Catalyst Selection over an Electrochemical Reductive Coupling Reaction toward Direct Electrosynthesis of Oxime from NOx and Aldehyde.

Aqueous electrochemical coupling reactions, which enable the green synthesis of complex organic compounds, will be a crucial tool in synthetic chemistry. However, a lack of informed approaches for screening suitable catalysts is a major obstacle to its development. Here, we propose a pioneering electrochemical reductive coupling reaction toward direct electrosynthesis of oxime from NOx and aldehyde. Through integrating experimental and theoretical methods, we screen out the optimal catalyst, i.e., metal Fe catalyst, that facilitates the enrichment and C-N coupling of key reaction intermediates, all leading to high yields (e.g., ∼99% yield of benzaldoxime) for the direct electrosynthesis of oxime over Fe. With a divided flow reactor, we achieve a high benzaldoxime production of 22.8 g h-1 gcat-1 in ∼94% isolated yield. This work not only paves the way to the industrial mass production of oxime via electrosynthesis but also offers references for the catalyst selection of other electrochemical coupling reactions.

Insights into the Crystallinity-Dependent Photochemical Productions of Reactive Oxygen Species from Iron Minerals.

Iron minerals are widespread in earth's surface water and soil. Recent studies have revealed that under sunlight irradiation, iron minerals are photoactive on producing reactive oxygen species (ROS), a group of key species in regulating elemental cycling, microbe inactivation, and pollutant degradation. In nature, iron minerals exhibit varying crystallinity under different hydrogeological conditions. While crystallinity is a known key parameter determining the overall activity of iron minerals, the impact of iron mineral crystallinity on photochemical ROS production remains unknown. Here, we assessed the photochemical ROS production from ferrihydrites with different degrees of crystallinity. All examined ferrihydrites demonstrated photoactivity under irradiation, resulting in the generation of hydrogen peroxide (H2O2) and hydroxyl radical (•OH). The photochemical ROS production from ferrihydrites increased with decreasing ferrihydrite crystallinity. The crystallinity-dependent photochemical •OH production was primarily attributed to conduction band reduction reactions, with the reduction of O2 by conduction band electrons being the rate-limiting key process. Conversely, the crystallinity of iron minerals had a negligible influence on photon-to-electron conversion efficiency or surface Fenton-like activity. The difference in ROS productions led to a discrepant degradation efficiency of organic pollutants on iron mineral surfaces. Our study provides valuable insights into the crystallinity-dependent ROS productions from iron minerals in natural systems, emphasizing the significance of iron mineral photochemistry in natural sites with abundant lower-crystallinity iron minerals such as wetland water and surface soils.

Field Quantification of Hydroxyl Radicals by Flow-Injection Chemiluminescence Analysis with a Portable Device.

Hydroxyl radical (•OH) is a powerful oxidant abundantly found in nature and plays a central role in numerous environmental processes. On-site detection of •OH is highly desirable for real-time assessments of •OH-centered processes and yet is restrained by a lack of an analysis system suitable for field applications. Here, we report the development of a flow-injection chemiluminescence analysis (FIA-CL) system for the continuous field detection of •OH. The system is based on the reaction of •OH with phthalhydrazide to generate 5-hydroxy-2,3-dihydro-1,4-phthalazinedione, which emits chemiluminescence (CL) when oxidatively activated by H2O2 and Cu3+. The FIA-CL system was successfully validated using the Fenton reaction as a standard •OH source. Unlike traditional absorbance- or fluorescence-based methods, CL detection could minimize interference from an environmental medium (e.g., organic matter), therefore attaining highly sensitive •OH detection (limits of detection and quantification = 0.035 and 0.12 nM, respectively). The broad applications of FIA-CL were illustrated for on-site 24 h detection of •OH produced from photochemical processes in lake water and air, where the temporal variations on •OH productions (1.0-12.2 nM in water and 1.5-37.1 × 107 cm-3 in air) agreed well with sunlight photon flux. Further, the FIA-CL system enabled field 24 h field analysis of •OH productions from the oxidation of reduced substances triggered by tidal fluctuations in coastal soils. The superior analytical capability of the FIA-CL system opens new opportunities for monitoring •OH dynamics under field conditions.

Interaction effects between sleep-related disorders and depression on hypertension among adults: a cross-sectional study.

BACKGROUND: Hypertension, sleep disorders, and depression represent notable public health issues, and their interconnected nature has long been acknowledged. The objective of this study is to explore the interplay between sleep disorders and depression in the context of hypertension. METHODS: This cross-sectional study involved 42,143 participants aged 18 and above from the NHANES database across seven survey cycles between 2005 and 2018. After excluding those with missing data on depression, sleep disorders, and hypertension, as well as incomplete main variables, 33,383 participants remained. We used weighted logistic regression to examine the relationship between sleep disorders, depression, and hypertension. Additionally, we assessed the interaction between sleep disorders and depression on hypertension using both multiplicative and additive approaches to quantify their combined effect. RESULTS: Compared to individuals without sleep disorders, those with sleep disorders have an increased risk of hypertension (OR = 1.51, 95% CI: 1.37-1.67). Furthermore, individuals with depression experience a significantly higher risk of hypertension compared to those with sleep disorders alone (OR = 2.34, 95% CI: 1.95-2.80). Our study reveals a positive interaction between sleep disorders and depression in relation to hypertension risk (OR = 1.07, 95% CI: 1.02-1.13). In addition, we observed the quantitative additive interaction indicators (RERI = 0.73, 95% CI: 0.56 ~ 0.92; API = 0.31, 95% CI: 0.11 ~ 0.46; SI = 2.19, 95% CI: 1.08-3.46) influencing hypertension risk. Furthermore, our research also identified that individuals with less than 7 h of sleep, a sleep latency period between 5 and 30 min, or a latency period exceeding 30 min experience a significantly increased risk of hypertension. CONCLUSIONS: Our research uncovered separate links between sleep disorders, depression, and hypertension prevalence. Moreover, we identified an interaction between depression and sleep disorders in hypertension prevalence. Enhancing mental well-being and tackling sleep disorders could help prevent and manage hypertension. Yet, more investigation is required to establish causation and clarify mechanisms.

NMDA receptor within nucleus accumbens shell regulates propofol self-administration through D1R/ERK/CREB signalling pathway.

Addictive properties of propofol have been demonstrated in both humans and animals. The nucleus accumbens (NAc) shell (NAsh) in the brain, along with the interactions between N-methyl-D-aspartate receptor (NMDAR) and the dopamine D1 receptor (D1R), as well as their downstream ERK/CREB signalling pathway in the NAc, are integral in regulating reward-seeking behaviour. Nevertheless, it remains unclear whether NMDARs and the NMDAR-D1R/ERK/CREB signalling pathway in the NAsh are involved in mediating propofol addiction. To investigate it, we conducted experiments with adult male Sprague-Dawley rats to establish a model of propofol self-administration behaviour. Subsequently, we microinjected D-AP5 (a competitive antagonist of NMDARs, 1.0-4.0 µg/0.3 µL/site) or vehicle into bilateral NAsh in rats that had previously self-administered propofol to examine the impact of NMDARs within the NAsh on propofol self-administration behaviour. Additionally, we examined the protein expressions of NR2A and NR2B subunits, and the D1R/ERK/CREB signalling pathways within the NAc. The results revealed that propofol administration behaviour was enhanced by D-AP5 pretreatment in NAsh, accompanied by elevated expressions of phosphorylation of NR2A (Tyr1246) and NR2B (Tyr1472) subunits. There were statistically significant increases in the expressions of D1Rs, as well as in the phosphorylated ERK1/2 (p-ERK1/2) and CREB (p-CREB). This evidence substantiates a pivotal role of NMDARs in the NAsh, with a particular emphasis on the NR2A and NR2B subunits, in mediating propofol self-administration behaviour. Furthermore, it suggests that this central reward processing mechanism may operate through the NMDAR-D1R/ERK/CREB signal transduction pathway.

High-Pressure Coupling Reactions to Produce a Spherical Bulk RexN/Fe3N Composite.

We report a novel high-pressure coupling (HPC) reaction that couples the nitridation of Re with high-pressure solid-state metathesis (HPSSM) of Fe3N to produce a spherical bulk RexN/Fe3N composite. Compared with conventional methods, upon coupling of the HPSSM reactions, the synthetic pressure for Re nitridation was successfully reduced from 13 to 10 GPa (for Re3N) and from 20 to 15 GPa (for Re2N). The product RexN species would be surrounded by product Fe3N, resulting in a spherical bulk RexN/Fe3N composite (x = 2 or 3). The composite exhibits a soft magnetic behavior, and the content of nitrogen in RexN (x = 2 or 3) was controlled by adjusting the P-T conditions. The HPC reaction establishes a new approach for the bulk synthesis of 5d transition metal nitride.

Dosimetric predictors of acute bowel toxicity after Stereotactic Body Radiotherapy (SBRT) in the definitive treatment of localized prostate cancer.

INTRODUCTION: SBRT is an increasingly popular treatment for localized prostate cancer, though considerable variation in technical approach is common and optimal dose constraints are uncertain. In this study, we sought to identify dosimetric and patient-related predictors of acute rectal toxicity. METHODS: Patients included in this study were treated with prostate SBRT on a prospective institutional protocol. Physician-graded toxicity and patient-reported outcomes were captured at one week, one month, and three months following SBRT. DVH data were extracted and converted into relative volume differential DVHs for NTCP modeling. Patient- and disease-related covariates along with NTCP model predictions were independently tested for significant association with physician-graded toxicity or a decline in bowel-related QoL. A multivariate model was constructed using forward selection, and significant parameter cutoff values were obtained with Fischer's exact test to group patients by risk of developing physician-graded toxicity or detriments in patient-reported QoL. RESULTS: One hundred and three patients treated for localized prostate cancer with SBRT were included in our analysis. 52% of patients experienced a clinically significant decline in bowel-related QOL within 1 week of completion of treatment, while only 27.5% of patients developed grade 2+ physician-graded rectal toxicity. Sequential feature selection multivariate logistic regression identified rectal V22.5 Gy (p = 0.001) and D19% (p = 0.001) as independent predictors of clinically significant toxicity, while rectal V20Gy (p = 0.004) and D25.3% (p = 0.007) were independently correlated with physician-graded toxicity. Global multivariate step-wise logistic regression identified only D19% (p = 0.001) and V20Gy (p = 0.004) as independent predictors of acute bowel bother or physician-graded rectal toxicity respectively. CONCLUSIONS: Moderate doses to large rectal volumes, D19% and V20Gy, were associated with an increased incidence of a clinically significant decrease in patient-reported bowel QOL and physician-scored grade 2+ rectal toxicity, respectively. These dosimetric parameters may help practitioners mitigate acute toxicity in patients treated with prostate SBRT.

Sunlight-Driven Production of Reactive Oxygen Species from Natural Iron Minerals: Quantum Yield and Wavelength Dependence.

Photochemically generated reactive oxygen species (ROS) play numerous key roles in earth's surface biogeochemical processes and pollutant dynamics. ROS production has historically been linked to the photosensitization of natural organic matter. Here, we report the photochemical ROS production from three naturally abundant iron minerals. All investigated iron minerals are photoactive toward sunlight irradiation, with photogenerated currents linearly correlated with incident light intensity. Hydroxyl radicals (•OH) and hydrogen peroxide (H2O2) are identified as the major ROS species, with apparent quantum yields ranging from 1.4 × 10-8 to 3.9 × 10-8 and 5.8 × 10-8 to 2.5 × 10-6, respectively. Photochemical ROS production exhibits high wavelength dependence, for instance, the •OH quantum yield decreases with the increase of light wavelength from 375 to 425 nm, and above 425 nm it sharply decreases to zero. The temperature shows a positive impact on •OH production, with apparent activation energies ranging from 8.0 to 17.8 kJ/mol. Interestingly, natural iron minerals with impurities exhibit higher ROS production than their pure crystal counterparts. Compared with organic photosensitizers, iron minerals exhibit higher wavelength dependence, higher selectivity, lower efficiency, and long-term stability in photochemical ROS production. Our study highlights natural inorganic iron mineral photochemistry as a ubiquitous yet previously overlooked source of ROS.

Redox Oscillations Activate Thermodynamically Stable Iron Minerals for Enhanced Reactive Oxygen Species Production.

Reactive oxygen species (ROS) play key roles in driving biogeochemical processes. Recent studies have revealed nonphotochemical electron transfer from redox-active substances (e.g., iron minerals) to oxygen as a new route for ROS production. Yet, naturally occurring iron minerals mainly exist in thermodynamically stable forms, restraining their potential for driving ROS production. Here, we report that tide-induced redox oscillations can activate thermodynamically stable iron minerals for enhanced ROS production. •OH production in intertidal soils (15.8 ± 0.5 µmol/m2) was found to be 5.9-fold more efficient than those in supratidal soils. Moreover, incubation of supratidal soils under tidal redox fluctuations dramatically enhanced •OH production by 4.3-fold. The tidal hydrology triggered redox alternation between biotic reduction and abiotic oxidation and could accelerate the production of reactive ferrous ions and amorphous ferric oxyhydroxides, making thermodynamically stable iron minerals into redox-active metastable iron phases (RAMPs) with reduced crystallinity and promoting surface electrochemical activities. Those RAMPs displayed enhanced redox activity for ROS production. Investigations of nationwide coastal soils verified that tide-induced redox oscillations could ubiquitously activate soils for enhanced ROS production. Our study demonstrates the effective formation of RAMPs from redox oscillations by hydrological perturbations, which provides new insights into natural ROS sources.

Trends in total cholesterol control among American adults with hypercholesterolemia, 1988-2018.

BACKGROUND AND AIMS: Cholesterol control and management in patients with hypercholesterolemia are significant for the primary and secondary prevention of atherosclerotic cardiovascular disease. This study analyzed the trend of serum total cholesterol (TC) control (<240 mg/dL and <200 mg/dL) in American adults with hypercholesterolemia and thereby make some effective recommendations for the public health measures. METHODS AND RESULTS: Basing on the National Health and Nutrition Examination Survey (NHANES) data from 1988 to 2018 (12 cycles), we calculated the weighted and representative rate of patients with hypercholesterolemia who had controlled TC, and then described the trend. Among the adults with hypercholesterolemia, the age-adjusted rate of those whose TC was less than 240 mg/dL increased from 7.67% (95%CI: 5.94%-9.40%) in 1988-1991 to 58.52% (95%CI: 55.89%-61.15%) in 2013-2014 and then remained stable; and the age-adjusted rate of those whose TC was less than 200 mg/dL increased from 2.49% (95%CI: 1.48%-3.50%) in 1988-1991 to 44.58% (95%CI: 40.00%-49.16%) in 2017-2018. CONCLUSION: We concluded that the rate of controlling TC below 200 mg/dL among all patients had shown an increasing trend from 1988 to 2018 in America, while the rate of controlling TC below 240 mg/dL remained stable in recent years after an increasing.

The excitatory transmission from basolateral nuclues of amygdala to nucleus accumbens shell regulates propofol self-administration through AMPA receptors.

Propofol addictive properties have been demonstrated in humans and rats. The glutamatergic transmission from basolateral nucleus of amygdala (BLA) to the nucleus accumbens (NAc) modulates reward-seeking behaviour; especially, NAc shell (NAsh) is implicated in reward-seeking response. Previous studies indicated the interactions between AMPA receptors (AMPARs) and dopamine D1 receptor (D1R) in NAc mediated drug addiction, but whether the circuit of BLA-to-NAsh and AMPARs regulate propofol addiction remains unclear. We trained adult male Sprague-Dawley rats for propofol self-administration to examine the changes of action potentials (APs) and spontaneous excitatory postsynaptic currents (sEPSCs) in the NAsh. Thereafter, optogenetic stimulation with adeno-associated viral vectors microinjections in BLA was used to explore the effect of BLA-to-NAsh on propofol self-administration behaviour (1.7 mg/kg/injection). The pretreatment effects with NBQX (0.25-1.0 µg/0.3 µl/site) or vehicle in the NAsh on propofol self-administration behaviour, the expressions of AMPARs subunits and D1R/ERK/CREB signalling pathway in the NAc were detected. The results showed that the number of APs, amplitude and frequency of sEPSCs were enhanced in propofol self-administrated rats. Propofol self-administration was inhibited in the NpHR3.0-EYFP group, but in the ChR2-EYFP group, there was a promoting effect, which could be weakened by NBQX pretreatment. NBQX pretreatment also significantly decreased the expressions of GluA2 subunit and D1R in the NAc but did not change the expressions of GluA1 and ERK/CREB signalling pathway. The evidence supports a vital role of BLA-to-NAsh circuit in regulating propofol self-administration and suggests this central reward processing may function through the interaction between AMPARs and D1R in the NAsh.

Rhizoaspergillin A and Rhizoaspergillinol A, including a Unique Orsellinic Acid-Ribose-Pyridazinone-N-Oxide Hybrid, from the Mangrove Endophytic Fungus Aspergillus sp. A1E3.

Two new compounds, named rhizoaspergillin A (1) and rhizoaspergillinol A (2), were isolated from the mangrove endophytic fungus Aspergillus sp. A1E3, associated with the fruit of Rhizophora mucronata, together with averufanin (3). The planar structures and absolute configurations of rhizoaspergillinol A (2) and averufanin (3) were established by extensive NMR investigations and quantum-chemical electronic circular dichroism (ECD) calculations. Most notably, the constitution and absolute configuration of rhizoaspergillin A (1) were unambiguously determined by single-crystal X-ray diffraction analysis of its tri-pivaloyl derivative 4, conducted with Cu Kα radiation, whereas those of averufanin (3) were first clarified by quantum-chemical ECD calculations. Rhizoaspergillin A is the first orsellinic acid-ribose-pyridazinone-N-oxide hybrid containing a unique ß-oxo-2,3-dihydropyridazine 1-oxide moiety, whereas rhizoaspergillinol A (2) and averufanin (3) are sterigmatocystin and anthraquinone derivatives, respectively. From the perspective of biosynthesis, rhizoaspergillin A (1) could be originated from the combined assembly of three building blocks, viz., orsellinic acid, ß-D-ribofuranose, and L-glutamine. It is an unprecedented alkaloid-N-oxide involving biosynthetic pathways of polyketides, pentose, and amino acids. In addition, rhizoaspergillinol A (2) exhibited potent antiproliferative activity against four cancer cell lines. It could dose-dependently induce G2/M phase arrest in HepG2 cells.

A pilot study of several environmental endocrine disrupting chemicals in children with autism spectrum disorder in south China.

Autism spectrum disorders (ASD) is a group of heterogeneous neurodevelopmental disorders. Evidence has implied that environmental pollutants are important factors related to ASD. In this study, several environmental endocrine-disrupting chemicals, including parabens, benzophenone-type ultraviolet filters, hydroxyl polycyclic aromatic hydrocarbons, triclosan and tetrabromobisphenol A were analyzed in blood plasma in ASD children (n = 34) and the control children (n = 28). The results showed that parabens were the most concentrated chemicals (2.18 ng/mL, median value), followed by hydroxyl polycyclic aromatic hydrocarbons (0.73 ng/mL), benzophenone-type ultraviolet filters (0.14 ng/mL), triclosan (0.13 ng/mL) and tetrabromobisphenol A (0.03 ng/mL). ASD children accumulated significantly lower 2-hydroxy-4-methoxybenzophenone, 2,4-dihydroxybenzophenone, 4-hydroxybenzophenone and triclosan but higher 2-hydroxyphenanthrene and tetrabromobisphenol A than the control children (0.02/0.09 ng/mL of 2-hydroxy-4-methoxybenzophenone, p < 0.05; 0.04/0.07 ng/mL of 2,4-dihydroxybenzophenone, p < 0.05; 0.03/0.04 ng/mL of 4-hydroxybenzophenone, p < 0.05; 0.13/1.22 ng/mL of triclosan, p < 0.01; 0.03 ng/mL/not detected of 2-hydroxyphenanthrene, p < 0.05; 0.03/0.004 ng/mL of tetrabromobisphenol A, p < 0.05). Gender differences in certain environmental endocrine-disrupting chemicals were evident, and the differences were more inclined toward boys. Positive associations between 2-hydroxy-4-methoxybenzophenone and triclosan, and tetrabromobisphenol A and 2-hydroxyphenanthrene were found in ASD boys. Binary logistic regression analysis showed that the adjusted odds ratio value of 2-hydroxyphenanthrene in ASD boys was 11.0 (1.45-84.0, p < 0.05). This is the first pilot study on multiple environmental endocrine-disrupting chemicals in children with ASD in China.

RNA-seq-based transcriptomic analysis of AHL-induced biofilm and pyocyanin inhibition in Pseudomonas aeruginosa by Lactobacillus brevis.

Quorum sensing (QS) regulates hundreds of genes in Pseudomonas aeruginosa, and many of which encode extracellular virulence factors. Lactobacillus as a probiotic has been verified to inhibit pathogenesis in P. aeruginosa via quenching QS. The objective of this study was to investigate mechanism of the QS quenching function of Lactobacillus via analyzing the gene expression by transcriptome. We previously isolated a Lactobacillus brevis strain 3M004 from an aquafeed and identified the strain has the function of degrading QS molecular AHL (OC12-HSL). The result showed that 3M004 cells/lysate inhibited biofilm and pyocyanin production of P. aeruginosa PA002. The biofilm inhibition rates were 16.92% and 33.0% after treatment by 1 and 2 mg/mL 3M004 lysate, respectively, and the rates for pyocyanin inhibition were 25.16% and 30.75%, respectively. Transcriptomic analysis showed that down-regulation of genes of LasA and LasB in PA002 was essential in regulating the QS system. The biofilm decrease of PA002 seems not only resulted from gene biosynthesizing of polysaccharides but also from other genes regulating components biosynthesis. Pyocyanin biosynthesis appears to be inhibited by down-regulating the key gene of PhzAB on the nonreversing action from chorismite to pyocyanin.

Diel Fluctuation of Extracellular Reactive Oxygen Species Production in the Rhizosphere of Rice.

Reactive oxygen species (ROS) are ubiquitous on earth and drive numerous redox-centered biogeochemical processes. The rhizosphere of wetland plants is a highly dynamic interface for the exchange of oxygen and electrons, presenting the basis of the precedent for ROS production, yet whether extracellular ROS are produced in the rhizosphere remains unknown. Here, we designed a microfluidic chip setup to detect in-situ ROS productions in the rhizosphere of rice with spatial and temporal resolutions. Fluorescence imaging clearly displayed the hot spots of ROS generation in the rhizosphere. The formation concentration of the hydroxyl radical (•OH, a representative ROS, 10-6 M) was comparable to those by the classical photochemical route (10-6-10-7 M) in aquatic systems, therefore highlighting the rhizosphere as an unrecognized hotspot for ROS production. Moreover, the rhizosphere ROS production exhibits diel fluctuation, which simultaneously fluctuated with dissolved oxygen, redox potential, and pH, all driven by radial oxygen loss near the root in the daytime. The production and diel fluctuation of ROS were confirmed in the rhizosphere of rice root incubated in natural soils. We demonstrated that the extracellular ROS production was triggered by the interplay between root-released oxygen and microbial respiration released extracellular electrons, while iron mineral and organic matter might play key roles in storing and shuttling electrons. Our results highlight the rhizosphere as a widespread but previously unappreciated hotspot for ROS production, which may affect pollutant redox dynamics and biogeochemical processes in soils.

Tide-Triggered Production of Reactive Oxygen Species in Coastal Soils.

We report an unrecognized, tidal source of reactive oxygen species (ROS). Using a newly developed ROS-trapping gel film, we observed hot spots for ROS generation within ∼2.5 mm of coastal surface soil. Kinetic analyses showed rapid production of hydroxyl radicals (•OH), superoxide (O2•-), and hydrogen peroxide (H2O2) upon a shift from high tide to low tide. The ROS production exhibited a distinct rhythmic fluctuation. The oscillations of the redox potential and dissolved oxygen concentration followed the same pattern as the •OH production, suggesting the alternating oxic-anoxic conditions as the main geochemical drive for ROS production. Nationwide coastal field investigations confirmed the widespread and sustainable production of ROS via tidal processes (22.1-117.4 µmol/m2/day), which was 5- to 36-fold more efficient than those via classical photochemical routes (1.5-7.6 µmol/m2/day). Analyses of soil physicochemical properties demonstrated that soil redox-metastable components such as redox-active iron minerals and organic matter played a key role in storing electrons at high tide and shuttling electrons to infiltrated oxygen at low tide for ROS production. Our work sheds light on a ubiquitous but previously overlooked tidal source of ROS, which may accelerate carbon and metal cycles as well as pollutant degradation in coastal soils.

The Effect of Allopurinol on Renal Outcomes in Patients with Diabetic Kidney Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Hyperuricemia is an independent risk factor for diabetic kidney disease (DKD) progression. Previous animal and cohort studies have reported that allopurinol administration could be of therapeutic benefit in diabetic subjects. However, there has been controversy regarding the effects of allopurinol on DKD. OBJECTIVES: The aim of our study was to investigate the efficacy of allopurinol on renal function in patients with DKD by meta-analysis of randomized controlled trials. METHOD: PubMed, EMBASE, and the Cochrane Library were searched from inception to October 2020. The primary outcome was a change in glomerular filtration rate (GFR). The secondary outcome was the change in albuminuria and serum uric acid (UA). Two reviewers independently assessed for risk of bias and extracted data. Standardized mean difference (SMD) or weighted mean difference (WMD) was calculated with random effects models and was reported with corresponding 95% confidence intervals (CIs). Grading of Recommendations Assessment, Development, and Evaluation (GRADE) of the evidence was performed after meta-analysis. International prospective register of systematic reviews registration CRD42020219132. RESULTS: From 642 potentially relevant citations, 3 studies were ultimately included. Our results showed evident reduction in serum UA after allopurinol intervention (WMD = -103.80, 95% CI -159.05, -48.55, I2 = 76%; p = 0.04), with a high GRADE of evidence. However, allopurinol did not significantly improve GFR (WMD = 1.07, 95% CI -1.68, 3.82, I2 = 33%; p = 0.45), with a moderate GRADE of evidence. There was no significant difference on improvement of albuminuria in patients of allopurinol and those in placebo groups (SMD = -0.26, 95% CI -1.03, 0.52, I2 = 94%; p = 0.52), with a moderate GRADE of evidence. CONCLUSIONS: The present research showed that allopurinol did not significantly improve renal function and albuminuria in patients with DKD.

Regulation of circadian rhythm and sleep by miR-375-timeless interaction in Drosophila.

MicroRNAs are important coordinators of circadian regulation that mediate the fine-tuning of gene expression. Although many studies have shown the effects of individual miRNAs on the circadian clock, the global functional miRNA-mRNA interaction network involved in the circadian system remains poorly understood. Here, we used CLEAR (Covalent Ligation of Endogenous Argonaute-bound RNAs)-CLIP (Cross-Linking and Immuno-Precipitation) to explore the regulatory functions of miRNAs in the circadian system by comparing the miRNA-mRNA interactions between Drosophila wild-type strain W1118 and a mutant of the key circadian transcriptional regulator Clock (Clkjrk ). This experimental approach unambiguously identified tens of thousands of miRNA-mRNA interactions in both the head and body. The miRNA-mRNA interactome showed dramatic changes in the Clkjrk flies. Particularly, among ~300 miRNA-mRNA circadian relevant interactions, multiple interactions involving core clock genes pdp1, tim, and vri displayed distinct changes as a result of the Clk mutation. Based on the CLEAR-CLIP analysis, we found a novel regulation of the circadian rhythm and sleep by the miR-375-timeless interaction. The results indicated that Clk disruption abolished normal rhythmic expression of miR-375 and the functional regulation occurred in the l-LNv neurons, where miR-375 modulated the circadian rhythm and sleep via targeting timeless. This work provides the first global view of miRNA regulation in the circadian rhythm.

The Adenosine A2A Receptor Activation in Nucleus Accumbens Suppress Cue-Induced Reinstatement of Propofol Self-administration in Rats.

Propofol has shown strong addictive properties in rats and humans. Adenosine A2A receptors (A2AR) in the nucleus accumbens (NAc) modulate dopamine signal and addictive behaviors such as cocaine- and amphetamine-induced self-administration. However, whether A2AR can modulate propofol addiction remains unknown. AAV-shA2AR was intra-NAc injected 3 weeks before the propofol self-administration training to test the impacts of NAc A2AR on establishing the self-administration model with fixed ratio 1 (FR1) schedule. Thereafter, the rats were withdrawal from propofol for 14 days and tested cue-induced reinstatement of propofol seeking behavior on day 15. The propofol withdrawal rats received one of the doses of CGS21680 (A2AR agonist, 2.5-10.0 ng/site), MSX-3 (A2AR antagonist, 5.0-20.0 µg/site) or eticlopride (D2 receptor (D2R) antagonist, 0.75-3.0 µg/site) or vehicle via intra-NAc injection before relapse behavior test. The numbers of active and inactive nose-poke response were recorded. Focal knockdown A2AR by shA2AR did not affect the acquisition of propofol self-administration behavior, but enhance cue-induced reinstatement of propofol self-administration compared with the AAV-shCTRLgroup. Pharmacological activation of the A2AR by CGS21680 (≥ 5.0 ng/site) attenuated cue-induced reinstatement of propofol self-administration behavior. Similarly, pharmacological blockade of D2R by eticlopride (0.75-3.0 µg/site) attenuated propofol seeking behavior. These effects were reversed by the administration of MSX-3 (5.0-20.0 µg/site). The A2AR- and D2R-mediated effects on propofol relapse were not confounded by the learning process, and motor activity as the sucrose self-administration and locomotor activity were not affected by all the treatments. This study provides genetic and pharmacological evidence that NAc A2AR activation suppresses cue-induced propofol relapse in rats, possibly by interacting with D2R.

High Sample Throughput LED Reactor for Facile Characterization of the Quantum Yield Spectrum of Photochemically Produced Reactive Intermediates.

Photochemically produced reactive intermediates (PPRIs) by natural photosensitizers such as chromophoric dissolved organic matter (CDOM) play numerous key roles in aquatic biogeochemical processes. PPRI productions rely on both the intensity and the spectrum of incident sunlight. While the impacts of sunlight intensity on PPRI productions are well-studied, there remains insufficient understanding of the spectrum-dependence of PPRI productions. Here we designed a high sample throughput reactor equipped with monochromatic LED lights for systematic assessments of wavelength-dependent productions of four important PPRI species, i.e., triplet-state excited CDOM (3CDOM*), singlet oxygen (1O2), hydrogen peroxide (H2O2), and hydroxyl radical (•OH), in CDOM solutions. The quantum yields of PPRIs followed the order: 3CDOM* > 1O2 ≫ H2O2 > •OH. Moreover, PPRI quantum yields decreased with the light wavelength increasing from 375 to 490 nm and sharply decreased to zero above 490 nm, while the shapes of quantum yield spectra differed among PPRI species. Simulations on PPRI productions under varying season, latitude, altitude, and cloud cover conditions show that the sunlight spectrum plays a role as equally important as intensity in determining PPRI productions and PPRI-mediated transformations of aquatic nutrients and micropollutants. Therefore, incorporating the spectrum dependence of PPRI productions will advance our understandings of PPRI-driven biogeochemical processes and pollutant dynamics under varying spatial-temporal and climatic conditions. Regarding this, the high sample throughput LED reactor sheds light on a new approach for the facile characterization of PPRI quantum yield spectrum.