FROM AUTHOR]

We herein report the hydrogenation of substituted aryl‐ and heteroaryl boronate esters for the selective synthesis of cis‐substituted borylated cycloalkanes and saturated heterocycles. A cyclic (alkyl)(amino)carbene‐ligated rhodium complex with two dimethyl groups at the ortho‐alkyl scaffold of the carbene showed high reactivity in promoting the hydrogenation, thereby enabling the hydrogenation of (hetero)arenes with retention of the synthetically valuable boronate group. This process constitutes a clean, atom‐economic, as well as chemo‐ and stereoselective route for the generation of cis‐configured, diversely substituted borylated cycloalkanes and saturated heterocycles that are usually elusive and difficult to prepare. [ABSTRACT FROM AUTHOR]

Dioxygen activation with both cyclic (amino)(alkyl)carbenes and di(amino)carbenes at ambient temperature is described. Theoretical studies suggest that electron rearrangement from the doubly filled σ orbital of carbene carbon to its vacant p orbital through the π* antibonding orbital of 3O2 can be considered for Ccarbene–O bond formation. [ABSTRACT FROM AUTHOR]

Purpose: To describe the trends in eye injuries and associated medical costs among children in the United States. Methods: Data were from the 2002-2014 Medical Expenditure Panel Survey (MEPS). Eye injuries in children aged <18 years were identified by the International Classification of Diseases-9 (ICD-9) codes. The trends of cumulative incidence of eye injury, total costs, and average costs were estimated from 2002-2014 MEPS data. All costs were adjusted to 2014 US dollars. Analyses accounted for the complex stratified multistage survey design of the MEPS. We used MarketScan data (2010-2013) to validate outpatient cost estimates. Results: The 3-year average cumulative incidence of eye injuries declined from 0.56% in 2002-2004 to 0.31% in 2012-2014 (Trend p < 0.001). The average annual total costs decreased from $193 million during 2002-2004 to $66 million during 2012-2014 (p < 0.001). Conclusion: The MEPS data showed that among children aged <18 years, the incidence of eye injuries and associated financial burden substantially declined during 2002-2014, highlighting the progress in preventing children eye injuries. Continuing efforts are needed to further reduce the burden in this population. [ABSTRACT FROM AUTHOR]

An iron-catalyzed oxidative coupling/cyclization reaction for the synthesis of benzoxazoles at room temperature is reported. This reaction was enabled by an inexpensive iron(iii) catalyst by treating readily available phenol derivatives with benzoyl aldehyde oximes. Mechanistic studies show that benzoyl aldehyde oxime is not only used as a substrate, but also serves as an ancillary ligand to support the iron salt in the promotion of the transformation. [ABSTRACT FROM AUTHOR]

This paper focuses on the problem of generating a line drawing from a given image for fused deposition modeling. The abstracted line drawing, comprising of lines with a single color and thickness, would preserve both tone and edges of the input image. We first partition the image into sub-regions manually. The boundaries of the sub-regions are extracted as the feature lines of the image. Next, a proper number of points are randomly placed on the image plane with a density proportional to the darkness of the image. We use Lloyd’s method to push the sampling points away from each other and the feature lines. The points within each sub-region are then connected by solving a travelling salesman problem (TSP). Finally, we further optimize the fairness and the spacing of the lines by minimizing a tailored objective function. A variety of experimental results are presented to show the effectiveness of our method for generating line drawings for 3D printing. [ABSTRACT FROM AUTHOR]

A single-frame complete spatiotemporal characteristics measurement method of ultrafast laser pulses, named Carrier Frequency Division Multiplexing Spectral Interferometry (CFDMSI), is proposed and demonstrated. Based on the idea of frequency division multiplexing, the 3D spatiotemporal field E (x , y , t) of a femtosecond laser pulse can be reconstructed from a single spectral interferogram. The implementation of CFDMSI is quite simple, just fixing a slit array at the entrance of an imaging spectrometer, then injecting the unknown pulse and the reference pulse into the imaging spectrometer at a certain cross angle. By recording and analyzing a single spectral interferogram, the unknown pulse's spatiotemporal field in the sampling area of the slit array can be obtained. The principle and implementation of CFDMSI are introduced, and its effectiveness is verified by a demonstration experiment. • A single-frame complete spatiotemporal characterization method is proposed. • The Spectral Interferometry technique is improved by frequency division multiplexing. • The spatiotemporal coupling of ultrafast lasers can be measured in real time. [ABSTRACT FROM AUTHOR]

An efficient 2-pyridyl directed C-H allylation of arenes is developed using a Grignard reagent as base and a simple Co(II)-salt as catalyst. [ABSTRACT FROM AUTHOR]