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A series of robust AgCl/WO 3 composite microrods (0.1–0.2 μ m) with different Ag/W molar ratios (0.25, 0.50, 0.75, 1.00, 1.25) were synthesized via hydrothermal-calcination process. The obtained samples were characterized by XRD, SEM, TEM, FT-IR, UV-vis DRS, PL, BET, Raman, transient TPRT and EIS. The photocatalytic test for organic dyes degradation showed that AgCl/WO 3 microrods possess much higher photocatalytic activities and stability than bare AgCl and WO 3. With optimal AgCl/WO 3 molar ratio (0.75 ∼ 1), 2 ∼ 5 times increase in dye decomposition efficiency was obtained over AgCl/WO 3 microrods. The formation of intimate WO 3 /AgCl heterojuction (interface) largely enhanced the separation efficiency of photogenerated carriers. This investigation suggested that AgCl/WO 3 microrods could a promising photocatalyst for environmental remediation. Image 1 • 100 ∼ 200 nm AgCl/WO3 composite nanorods were synthesized. • With molar ratio of 0.75 ∼ 1(AgCl/WO3), 2 ∼ 5 times increase in activity was obtained. • The WO3/AgCl interface boosted the separation of photo-induced carriers. [ABSTRACT FROM AUTHOR]

Introduction: Grazer exclosure is widely regarded as an effective measure for restoring degraded grasslands, having positive effects on soil microbial diversity. The Intergovernmental Panel on Climate Change (IPCC) predicts that global surface temperatures will increase by 1.5-4.5°C by the end of the 21st century, which may affect restoration practices for degraded grasslands. This inevitability highlights the urgent need to study the effect of temperature on grassland soil microbial communities, given their critical ecological functions., Methods: Here, we assessed the effects of heavy grazing (control), grazer exclosure, and grazer exclosure plus warming by 1.5°C on soil microbial community diversity and network properties as well as their relationships to soil physicochemical properties., Results and Discussion: Our results showed that grazer closure increased soil microbial richness relative to heavy grazing controls. Specifically, bacterial richness increased by 7.9%, fungal richness increased by 20.2%, and the number of fungal network nodes and edges increased without altering network complexity and stability. By contrast, grazer exclosure plus warming decreased bacterial richness by 9.2% and network complexity by 12.4% compared to heavy grazing controls, while increasing fungal network complexity by 25.8%. Grazer exclosure without warming increased soil ammonium nitrogen content, while warming increased soil nitrate nitrogen content. Soil pH and organic carbon were not affected by either exclosure strategy, but nitrate nitrogen was the dominant soil factor explaining changes in bacterial communities., Conclusion: Our findings show that grazer exclosure increases soil microbial diversity which are effective soil restoration measures for degraded desert steppe, but this effect is weakened under warming conditions. Thus, global climate change should be considered when formulating restoration measures for degraded grasslands., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qiao, Zheng, Li, Zhang, Zhang and Zhao.)

The compound 1,2-dichloroethane (1,2-DCA), a persistent and ubiquitous pollutant, is often found in groundwater and can strongly affect the ecological environment. However, the extreme bio-impedance of C-Cl bonds means that a high energy input is needed to drive biological dechlorination. Biotechnology techniques based on microbial photoelectrochemical cell (MPEC) could potentially convert solar energy into electricity and significantly reduce the external energy inputs currently needed to treat 1,2-DCA. However, low electricity-generating efficiency at the anode and sluggish bioreaction kinetics at the cathode limit the application of MPEC. In this study, a g-C 3 N 4 /Blue TiO 2 -NTA photoanode was fabricated and incorporated into an MPEC for 1,2-DCA removal. Optimal performance was achieved when Blue TiO 2 nanotube arrays (Blue TiO 2 -NTA) were loaded with graphitic carbon nitride (g-C 3 N 4 ) 10 times. The photocurrent density of the g-C 3 N 4 /Blue TiO 2 -NTA composite electrode was 2.48-fold higher than that of the pure Blue TiO 2 -NTA electrode under light irradiation. Furthermore, the MPEC equipped with g-C 3 N 4 /Blue TiO 2 -NTA improved 1,2-DCA removal efficiency by 45.21% compared to the Blue TiO 2 -NTA alone, which is comparable to that of a microbial electrolysis cell. In the modified MPEC, the current efficiency reached 69.07% when the light intensity was 150 mW cm -2 and the 1,2-DCA concentration was 4.4 mM. The excellent performance of the novel MPEC was attributed to the efficient direct electron transfer process and the abundant dechlorinators and electroactive bacteria. These results provide a sustainable and cost-effective strategy to improve 1,2-DCA treatment using a biocathode driven by a photoanode., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The difunctionalization of vinylpyridines based on the cyclization strategy remains rare and underdeveloped, in contrast to the well-developed hydrogen functionalization. Current exploration on [4 + 2] cyclization of vinylpyridines mainly relies on extremely high temperatures and the LUMO activation of vinylpyridines using boron trifluoride as a strong Lewis acid. Herein, we established a phosphoric acid-catalyzed [4 + 2] cyclization reaction of 3-vinyl-1H-indoles and 2-vinylpyridines by means of the LUMO/HOMO bifunctional activation model. This protocol features mild reaction conditions, high functional group tolerance, broad substrate compatibility, and high diastereoselectivity, enabling the efficient construction of various functionalized pyridine-substituted tetrahydrocarbazoles with prominent potential in drug discovery.

Background: Pre-exposure prophylaxis (PrEP) is proven to prevent HIV infection. However, PrEP uptake to date has been limited and inequitable. Analyzing the readability of existing PrEP-related information is important to understand the potential impact of available PrEP information on PrEP uptake and identify opportunities to improve PrEP-related education and communication., Objective: We examined the readability of web-based PrEP information identified using search engines and on Twitter. We investigated the readability of web-based PrEP documents, stratified by how the PrEP document was obtained on the web, information source, document format and communication method, PrEP modality, and intended audience., Methods: Web-based PrEP information in English was systematically identified using search engines and the Twitter API. We manually verified and categorized results and described the method used to obtain information, information source, document format and communication method, PrEP modality, and intended audience. Documents were converted to plain text for the analysis and readability of the collected documents was assessed using 4 readability indices. We conducted pairwise comparisons of readability based on how the PrEP document was obtained on the web, information source, document format, communication method, PrEP modality, and intended audience, then adjusted for multiple comparisons., Results: A total of 463 documents were identified. Overall, the readability of web-based PrEP information was at a higher level (10.2-grade reading level) than what is recommended for health information provided to the general public (ninth-grade reading level, as suggested by the Department of Health and Human Services). Brochures (n=33, 7% of all identified resources) were the only type of PrEP materials that achieved the target of ninth-grade reading level., Conclusions: Web-based PrEP information is often written at a complex level for potential and current PrEP users to understand. This may hinder PrEP uptake for some people who would benefit from it. The readability of PrEP-related information found on the web should be improved to align more closely with health communication guidelines for reading level to improve access to this important health information, facilitate informed decisions by those with a need for PrEP, and realize national prevention goals for PrEP uptake and reducing new HIV infections in the United States., (©Albert Park, Fatima Sayed, Patrick Robinson, Latesha Elopre, Yaorong Ge, Shaoyu Li, Christian Grov, Patrick Sean Sullivan. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 04.09.2023.)

From the viewpoint of synthetic accessibility and functional group compatibility, photoredox-catalyzed sulfur dioxide insertion strategy enables in situ generation of functionalized sulfonyl radicals from easily accessible starting materials under mild conditions, thereby conferring broader application potential. Here we present two complementary photoinduced sulfur dioxide insertion systems to trigger radical asymmetric Truce-Smiles rearrangements for preparing a variety of chiral sulfones that bear a quaternary carbon stereocenter. This protocol features broad substrate scope and excellent stereospecificity. Aside from scalability, the introduction of a quaternary carbon stereocenter at position β to bioactive molecule-derived sulfones further demonstrates the practicality and potential of this methodology., (© 2022. The Author(s).)

Complete deconvolution analysis for bulk RNA-seq data is important and helpful to distinguish whether the differences of disease-associated GEPs (gene expression profiles) in tissues of patients and normal controls are due to changes in cellular composition of tissue samples, or due to GEPs changes in specific cells. One of the major techniques to perform complete deconvolution is nonnegative matrix factorization (NMF), which also has a wide-range of applications in the machine learning community. However, the NMF is a well-known strongly ill-posed problem, so a direct application of NMF to RNA-seq data will suffer severe difficulties in the interpretability of solutions. In this paper, we develop an NMF-based mathematical model and corresponding computational algorithms to improve the solution identifiability of deconvoluting bulk RNA-seq data. In our approach, we combine the biological concept of marker genes with the solvability conditions of the NMF theories, and develop a geometric structures guided optimization model. In this strategy, the geometric structure of bulk tissue data is first explored by the spectral clustering technique. Then, the identified information of marker genes is integrated as solvability constraints, while the overall correlation graph is used as manifold regularization. Both synthetic and biological data are used to validate the proposed model and algorithms, from which solution interpretability and accuracy are significantly improved.

Background: Tim-3/Galectin-9 is involved in the immune escape of many pathogens. However, the role of Tim-3/Galectin-9 in persistent infection of Echinococcus multilocularis (Em), which is related to immune escape, is still unclear., Objective: To investigate the role of Tim-3/Galectin-9 and related cytokines in mice with persistent infection of Em., Methods: Em infection model was established by injecting the protoscoleces. Serum was collected at days 2, 8, 30, 60, 90, 180 and 270 after infection. Lymphocytes were isolated from liver tissue samples with Ficoll. Tim-3 + CD4 + T percentage was analyzed by flow cytometry. CD4 + T cells were isolated from liver tissues of Em infected mice and cultured in vitro. The mRNA levels of Tim-3, Galectin-9, IFN-γ and IL-4 were detected by qRT-PCR. Cytokine levels in serum and culture supernatant (IFN-γ and IL-4) were analyzed by cytometric bead array., Results: The expression of Tim-3 and Galectin-9 mRNA significantly increased after 30 days of infection, reached peak on day 90, and then decreased slightly on days 180-270. The expression of IFN-γ mRNA, increased on day 2 and 8 after infection, slightly decreased on days 30-60, and obvious decreased on days 90-270, but were still higher than those of the control group. The expression of IL-4 mRNA gradually increased along with the time of infection. In serum of Em infected mice, level of IFN-γ peaked at day 30 and then gradually decreased; whereas IL-4 level peaked at day 90 and then gradually decreased. In vitro experiment found that Tim-3/Galectin-9 directly caused the changes in the levels of IFN-γ and IL-4., Conclusions: Tim-3/Galectin-9 signaling pathway may be involved in the development of persistent infection of Em by regulating the production of Th1 and Th2 cytokines., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen in the pig industry worldwide. Many viruses manipulate their cellular metabolism to replicate themselves and cause infection. A conserved cellular energy sensor, 5'-AMP-activated protein kinase (AMPK), maintains cellular energy homeostasis. We found that PRRSV infection caused significant AMPK activation in a time-dependent manner via the ROS-calcium/calmodulin-dependent protein kinase-2 pathway. RNA interference-mediated AMPK knockdown could increase PRRSV replication in MARC-145 cells, suggesting that AMPK contributed to PRRSV infection regulation. Moreover, investigation of the effect of AMPK activity on PRRSV replication showed that PRRSV replication could be suppressed by the pharmacological agonists 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside and A769662. Conversely, an AMPK inhibitor, compound C, markedly enhanced PRRSV infection. Furthermore, the AMPK agonist A769662 was found to exert no effect on PRRSV entry, assembly, and release, suggesting that A769662 may hinder the PRRSV genome replication in MARC-145 cells. In conclusion, AMPK may be a promising antiviral drug target against PRRSV infection., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

N -Heterobiaryls are common skeletons found in biological molecules, pharmaceuticals and ligands. Herein, we document an efficient and redox-neutral photocatalytic system to obtain functionalized N -heterobiaryls under mild conditions. Substrates bearing variegated functional groups are compatible with the developed photocatalytic conditions. This method is translatable to gram-scale synthesis, with a photocatalyst loading as low as 0.1 mol% and minimal variation of the yield. The starting materials are commercially available, demonstrating the practicality and accessibility of this methodology. Interestingly, phenols can serve both as coupling partners and proton donors. Arenes without a phenolic hydroxyl group also underwent efficient coupling with HFIP as a solvent.

This study was conducted to evaluate the effects of Clostridium butyricum dietary supplementation on the growth, antioxidant, immune response, gut microbiota, and intestinal barrier function of broilers under high stocking density (HSD) stress. A total of 324 1-day-old Arbor Acres male broilers were randomly assigned to three treatments with six replicates, each replicate including 18 chickens (18 birds/m 2 ). The experiment lasted 6 weeks. The three treatments were basal diet (control, CON), basal diet supplemented with 1 × 10 9 colony forming units (cfu)/kg C. butyricum (CB), and basal diet supplemented with 10 mg/kg virginiamycin (antibiotic, ANT). The results showed that the body weight (BW) and average daily gain (ADG) of broilers in the CB group were significantly higher than those in the CON group in three periods ( p < 0.05). The total antioxidant capacity (T-AOC) and the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity in serum of the CB group were significantly increased compared with those in the CON and ANT groups at 42 days ( p < 0.05). At 42 days, the serum immunoglobulin M (IgM) and immunoglobulin G (IgG) levels of the CB group were significantly higher than those of the CON group. Compared with the CON group, interleukin-1β (IL-1β) in the CB group was significantly decreased in the starter and grower stages ( p < 0.05), but there was no significant difference between the two treatment groups ( p > 0.05). C. butyricum significantly decreased the high stocking density-induced expression levels of IL-1β and tumor necrosis factor-α (TNF-α) in the ileum of broilers at different stages. Additionally, C. butyricum could increase the expressions of claudin-1 and zonula occludens-1 (ZO-1) in intestinal tissue. Moreover, C. butyricum significantly increased the Sobs and Shannon indices in the CB group compared with the ANT group ( p < 0.05), while the Ace index in the CB group was significantly higher than that of the CON group ( p < 0.05). Furthermore, by using 16S rRNA gene sequencing, the proportion of Bacteroides in the CB group was increased compared to those in the CON and ANT groups at the genus level. In conclusion, C. butyricum supplemented into feed could improve the growth performance and feed utilization of broilers by promoting immune and intestinal barrier function and benefiting the cecal microflora., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Xu, Wang, Sun, Deng, Wei, Ma, Fu, Wang and Li.)

Over the past three decades, organocatalysis has emerged as a powerful catalysis platform and has gradually been incorporated into the routine synthetic toolbox to obtain chiral molecules. However, its application in the site- and enantioselective functionalization of inactive aryl C-H bonds remains in its infancy. Here, we present an organocatalyst-controlled para-selective arene C-H functionalization strategy that addresses this issue, which remains an enduring challenge in arene functionalization chemistry. By emulating enzyme catalysis, the chiral phosphoric acid catalyst offers an ideal chiral environment for stereoinduction, and the projecting substituents give control of chemo- and site-selectivity. Various types of nucleophile are compatible with this method, affording more than 100 para-selective adducts with stereodefined carbon centres or axes in viable molecular contexts. This protocol is expected to provide a general strategy for para-selective functionalization of arene C-H bonds in a controlled manner., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

N-Phenylphenothiazine as an inexpensive, highly reductive and oxygen tolerant organophotocatalyst has exhibited potential in various challenging photochemical transformations. Here we report a general and straightforward method to access structurally diverse N-phenylphenothiazine derivatives by means of a novel electrochemical tool. The introduction of a 2-naphthylamine moiety with an extended π-system and an amine group led to the variation of spectral characterization. Photochemical verification experiments demonstrated that the formed N-arylation products with good efficacy and chemo/site-control displayed competitive catalytic activity in challenging transformations.

Background: Substance abuse represents a foremost national concern for adolescents and adults; investigators have implemented a variety of interventions, delivered with both in-person and mobile-based apps' modalities. The electronic techniques could be more effective because they avoid the cost, privacy, and accessibility issues associated with in-person intervention. To address this issue, a systematic review of the scientific evidence relative to the efficacy of app-based interventions delivered by mobile devices (smartphones) to reduce substance abuse in adolescents and adults was carried out., Methods: To identify relevant studies published from 2005 to 2019, a comprehensive search was conducted. Databases that were searched include CINAHL, Cochrane CENTRAL, Embase, PsycINFO, PubMed, and Web of Science. Keywords and relevant controlled vocabulary terms related to substance abuse and technology were included. Studies were included if they had examined reductions in substance abuse and problem behaviors as a primary outcome with app-based interventions delivered to adolescents and adults., Results: The initial search yielded 21,641 articles, duplicates were removed, and 14,797 citations remained; title/abstract screening yielded 190 full-text articles. One hundred seventy-three were excluded because they did not meet the inclusion criteria, leaving 17 final articles to be analyzed in this review. Use of app-based interventions showed some evidence of effectiveness in reducing substance abuse in the adolescent adult population., Conclusion: Most intervention studies analyzed focused on alcohol reduction. Further research is needed on diverse substance abuse utilizing larger sample sizes, longitudinal studies, and theoretical foundations on the practice of delivering interventions using mobile-based apps., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article., (Copyright © 2021 International Nurses Society on Addictions.)

Non-standard structured, multivariate data are emerging in many research areas, including genetics and genomics, ecology, and social science. Suitably defined pairwise distance measures are commonly used in distance-based analysis to study the association between the variables. In this work, we consider a linear quantile regression model for pairwise distances. We investigate the large sample properties of an estimator of the unknown coefficients and propose statistical inference procedures correspondingly. Extensive simulations provide evidence of satisfactory finite sample properties of the proposed method. Finally, we applied the method to a microbiome association study to illustrate its utility., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest.

Pnictogen-bonding catalysis based on σ-hole interactions has recently attracted the attention of synthetic chemists. As a proof-of-concept for asymmetric pnictogen-bonding catalysis, we report herein an enantioselective transfer hydrogenation of benzoxazines catalyzed by a novel chiral antimony cation/anion pair. The chiral pnictogen catalyst library could be rapidly accessed from triarylstibine with readily available mandelic acid analogues, and the catalyst displays remarkable efficiency and enantiocontrol potency even at 0.05 mol % loading. Moreover, the properties of the catalyst and the mechanistic insights have been investigated by nonlinear effect studies, 1 H NMR, LC-MS, and control experiments.

Atropisomerism is a stereochemical behavior portrayed by three-dimensional molecules that bear rotationally restricted σ bond. Akin to the well-represented point-chiral molecules, atropisomerically chiral compounds are finding increasing utilities in many disciplines where molecular asymmetry is influential. This provides steady demand on atroposelective synthesis, where numerous synthetic pursuits have been rewarded with conceptually novel and streamlined methods while expanding the structural diversity of atropisomers. This review summarizes key achievements in stereoselective preparation of biaryl, heterobiaryl, and nonbiaryl atropisomers documented between 2015 and 2020. Emphasis is placed on the synthetic strategies for each structural class, while examples are cited to illustrate the potential applications of the accessed atropochiral targets.

As an important platform molecule, atropisomeric QUINOL plays a crucial role in the development of chiral ligands and catalysts in asymmetric catalysis. However, efficient approaches towards QUINOL remain scarce, and the resulting high production costs greatly impede the related academic research as well as downstream industrial applications. Here we report a direct oxidative cross-coupling reaction between isoquinolines and 2-naphthols, providing a straightforward and scalable route to acquire the privileged QUINOL scaffolds in a metal-free manner. Moreover, a NHC-catalyzed kinetic resolution of QUINOL N-oxides with high selectivity factor is established to access two types of promising axially chiral Lewis base catalysts in optically pure forms. The utility of this methodology is further illustrated by facile transformations of the products into QUINAP, an iconic ligand in asymmetric catalysis.

The objective of present study was to investigate the effects of alpha-lipoic acid (ALA) dietary supplementation on the behavior, physiological and oxidant stress indicators, and bone quality in broilers under high stocking density (HSD) stress. A total of one thousand eight hundred 22-day-old Arbor Acres male broiler chicks were randomly allocated to 18 pens (2.97 × 2.03 m) in 3 groups: 14 birds/m 2 (NSD, normal stocking density) or 18 birds/m 2 (HSD) or 18 birds/m 2 plus 300 mg/kg ALA dietary supplement (HSD + ALA, high stocking density + alpha-lipoic acid). Each treatment had 6 replicates, and the experiment lasted 3 wk. The HSD group was significantly lower than the NSD group (P < 0.05) in the frequency of eating, walking, and preening behavior. The alkaline phosphatase activity and serum calcium content were significantly higher, and the parathyroid hormone (PTH) level was significantly lower in the HSD group than in the NSD group (P < 0.05). When compared with the NSD group, the HSD group showed an increase (P < 0.05) in serum heterophil/lymphocyte ratio (H/L ratio), corticosterone (CORT), malondialdehyde (MDA) content, and catalase (CAT) activity, whereas a decrease (P < 0.05) in total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) concentrations. The HSD group was also significantly lower (P < 0.05) than the NSD group in the tibia and femur breaking strength, bone mineral density, and BMC. Importantly, the addition of ALA into the diets of the HSD group enabled the HSD + ALA group to recover to the levels of NSD group (P > 0.05) in the standing and preening behavior, alkaline phosphatase activity, PTH concentration, H/L ratio, CAT, T-AOC, MDA, SOD, and GSH-Px. These results indicate that the increase of stocking density lowered the bone quality, increased the physiological and oxidative stress indicators, and modified the behavior of broilers, whereas ALA dietary supplementation could counteract the reduction in the performance and physiological responses of broilers under high-density environmental stress., (Copyright © 2020. Published by Elsevier Inc.)

N-arylcarbazole structures are important because of their prevalence in natural products and functional OLED materials. C-H amination of arenes has been widely recognized as the most efficient approach to access these structures. Conventional strategies involving transition-metal catalysts suffer from confined substrate generality and the requirement of exogenous oxidants. Organocatalytic enantioselective C-N chiral axis construction remains elusive. Presented here is the first organocatalytic strategy for the synthesis of novel axially chiral N-arylcarbazole frameworks by the assembly of azonaphthalenes and carbazoles. This reaction accommodates broad substrate scope and gives atropisomeric N-arylcarbazoles in good yields with excellent enantiocontrol. This approach not only offers an alternative to metal-catalyzed C-N cross-coupling, but also brings about opportunities for the exploitation of structurally diverse N-aryl atropisomers and OLED materials., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Heavy alcohol use is a serious health issue in the United States with consequences such as illness, injury, and death. College students are among the most vulnerable to problems associated with risky drinking. This demographic is known as the Net Generation because members have grown up with digital technologies such as smartphones and apps. Thus, mobile health (mHealth) applications, successful in the delivery of health information and interventions to tech-savvy individuals, are a promising means of reaching them. To that end, we developed a smartphone application (SmarTrek) that targets college students and aims to reduce risky alcohol use. SmarTrek features are easy to use and have interactive components including text messages that incorporate motivational interviewing and ecological momentary interventions. We conducted iterative theater testing, field testing, and focus groups to evaluate the acceptability of SmarTrek with college students. We identified salient issues that might arise from SmarTrek use and modified the app based on feedback from participants. Participants were assigned to 2 groups (Group 1 [n = 4] and Group 2 [n = 6]). At baseline, participants completed 2 standardized surveys. Following their field testing, each group of participants was then invited to a focus group session of the app in which they provided feedback. The majority of participants (90%) agreed that SmarTrek was easy to use and that the information provided was useful and had a positive effect on decreasing their drinking. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

With the advancement of biotechniques, a vast amount of genomic data is generated with no limit. Predicting a disease trait based on these data offers a cost-effective and time-efficient way for early disease screening. Here we proposed a composite kernel partial least squares (CKPLS) regression model for quantitative disease trait prediction focusing on genomic data. It can efficiently capture nonlinear relationships among features compared with linear learning algorithms such as Least Absolute Shrinkage and Selection Operator or ridge regression. We proposed to optimize the kernel parameters and kernel weights with the genetic algorithm (GA). In addition to improved performance for parameter optimization, the proposed GA-CKPLS approach also has better learning capacity and generalization ability compared with single kernel-based KPLS method as well as other nonlinear prediction models such as the support vector regression. Extensive simulation studies demonstrated that GA-CKPLS had better prediction performance than its counterparts under different scenarios. The utility of the method was further demonstrated through two case studies. Our method provides an efficient quantitative platform for disease trait prediction based on increasing volume of omics data., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Telomerase activation is critical in many cancers including central nervous system (CNS) tumors. Imetelstat is an oligonucleotide that binds to the template region of the RNA component of telomerase, inhibiting its enzymatic activity. We conducted an investigator-sponsored molecular biology (MB) and phase II study to estimate inhibition of tumor telomerase activity and sustained responses by imetelstat in children with recurrent CNS malignancies. In the MB study, patients with recurrent medulloblastoma, high-grade glioma (HGG) or ependymoma undergoing resection received one dose of imetelstat as a 2-h intravenous infusion at 285 mg/m(2), 12-24 h before surgery. Telomerase activity was evaluated in fresh tumor from surgery. Post-surgery and in the phase II study, patients received imetelstat IV (days 1 and 8 q21-days) at 285 mg/m(2). Imetelstat pharmacokinetic and pharmacodynamic studies were performed. Of two evaluable patients on the MB trial, intratumoral telomerase activity was inhibited by 95 % compared to baseline archival tissue in one patient and was inevaluable in one patient. Forty-two patients (40 evaluable for toxicity) were enrolled: 9 medulloblastomas, 18 HGG, 4 ependymomas, 9 diffuse intrinsic pontine gliomas. Most common grade 3/4 toxicities included thrombocytopenia (32.5 %), lymphopenia (17.5 %), neutropenia (12.5 %), ALT (7.5 %) and AST (5 %) elevation. Two patients died of intratumoral hemorrhage secondary to thrombocytopenia leading to premature study closure. No objective responses were observed. Telomerase inhibition was observed in peripheral blood mononuclear cells (PBMCs) for at least 8 days. Imetelstat demonstrated intratumoral and PBMC target inhibition; the regimen proved too toxic in children with recurrent CNS tumors., Competing Interests: None.

A multicomponent reaction of 2-alkynylbenzaldehyde, sulfonohydrazide, and tertiary amine is discovered, which generates the unexpected H-pyrazolo[5,1-a]isoquinolines in good yields under mild conditions. In the reaction process, silver(I)-catalyzed intramolecular cyclization and copper(II)-catalyzed oxidation of an aliphatic C-H bond of tertiary amine in air are involved.

Genetic linkage analysis has been a traditional means for identifying regions of the genome with large genetic effects that contribute to a disease. Following linkage analysis, association studies are widely pursued to fine-tune regions with significant linkage signals. For complex diseases which often involve function of multi-genetic variants each with small or moderate effect, linkage analysis has little power compared to association studies. In this chapter, we give a brief review of design issues related to linkage analysis and association studies with human genetic data. We introduce methods commonly used for linkage and association studies and compared the relative merits of the family-based and population-based association studies. Compared to candidate gene studies, a genomewide blind searching of disease variant is proving to be a more powerful approach. We briefly review the commonly used two-stage designs in genome-wide association studies. As more and more biological evidences indicate the role of genomic imprinting in disease, identifying imprinted genes becomes critically important. Design and analysis in genetic mapping imprinted genes are introduced in this chapter. Recent efforts in integrating gene expression analysis and genetic mapping, termed expression quantitative trait loci (eQTLs) mapping or genetical genomics analysis, offer new prospect in elucidating the genetic architecture of gene expression. Designs in genetical genomics analysis are also covered in this chapter.