Miracle-dz/UniFAR-FTUs huggingface dataset:
How Lewis Acids Catalyze Diels–Alder Reactions

Abstract The Lewis acid(LA)‐catalyzed Diels–Alder reaction between isoprene and methyl acrylate was investigated quantum chemically using a combined density functional theory and coupled‐cluster theory approach. Computed activation energies systematically decrease as the strength of the LA increases along the series I2<SnCl4<TiCl4<ZnCl2<BF3<AlCl3. Emerging from our activation strain and Kohn–Sham molecular orbital bonding analysis was an unprecedented finding, namely that the LAs accelerate the Diels–Alder reaction by a diminished Pauli repulsion between the π‐electron systems of the diene and dienophile. Our results oppose the widely accepted view that LAs catalyze the Diels–Alder reaction by enhancing the donor–acceptor [HOMOdiene–LUMOdienophile] interaction and constitute a novel physical mechanism for this indispensable textbook organic reaction.
Robust kernel association testing (RobKAT)

Testing the association between single‐nucleotide polymorphism (SNP) effects and a response is often carried out through kernel machine methods based on least squares, such as the sequence kernel association test (SKAT). However, these least‐squares procedures are designed for a normally distributed conditional response, which may not apply. Other robust procedures such as the quantile regression kernel machine (QRKM) restrict the choice of the loss function and only allow inference on conditional quantiles. We propose a general and robust kernel association test with a flexible choice of the loss function, no distributional assumptions, and has SKAT and QRKM as special cases. We evaluate our proposed robust association test (RobKAT) across various data distributions through a simulation study. When errors are normally distributed, RobKAT controls type I error and shows comparable power with SKAT. In all other distributional settings investigated, our robust test has similar or greater power than SKAT. Finally, we apply our robust testing method to data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) clinical trial to detect associations between selected genes including the major histocompatibility complex (MHC) region on chromosome six and neurotropic herpesvirus antibody levels in schizophrenia patients. RobKAT detected significant association with four SNP sets (HST1H2BJ, MHC, POM12L2, and SLC17A1), three of which were undetected by SKAT.
Liganded T3 receptor β2 inhibits the positive feedback autoregulation of the gene for GATA2, a transcription factor critical for thyrotropin production

The serum concentration of thyrotropin (thyroid stimulating hormone, TSH) is drastically reduced by small increase in the levels of thyroid hormones (T3 and its prohormone, T4); however, the mechanism underlying this relationship is unknown. TSH consists of the chorionic gonadotropin α (CGA) and the β chain (TSHβ). The expression of both peptides is induced by the transcription factor GATA2, a determinant of the thyrotroph and gonadotroph differentiation in the pituitary. We previously reported that the liganded T3 receptor (TR) inhibits transactivation activity of GATA2 via a tethering mechanism and proposed that this mechanism, but not binding of TR with a negative T3-responsive element, is the basis for the T3-dependent inhibition of the TSHβ and CGA genes. Multiple GATA-responsive elements (GATA-REs) also exist within the GATA2 gene itself and mediate the positive feedback autoregulation of this gene. To elucidate the effect of T3 on this non-linear regulation, we fused the GATA-REs at -3.9 kb or +9.5 kb of the GATA2 gene with the chloramphenicol acetyltransferase reporter gene harbored in its 1S-promoter. These constructs were co-transfected with the expression plasmids for GATA2 and the pituitary specific TR, TRβ2, into kidney-derived CV1 cells. We found that liganded TRβ2 represses the GATA2-induced transactivation of these reporter genes. Multi-dimensional input function theory revealed that liganded TRβ2 functions as a classical transcriptional repressor. Then, we investigated the effect of T3 on the endogenous expression of GATA2 protein and mRNA in the gonadotroph-derived LβT2 cells. In this cell line, T3 reduced GATA2 protein independently of the ubiquitin proteasome system. GATA2 mRNA was drastically suppressed by T3, the concentration of which corresponds to moderate hypothyroidism and euthyroidism. These results suggest that liganded TRβ2 inhibits the positive feedback autoregulation of the GATA2 gene; moreover this mechanism plays an important role in the potent reduction of TSH production by T3.
SERS-Based Liquid Biopsy of Gastrointestinal Tumors Using a Portable Raman Device Operating in a Clinical Environment

Early diagnosis based on screening is recognized as one of the most efficient ways of mitigating cancer-associated morbidity and mortality. Therefore, reliable but cost-effective methodologies are needed. By using a portable Raman spectrometer, a small and easily transportable instrument, the needs of modern diagnosis in terms of rapidity, ease of use and flexibility are met. In this study, we analyzed the diagnostic accuracy yielded by the surface-enhanced Raman scattering (SERS)-based profiling of serum, performed with a portable Raman device operating in a real-life hospital environment, in the case of 53 patients with gastrointestinal tumors and 25 control subjects. The SERS spectra of serum displayed intense bands attributed to carotenoids and purine metabolites such as uric acid, xanthine and hypoxanthine, with different intensities between the cancer and control groups. Based on principal component analysis-quadratic discriminant analysis (PCA-QDA), the cancer and control groups were classified with an accuracy of 76.92%. By combining SERS spectra with general inflammatory markers such as C-reactive protein levels, neutrophil counts, platelet counts and hemoglobin levels, the discrimination accuracy was increased to 83.33%. This study highlights the potential of SERS-based liquid biopsy for the point-of-care diagnosis of gastrointestinal tumors using a portable Raman device operating in a clinical setting.
Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination

Oligodendrocytes (OLs) myelinate axons and provide electrical insulation and trophic support for neurons in the central nervous system (CNS). Platelet-derived growth factor (PDGF) is critical for steady-state number and differentiation of oligodendrocyte precursor cells (OPCs), but its downstream targets are unclear. Here, we show for the first time that Gab1, an adaptor protein of receptor tyrosine kinase, is specifically expressed in OL lineage cells and is an essential effector of PDGF signaling in OPCs in mice. Gab1 is downregulated by PDGF stimulation and upregulated during OPC differentiation. Conditional deletions of Gab1 in OLs cause CNS hypomyelination by affecting OPC differentiation. Moreover, Gab1 binds to downstream GSK3β and regulated its activity, and thereby affects the nuclear accumulation of β-catenin and the expression of a number of transcription factors critical to myelination. Our work uncovers a novel downstream target of PDGF signaling, which is essential to OPC differentiation and CNS myelination.
Inferior turbinate outfracture for successful nasotracheal intubation in a patient undergoing maxillofacial surgery: case report

An enlarged inferior turbinate is a predisposing factor for difficult nasotracheal intubation. We describe a case of successful nasotracheal intubation by induced outfracture of the inferior turbinate during maxillofacial surgery, and discuss the importance of adequate airway evaluation and anesthetic management for successful nasal intubation.
Hypertension testing and treatment in Uganda and Kenya through the SEARCH study: An implementation fidelity and outcome evaluation

Background Hypertension (HTN) is the single leading risk factor for human mortality worldwide, and more prevalent in sub-Saharan Africa than any other region [1]–although resources for HTN screening, treatment, and control are few. Most regional pilot studies to leverage HIV programs for HTN control have achieved blood pressure control in half of participants or fewer [2,3,4]. But this control gap may be due to inconsistent delivery of services, rather than ineffective underlying interventions. Methods We sought to evaluate the consistency of HTN program delivery within the SEARCH study (NCT01864603) among 95,000 adults in 32 rural communities in Uganda and Kenya from 2013–2016. To achieve this objective, we designed and performed a fidelity evaluation of the step-by-step process (cascade) of HTN care within SEARCH, calculating rates of HTN screening, linkage to care, and follow-up care. We evaluated SEARCH’s assessment of each participant’s HTN status against measured blood pressure and HTN history. Findings SEARCH completed blood pressure screens on 91% of participants. SEARCH HTN screening was 91% sensitive and over 99% specific for HTN relative to measured blood pressure and patient history. 92% of participants screened HTN+ received clinic appointments, and 42% of persons with HTN linked to subsequent care. At follow-up, 82% of SEARCH clinic participants received blood pressure checks; 75% received medication appropriate for their blood pressure; 66% remained in care; and 46% had normal blood pressure at their most recent visit. Conclusion The SEARCH study’s consistency in delivering screening and treatment services for HTN was generally high, but SEARCH could improve effectiveness in linking patients to care and achieving HTN control. Its model for implementing population-scale HTN testing and care through an existing HIV test-and-treat program–and protocol for evaluating the intervention’s stepwise fidelity and care outcomes–may be adapted, strengthened, and scaled up for use across multiple resource-limited settings.
A LuxR‐type regulator, AcrR, regulates flagellar assembly and contributes to virulence, motility, biofilm formation, and growth ability of Acidovorax citrulli

Abstract LuxR‐type regulators regulate many bacterial processes and play important roles in bacterial motility and virulence. Acidovorax citrulli is a seedborne bacterial pathogen responsible for bacterial fruit blotch, which causes great losses in melon and watermelon worldwide. We identified a LuxR‐type, nonquorum sensing‐related regulator, AcrR, in the group II strain Aac‐5 of A. citrulli. We found that the acrR mutant lost twitching and swimming motilities, and flagellar formation. It also showed reduced virulence, but increased biofilm formation and growth ability. Transcriptomic analysis revealed that 394 genes were differentially expressed in the acrR mutant of A. citrulli, including 33 genes involved in flagellar assembly. Our results suggest that AcrR may act as a global regulator affecting multiple important biological functions of A. citrulli.
High-Performance Lithium-Rich Layered Oxide Material: Effects of Preparation Methods on Microstructure and Electrochemical Properties

Lithium-rich layered oxide is one of the most promising candidates for the next-generation cathode materials of high-energy-density lithium ion batteries because of its high discharge capacity. However, it has the disadvantages of uneven composition, voltage decay, and poor rate capacity, which are closely related to the preparation method. Here, 0.5Li2MnO3·0.5LiMn0. 8Ni0.1Co0. 1O2 was successfully prepared by sol–gel and oxalate co-precipitation methods. A systematic analysis of the materials shows that the 0.5Li2MnO3·0.5LiMn0. 8Ni0.1Co0. 1O2 prepared by the oxalic acid co-precipitation method had the most stable layered structure and the best electrochemical performance. The initial discharge specific capacity was 261.6 mAh·g−1 at 0.05 C, and the discharge specific capacity was 138 mAh·g−1 at 5 C. The voltage decay was only 210 mV, and the capacity retention was 94.2% after 100 cycles at 1 C. The suppression of voltage decay can be attributed to the high nickel content and uniform element distribution. In addition, tightly packed porous spheres help to reduce lithium ion diffusion energy and improve the stability of the layered structure, thereby improving cycle stability and rate capacity. This conclusion provides a reference for designing high-energy-density lithium-ion batteries.
Modeling Possible Outcomes of Updated Daily Values on Nutrient Intakes of the United States Adult Population

The United States (US) Food and Drug Administration has updated the Daily Values (DVs) for the Nutrition Facts Label on packaged foods. We used the National Health and Nutrition Examination Survey 2009–2012 data with the International Life Sciences Institute, North America Fortification Database, which identifies intrinsic, mandatory enriched, and fortified sources of nutrients in foods and beverages, to model the new DVs’ potential impact on adult (≥19 years of age) intake. We assumed that manufacturers will adjust voluntary fortification to maintain percent DV claims. We assessed the percent of the US population whose usual intake (UI) was < the Estimated Average Requirement (EAR), and ≥ the Upper Limit (UL) based on the current DVs, and modeled estimated UI and %<EAR with the new DVs (Updated DV) for 12 micronutrients. Modeling for vitamins B12, A, B6, riboflavin, niacin, thiamin, and zinc predicts fewer voluntarily fortified foods and reduced adult UI. Assuming manufacturers add more vitamins C and D and calcium to foods, the Updated DV predicts the adult UI will increase for these nutrients. Our modeling predicts a 15% reduction in overall adult vitamin A intake, a recognized “shortfall nutrient” and that even with the increased DV for vitamin D, 70% of US adults are predicted to have an intake <EAR.
Influence of fatty acid desaturase (FADS) genotype on maternal and child polyunsaturated fatty acids (PUFA) status and child health outcomes: a systematic review.

CONTEXT Polyunsaturated fatty acids (PUFA) are important during pregnancy for fetal development and child health outcomes. The fatty acid desaturase (FADS) genes also influence PUFA status, with the FADS genes controlling how much product (eg, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid) is metabolized from the precursor molecules linoleic acid and α-linolenic acid. OBJECTIVE The current review discusses the influence of FADS genotype on PUFA status of pregnant women, breast milk, and children, and also how FADS may influence child health outcomes. DATA SOURCES The Ovid Medline, Scopus, Embase, Cochrane Library, CINAHL Plus, PubMed and Web of Science databases were searched from their inception to September 2018. DATA EXTRACTION Eligible studies reported FADS genotype and blood concentrations of PUFA during pregnancy, in childhood, breast milk concentrations of PUFA or child health outcomes. DATA ANALYSIS In pregnant and lactating women, minor allele carriers have higher concentrations of linoleic acid and α-linolenic acid, and lower concentrations of arachidonic acid, in blood and breast milk, respectively. In children, FADS genotype influences PUFA status in the same manner and may impact child outcomes such as cognition and allergies; however, the direction of effects for the evidence to date is not consistent. CONCLUSION Further studies are needed to further investigate associations between FADS and outcomes, as well as the diet-gene interaction.
Prevalence of virulence and antimicrobial resistance genes in Aeromonas species isolated from marketed cockles (Tegillarca granosa) in Korea

This study aimed to examine incidence, virulence and antimicrobial properties in Aeromonas spp. isolated from cockles (Tegillarca granosa) in Korea. Firstly, genomic DNA was extracted from 32 Aeromonas spp. isolates, and PCR screening for virulence, antimicrobial resistance genes was carried out. The disk diffusion assay was used to examine antimicrobial susceptibility. Aeromonas spp. isolates comprised, A. hydrophila (n = 8), A. veronii (n = 15), A. media (n = 2), A. salmonicida (n = 2), A. allosaccharophila (n = 1), A. bestiarum (n = 1), A. culicicola (n = 1), A. enteropelogenes (n = 1) and A. rivipollensis (n = 1). High prevalence of virulence‐related genes reported as; act (69%), alt (47%), ast (41%), aerA (56%), lip (50%), ahyB (47%), ser (28%), fla (66%), gcat (44%), ascV (50%) and hlyA (72%). All isolates were multidrug resistant, while highest resistance level observed for ampicillin (100%), followed by imipenem (81%), rifampicin (78%), cephalothin (72%), piperacillin (47%) and Colistin sulfate (31%). The presence of blaSHV, blaCTX, tetE, aac(6’)‐Ib, strA‐strB, qnrS, qnrB and IntI1 genes were reported in varying combinations. Nevertheless, blaTEM, blaIMP, tetA, tetB, qnrA, qnrB and aphAI‐IAB genes and the class1 integron were not detected. The high occurrence of virulence and antimicrobial resistance genes in cockles reveals that it can be a potential health risk source for consumers.
Three previously characterized resistances to yellow rust are encoded by a single locus Wtk1

The wild emmer wheat (Triticum turgidum ssp. dicoccoides; WEW) yellow (stripe) rust resistance genes Yr15, YrG303 and YrH52 were discovered in natural populations from different geographic locations. They all localize to chromosome 1B but were thought to be non-allelic based on differences in resistance response. We recently cloned Yr15 as a Wheat Tandem Kinase 1 (WTK1) and showed here that these three resistance loci co-segregate in fine-mapping populations and share identical full-length genomic sequence of functional Wtk1. Independent EMS mutagenized susceptible yrG303 and yrH52 lines carried single nucleotide mutations in Wtk1 that disrupted function. A comparison of the mutations for yr15, yrG303 and yrH52 mutants showed that while key conserved residues were intact, other conserved regions in critical kinase subdomains were frequently affected. Thus, we concluded that Yr15-, YrG303- and YrH52-mediated resistances to yellow rust are encoded by a single locus Wtk1. Introgression of Wtk1 into multiple genetic backgrounds resulted in variable phenotypic responses, confirming that Wtk1-mediated resistance is part of a complex immune response network. WEW natural populations subjected to natural selection and adaptation have potential to serve as a good source for evolutionary studies of different traits and multifaceted gene networks. Highlight We demonstrate that Yr15, YrG303 and YrH52 resistances are encoded by the Wtk1 locus, but express variable resistance responses to yellow rust in a genetic background dependent manner.
Symbiodiniaceae-bacteria interactions: rethinking metabolite exchange in reef-building corals as multi-partner metabolic networks.

The intimate relationship between scleractinian corals and their associated microorganisms is fundamental to healthy coral reef ecosystems. Coral-associated microbes (Symbiodiniaceae and other protists, bacteria, archaea, fungi, and viruses) support coral health and resilience through metabolite transfer, inter-partner signalling, and genetic exchange. However, much of our understanding of the coral holobiont relationship has come from studies that have investigated either coral-Symbiodiniaceae or coral-bacteria interactions in isolation, while relatively little research has focused on other ecological and metabolic interactions potentially occurring within the coral multi-partner symbiotic network. Recent evidences of intimate coupling between phytoplankton and bacteria have demonstrated that obligate resource exchange between partners fundamentally drives their ecological success. Here, we posit that similar associations with bacterial consortia regulate Symbiodiniaceae productivity and are in turn central to the health of corals. Indeed, we propose that this bacteria-Symbiodiniaceae-coral relationship underpins the coral holobiont's nutrition, stress tolerance, and potentially influences the future survival of coral reef ecosystems under changing environmental conditions. Resolving Symbiodiniaceae-bacteria associations is therefore a logical next step towards understanding the complex multi-partner interactions occurring in the coral holobiont. This article is protected by copyright. All rights reserved.
Thermal Upgrade of Enzymatically Synthesized Aliphatic and Aromatic Oligoesters

The enzymatic synthesis of polyesters in solventless systems is an environmentally friendly and sustainable method for synthetizing bio-derived materials. Despite the greenness of the technique, in most cases only short oligoesters are obtained, with limited practical applications or requiring further chemical processing for their elongation. In this work, we present a catalyst-free thermal upgrade of enzymatically synthesized oligoesters. Different aliphatic and aromatic oligoesters were synthesized using immobilized Candida antarctica lipase B (iCaLB) as the catalyst (70 °C, 24 h) yielding poly(1,4-butylene adipate) (PBA, Mw = 2200), poly(1,4-butylene isophthalate) (PBI, Mw = 1000), poly(1,4-butylene 2,5-furandicarboxylate) (PBF, Mw = 600), and poly(1,4-butylene 2,4-pyridinedicarboxylate) (PBP, Mw = 1000). These polyesters were successfully thermally treated to obtain an increase in Mw of 8.5, 2.6, 3.3, and 2.7 folds, respectively. This investigation focused on the most successful upgrade, poly(1,4-butylene adipate), then discussed the possible effect of di-ester monomers as compared to di-acids in the thermally driven polycondensation. The herein-described two-step synthesis method represents a practical and cost-effective way to synthesize higher-molecular-weight polymers without the use of toxic metal catalysts such as titanium(IV) tert-butoxide, tin(II) 2-ethylhexanoate, and in particular, antimony(IV) oxide. At the same time, the method allows for the extension of the number of reuses of the biocatalyst by preventing its exposure to extreme denaturating conditions.
The mercapturic acid pathway

Abstract The mercapturic acid pathway is a major route for the biotransformation of xenobiotic and endobiotic electrophilic compounds and their metabolites. Mercapturic acids (N-acetyl-l-cysteine S-conjugates) are formed by the sequential action of the glutathione transferases, γ-glutamyltransferases, dipeptidases, and cysteine S-conjugate N-acetyltransferase to yield glutathione S-conjugates, l-cysteinylglycine S-conjugates, l-cysteine S-conjugates, and mercapturic acids; these metabolites constitute a “mercapturomic” profile. Aminoacylases catalyze the hydrolysis of mercapturic acids to form cysteine S-conjugates. Several renal transport systems facilitate the urinary elimination of mercapturic acids; urinary mercapturic acids may serve as biomarkers for exposure to chemicals. Although mercapturic acid formation and elimination is a detoxication reaction, l-cysteine S-conjugates may undergo bioactivation by cysteine S-conjugate β-lyase. Moreover, some l-cysteine S-conjugates, particularly l-cysteinyl-leukotrienes, exert significant pathophysiological effects. Finally, some enzymes of the mercapturic acid pathway are described as the so-called “moonlighting proteins,” catalytic proteins that exert multiple biochemical or biophysical functions apart from catalysis.
Review on Research and Application of Medical Adverse Events Reporting System in China

Reporting of medical adverse events is an important measure to prevent recurrence of adverse events and to improve the quality of medical care.Through starting with policies about medical adverse event reporting system,existing medical adverse event reporting system is summarized and analyzed,the characteristics and defects are summed up,and the prospect of improving the reporting system of adverse events is made.