The 90% effective concentration of alfentanil combined with 0.075% ropivacaine for epidural labor analgesia: a single-center, prospective, double-blind sequential allocation biased-coin design.

PURPOSE: More literature studies have reported that alfentanil is safe and effective for labor analgesia. However, there is no unified consensus on the optimal dosage of alfentanil used for epidural analgesia. This study explored the concentration at 90% of minimum effective concentration (EC90) of alfentanil combined with 0.075% ropivacaine in patients undergoing epidural labor analgesia to infer reasonable drug compatibility and provide guidance for clinical practice. METHODS: In this prospective, single-center, double-blind study, a total of 45 singleton term primiparas with vaginal delivery who volunteered for epidural labor analgesia were recruited. The first maternal was administered with 3 µg/mL alfentanil combined with 0.075% ropivacaine with the infusion of 10 mL of the mixture every 50 min at a background dose of 3 mL/h. In the absence of PCEA, a total of 15 mL of the mixture is injected per hour. The subsequent alfentanil concentration was determined on the block efficacy of the previous case, using an up-down sequential allocation with a bias-coin design. 30 min after epidural labor analgesia, the block of patient failed with visual analog score (VAS) > 3, the alfentanil concentration was increased in a 0.5 µg/mL gradient for the next patient, while the block was successful with VAS ≤ 3, the alfentanil concentration was remained or decreased in a gradient according to a randomized response list for the next patient. EC90 and 95% confidence interval were calculated by linear interpolation and prediction model with R statistical software. RESULTS: In this study, the estimated EC90 of alfentanil was 3.85 µg/mL (95% confidence interval, 3.64-4.28 µg/mL). CONCLUSION: When combined with ropivacaine 0.075%, the EC90 of alfentanil for epidural labor analgesia is 3.85 µg/mL in patients undergoing labor analgesia.

A Conformational Restriction Strategy for the Control of CRISPR/Cas Gene Editing with Photoactivatable Guide RNAs.

The CRISPR/Cas system is one of the most powerful tools for gene editing. However, approaches for precise control of genome editing and regulatory events are still desirable. Here, we report the spatiotemporal and efficient control of CRISPR/Cas9- and Cas12a-mediated editing with conformationally restricted guide RNAs (gRNAs). This approach relied on only two or three pre-installed photo-labile substituents followed by an intramolecular cyclization, representing a robust synthetic method in comparison to the heavily modified linear gRNAs that often require extensive screening and time-consuming optimization. This tactic could direct the precise cleavage of the genes encoding green fluorescent protein (GFP) and the vascular endothelial growth factor A (VEGFA) protein within a predefined cutting region without notable editing leakage in live cells. We also achieved light-mediated myostatin (MSTN) gene editing in embryos, wherein a new bow-knot-type gRNA was constructed with excellent OFF/ON switch efficiency. Overall, our work provides a significant new strategy in CRISPR/Cas editing with modified circular gRNAs to precisely manipulate where and when genes are edited.

The Chemistry behind ThiC Rearrangement.

Thiamine (vitamin B1) is crucial for life and plays a central role in metabolism. It contains thiazole and pyrimidine moieties that are constructed independently and then assembled together to generate thiamine phosphate. The study of the thiazole moiety is relatively clear, but deciphering the mechanistic enzymology of thiamine pyrimidine is more difficult. This review aims to summarize the recent research progress on ThiC rearrangement, mainly including the mechanism, related enzymes, and genes involved in the rearrangement.

A Light-Controllable Chemical Modulation of m6 A RNA Methylation.

Bioactive small molecules with photo-removable protecting groups have provided spatial and temporal control of corresponding biological effects. We present the design, synthesis, computational and experimental evaluation of the first photo-activatable small-molecule methyltransferase agonist. By blocking the functional N-H group on MPCH with a photo-removable ortho-nitrobenzyl moiety, we have developed a promising photo-caged compound that had completely concealed its biological activity. Short UV light exposure of cells treated with that caged molecule in a few minutes resulted in a considerable hypermethylation of m6 A modification in transcriptome RNAs, implicating a rapid release of the parent active compound. This study validates for the first time the photo-activatable small organic molecular concept in the field of RNA epigenetic research, which represents a novel tool in spatiotemporal and cellular modulation approaches.

Transformation of dissolved organic matter in concentrated leachate from nanofiltration during ozone-based oxidation processes (O3, O3/H2O2 and O3/UV).

In this study, the transformation of dissolved organic matter (DOM) in nanofiltration concentrated leachate during three ozone-based oxidation processes (i.e., O3, O3/H2O2 and O3/UV) was investigated. The transformation characteristics of DOM were evaluated by gel filtration chromatography (GFC), XAD-8 resin fractionation, excitation-emission matrix fluorescence spectroscopy (EEM) and Fourier transform infrared spectroscopy (FTIR). Compared with O3-alone process, the removal efficiencies of COD, TOC, and color were improved in O3-combined processes (i.e., O3/H2O2 and O3/UV) approximately by 10-15%, 7-15%, and 15-20%, respectively. Humic acid (HA) was completely degraded and preferentially reacted with the oxidants during ozonation processes. HA was first converted into fulvic acid (FA), and then the majority of these intermediates were further converted to hydrophilic fraction (HyI). The GFC results indicated that the broader molecular weight distribution of DOM was observed, and high molecular weight DOM (i.e., 0.45 µm-100 kDa) was successfully converted to low molecular weight organics in the range of 1-10 kDa after ozonation reactions. The EEM spectra also showed that HA and FA were effectively converted into HyI after ozonation for 90 min. It is suggested that ozone-based oxidation processes could effectively change the DOM distribution and fluorescence features of concentrated leachate.

The LXR ligand GW3965 inhibits Newcastle disease virus infection by affecting cholesterol homeostasis.

Newcastle disease (ND) is a contagious disease that affects most species of birds. Its causative pathogen, Newcastle disease virus (NDV), also exhibits considerable oncolytic activity against mammalian cancers. A better understanding of the pathogenesis of NDV will help us design efficient vaccines and novel anticancer strategies. GW3965, a widely used synthetic ligand of liver X receptor (LXR), induces the expression of LXRs and its downstream genes, including ATP-binding cassette transporter A1 (ABCA1). ABCA1 regulates cellular cholesterol homeostasis. Here, we found that GW3965 inhibited NDV infection in DF-1 cells. It also inhibited NF-κB activation and reduced the upregulation of proinflammatory cytokines induced by the infection. Further studies showed that GW3965 exerted its inhibitory effects on virus entry and replication. NDV infection increased the mRNA levels of several lipogenic genes but decreased the ABCA1 mRNA level. Overexpression of ABCA1 inhibited NDV infection and reduced the cholesterol content in DF-1 cells, but when the cholesterol was replenished, NDV infection was restored. GW3965 treatment prevented cholesterol accumulation in the perinuclear area of the infected cells. In summary, our studies suggest that GW3965 inhibits NDV infection, probably by affecting cholesterol homeostasis.

Pyrolysis Treatment of Chromite Ore Processing Residue by Biomass: Cellulose Pyrolysis and Cr(VI) Reduction Behavior.

The pyrolysis treatment with biomass is a promising technology for the remediation of chromite-ore-processing residue (COPR). However, the mechanism of this process is still unclear. In this study, the behavior of pyrolysis reduction of Cr(VI) by cellulose, the main component of biomass, was elucidated. The results showed that the volatile fraction (VF) of cellulose, ie. gas and tar, was responsible for Cr(VI) reduction. All organic compounds, as well as CO and H2 in VF, potentially reduced Cr(VI). X-ray absorption near-edge structure (XANES) spectroscopy and extended X-ray absorption fine-structure (EXAFS) spectroscopy confirmed the reduction of Cr(VI) to Cr(III) and the formation of amorphous Cr2O3. The remnant Cr(VI) content in COPR can be reduced below the detection limit (2 mg/kg) by the reduction of COPR particle and extension of reaction time between VF and COPR. This study provided a deep insight on the co-pyrolysis of cellulose with Cr(VI) in COPR and an ideal approach by which to characterize and optimize the pyrolysis treatment for COPR by other organics.

Probiotics can alleviate cardiopulmonary bypass-induced intestinal mucosa damage in rats.

BACKGROUND: Cardiopulmonary bypass (CPB) is commonly applied to support circulation during heart surgery but frequently causes adverse effects. AIMS: The purpose of this study was to examine the potential of probiotics to improve small intestinal mucosa barrier function after CPB. METHODS: Twenty-four adult male SD rats were randomly divided into sham-operated (S), CPB-operated (CPB), and probiotic-fed (Y) groups. Diamine oxidase (DAO) activity and concentrations of D-lactic acid, endotoxin, TNFα, and IL-6 were measured in portal vein blood. IgA concentrations were determined in plasma and the small intestine. Vena cava blood and tissue samples were used to monitor bacterial growth. Intestinal epithelial ultrastructure was analyzed by transmission electron microscopy (TEM). Occludin and ZO-1 expression levels in the intestinal epithelium were detected by western blotting and immunohistochemistry, respectively. RESULTS: D-lactic acid, endotoxin, TNFα and IL-6 levels, DAO activity, and bacterial translocation rate were increased (P < 0.05) in CPB and Y compared to the S group. The above indices were relatively lower (P < 0.05) in Y than in CPB. Plasma and small intestinal IgA levels were significantly lower (P < 0.05) in CPB, while in Y they were significantly increased (P < 0.05) but lower than in S (P < 0.05). These results were confirmed by TEM. Consistently, occludin and ZO-1 expression levels were significantly higher in Y than in CPB (P < 0.05) but still lower compared to S (P < 0.05). CONCLUSION: Pre-administration of probiotics can improve, to some extent, intestinal barrier function after CPB in rats, and this effect is likely related to inhibition of the CPB-induced inflammatory response, improvement in local intestinal immune function, and increased expression of intestinal epithelial tight junction proteins.

Penehyclidine hydrochloride attenuates the cerebral injury in a rat model of cardiopulmonary bypass.

This study investigated the effect of penehyclidine hydrochloride (PHC) on regulatory mediators during the neuroinflammatory response and cerebral cell apoptosis following cardiopulmonary bypass (CPB). Forty-eight rats were randomly divided among 4 groups as follows: sham-operation, vehicle, low-dose PHC (0.6 mg·(kg body mass)(-1)), and high-dose PHC (2.0 mg·(kg body mass)(-1)). CPB was performed in the latter 3 groups. The plasma levels of neuron specific enolase (NSE) and S-100B were tested with ELISA. Real-time PCR and Western blotting were used to evaluate the expression levels of matrix metalloproteinase-9 (MMP-9), IL-10, caspase-3, Bcl-2, and p38 in brain tissue. The ultrastructure of hippocampus tissue was examined under an electron microscope. PHC attenuated the increase of plasma NSE and S-100B following CPB. MMP-9, cleaved caspase-3, and phosphorylated p38 expression were substantially increased in the vehicle group compared with the sham-operation group and gradually diminished with increasing doses of PHC. IL-10 and Bcl-2 expression were markedly lower in the vehicle group than in the sham-operation group and gradually recovered with increasing doses of PHC. PHC attenuated the histopathological changes of cerebral injury following CPB. PHC favorably regulates the inflammatory response and reduces markers of neuronal injury following CPB, potentially by reducing p38 and caspase-3 activation.

Puerol and pueroside derivatives from Pueraria lobata and their anti-inflammatory activity.

Five undescribed puerols and puerosides and three known analogues were obtained from the roots of Pueraria lobata. Their structures were determined by comprehensive analysis of spectroscopic data and chemical methods. Since puerol D and puerol C were racemic compounds, resolved into their enantiomers, and their absolute configurations were determined by experimental and calculated ECD spectra. Six of the isolates were evaluated for their inhibitory activities on NO generation and the expression of inflammatory factors in the LPS-stimulated RAW 264.7 macrophage cells. The results showed that (S)-puerol C, (R)-puerol C, isokuzubutenolide A and kuzubutenolide A significantly decreased the NO production (IC50 values in the range of 16.87-39.95 µM). Meanwhile, (S)-puerol C, isokuzubutenolide A and kuzubutenolide A also reduced the mRNA expression of inflammatory factors (TNF-α, IL-1ß and IL-6).

[Influence of the Classification of Municipal Solid Wastes on the Reduction of Greenhouse Gas Emissions: A Case Study of Qingdao City, China].

The municipal solid waste (MSW) sector is an important source of greenhouse gas (GHG) emissions. MSW classification can achieve waste reduction and improve resource utilization. However, few studies have investigated the effects of MSW classification on GHG emission reduction. Therefore, the GHG emissions under different MSW disposal modes before and after classification were studied based on the life cycle assessment method in the four districts of Qingdao City. The results showed that MSW classification could significantly reduce the GHG emissions during the whole MSW treatment process. The net carbon emissions(in CO2/MSW)during the whole process of waste treatment for mode 1 (mixed collection+landfill), mode 2 (mixed collection+incineration), mode 3 (waste classification+anaerobic digestion of food waste and other incineration), and mode 4 (waste classification+anaerobic digestion of food waste, recycling of recyclable waste, and other incineration) were 686.39, -130.12, -61.88, and -230.17 kg·t-1, respectively. Improving the classification efficiency of food waste had no significant impact on carbon emissions. The reduction in carbon emissions increased linearly with the improvement of waste recycling efficiency. For every 10% increase in the recovery efficiency of recyclable waste, the net carbon emission decreased by 26.6%(16.5 kg·t-1). Appropriate separation of food waste, improving the recycling efficiency of recyclable waste, and reducing the leakage rate of biogas from anaerobic digestion are feasible strategies to reduce carbon emissions from MSW disposal units through the classification of MSW.

[Spatio-temporal Change in City-level Greenhouse Gas Emissions from Municipal Solid Waste Sector in China During the Last Decade and Its Potential Mitigation].

The waste sector is a significant source of greenhouse gas(GHG) emissions and clarifying its emission trends and characteristics is the premise for formulating GHG emission reduction strategies. Using the IPCC inventory model, the GHG emissions from the municipal solid waste(MSW) sector in China during 2010 to 2020 were estimated. The results showed that GHG emissions increased from 42.5 Mt in 2010 to 75.3 Mt in 2019, then decreased to 72.1 Mt in 2020. MSW landfills were the main source of GHG emissions. Further, with the increase in the proportion of waste incineration, the proportion of GHG incineration increased rapidly from 16.5% in 2010 to 60.1% in 2020. In terms of regional distribution, East and South China were the regions with the highest emissions, and Guangdong, Shandong, Jiangsu, and Zhejiang were the provinces with the largest GHG emissions. Implementing MSW classification, changing the MSW disposal modes from landfilling to incineration, improving the LFG collection efficiency of landfills, and using biological functional materials as the cover soil to strengthen the methane oxidation efficiency are the main measures to achieve GHG emission reduction in waste sectors.

[Effects of Biochar Application on Soil Organic Nitrogen Component and Active Nitrogen in Eucalyptus Plantations After Five Years in Northern Guangxi].

The objective of this study was to research the characteristics of fractions of organic nitrogen and active nitrogen and their relationship under different biochar applications and to provide a basis for the preparation and practical application of biochar from Eucalyptus forest wastes. In a long-term positioning test of biochar application from 2017, six different treatments were selected:0(CK), 0.5%(T1), 1%(T2), 2%(T3), 4%(T4), and 6%(T5). The contents of soil organic nitrogen components, total nitrogen(TN), dissolved organic nitrogen(DON), and microbial biomass nitrogen(MBN) following the different treatments were measured. The results showed that:① compared with that of the control, with the increase in biochar application, the contents of soil TN, acidolysis of total organic nitrogen(AHON), ammonia nitrogen(AN), amino acid nitrogen(AAN), MBN, DON, and nitrogen storage(NS) increased significantly by 45.48%-156.32%, 44.31%-171.31%, 38.06%-223.37%, 39.42%-163.32%, 36.72%-109%, 23.27%-113.51%, and 29.45%-62.37%, respectively. The contents of soil hydrolyzable unknown nitrogen(HUN) and non-hydrolyzable nitrogen(NHN) also increased significantly by 88.41%-158.71% and 50.24%-139.01%, respectively. The contents of soil amino sugar nitrogen(ASN) decreased by 7.72%-32.73%. The contents of different forms of organic nitrogen fractions in all treatments displayed an order of AN > AAN > NHN > HUN > ASN. Compared with the no biochar treatment, each biochar treatment increased the contents and proportion of AHON in the TN. ② With the exception of HUN, the contents of other soil organic nitrogen components and active nitrogen content decreased with the increase in soil depth. ③ There were significantly positive correlations between TN, MBN, and DON and AHON, NHN, and NS contents. The principal component analysis showed that bulk density and ASN and TN and HUN, AAN, DON, and AHON were closely related, respectively. In conclusion, the application of forestry waste biochar for five years could significantly increase the content of soil organic nitrogen component and active nitrogen, thereby improving the capacity of the soil to supply nitrogen. AHON, AN, and AAN were the main factors contributing to soil active nitrogen content.

[Remediation of Three Oxidants on Polycyclic Aromatic Hydrocarbons in Coking Contaminated Soil and Its Response to Indigenous Microorganisms].

To explore the influences of chemical oxidation on the physiological and ecological functions of indigenous microorganisms during contaminated soil remediation, three oxidants, including KMnO4, Na2S2O8, and O3, were selected to investigate their remediation effects on PAHs and the responses to indigenous microorganisms under different liquid-solid ratios, in this study. The results showed that:when the ΣPAHs concentration was 679.1 mg·kg-1 and the dosage of KMnO4 and Na2S2O8 was 1%, the removal efficiency of ΣPAHs reached up to 96.9% and 95.7% under the liquid-solid ratio of 6:1; for the O3 treatment, the removal efficiency of ΣPAHs was the highest(82.3%) at the O3 dosage and the liquid-solid ratio of 72 mg·min-1 and 8:1, respectively. The removal efficiency of low ring(3-4 rings) PAHs was higher than that of high ring(5-6 rings) PAHs under different liquid-solid ratios. The highest removal efficiencies were observed for phenanthrene and acenaphthene, whereas for benzo[a]pyrene, only the KMnO4treatment provided an effective performance, showing the highest removal efficiency of 97.4%. The microbial quantity analysis indicated that the quantity of soil microorganisms in the soil dropped sharply after being treated with KMnO4, decreasing from 108 copies·g-1 to 105 copies·g-1, whereas it changed only slightly after being treated with Na2S2O8 and O3. The community structure analysis showed that Proteobacteria were predominant in the contaminated soil, with the relative abundance of 99.5%. The addition of KMnO4 and Na2S2O8 significantly increased the microbial diversity; in particular, the relative abundance of a variety of microorganisms(such as Ralstonia and Acinetobacter) that can degrade PAHs was remarkably increased. The analysis of microbial metabolic function pathways revealed that chemical oxidation could simultaneously increase the relative abundance of PAHs-degrading bacteria and improve the ability of organic metabolism. Overall, the KMnO4 treatment greatly altered the quantity of microorganisms and the structure of the microbial community and the relative abundance of PAHs-degrading microorganisms at the liquid-solid ratio of 6:1.

Encapsulating N­doped graphite carbon in MoO2 as a novel cocatalyst for boosting photocatalytic hydrogen evolution.

Generally, it is important to ameliorate the co-catalyst used in photocatalytic hydrogen evolution reactions (PHERs) to achieve efficient transfer and separation of photogenerated carriers, decrease the surface reaction energy barrier, and hence improve the photocatalytic activity. In this study, N-doped graphite carbon (GC) was introduced in situ to MoO2 to ensure the presence of well-dispersed active sites, lower the overpotential of hydrogen evolution, and further achieve high conductivity. Then, the MoO2/GC composite obtained was used as a co-catalyst of ZnIn2S4 (ZIS) in a PHER, resulting in a great improvement in the photocatalytic activity. Given the metallicity and large work function of MoO2/GC, a Schottky interface can form between MoO2/GC and ZIS, which accelerates the transmission of photogenerated electrons. As a result, the separation efficiency of photogenerated carriers improves, whereas the surface overpotential of PHERs clearly decreases for ZIS. This study proposes a new idea for exploiting efficient co-catalysts and promotes the wide and heavy use of carbon materials in the field of solar energy conversion.

κ-Opioid Receptor Agonist U50448H Protects Against Acute Lung Injury in Rats with Cardiopulmonary Bypass via the CAP-NLRP3 Signaling Pathway.

Objective: Acute lung injury (ALI) is one of the common and severe complications of cardiopulmonary bypass (CPB), which is the primary cause of death in intensive care units. Nevertheless, there is a lack of effective treatment for ALI secondary to CPB. κ-Opioid receptor (KOR) agonists have been demonstrated to improve lung function after pulmonary hypertension. However, its protective role has been barely reported in CPB-induced acute respiratory distress syndrome (ARDS). Therefore, this research focused on the protective effect of a KOR agonist U50448H on ARDS and investigated its potential relationship with the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. Method: Forty-five rats were randomly allocated into Sham, CPB, and U50448 groups (n = 15 rats/group). After a CPB model was successfully established in rats, CPB rats were treated with the KOR agonist U50448H. The values of extravascular lung water (EVLW), alveolar-arterial oxygen tension difference (AaDO2), and respiratory index (RI) were examined, and the lung wet/dry (W/D) weight ratio was also calculated. Western blot (WB) was utilized to measure the expression of MMP-9, GSDMD-C, GSDMD-N, NLRP3, ASC, pro-Caspase-1, pro-IL-1ß, and α7-nAChR. The immunofluorescence assay was performed for examining the expression of ROS, F480, iNOS, CD206, and α7-nAChR. Cell apoptosis was detected by the TUNEL assay. ELISA was used to test the level of LPS in serum and the level of MDA, GSH, SOD, TNF-α, IL-4, IL-6, IL-18, and IL-1ß in lung tissues. Results: It was observed that the administration of U50448H significantly reduced EVLW values and LPS levels in the lung of rats. Meanwhile, U50448H increased AaDO2 values while decreasing RI values. Moreover, the administration of U50448H alleviated the pathological damage caused by ALI secondary to CPB. U50448H repressed ROS release and oxidative stress responses, as well as lowered LPS levels in plasma and MMP-9 expression in the lung of CPB rats. Furthermore, U50448H facilitated the shift of macrophage phenotype to M2. In addition, U50448H decreased the activity of the CAP-NLRP3 inflammasome and suppressed pyroptosis in pulmonary cells. Conclusion: The KOR agonist U50448H improved lung function and relieved lung injury in CPB rats, accompanied by diminished ROS and MMP-9 levels in lung tissues, promoted macrophage polarization from M1 to M2, and reduced NLRP3 inflammasome activities. These results indicated U50448H as a promising drug for the treatment of ALI secondary to CPB.

Promoting photocatalytic CO2 reduction to CH4 via a combined strategy of defects and tunable hydroxyl radicals.

A well-designed photocatalyst with excellent activity and selectivity is crucial for photocatalytic CO2 conversion and utilization. TiO2 is one of the most promising photocatalysts. However, its excessive surface oxidation potential and insufficient surface active sites inhibit its activity and photocatalytic CO2 reduction selectivity. In this work, highly dispersed Bi2Ti2O7 was introduced into defective TiO2 to adjust its oxidation potential and the generation of radicals, further inhibiting reverse reactions during the photocatalytic conversion of CO2. Moreover, an in situ topochemical reaction etching route was designed, which achieved defective surfaces, a contacted heterophase interface, and an efficient electron transfer path. The optimized heterophase photocatalyst exhibited 93.9% CH4 selectivity at a photocatalytic rate of 6.8 µmol·g-1·h-1, which was 7.9 times higher than that of P25. This work proposes a feasible approach to fabricating photocatalysts with well-designed band structures, highly dispersed heterophase interfaces, and sufficient surface active sites to effectively modulate the selectivity and activity of CO2 photoreduction by manipulating the reaction pathways.

[Characteristics and Health Risk Assessment of Trace Elements in Atmospheric PM1 During Autumn and Winter in Qingdao].

From November 1,2018 to January 31,2019 (OP2018-2019) and from November 1,2019 to January 20, 2020 (OP2019-2020), PM1 measurement was conducted daily for two consecutive years. The concentration of trace elements in the atmospheric PM1 in Qingdao in autumn and winter was analyzed. The observation period was divided into four air quality levels (Level Ⅰ, Level Ⅱ, Level Ⅲ, and Level Ⅳ), and the characteristics and sources of the concentration of trace elements in PM1 were analyzed. The non-carcinogenic risks (Zn, Pb, Mn, Cu, and V) and carcinogenic risks (As, Cr, Ni, Cd, and Co) of different people with different air quality levels were evaluated. The results showed that the changes in total metal element concentrations were associated with changes in Ca, K, and Al concentrations at different air quality classes during OP2019-2020 compared to those during OP2018-2019 and were more influenced by dust and biomass combustion sources. Compared with that during OP2018-2019, the V concentration in different air quality levels (Level Ⅰ, Level Ⅱ, Level Ⅲ, and Level Ⅳ) during OP2019-2020 decreased by 19.0%, 60.5%, 82.7%, and 77.5%, respectively. This was presumed to be related to the implementation of the Domestic Emission Control Area (DECA) policy for ships, which led to the significant reduction in V concentration due to the change in fuel quality of ships in the waters around Qingdao. The results of the enrichment factor, the ratio method, and the backward trajectory of airflow further indicated that the changes in V concentrations were mainly influenced by the DECA policy. However, after the implementation of the DECA, the V/Ni value as a limit for judging the influence of ship sources in the area required further exploration. The health risk assessment results showed that the risk factor of Mn ranged from 0.07 to 1.22 during OP2018-2019 and OP2019-2020. It was recommended to strengthen the management and control of Mn-containing pollution sources. The lifetime carcinogenic risk (ILCR) value of As and Cd under different air qualities during OP2018-2019 and OP2019-2020 was lower than 10-4 but higher than 10-6, indicating that there was a carcinogenic probability, although it was still at an acceptable level. During OP2018-2019, when the air quality was Ⅳ, the ILCR value of Cr was higher than 10-4, and there was a risk of cancer.

A photo-responsive chemical modulation of m6A RNA demethylase FTO.

The adenine N6-methylation m6A is a crucial modification that is associated with several biological functions. One of the two m6A demethylases FTO has arisen as an attractive target for the development of novel cancer therapies. Here, we describe a new design, synthesis and evaluation of a photo-responsive and selective inhibitor of FTO.

Regioselective synthesis and anticancer evaluation of H2O2-activable nucleosides.

We describe here the design, synthesis, and biological evaluation of H2O2-activatable nucleosides via an efficient and regioselective functionalization of unprotected precursors. Biological evaluation of a H2O2-specific responsive prodrug of gemecitabin demonstrates an extremely fast activation, low toxicity and enhanced anticancer effects in two cell lines.