Functional polymorphisms in Benzo(a)Pyrene-induced toxicity pathways associated with the risk on laryngeal squamous cell carcinoma.

Benzo(a)Pyrene (BaP) is a well-known environmental carcinogen that poses a significant risk to human health. The pivotal genes and toxicity pathways have been identified as key events to construct the mode of action (MOA) of BaP. In this study, we focused on evaluating the association between genetic variants in BaP-disturbed toxicity pathways and the susceptibility of laryngeal squamous cell carcinoma (LSCC), based on the data of our previous genome-wide association analysis (GWAS). In addition, we investigated the biological roles of these significant polymorphisms by integrating bioinformatic annotation and experimental validation. Our findings revealed that 15 functional polymorphisms in AHR signaling, p53 signaling, NRF2 signaling, TGF-ß signaling, STAT3 signaling, and IL-8 signaling pathways were significantly associated with susceptibility to LSCC. Our study provides a novel approach for identifying novel risk genetic loci utilizing GWAS data, and suggests potential targets for early detection of LSCC in the future.

Combined linkage analysis and association mapping identifies genomic regions associated with yield-related and drought-tolerance traits in wheat (Triticum aestivum L.).

KEY MESSAGE: Combined linkage analysis and association mapping identified genomic regions associated with yield and drought tolerance, providing information to assist breeding for high yield and drought tolerance in wheat. Wheat (Triticum aestivum L.) is one of the most widely grown food crops and provides adequate amounts of protein to support human health. Drought stress is the most important abiotic stress constraining yield during the flowering and grain development periods. Precise targeting of genomic regions underlying yield- and drought tolerance-responsive traits would assist in breeding programs. In this study, two water treatments (well-watered, WW, and rain-fed water stress, WS) were applied, and five yield-related agronomic traits (plant height, PH; spike length, SL; spikelet number per spike, SNPS; kernel number per spike, KNPS; thousand kernel weight, TKW) and drought response values (DRVs) were used to characterize the drought sensitivity of each accession. Association mapping was performed on an association panel of 304 accessions, and linkage analysis was applied to a doubled haploid (DH) population of 152 lines. Eleven co-localized genomic regions associated with yield traits and DRV were identified in both populations. Many previously cloned key genes were located in these regions. In particular, a TKW-associated region on chromosome 2D was identified using both association mapping and linkage analysis and a key candidate gene, TraesCS2D02G142500, was detected based on gene annotation and differences in expression levels. Exonic SNPs were analyzed by sequencing the full length of TraesCS2D02G142500 in the association panel, and a rare haplotype, Hap-2, which reduced TKW to a lesser extent than Hap-1 under drought stress, and the Hap-2 varieties presented drought-insensitive. Altogether, this study provides fundamental insights into molecular targets for high yield and drought tolerance in wheat.

Threshold dynamics of a viral infection model with defectively infected cells.

In this paper, we investigate the global dynamics of a viral infection model with defectively infected cells. The explicit expression of the basic reproduction number of virus is obtained by using the next generation matrix approach, where each term has a clear biological interpretation. We show that the basic reproduction number serves as a threshold parameter. The virus dies out if the basic reproduction number is not greater than unity, otherwise the virus persists and the viral load eventually approaches a positive number. The result is established by Lyapunov's direct method. Our novel arguments for the stability of the infection equilibrium not only simplify the analysis (compared with some traditional ones in the literature) but also demonstrate some correlation between the two Lyapunov functions for the infection-free and infection equilibria.

Manipulation of Electrode Composition for Effective Water Management in Fuel Cells Fed with an Electrically Rechargeable Liquid Fuel.

The liquid fuel cell, with its high energy density and ease of fuel handling, has attracted great attention worldwide. However, its real application is still being greatly hindered by its limited power density. Hence, the recently proposed and demonstrated fuel cell, using an electrically rechargeable liquid fuel (e-fuel), is believed to be a candidate with great potential due to its significant performance advancement. Unlike the conventional alcoholic liquid fuels, the e-fuel possesses excellent reactivity, even on carbon-based materials, which therefore allows the e-fuel cell to achieve superior performance without any noble metal catalysts. However, it is found that, during the cell operation, the water generated at the cathode following the oxygen reduction reaction could lead to a water flooding problem and further limit the cell performance. To address this issue, in this work, by manipulating the cathode composition, a blended binder cathode using both Nafion and polytetrafluoroethylene as binding agents is fabricated and demonstrated its superiority in the fuel cell to achieve an enhanced water management and cell performance. Furthermore, using the developed cathode, a fuel cell stack is designed and fabricated to power a 3D-printed toy car, presenting this system as a promising device feasible for future study and real applications.

A Passive Fuel Cell Fed with an Electrically Rechargeable Liquid Fuel.

Passive fuel cells, using diffusion and natural convection for fuel delivery, are regarded as promising candidates for powering portable devices including mobile phones and laptops. However, the performance of passive fuel cells which employ typical liquid alcohol fuels are still limited, which thereby greatly hampered their commercialization progress. Recently, a novel concept named the electrically rechargeable liquid fuel (e-fuel), with its rechargeability, cost-effectiveness, and superior reactivity, has attracted increasing attention. In this study, a passive fuel cell using the liquid e-fuel and the ambient air for electricity production is designed and fabricated. This passive fuel cell is demonstrated to achieve a peak power density of 116.2 mW cm-2 along with a stable operation for over 350 h, exhibiting great prospect for future applications.

Variations of disinfection byproduct precursors through conventional drinking water treatment processes and a real-time monitoring method.

In this investigation, raw water (RW), settled water (SW), and filtered water (FW) collected from a drinking water treatment plant were fractionated into 24 natural organic matter (NOM) fractions with varying molecular weights and hydrophobicity. The yields of disinfection byproducts (DBPs) obtained during the chlorination of the NOM fractions were explored. Results revealed that the 0-1 kDa, 5-10 kDa, and hydrophobic DBP precursors dominated RW. Hydrophobic fractions cannot be effectively removed, which contributed to the high DBP precursors remaining in the FW. The optional optical parameters, including UVA (UV340, UV360, and UV380), UVB (UV280, UV300, and UV310), and UVC (UV254, UV260, and UV272), were analyzed to determine the DBP yields during chlorination of different NOM fractions. Results revealed that UVC could be applied to indicate the regulated DBP yields of the humified precursors. Contrary to the generally accepted view, for biologically derived precursors, their regulated DBPs and dichloroacetonitrile correlated better with UVA (e.g. UV340). Moreover, PARAFAC analysis was applied to decompose an array of 24 EEM spectra. Good linear correlations were found between the PARAFAC components and most DBP yields. Furthermore, four fluorescence parameters were proposed via a modified fluorescence picking method, which can serve as excellent surrogates of PARAFAC components. These fluorescence parameters were found to be effective in indicating most DBP yields. Finally, the fluorescence intensity at excitation wavelength/emission wavelength = 310/416 nm was found to be a promising built-in parameter for the real-time monitoring of DBP precursors, regardless of the humification degree of the precursors.

Application of Fourier transform ion cyclotron resonance mass spectrometry in deciphering molecular composition of soil organic matter: A review.

Swiftly deciphering soil organic matter (SOM) composition is critical for research on soil degradation and restoration. Recent advances in analytical techniques (e.g., optical methods and mass spectrometry) have expanded our understanding of the composition, origin, and evolution of SOM. In particular, the use of Fourier transform ion cyclotron resonance mass spectrometers (FTICR-MS) makes it possible to interpret SOM compositions at the molecular level. In this review, we discuss extraction, enrichment, and purification methods for SOM using FTICR-MS analysis; summarize ionization techniques, FTICR-MS mechanisms, data analysis methods, and molecular compositions of SOM in different environments (providing new insights into its origin and evolution); and discuss factors affecting its molecular diversity. Our results show that digenesis, combustion, pyrolysis, and biological metabolisms jointly contribute to the molecular diversity of SOM molecules. The SOM thus formed can further undergo photodegradation during transportation from land to fresh water (and subsequently oceans), resulting in the formation of dissolved organic matter (DOM). Better understanding the molecular features of DOM therefore accelerates our understanding of SOM evolution. In addition, we assess the degradation potential of SOM in different environments to better inform soil remediation methods. Finally, we discuss the merits and drawbacks of applying FTICR-MS on the analysis of SOM molecules, along with existing gaps in knowledge, challenges, and new opportunities for research in FTICR-MS applications and SOM identification.

One-pot chemo-enzymatic conversion of D-xylose to furfuralcohol by sequential dehydration with oxalic acid plus tin-based solid acid and bioreduction with whole-cells.

In this study, organic acid could be used as co-catalyst for assisting solid acid SO42-/SnO2-argil to convert hemicellulose-derived D-xylose into furfural. The relationship between pKa of organic acid and turnover frequency (TOF) of co-catalysis with organic acid plus SO42-/SnO2-argil was explored on the conversion of D-xylose to furfural. Oxalic acid (pKa = 1.25) (0.35 wt%) was found to be the optimum co-catalyst for assisting SO42-/SnO2-argil (3.6 wt%) to synthesize furfural from D-xylose (20 g/L) at 180 °C for 20 min, and the furfural yield and TOF could be obtained at 57.07% and 6.26 h-1, respectively. Finally, the obtained furfural (107.6 mM) could be completely biotransformed to furfuralcohol by recombinant Escherichia coli CCZU-K14 whole-cells at 30 °C and pH 6.5 in the presence of 1.5 mol glucose/mol furfural and 400 mM D-xylose. Clearly, this strategy shows high potential application for the effective synthesis of furfuralcohol from biomass-derived D-xylose.

Copper-Catalyzed Ring Expansion of Cyclopropyl Ketones/Formation of N-acyliminium/Hetero-[4 + 2]-Cycloaddition: A Route to Substituted Pentacyclic Isoindolin-1-one.

A Cu-catalyzed three-component cascade cyclization among 2-formylbenzonitrile, cyclopropyl ketones, and diaryliodonium salts for the construction of fused isoindolin-1-one compounds is achieved. Pentacyclic isoindolinone derivatives could be obtained in moderate to good yields. The proposed mechanism involved a ring expansion of cyclopropyl ketones/formation of N-acyliminium/hetero-[4 + 2]-cycloaddition process.

Structure of NADP+-bound 7ß-hydroxysteroid dehydrogenase reveals two cofactor-binding modes.

In mammals, bile acids/salts and their glycine and taurine conjugates are effectively recycled through enterohepatic circulation. 7ß-Hydroxysteroid dehydrogenases (7ß-HSDHs; EC 1.1.1.201), including that from the intestinal microbe Collinsella aerofaciens, catalyse the NADPH-dependent reversible oxidation of secondary bile-acid products to avoid potential toxicity. Here, the first structure of NADP+ bound to dimeric 7ß-HSDH is presented. In one active site, NADP+ adopts a conventional binding mode similar to that displayed in related enzyme structures. However, in the other active site a unique binding mode is observed in which the orientation of the nicotinamide is different. Since 7ß-HSDH has become an attractive target owing to the wide and important pharmaceutical use of its product ursodeoxycholic acid, this work provides a more detailed template to support rational protein engineering to improve the enzymatic activities of this useful biocatalyst, further improving the yield of ursodeoxycholic acid and its other applications.

Characterization of a novel cytochrome P450 from Amycolatopsis sp. CGMCC1149 for hydroxylation of lovastatin.

Wuxistatin, a novel and potent statin, is converted from lovastatin by Amycolatopsis sp. CGMCC1149. In the bioconversion, lovastatin is firstly hydroxylated to 3-hydroxymethyl lovastatin (product I) by a hydroxylase. In the current study, a novel hydroxylase gene p450lov was isolated from Amycolatopsis sp. CGMCC1149 by degenerate PCR and self-formed adaptor PCR and expressed in Escherichia coli. The gene encodes a 403-amino-acid protein with a molecular weight of 44.8 kDa and was designated as a new member of cytochrome P450 (CYP) 105 family, CYP105A44. Meanwhile, a lovastatin catalytic in vitro system was established, and an optimal hydroxylation reaction system contained 30 µM lovastatin, 600 µM NADH, 120 µM ferredoxin, 0.04 U ferredoxin-nicotinamide adenine dinucleotide phosphate reductase, and 100 µM CYP105A44 in a final volume of 200 µL Tris HCl buffer (50 mM, pH 7.4). These would be helpful for further studies on the hydroxylation of statins.

[Cloning and application of a novel hydroxylase in lovastatin conversion].

Wuxistatin, a novel and potent statin, is converted from lovastatin by Amycolatopsis sp. CGMCC1149. In the bioconversion, lovastatin is firstly hydroxylated by a hydroxylase. To obtain the critical hydroxylase, a novel hydroxylase gene was isolated from Amycolatopsis sp. CGMCC1149 by Degenerate PCR and Self-Formed Adaptor PCR and expressed in Escherichia coli. BLAST sequence analysis revealed that the gene belonged to cytochrome P450 gene superfamily and could encode a 403-amino-acid protein with a molecular weight of 44.8 kDa. The secondary structure prediction result showed that this protein contained many typical functional regions of P450, such as oxygen binding site, ion-pair region and heme binding region. Meanwhile, a catalytic function verification system was constructed by NADH, ferredoxin and ferredoxin reductase which could catalyze lovastatin hydroxylation into the target product. These would be helpful for further studies in large-scale production of wuxistatin.