Epidemiology and viral loads of respiratory syncytial virus in hospitalized children prior to and during COVID-19 pandemic in Hangzhou, China.

Non-pharmaceutical interventions (NPIs) implemented to control SARS-CoV-2 have significantly influenced the activity of respiratory pathogens. This study investigated epidemiological changes among hospitalized patients with respiratory syncytial virus (RSV) before (2017-2019) and during (2020-2022) the COVID-19 pandemic in Hangzhou, China. We also examined viral load distribution across demographic and temporal variables. Nasopharyngeal swabs were collected and RSV loads were quantified using reverse transcriptase polymerase chain reaction (RT-qPCR). RSV epidemic characteristics, seasonal dynamics, and viral load distributions were compared between pre- and pandemic years. General linear models were employed to assess associations between viral loads and age. Among 19 742 cases, 1576 and 2092 tested positive during the pre- and pandemic years, respectively. From February to July 2020, the implementation of NPIs led to the cessation of RSV circulation. However, after these measures were relaxed, RSV cases resurged over two consecutive seasons during the pandemic, notably affecting older children compared to those in the pre-pandemic years (1.00 years, IQR: 0.50-2.00 vs. 0.58 years, IQR: 0.27-1.00, p < 0.001). Specifically, in 2021-2022, an off-season resurgence of RSV began earlier (mid-June), lasted longer (40 weeks), and involved more positive cases (1238 cases) than both 2020-2021 and pre-pandemic years. Viral load distribution demonstrated a clear age-related relationship in both pre- and pandemic years, with younger children consistently showing higher viral loads, independently of gender and season (all p-values for trends <0.001). These findings highlight the impact of NPIs on RSV epidemiology and underscore the need to prioritize RSV infection prevention in younger children from the perspective of viral load.

The contrasting effects of fluctuating temperature on bacterial diversity and performances in temperate and subtropical soils.

The extremely high species diversity of soil bacterial community has fascinated and puzzled community ecologists. Although theory predicts that fluctuations in environments can facilitate diversity maintenance, the effects of fluctuating temperature on species diversity have rarely been investigated in species-rich microbial communities. Here, we examined whether fluctuating temperature had positive effects on species diversity relative to constant temperatures in soil bacterial communities, and investigated the effects of fluctuating temperature on bacterial performances (changes in relative abundance). We performed a temperature manipulation experiment with soils collected from temperate and subtropical zones, where the soils were subjected to constant high, low or fluctuating temperatures. We found that fluctuating temperatures showed significant positive effects on species diversity. The time-averaged effect of fluctuating temperatures (i.e., averaging out the differences between species in their environment-dependent performances) appeared to delay species loss in both the temperate and the subtropical communities. In addition, we found that the performances of temperature-responsive species at fluctuating temperatures significantly deviated from their time-weighted average performances at constant high and low temperatures, which was defined as fluctuation-dependent effects in our study. Intriguingly, fluctuation-dependent effects beyond time-averaged effect led to an opposite trend: differences in temperature-responsive species' performances decreased in the temperate communities, but increased in the subtropical communities. Our findings provide new insights into diversity maintenance in soil bacterial communities, and imply that the effects of fluctuating temperature on species diversity in soil bacterial community might vary across latitude.

Affinity Chromatographic Method for Determining Drug-Protein Interaction with Enhanced Speed Than Typical Frontal Analysis.

Revealing drug-protein interaction is highly important to select a drug candidate with improved drug-like properties in the early stages of drug discovery. This highlights the urgent need to develop assays that enable the analysis of drug-protein interaction with high speed. Herein, this purpose was realized by the development of an affinity chromatographic method with a two-fold higher speed than typical assays like frontal analysis and zonal elution. The method involved synthesis of a stationary phase by immobilizing poly(ADP-ribose) polymerase-1 (PARP1) onto macroporous silica gel through a one-step bioorthogonal reaction, characterization of mutual displacement interaction of two canonical drugs to the immobilized PARP1, determination of the interaction between three (iniparib, rucaparib, and olaparib) drugs and the protein, and validation of these parameters by typical frontal analysis. The numbers of binding sites on the column were (2.85 ± 0.05) × 10-7, (1.89 ± 0.71) × 10-6, and (1.49 ± 0.06) × 10-7 M for iniparib, rucaparib, and olaparib, respectively. On these sites, the association constants of the three drugs to the protein were (9.85 ± 0.56) × 104, (2.85 ± 0.34) × 104, and (1.07 ± 0.35) × 105 M-1. The determined parameters presented a good agreement with the calculation by typical frontal analyses, which indicated that the current continuous competitive frontal analysis method was reliable for determining drug-protein interaction. Application of the methods was achieved by screening tubeimosides I and II as the bioactive compounds against breast cancer in Bolbostemma paniculatum. Their mechanism may be the interference of DNA repair via down-regulating PARP1 and meiotic recombination 11 expressions, thus leading to oncogene mutations and death of cancer cells. The method was high speed since it allowed simultaneous determination of binding parameters between two drugs and a protein with a smaller number of experiments to be performed. Such a feature made the method an attractive alternative for high-speed analysis of drug-protein interaction or the other bindings in a binary system.

Stepwise Frontal Analysis Coupled with Affinity Chromatography: A Fast and Reliable Method for Potential Ligand Isolation and Evaluation from Mahuang-Fuzi-Xixin Decoction.

Mahuang-Fuzi-Xixin Decoction (MFXD) is widely used in the treatment of asthma, however, the functional components in the decoction targeting beta2-adrenoceptor (ß2 -AR) remain unclear. Herein, we immobilized the haloalkane dehalogenase (Halo)-tagged ß2 -AR on the 6-chlorocaproic acid-modified microspheres. Using the affinity stationary phase, the interactions of four ligands with the receptor were analyzed by stepwise frontal analysis. The association constants were (4.75±0.28)×104  M-1 for salbutamol, (2.93±0.15)×104  M-1 for terbutaline, (1.23±0.03)×104  M-1 for methoxyphenamine, (5.67±0.38)×104  M-1 for clorprenaline at high-affinity binding site, and (2.73±0.05)×103  M-1 at low-affinity binding site. These association constants showed the same rank order as the radioligand binding assay, demonstrating that immobilized ß2 -AR had capacity to screen bioactive compounds binding to the receptor while stepwise frontal analysis could predict their binding affinities. Application of the immobilized receptor in analysis of MFXD by chromatographic method revealed that ephedrine, aconifine, karakoline, and chasmanine were the bioactive compounds targeting ß2 -AR. Among them, ephedrine and chasmanine exhibited association constants of (2.94±0.02)×104 M-1 and (4.60±0.15)×104  M-1 to the receptor by stepwise frontal analysis. Molecular docking analysis demonstrated that ephedrine, chasmanine, and the other two compounds interact with ß2 -AR through the same pocket involving the key amino acids such as Asn312, Asp113, Phe289, Trp286, Tyr316, and Val114. As such, we reasoned that the four compounds dominate the therapeutic effect of MFXD against asthma through ß2 -AR mediating pathway. This work shed light on the potential of immobilized ß2 -AR for drug discovery and provided a valuable methodology for rapid screening.

Progress in Active Infrared Imaging for Defect Detection in the Renewable and Electronic Industries.

In recent years, infrared thermographic (IRT) technology has experienced notable advancements and found widespread applications in various fields, such as renewable industry, electronic industry, construction, aviation, and healthcare. IRT technology is used for defect detection due to its non-contact, efficient, and high-resolution methods, which enhance product quality and reliability. This review offers an overview of active IRT principles. It comprehensively examines four categories based on the type of heat sources employed: pulsed thermography (PT), lock-in thermography (LT), ultrasonically stimulated vibration thermography (UVT), and eddy current thermography (ECT). Furthermore, the review explores the application of IRT imaging in the renewable energy sector, with a specific focus on the photovoltaic (PV) industry. The integration of IRT imaging and deep learning techniques presents an efficient and highly accurate solution for detecting defects in PV panels, playing a critical role in monitoring and maintaining PV energy systems. In addition, the application of infrared thermal imaging technology in electronic industry is reviewed. In the development and manufacturing of electronic products, IRT imaging is used to assess the performance and thermal characteristics of circuit boards. It aids in detecting potential material and manufacturing defects, ensuring product quality. Furthermore, the research discusses algorithmic detection for PV panels, the excitation sources used in electronic industry inspections, and infrared wavelengths. Finally, the review analyzes the advantages and challenges of IRT imaging concerning excitation sources, the PV industry, the electronics industry, and artificial intelligence (AI). It provides insights into critical issues requiring attention in future research endeavors.

Development of an Allostery Responsive Chromatographic Method for Screening Potential Allosteric Modulator of Beta2-adrenoceptor from a Natural Product-Derived DNA-Encoded Chemical Library.

Allosteric ligands are promising drugs owing to their remote regulations of the orthosteric ligand signaling pathway. There are few allosteric ligands due to the lack of handy and efficacious method for the screening. Herein, we developed an affinity chromatographic method for allosteric ligand screening by immobilizing purified beta2 adrenoceptor (ß2-AR) onto macroporous silica gel by a two-point tethering method. The method relies on the occupation of the orthosteric site by an antagonist and the chelation of N-terminal His-tag of the receptor and Ni2+ coated on the gel. The immobilized ß2-AR demonstrated the greatest allosteric responsive feature when Cmpd-15 (0.25 µM) was included in the mobile phase. Under the same conditions, the association constants of three agonists (salbutamol, terbutaline, and tulobuterol) reduced to 47%, 19%, and 27% compared with the data without the inclusion of Cmpd-15 in the mobile phase. APF was screened as a potential allosteric modulator of ß2-AR by applying the immobilized receptor in a natural product-derived DNA-encoded chemical library (DEL). Relying on these results, we reasoned that the current method has potential in screening allosteric ligands of the receptor. We expect that it is applicable for the discovery of new allosteric binding sites of a target protein and screening allosteric modulators of the other receptors from complex samples.

Enhancing Chromatographic Performance of Immobilized Angiotensin II Type 1 Receptor by Strain-Promoted Alkyne Azide Cycloaddition through Genetically Encoded Unnatural Amino Acid.

During integration to the solid surface, the effects of tags introduced for bioorthogonal reactions on protein activity have received far less investigation. This represents the major challenge of improving the performance of the immobilized protein-based assays. Herein, the relationship between the fusion tags and their reaction efficiency in mediating the assay performance was realized by determining the chromatographic performance using genetically encoded azide-alkyne cycloaddition, and Halo- and SNAP-tagged bioorthogonal reactions for synthesizing immobilized angiotensin II type 1 receptor (AT1R). We demonstrated that immobilization with the incorporation of unnatural amino acid in the receptor minimizes the peak tailings and broadenings of irbesartan, fimasartan, losartan, and tasosartan, while attachment via large tags (SNAP and Halo) leads to serious asymmetry peaks. Upon the first immobilization, the association constants of the four drugs to AT1R appeared to be 1 order of magnitude greater than the other two attachments. Such enhancement is likely reasoned by the improved association rate constants and the relatively identical dissociation rates due to the small tag. While demonstrating improved chromatographic performance, the immobilized AT1R prepared by the genetically encoded azide-alkyne reaction was applied in analyzing Uncaria Schreber nom. cons. extract, which identified hynchophylline as a specific ligand binding to the receptor. As immobilized proteins move toward diverse assays, our findings provide an unprecedented insight into the relation between fusion tags and their reaction efficiency in mediating the assay performance, which is thus dedicated to the creation of a protein-functionalized surface for precisely determining the drug-protein interaction and discovering the specific partner of the protein.

Discovery and therapeutic implications of bioactive dihydroxylated phenolic acids in patients with severe heart disease and conditions associated with inflammation and hypoxia.

Our initial studies detected elevated levels of 3,4-dihydroxyphenyllactic acid (DHPLA) in urine samples of patients with severe heart disease when compared with healthy subjects. Given the reported anti-inflammatory properties of DHPLA and related dihydroxylated phenolic acids (DPAs), we embarked on an exploratory multi-centre investigation in patients with no urinary tract infections to establish the possible pathophysiological significance and therapeutic implications of these findings. Chinese and Caucasian patients being treated for severe heart disease or those conditions associated with inflammation (WBC ≥ 10 ×109/L or hsCRP ≥ 3.0 mg/L) and/or hypoxia (PaO2 ≤ 75 mmHg) were enrolled; their urine samples were analyzed by HPLC, HPLC-MS, GC-MS and biotransformation assays. DHPLA was detected in urine samples of patients, but undetectable in healthy volunteers. Dynamic monitoring of inpatients undergoing treatment showed their DHPLA levels declined in proportion to their clinical improvement. In DHPLA-positive patients' fecal samples, Proteus vulgaris and P. mirabilis were more abundant than healthy volunteers. In culture, these gut bacteria were capable of reversible interconversion between DOPA and DHPLA. Furthermore, porcine and rodent organs were able to metabolize DOPA to DHPLA and related phenolic acids. The elevated levels of DHPLA in these patients suggest bioactive DPAs are generated de novo as part of a human's defense mechanism against disease. Because DHPLA isolated from Radix Salvia miltiorrhizae has a multitude of pharmacological activities, these data underpin the scientific basis of this medicinal plant's ethnopharmacological applications as well as highlighting the therapeutic potential of endogenous, natural or synthetic DPAs and their derivatives in humans.

Seasonal Climate Variations Promote Bacterial α-Diversity in Soil.

Ecological theory suggests that temporal environmental fluctuations can contribute greatly to diversity maintenance. Given bacteria's short generation time and rapid responses to environmental change, seasonal climate fluctuations are very likely to play an important role in maintaining the extremely high α-diversity of soil bacterial community, which has been unfortunately neglected in previous studies. Here, with in-depth analyses of two previously published soil bacterial datasets at global scale, we found that soil bacterial α-diversity was positively correlated with both seasonal variations of temperature and precipitation. Furthermore, piecewise structural equation models showed that seasonal variations of temperature or precipitation had weak but significant positive effect on soil bacterial α-diversity in each dataset. However, it is noteworthy that the importance of seasonal climate variations might be underestimated in the above analyses, due to the potential confounding factors (such as vegetation type) and the lack of sampling across seasons. As a supplement, we analyzed a previously published wheat cropland dataset with samples collected in both winter and the following summer across North China Plain. As expected, bacterial α-diversity was positively correlated with seasonal climate variations in the cropland dataset, and climate seasonality explained a larger proportion of variations in bacterial α-diversity. Collectively, these findings implied that fluctuation-dependent mechanisms of diversity maintenance presumably operate in soil bacterial communities. Based on existing evidence, we speculated that the storage effect may be the main mechanism responsible for diversity maintenance in soil bacterial community, but rigorous experimental tests are needed in the future.

Early potential evaluation of lead compounds from a DNA-encoded library by the determination of their thermodynamics through a chromatographic method based on immobilized ß2-adrenoceptor.

Early potential evaluation of lead compounds is critical to decrease downstream lead-optimization cycle times and clinical attrition rates for drug development. This increasingly necessitates the methodologies for accurately evaluating the potential compounds. This work immobilized ß2-adrenoceptor (ß2-AR) onto microspheres through Halo-tag mediated reaction. Characterizing the resulting microspheres by elemental and functional analysis, we utilized the immobilized receptor to determine the thermodynamics of terbutaline, tulobuterol, clorprenaline, salbutamol, and methoxyphenamine. The association constants correlated to their capacity factors on the column containing the immobilized ß2-AR, thus providing a possibility for early potential evaluation of lead compounds from complex matrices like a DNA-encoded library. By this model, the lead compound (XC267) was predicted to have an association constant higher than terbutaline, salbutamol, and methoxyphenamine, but lower than tulobuterol and clorprenaline. The binding interaction between XC267 and ß2-AR is a spontaneous endothermic process with an association constant of (6.62 ± 0.13) × 104 M-1 at 37 °C. The change of Gibbs free energy(ΔGθ), enthalpy change (ΔHθ), and entropy change (ΔSθ) was -28.49 kJ/mol, -10.58 kJ/mol, and 57.79 J/moL·K at 37 °C. By the semi-empirical rule of Ross, the driving force of the interaction between XC267 and ß2-AR was electrostatic interaction. Such binding force was also achieved by molecular docking. These results suggested that XC267 is a candidate to treat asthma by specific binding to ß2-AR. We reasoned that receptor chromatography is able to the early potential evaluation of lead compounds from complex matrices.

Combination of C-reactive protein, procalcitonin, IL-6, IL-8, and IL-10 for early diagnosis of hyperinflammatory state and organ dysfunction in pediatric sepsis.

BACKGROUND: Although early diagnosis and management are critical for prognosis of pediatric sepsis, there are no specific diagnostic biomarkers for the hyperinflammatory state and organ dysfunction, important stages of sepsis. METHODS: We enrolled 129 children with infection into three groups: non-sepsis infection (33), Sepsis 1.0 (hyperinflammatory state, 67), and Sepsis 3.0 (organ dysfunction, 29). Another 32 children with no infections were included as controls. Serum C-reactive protein (CRP), procalcitonin (PCT), interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, tumor necrosis factor (TNF)-α, interferon (IFN)-α, and IFN-γ were assessed to diagnose the two stages, and their diagnostic capacities were evaluated using receiver operating characteristic (ROC) curves. We also examined whether combining biomarkers improved diagnostic efficiency. RESULTS: Significantly higher CRP, PCT, and IL-6 levels were detected in the Sepsis 1.0 than the non-sepsis infection group (p < 0.001). The areas under the curve (AUCs) for diagnosing Sepsis 1.0 were 0.974 (CRP), 0.913 (PCT) and 0.919 (IL-6). A combination of any two biomarkers increased diagnostic sensitivity to ≥92.54% and specificity to 100.00%. Significantly higher PCT, IL-8, and IL-10 levels were found in the Sepsis 3.0 than the Sepsis 1.0 group (p ≤ 0.01), with AUCs for diagnosing Sepsis 3.0 0.807 (PCT), 0.711 (IL-8), and 0.860 (IL-10). Combining these three biomarkers increased diagnostic sensitivity to 96.55% and specificity to 94.03%. CONCLUSION: In pediatric sepsis, combining any two of CRP, PCT, and IL-6 can accurately diagnose the hyperinflammatory state and increase diagnostic specificity. Early diagnosis of organ dysfunction requires a combination of PCT, IL-8, and IL-10.

Identification of selective ligands targeting two GPCRs by receptor-affinity chromatography coupled with high-throughput sequencing techniques.

The rapid growth of demands for drug discovery has necessitated the ongoing pursuit of new methods for specific ligands screening and identification. This work combined receptor-affinity chromatography (RAC) with high-throughput sequencing techniques to rapidly screen and identify the specific ligands. By this method, immobilized angiotensin II type I receptor (AT1R) and endothelin receptor A (ETAR) based on RAC were utilized for lead screening from a DNA-encoded library. The specific ligands of AT1R (ligand A1, A2) and ETAR (ligand B1, B2) were synthesized after decoding by high-throughput sequencing techniques. The dissociation rate constants (kd) of ligand A1, A2 to AT1R and B1, B2 to ETAR were 9.65 × 10-4, 31.1 × 10-4 and 0.66, 1.22 s-1 by peak profiling assay. The association constant (KA) to the receptors of four ligands was 5.4 × 106, 3.3 × 106 and 1.6 × 106, 2.2 × 105 by injection amount dependent method. The kinetic and thermodynamic parameters of the four specific ligands are similar to those of the positive drugs. This indicates that they are promising to drug candidates. The druggability of the four ligands through pharmacokinetic investigation by HPLC-MS/MS presented desired pharmacokinetic behavior including the fast absorption, the relatively slow elimination. These results, taking together, indicated that the RAC combined with high-throughput sequencing techniques can screen and identify the specific ligands according to various proteins, thus creating a general strategy for rapid discovery of promising drug candidates.

Rapidly identifying bioactive compounds from Zhisou oral liquid by immobilized receptor-based high-performance affinity chromatography.

The identification of bioactive compounds in complex matrices remains a major challenge due to the lack of highly efficient and specific methods. This work developed an approach based on high-performance affinity chromatography to identify the potential antitussive compounds from Zhisou oral liquid . The main methods include the synthesis of immobilized beta2-adrenoceptor by a one-step method, the screening and identification of the potential bioactive compounds by the receptor column coupled with mass spectrometry, and the binding mechanism analysis of the compounds to the receptor by the in vivo experiment, injection amount dependent method and molecular simulation. We identified the potential bioactive compounds of Zhisou oral liquid as glycyrrhizic acid, platycodin D, tuberostemonine, and hesperidin. In vivo experiment showed that the combinational utilization of the four compounds was possible to present an equivalent antitussive effect to the formula. The docking results demonstrated that hydrogen bonds and Van der Waals forces were the main forces to drive the binding of the four compounds to beta2-adrenoceptor. We concluded that the four compounds are the effective components in Zhisou oral liquid. The proposed strategy is possible to provide an alternative for the development of highly efficient methods to pursue the bioactive compounds of complex matrices.

Lipidomic profiling reveals soluble epoxide hydrolase as a therapeutic target of obesity-induced colonic inflammation.

Obesity is associated with enhanced colonic inflammation, which is a major risk factor for colorectal cancer. Considering the obesity epidemic in Western countries, it is important to identify novel therapeutic targets for obesity-induced colonic inflammation, to develop targeted strategies for prevention. Eicosanoids are endogenous lipid signaling molecules involved in regulating inflammation and immune responses. Using an LC-MS/MS-based lipidomics approach, we find that obesity-induced colonic inflammation is associated with increased expression of soluble epoxide hydrolase (sEH) and its eicosanoid metabolites, termed fatty acid diols, in colon tissue. Furthermore, we find that pharmacological inhibition or genetic ablation of sEH reduces colonic concentrations of fatty acid diols, attenuates obesity-induced colonic inflammation, and decreases obesity-induced activation of Wnt signaling in mice. Together, these results support that sEH could be a novel therapeutic target for obesity-induced colonic inflammation and associated diseases.

ATP-Triggered, Allosteric Self-Assembly of DNA Nanostructures.

Responsive self-assembly is a general process in biological systems and is highly desired in engineered systems. DNA nanostructures provide a versatile molecular platform for studying such responsive self-assembly. Various triggers have been explored for DNA nanostructures. However, each trigger requires a unique mechanism for its response. This situation brings a great challenge to engineer the responsiveness. Herein, we propose an aptamer-based, allosteric mechanism for responsive DNA self-assembly. The aptamer-ligand binding causes the DNA motif to change its conformation and thus influences the motif assembly. With a model of an ATP aptamer, we have demonstrated the responsive assembly. Such responsive behavior, we believe, will be an important element for molecular machines, bioimaging/biosensing, and drug delivery.

Covalent Inhibitor-Based One-Step Method for Endothelin Receptor A Immobilization: from Ligand Recognition to Lead Identification.

Protein immobilization is particularly significant in proteomics, interactomics, and in vitro drug screening. It is an essential primary step for numerous biological techniques that rely on immobilized proteins with controlled orientation, high conformational stability, and high activity (CHH). These have challenged the current immobilization strategy and demanded increasing efforts for an efficient method to meet the CHH immobilization in a single step. Herein, we proposed a covalent inhibitor-based, one-step method for G protein-coupled receptor (GPCR) immobilization inspired by the covalent reaction between an epidermal growth factor receptor (EGFR)-tag and its inhibitor ibrutinib. We immobilized endothelin receptor A (ETA) containing a fusion EGFR tag onto an ibrutinib-coated macroporous silica gel. The immobilized ETA proved to have demonstrable ligand-binding activity and specificity, thus resulting in a chromatographic technology allowing receptor-ligand interaction analysis and lead identification. Such immobilization method is attractable, owing to the properties of mild reacting conditions, fast rate, high yield, and good stability of the conjugated protein. It will be applicable to biochips, biosensors, and biocatalysts.

The Evolution of Policy Instruments for Air Pollution Control in China: A Content Analysis of Policy Documents from 1973 to 2016.

China's portfolio of air-pollution control policy instruments has gradually broadened since the 1970s from regulatory instruments to include numerous market-based and voluntary policy instruments. We demonstrate this broadened portfolio of policy instruments for air-pollution control with a computer-assisted content analysis of 148 central-level policy documents from 1973 to 2016. We identify 20 types of policy instruments in these documents, and analyze such things as their historical evolution, main subjects, frequency of use, and whether they were issued by a single agency or jointly with other agencies. Prior research has found several factors complicating the diversification of policy instruments in China, including the late start of coordinated governance of air pollution, overreliance on regulatory instruments, insufficient use of market-based and voluntary instruments, the high cost of collecting shared information on a web-based platform, and the choice of policy instruments resulting from the "campaign-style" of governance. Given such challenges, we expected the policy documents to show little diversification of policy instruments and little coordination among agencies. The content analysis results show, however, a gradual shift from a centralized, regulatory model to an increasingly coordinated model using a diverse portfolio of policy instruments.

Eicosanoid signaling in carcinogenesis of colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in the USA. It is of practical importance to identify novel therapeutic targets of CRC to develop new anti-cancer drugs and to discover novel biomarkers of CRC to develop new detection methods. Eicosanoids, which are metabolites of polyunsaturated fatty acids produced by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) enzymes, are important lipid-signaling molecules involved in the regulation of inflammation and tumorigenesis. Substantial studies have shown that the profiles of eicosanoids are deregulated in CRC, and the enzymes, metabolites, and receptors in the eicosanoid signaling cascade play critical roles in regulating colonic inflammation and colon tumorigenesis. In this review, we discuss the roles of the COX, LOX, and CYP pathways in the carcinogenesis of CRC.

Site-Specific Immobilization of ß2-AR Using O6-Benzylguanine Derivative-Functionalized Supporter for High-Throughput Receptor-Targeting Lead Discovery.

The past decade has witnessed the great promise of strategies for ligand discovery based on surface-immobilized GPCRs. We present here a method for preparation of immobilized GPCRs. Key features include covalent immobilization with high specificity and robust application in drug-receptor interaction analysis and ligand screening. In our example assay using beta2-adrenergic receptor (ß2-AR), the human DNA repair protein O6-alkylguanine-DNA alkyltransferase (hAGT) fusion receptor expressed in Escherichia coli was directly captured onto polyethylene glycol polyacrylamide (PEGA) resin. We observed even distribution and physiological functions of ß2-AR on the resin. The immobilized ß2-AR as a stationary phase enabled us to rapidly determine the binding of four drugs to ß2-AR. By coupling this assay to mass spectrometry, we screened rosmarinic acid as a bioactive compound targeting ß2-AR in Fructus Perillae. We concluded that O6-benzylguanine derivative-functionalized supporter is promising for specific immobilization of hAGT-tagged proteins; immobilized receptor chromatography has great potential in screening receptor-binding leads from herbal plants or traditional medicine recipes.

Assessment of Metal Pollution, Its Potential Health Risks, and Origin in Different Land Use Types in Zhuhai City, China.

The purpose of this study was to evaluate the current status of metal concentrations in soil from Zhuhai City. We detected the concentrations of eight metal elements in 67 topsoil samples collected from three typical land use types (water source land, n = 27; industrial land, n = 25; and farmland, n = 15) in Zhuhai. Multivariate geostatistical analyses indicated that the concentrations of Cu, Zn, and Cd may have originated from anthropogenic sources, whereas Pb and As mostly originated from natural sources. Additionally, Cr, Ni, and Hg may have come from mixed sources. The pollution index and the potential ecological risk were used to identify the general contamination characteristics of soil metals. The soil samples from industrial land were more polluted (60% of soil samples in industrial land were unpolluted to moderately polluted, and 40% were moderately polluted) and posed greater risk (28.6% of industrial soil samples were very high risk, and 71.4% were considerable risk) than samples from water source land and farmland. On the whole, the health risks posed by soil metals were acceptable or close to tolerable, and Cd was the most important pollutant contributing to human health risks. Comparatively speaking, children were the most vulnerable population to the non-carcinogenic and carcinogenic risks of contaminated soils from industrial land. Our results provide fundamental information for improving soil environmental management and metal pollution prevention and control in Zhuhai City.