CD73 polymorphisms are associated with schizophrenia.

Ecto-5'-nucleotidase/CD73 enzyme plays a key role in the regulation of extracellular adenosine levels, thereby exerting influence on adenosine homeostasis. Emerging evidence suggests that perturbations in purines and ecto-5'-nucleotidase activity are associated with an augmented susceptibility to schizophrenia. However, the precise impact of genetic variations in CD73 on individuals with schizophrenia remains poorly understood. Here, our study demonstrated that rs3734442 allele and rs4431401 heterozygote were conferred a significant risk of schizophrenia disease (rs3734442: odds ratio, 0.556; 95% CI, 0.375 to 0.825; p = 0.004; rs4431401: odds ratio, 1.881, 95% CI, 1.117 to 3.166; p = 0.020). Comparing different genders, we observed a significant association between rs3734442 genotypes and male cases (rs3734442: odds ratio, 0.452; 95% CI, 0.257 to 0.796; p = 0.007). Likewise, there was a significant association between rs4431401 genotypes and male patients (rs4431401: odds ratio, 2.570; 95% CI, 1.196 to 5.522; p = 0.015). Based on family history and antipsychotics medication usage, our data reveals that the rs9444348 allele exhibits the most significant association with familial susceptibility to schizophrenia (odds ratio, 1.541; 95% CI, 1.009 to 2.353; p = 0.048 for A vs G). Moreover, individuals carrying variants of rs6922, rs2229523, and rs2065114 while being treated with clozapine demonstrate a higher frequency proportion compared to those receiving risperidone treatment (p = 0.035; p = 0.049; p = 0.027 respectively). Additionally, our results indicate that patients with GG genotype of rs9444348 had significantly higher likelihood of using clozapine instead of sulpiride (p = 0.048). Overall, our data strongly suggest that genetic variations in CD73 are significantly associated with schizophrenia risk and may serve as valuable resources for identifying therapeutic targets.

Importance of habitat heterogeneity in tidal flats to the conservation of migratory shorebirds.

Understanding species distribution patterns and what determines them is critical for effective conservation planning and management. In the case of shorebirds migrating along the East Asian-Australasian Flyway (EAAF), the loss of stopover habitat in the Yellow Sea region is thought to be the primary reason for the precipitous population declines. However, the rates of decline vary considerably among species, and it remains unclear how such differences could arise within a group of closely related species using apparently similar habitats at the same locales. We mapped the spatial distributions of foraging shorebirds, as well as biotic (benthic invertebrates consumed by migrating shorebirds) and abiotic (sediment characteristics) environmental factors, at a key stopover site in eastern China. Five of the six sediment characteristics showed significant spatial variation with respect to distance along the shoreline or distance from the seawall in the same tidal flat. The biomasses of four of the six most abundant benthic invertebrates were concentrated in the upper or middle zones of the tidal flat. The distribution patterns of all three focal shorebird species on the tidal flat were best explained jointly by this heterogeneity of sediment characteristics and invertebrate prey. These results suggest that the loss of tidal flats along the Yellow Sea, which is typically concentrated at the upper and middle zones, may not only reduce the overall amount of staging habitat, but also disproportionately affect the most resource-rich portions for the birds. Effective conservation of shorebird staging areas along the EAAF and likely elsewhere must consider the subtle habitat heterogeneity that characterizes these tidal flats, prioritizing the protection of those portions richest in food resources, most frequently used by focal bird species, and most vulnerable to anthropogenic threats. Article impact statement: Heterogeneity of tidal flats with respect to biotic and abiotic factors must be considered in shorebird conservation planning.

Importancia de la heterogeneidad de hábitat en las llanuras intermareales para la conservación de aves playeras migratorias Resumen Entender las pautas de distribución de las especies y los factores que las determinan es fundamental para planificar y gestionar eficazmente su conservación. En el caso de las aves playeras que migran a lo largo de la ruta migratoria Asia Oriental-Australasia (EAAF, en inglés), se cree que la pérdida de puntos de parada en la región del Mar Amarillo es la razón principal de la declinación poblacional precipitada. Sin embargo, las tasas de declinación varían considerablemente entre especies, y sigue sin estar claro cómo pueden surgir tales diferencias dentro de un grupo de especies emparentadas que utilizan hábitats aparentemente similares en los mismos lugares. Mapeamos las distribuciones espaciales de las aves playeras forrajeras, así como los factores ambientales bióticos (invertebrados bénticos consumidos por las aves playeras migratorias) y abióticos (características de los sedimentos), en un punto de parada clave en el este de China. Cinco de las seis características de los sedimentos mostraron una variación espacial significativa con respecto a los cambios lineales en la distancia a lo largo de la costa o la distancia desde el malecón en la misma llanura mareal. La biomasa de cuatro de los seis invertebrados bénticos más abundantes se concentró en las zonas superior o media de la llanura mareal. Esta heterogeneidad de las características de los sedimentos y de las presas invertebradas es la que mejor explica los patrones de distribución de las tres especies de aves playeras en la llanura mareal. Estos resultados sugieren que la pérdida de llanuras mareales a lo largo del Mar Amarillo, que suele concentrarse en las zonas superior y media, puede no sólo reducir la cantidad total de hábitat de parada, sino también afectar de manera desproporcionada a las partes más ricas en recursos para las aves. La conservación eficaz de los puntos de parada de las aves playeras a lo largo del EAAF, y probablemente en otros lugares, debe tener en cuenta la sutil heterogeneidad del hábitat que caracteriza a estas llanuras mareales, priorizando la protección de las partes más ricas en recursos alimenticios, más frecuentemente utilizadas por las especies de aves focales y más vulnerables a las amenazas antropogénicas.

Exploiting Photoinduced Atom Transfer Radical Polymerizations with Boron-Dopant and Nitrogen-Defect Synergy in Carbon Nitride Nanosheets.

Graphitic carbon nitrides (g-C3N4) possess various benefits as heterogeneous photocatalysts, including tunable bandgaps, scalability, and chemical robustness. However, their efficacy and ongoing advancement are hindered by challenges like limited charge-carrier separation rates, insufficient driving force for photocatalysis, small specific surface area, and inadequate absorption of visible light. In this study, boron dopants and nitrogen defects synergy are introduced into bulk g-C3N4 through the calcination of a blend of nitrogen-defective g-C3N4 and NaBH4 under inert conditions, resulting in the formation of BCN nanosheets characterized by abundant porosity and increased specific surface area. These BCN nanosheets promote intermolecular single electron transfer to the radical initiator, maintaining radical intermediates at a low concentration for better control of photoinduced atom transfer radical polymerization (photo-ATRP). Consequently, this method yields polymers with low dispersity and tailorable molecular weights under mild blue light illumination, outperforming previous reports on bulk g-C3N4. The heterogeneity of BCN enables easy separation and efficient reuse in subsequent polymerization processes. This study effectively showcases a simple method to alter the electronic and band structures of g-C3N4 with simultaneously introducing dopants and defects, leading to high-performance photo-ATRP and providing valuable insights for designing efficient photocatalytic systems for solar energy harvesting.

Evaluation of Early Psychological Interventions in Patients with Intracranial Aneurysm Embolism: A Nursing Business Process Reengineering Perspective.

Objective: This study examines the impact of early psychological intervention for patients undergoing nursing process modification through a business process reengineering (BPR) approach in preventing intracranial aneurysm embolism. Methods: A randomized controlled trial (RCT) design was employed in this study. A randomized method was utilized to allocate a total of 201 cases into two distinct groups. 10 patients experiencing delirium and coma due to drug sedation were excluded from the analysis. Consequently, the final distribution included 96 cases in the nursing group and 95 cases in the routine group. Results: In the nursing group, waiting time, nursing staff working hours, and hospital stay were significantly lower compared to the routine group (t = 50.916, 28.893, 4.298, P < .05). No substantial difference in actual running time between the groups was observed (t=0.289, P > .05). Scores for physical pain, psychological well-being, material life status, and social function were notably higher in the nursing group than in the routine group (t=19.109, 20.658, 21.165, 24.014, P < .05). Post-intervention, SAS and SDS scores in the nursing group were significantly lower than those in the routine group (t=21.910, 25.808, P < .05). The complication rate in the nursing group (1.04%) was significantly lower than that in the routine group (8.42%) (χ2=5.791, P < .05). Furthermore, nursing staff job satisfaction (92.71%) was significantly higher than that in the routine group (78.13%) (χ2=7.449, P < .05). Conclusions: The modification of the nursing process demonstrates a positive impact on efficiency and quality of care, ensuring patient safety and meeting patient needs without altering surgical techniques. The findings highlight substantial enhancements and effectiveness of nursing process, providing strong support for the broad implementation of these interventions.

In vivo pharmacodynamic study of contezolid acefosamil, a prodrug of contezolid for oral and intravenous administration.

OBJECTIVES: Contezolid acefosamil is a novel O-acyl phosphoramidate prodrug of contezolid. In the current study, we aimed to systemically evaluate the efficacy of contezolid acefosamil against infections caused by multiple Gram-positive pathogens, and compare the efficacy of the prodrug by oral and intravenous administrations. METHODS: The in vivo pharmacodynamic efficacy of contezolid acefosamil was evaluated in mouse models of systemic (with five S. aureus, three S. pneumoniae and two S. pyogenes bacterial isolates) and thigh (with two S. aureus isolates) infections using linezolid as the reference agent. RESULTS: In both models, contezolid acefosamil administrated either orally or intravenously, demonstrated high antibacterial efficacy similar to linezolid, and the antibacterial efficacy of oral and intravenous contezolid acefosamil were comparable. CONCLUSIONS: The high aqueous solubility and great efficacy of contezolid acefosamil support its clinical development as an injectable and oral antibiotic suitable for serious Gram-positive infections.

Arriving late and lean at a stopover site is selected against in a declining migratory bird population.

Loss and/or deterioration of refuelling habitats have caused population declines in many migratory bird species but whether this results from unequal mortality among individuals varying in migration traits remains to be shown. Based on 13 years of body mass and size data of great knots (Calidris tenuirostris) at a stopover site of the Yellow Sea, combined with resightings of individuals marked at this stopover site along the East Asian-Australasian Flyway, we assessed year to year changes in annual apparent survival rates, and how apparent survival differed between migration phenotypes (i.e. migration timing and fuel stores). The measurements occurred over a period of habitat loss and/or deterioration in this flyway. We found that the annual apparent survival rates of great knots rapidly declined from 2006 to 2018, late-arriving individuals with small fuel stores exhibiting the lowest apparent survival rate. There was an advancement in mean arrival date and an increase in the mean fuel load of stopping birds over the study period. Our results suggest that late-arriving individuals with small fuel loads were selected against. Thus, habitat loss and/or deterioration at staging sites may cause changes in the composition of migratory phenotypes at the population-level.

Promoting Cross-Regional Integration of Maritime Emission Management: A Euro-American Linkage of Carbon Markets.

Reducing greenhouse gas emissions from maritime transport is an urgent topic. Some regional emissions trading systems (ETSs), buoyed by the globalized market-based measures (MBMs) plan of the International maritime organization, have initially assessed the feasibility of including maritime emissions under compliance obligations. However, including maritime emissions (which are interjurisdictional) in the existing ETSs is controversial, and globalized maritime MBMs remain elusive. Therefore, this study designed a joint bilateral maritime carbon market (BMCM) model based on the European ETS (EU-ETS) and Quebec ETS (QC-ETS). The carbon costs, speed optimization, and marginal abatement costs of three container routes under BMCM were analyzed. The results show that this Euro-American linkage achieves adequate emission coverage on specific routes and generates acceptable carbon costs for charterers. This study yields a positive result for the equal division of ETSs' exercising competence in cross-regional maritime transport and provides evidence for sector-specific ETS links based on quantitative analysis.

A Pneumatic Particle-Blocking Variable-Stiffness Actuator.

In order to improve the stiffness of flexible robots, this paper proposes a variable-stiffness elastic actuator. The actuator integrates the working principles of a pneumatic drive, wedge structure, and particle blockage. The anti-tensile stiffness of the actuator is nonlinearly negatively correlated with the air pressure because of the structural and material properties. The anti-compressive stiffness and lateral stiffness increase nonlinearly as air pressure increases, being 3 and 121 times greater at 0.17 MPa compared to 0 MPa, respectively. Beyond 0.17 MPa, the two stiffnesses of the actuator experience incremental growth due to wedge resistance forces.

Discrepancy between Proline and Homoproline in Chiral Recognition and Diastereomeric Photoreactivity with Iridium(III) Complexes.

The chiral-recognition processes of homoproline (hpro) and [Ir(pq)2(MeCN)2](PF6) (pq is 2-phenylquinoline; MeCN is acetonitrile) are investigated, in favor of formation of the thermodynamically stable diastereomers Λ-[Ir(pq)2(d-hpro)] and Δ-[Ir(pq)2(l-hpro)]. Moreover, the diastereoselective photoreactions of Δ-[Ir(pq)2(d-hpro)] and Δ-[Ir(pq)2(l-hpro)] are reported in the presence of O2 at room temperature. Diastereomer Δ-[Ir(pq)2(l-hpro)] is dehydrogenatively oxidized into imino acid complex Δ-[Ir(pq)2(hpro-2H2)] (hpro-2H2 is 3,4,5,6-tetrahydropicalinate), while diastereomer Δ-[Ir(pq)2(d-hpro)] occurs by interligand C-N cross-coupling and dehydrogenative oxidation reactions, affording three products: Δ-[Ir(pq)(d-pqh)] [pqh is N-(2-phenylquinolin-8-yl)homoproline], Δ-[Ir(pq)2(hpro-2H2)], and Δ-[Ir(pq)2(d-hpro-2H6)] [hpro-2H6 is 2,3,4,5-tetrahydropicalinate]. The C-N cross-coupling and dehydrogenative oxidation reactions are competitive, and the dehydrogenative oxidation reactions are regioselective. By optimization of the photoreaction parameters such as the diastereomeric substrate, solvent, and temperature as well as base, each possible competitive product is selectively controlled. In addition, density functional theory calculations are performed to elucidate the distinctly chiral recognition between proline and hpro with an iridium(III) complex.

Visible-Light-Induced Amination of Quinoline at the C8 Position via a Postcoordinated Interligand-Coupling Strategy under Mild Conditions.

The postcoordinated interligand-coupling strategy provides a useful and complementary protocol for synthesizing polydentate ligands. Herein, diastereoselective photoreactions of Λ-[Ir(pq)2(d-AA)] (Λ-d) and Λ-[Ir(pq)2(l-AA)] (Λ-l, where pq is 2-phenylquinoline and AA is an amino acid) are reported in the presence of O2 under mild conditions. Diastereomer Λ-d is dehydrogenatively oxidized into an imino acid complex, while diastereomer Λ-l mainly occurs via interligand C-N cross-dehydrogenative coupling between quinoline at the C8 position and AA ligands at room temperature, affording Λ-[Ir(pq)(l-pq-AA)]. Furthermore, the photoreaction of diastereomer Λ-l is temperature-dependent. Mechanistic experiments reveal the ligand-radical intermediates may be involved in the reaction. Density functional theory calculations were used to eluciate the origin of diastereoselectivity and temperature dependence. This will provide a new protocol for the amination of quinoline at the C8 position via the postcoordinated interligand C-N cross-coupling strategy under mild conditions.

Identifying potential biomarkers of nonalcoholic fatty liver disease via genome-wide analysis of copy number variation.

BACKGROUND: The prevalence of Non-alcoholic fatty liver disease (NAFLD) is increasing and emerging as a global health burden. In addition to environmental factors, numerous studies have shown that genetic factors play an important role in the development of NAFLD. Copy number variation (CNV) as a genetic variation plays an important role in the evaluation of disease susceptibility and genetic differences. The aim of the present study was to assess the contribution of CNV to the evaluation of NAFLD in a Chinese population. METHODS: Genome-wide analysis of CNV was performed using high-density comparative genomic hybridisation microarrays (ACGH). To validate the CNV regions, TaqMan real-time quantitative PCR (qPCR) was utilized. RESULTS: A total of 441 CNVs were identified, including 381 autosomal CNVs and 60 sex chromosome CNVs. By merging overlapping CNVs, a genomic CNV map of NAFLD patients was constructed. A total of 338 autosomal CNVRs were identified, including 275 CNVRs with consistent trends (197 losses and 78 gains) and 63 CNVRs with inconsistent trends. The length of the 338 CNVRs ranged from 5.7 kb to 2.23 Mb, with an average size of 117.44 kb. These CNVRs spanned 39.70 Mb of the genome and accounted for ~ 1.32% of the genome sequence. Through Gene Ontology and genetic pathway analysis, we found evidence that CNVs involving nine genes may be associated with the pathogenesis of NAFLD progression. One of the genes (NLRP4 gene) was selected and verified by quantitative PCR (qPCR) method with large sample size. We found the copy number deletion of NLRP4 was related to the risk of NAFLD. CONCLUSIONS: This study indicate the copy number variation is associated with NAFLD. The copy number deletion of NLRP4 was related to the risk of NAFLD. These results could prove valuable for predicting patients at risk of developing NAFLD.

Evaluation of phytoremediation potential of native dominant plants and spatial distribution of heavy metals in abandoned mining area in Southwest China.

A field investigation on the content of heavy metals in soils and dominant plants was conducted in three sites (A<0.5 km, B<1.0 km, C<1.5 km) with different distances of mine tailings. The spatial distribution of heavy metals and the accumulation in plants were compared, and the candidate species for ecosystem restoration were selected. The results indicated that the soil was polluted by chromium (Cr), Cadmium (Cd), copper (Cu), nickel (Ni) in varying degrees, which is 2.07, 2.60, 1.79, and 4.49 times higher than the Class-Ⅱ standard in China. The concentrate of Ni, Cd, and Zinc (Zn) increased, while Cr, Lead (Pb), and Cu decreased with the distance from the mine tailings. 73 species (34 families) were found and mainly herbaceous plants. The concentrate of Cd, Cu, Cr, and Ni in 29 dominant plants were measured and 66.67%, 21.43%, 100%, 47.62% plants exceeded the normal concentration range. Based on the comparative analysis of heavy metal content, bioconcentration factor, and translocation factor in plants, Polygonum capitatum has good phytoextraction ability, Boehmeria nivea, Chrysanthemum indicum, Miscanthus floridulus, Conyza canadensis, Rubus setchuenensis, Senecio scandens, and Arthraxon hispidus showed remarkable phytostabilization abilities of Cr, Cd, Ni, and Cu, which can be used as potential phytoremediation candidate.

A system-scale environmental risk analysis with considering a conceptual conversion from material/energy flow to information flow under uncertainties.

A conceptual conversion from material/energy flow to information flow is presented in this study for evaluating network environment analysis (NEA) within the naphthalene-contaminated groundwater ecosystems under stochastic-fuzzy uncertainties. Four components (i.e., vegetation, herbivore, soil microorganism, and carnivore) are considered into the NEA framework for quantifying their direct and integral ecological risks. Carcinogenic risk related to human health concern is also evaluated under four remediation periods. The developed method is then applied to a power plant site. Results reveal that the average naphthalene concentration after pump-and-treat treatment would significantly decrease from 8.672 to 1.232 µg/L when remediation period extends to 10 years. The probabilities of suffering from carcinogenic risk would reach 0.9862, 0.9566, 0.8746, and 0.6142 under different remediation periods. Soil microorganism would receive more input risk than vegetation owing to its higher vulnerability. Although the upper-layer components (such as herbivore and carnivore) are not exposed to risk sources, they would gradually accumulate to a high-level ecological risk through food chains. Sensitivity analysis shows that variations in standard boundaries would have a significant impact on the risks of all components within groundwater ecosystems. This study can offer a novel perspective and methodology for comprehensively assessing the system-scale environment risks.

A component overlapping attribute clustering (COAC) algorithm for single-cell RNA sequencing data analysis and potential pathobiological implications.

Recent advances in next-generation sequencing and computational technologies have enabled routine analysis of large-scale single-cell ribonucleic acid sequencing (scRNA-seq) data. However, scRNA-seq technologies have suffered from several technical challenges, including low mean expression levels in most genes and higher frequencies of missing data than bulk population sequencing technologies. Identifying functional gene sets and their regulatory networks that link specific cell types to human diseases and therapeutics from scRNA-seq profiles are daunting tasks. In this study, we developed a Component Overlapping Attribute Clustering (COAC) algorithm to perform the localized (cell subpopulation) gene co-expression network analysis from large-scale scRNA-seq profiles. Gene subnetworks that represent specific gene co-expression patterns are inferred from the components of a decomposed matrix of scRNA-seq profiles. We showed that single-cell gene subnetworks identified by COAC from multiple time points within cell phases can be used for cell type identification with high accuracy (83%). In addition, COAC-inferred subnetworks from melanoma patients' scRNA-seq profiles are highly correlated with survival rate from The Cancer Genome Atlas (TCGA). Moreover, the localized gene subnetworks identified by COAC from individual patients' scRNA-seq data can be used as pharmacogenomics biomarkers to predict drug responses (The area under the receiver operating characteristic curves ranges from 0.728 to 0.783) in cancer cell lines from the Genomics of Drug Sensitivity in Cancer (GDSC) database. In summary, COAC offers a powerful tool to identify potential network-based diagnostic and pharmacogenomics biomarkers from large-scale scRNA-seq profiles. COAC is freely available at https://github.com/ChengF-Lab/COAC.

Physical activity intervention for non-diabetic patients with non-alcoholic fatty liver disease: a meta-analysis of randomized controlled trials.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease nowadays. Changes in diet and lifestyle have led to a dramatic increase in the prevalence of NAFLD around the world. This meta-analysis is to investigate the efficacy of physical activity intervention on liver-specific endpoints in the population with NAFLD, including hepatic enzyme, serum lipid, glucose metabolism and intra-hepatic lipid. METHODS: PubMed and China National Knowledge Infrastructure (CNKI) databases were searched for randomized clinical trials of physical activity intervention on NAFLD patients through April 20th, 2019. Effect sizes were reported as standardized mean difference (SMD) and 95% confidence intervals (CI). Quality of included studies was assessed according to the Cochrane risk of bias tool. Meta-analyses were conducted using random-effect or fixed-effect models depending on the significance of heterogeneity. Subgroup analyses according to types and duration of physical activity were conducted to investigate clinical variability. RESULTS: Nine studies with a cumulative total of 951 participants met selection criteria. Physical activity was found associated with small reductions in hepatic enzyme parameters: ALT (SMD -0.17, 95% CI:-0.30 to - 0.05), AST (SMD -0.25, 95% CI: - 0.38, - 0.13) and GGT (SMD -0.22, 95% CI: - 0.36, - 0.08). Significant small improvements were also found in serum lipid parameters including TC (SMD = - 0.22, 95% CI: - 0.34, - 0.09), TG (SMD = - 0.18, 95% CI: - 0.31 to - 0.06) and LDL-C (SMD = - 0.26, 95% CI: - 0.39 to - 0.13). Significant improvement was also found in intra-hepatic lipid content (SMD = - 0.21, 95% CI: - 0.36 to - 0.06) There was no difference between physical intervention group and control group in HDL and three glucose metabolism parameters. Subgroup analysis suggested both aerobic exercise alone and resistance exercise alone can improve most liver function and longer period of exercise generally had better improvement effect. CONCLUSIONS: Our findings suggest that physical activity alone can only slightly improve hepatic enzyme levels, most serum lipid levels and intra-hepatic lipid content in non-diabetic patients with NAFLD.

The role of hepatitis B infection in anti-tuberculosis drug-induced liver injury: a meta-analysis of cohort studies.

Drug-induced liver injury (DILI) is a common adverse drug reaction leading to the interruption of tuberculosis (TB) therapy. We aimed to identify whether the hepatitis B virus (HBV) infection would increase the risk of DILI during first-line TB treatment. A meta-analysis of cohort studies searched in PubMed, Web of Science and China National Knowledge Infrastructure was conducted. Effect sizes were reported as risk ratios (RRs) and 95% confidence intervals (CIs) and calculated by R software. Sixteen studies with 3960 TB patients were eligible for analysis. The risk of DILI appeared to be higher in TB patients co-infected with HBV (RR 2.66; 95% CI 2.13-3.32) than those without HBV infection. Moreover, patients with positive hepatitis B e antigen (HBeAg) were more likely to develop DILI (RR 3.42; 95% CI 1.95-5.98) compared to those with negative HBeAg (RR 2.30; 95% CI 1.66-3.18). Co-infection with HBV was not associated with a higher rate of anti-TB DILI in latent TB patients (RR 4.48; 95% CI 0.80-24.99). The effect of HBV infection on aggravating anti-TB DILI was independent of study participants, whether they were newly diagnosed with TB or not. Besides, TB and HBV co-infection patients had a longer duration of recovery from DILI compared to non-co-infected patients (SMD 2.26; 95% CI 1.87-2.66). To conclude, the results demonstrate that HBV infection would increase the risk of DILI during TB therapy, especially in patients with positive HBeAg, and close liver function monitoring is needed for TB and HBV co-infection patients.

Thermodynamic Resolution and Enantioselective Synthesis of C2-Symmetric Bis-sulfoxides Based on Chiral Iridium(III) Complexes.

Enantiopure Λ-[Ir(dfppy)2(MeCN)2](PF6) and Δ-[Ir(dfppy)2(MeCN)2](PF6) (where dfppy is (4,6-difluoropheny)pyridine) were demonstrated to preferentially react with (S,S)-1,2-bis(arylsulfinyl)ethane and (R,R)-1,2-bis(arylsulfinyl)ethane, respectively, under thermodynamic equilibrium. Sequential treatment of Λ-[Ir(dfppy)2(MeCN)2](PF6) and Δ-[Ir(dfppy)2(MeCN)2](PF6) with C2-symmetric bis-sulfoxides led to diastereoselective formation of the corresponding diastereomers Λ-[Ir(dfppy)2(R,R)-bis-sulfoxide)](PF6) in 90-92% and Δ-[Ir(dfppy)2(S,S)-bis-sulfoxide)](PF6) in 88-90%, respectively. The uncoordinated (R,S)-bis-sulfoxides were afforded in 45% with >97% de values. Enantiopure (S,S)-bis-sulfoxides and (R,R)-bis-sulfoxides were respectively obtained by the release of sulfoxide ligands from the corresponding complexes in the presence of glycine in yields of 20-21% with 97-99% ee values. The enantioreceptors Λ-[Ir(dfppy)2(MeCN)2](PF6) and Δ-[Ir(dfppy)2(MeCN)2](PF6) can be recycled and reused in the next reaction cycle. Moreover, a protocol for asymmetric oxidation of prochiral bis-sulfide into enantiopure C2 symmetric bis-sulfoxide was also developed in a high enantioselectivity. The absolute configurations at the metal centers and sulfur atoms were determined by X-ray crystallography.

Diastereoselective Photooxidation and Reduction of Chiral Iridium(III) Complexes.

A diastereoselective photooxidation of α-amino acid (AA) complexes into imino acid complexes using a chiral iridium(III) complex as a photosensitizer and stereo-controller under visible light irradiation and oxygen was developed. It was found that the oxidative rate of Δ-[Ir(pq)2( L-AA)] (pq is 2-phenylquinoline) diastereomer is significantly higher than that of the corresponding Δ-[Ir(pq)2( D-AA)] diastereomer, providing a new protocol for kinetic resolution of AAs via a nonenzymatic pathway. Moreover, the thermodynamic controlled strategy offered a complemental method for the diastereoselective hydrogenation of imine bonds using NaBH4 as a reductant under the chiral Ir(III) complex as a stereo-controller. The combination of diastereoselective photooxidation and reduction processes results in a new protocol for deracemization of α-amino acids under mild conditions. Mechanism study strongly indicates that singlet oxygen is a key participant in the reaction and the α-C-H bond cleavage of AAs is the rate-determining step.

Estimation of the benchmark dose of urinary cadmium as the reference level for renal dysfunction: a large sample study in five cadmium polluted areas in China.

BACKGROUND: Itai-itai disease primarily results from cadmium (Cd) exposure and is known as one of the four major pollution diseases in Japan. Cd pollution is more serious in several areas of China than in Japan. However, there is still a lack of information regarding the threshold level of Cd exposure for the adverse health effects in the general Chinese population. This study aims to evaluate the reference value of urinary Cd (UCd) for renal dysfunction in a Chinese population as the benchmark dose lower confidence limit (BMDL) based on a large sample survey. METHODS: A total of 6103 participants who lived in five Cd polluted areas of China participated in this study. We analyzed UCd levels as a biomarker of exposure and urinary ß2-microglobulin (Uß2-MG) levels as a renal tubular effect biomarker. The BMD studies were performed using BMD software. The benchmark response (BMR) was defined as a 10% additional risk above the background. RESULTS: There was a positive correlation between the UCd levels and the prevalence of Uß2-MG. The BMD of UCd for Uß2-MG was estimated for each province. The findings showed that the BMD levels were related to the participants' geographic region, which may be partially due to the large differences in Cd exposure level, ethnic group, lifestyle and diet of the sample population in these study areas. The reference level of UCd for the renal effects was further evaluated by combining the five sets of data from all 6103 subjects. The overall BMDLs of UCd for Uß2-MG with an excess risk of 10% were 2.00 µg/g creatinine (µg/g cr) in males and 1.69 µg/g cr in females, which were significantly lower than the World Health Organization (WHO) threshold level of 5 µg/g cr for Cd-related renal effects. CONCLUSIONS: The selection of the sample population and geographic region affected the BMDL evaluation. Based on the findings of this survey of a large sample population, the UCd BMDLs for Uß2-MG in males with BMRs at 10% were 2.00 µg/g cr. The BMD was slightly lower in females, which indicated that females may be relatively more sensitive to Cd exposure than males.

MicroRNA-1269 promotes proliferation in human hepatocellular carcinoma via downregulation of FOXO1.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies and a major cause of cancer-related mortality in the world. MicroRNAs (miRNAs) are small, noncoding RNAs that play essential roles in various stages during cancer progression. The aim of the current study was to elucidate the role of miR-1269 in the pathogenesis of HCC. METHODS: The expression of miR-1269 in HCC cells and tissues were determined by Real-time PCR analysis. Cell viability, colony formation and anchorage-independent growth ability assays were performed to examine cell proliferative capacity and tumorigenicity. Flow cytometry analysis was conducted to determine cell cycle progression. The expression of p21, CyclinD1, phosphorylated Rb, Rb and FOXO1 were examined by Western blotting analysis. Luciferase assay was used to determine whether FOXO1 is the direct target of miR-1269. RESULTS: miR-1269 was upregulated in HCC cells and tissues. Ectopic miR-1269 expression promoted, but inhibition of miR-1269 reduced, proliferation, tumorigenicity and cell cycle progression of HCC cells. Furthermore, we demonstrated that FOXO1 was a direct target of miR-1269. Suppression of FOXO1 by miR-1269 was associated with dysregulation of p21, cyclin D1, phosphorylated Rb and Ki67 expression, thereby playing an essential role in the growth of HCC cells. CONCLUSIONS: Our study indicated that overexpression of miR-1269 promotes cell proliferation in HCC through directly suppressing FOXO1, and functions as an oncomiR in HCC.