Differences in antibiotic use between COPD and non-COPD residents based on the health information system.

OBJECTIVES: To compare the differences in antibiotic use between COPD and non-COPD residents, and to explore the effect of COPD on antibiotic use. METHODS: Participants aged 40 years old or over from the Songjiang Adult Cohort were included. Information on prescription and baseline survey was collected based on the health information system. A logit-negative binomial Hurdle model was used to explore correlations between COPD and percentage of antibiotic use and average rate of antibiotic prescribing of different types of antibiotic. Multinomial logistic regression was used to assess the association between COPD and antimicrobial combination therapy and routes of administration. RESULTS: A total of 34576 individuals were included and 1594 (4.6%) were COPD patients. During the 6 years' follow-up, the percentage of antibiotic use for COPD patients was 98.4%, which was 7.88 (95%CI: 5.24-11.85) times of that for non-COPD patients after adjusting for potential confounders. The prescribing rate was 3220 prescriptions (95%CI: 3063.6-3385.2) per 1000 person-years for COPD patients, which was 1.96 (95%CI: 1.87-2.06) times of that for non-COPD patients. Other beta-lactam antibacterials, Macrolides, lincosamides and streptogramins, and quinolone antibacterials were the most commonly used types of antibiotic. Except for aminoglycoside antibacterials, both percentage of antibiotic use and rate of antibiotic prescription were increased in COPD patients. COPD patients were more likely to be prescribed a maximum of two antibiotics (OR=1.34, 95%CI: 1.20-1.50); and were more likely to use antibiotics intravenously (OR=2.77, 95%CI: 2.47-3.11). CONCLUSION: COPD patients were more likely to have increased antibiotic use in a large-scale population-based adult cohort, suggesting COPD patients are a high-priority group for the management of antibiotic use in communities.

MiR-375 impairs breast cancer cell stemness by targeting the KLF5/G6PD signaling axis.

Recurrence of breast cancer may be due to the presence of breast cancer stem cells (BCSC). Abnormal tumor cell growth is closely associated with increased reactive oxygen species (ROS) and disruption of redox homeostasis, and BCSCs exhibit low levels of ROS. The detailed mechanism between the low levels of ROS in BCSCs and their maintenance of stemness characteristics has not been reported. A growing number of studies have shown that tumor development is often accompanied by metabolic reprogramming, which is an important hallmark of tumor cells. As the first rate-limiting enzyme of pentose phosphate pathway (PPP), the expression of G6PD is precisely regulated in tumor cells, and there is a certain correlation between PPP and BCSCs. MiR-375 has been shown to inhibit stem cell-like properties in breast cancer, but the exact mechanism is not clear. Here, KLF5, as a transcription factor, was identified to bind to the promoter of G6PD to promote its expression, whereas miR-375 inhibited the expression of KLF5 by binding to the 3'UTR region of KLF5 mRNA and thus reduced the expression of G6PD expression, inhibits PPP to reduce NADPH, and increases ROS levels in breast cancer cells, thereby weakening breast cancer cell stemness. Our study reveals the specific mechanism by which miR-375 targets the KLF5/G6PD signaling axis to diminish the stemness of breast cancer cells, providing a therapeutic strategy against BCSCs.

The role of curcumin in the liver-gut system diseases: from mechanisms to clinical therapeutic perspective.

Natural products have provided abundant sources of lead compounds for new drug discovery and development over the past centuries. Curcumin is a lipophilic polyphenol isolated from turmeric, a plant used in traditional Asian medicine for centuries. Despite the low oral bioavailability, curcumin exhibits profound medicinal value in various diseases, especially liver and gut diseases, bringing an interest in the paradox of its low bioavailability but high bioactivity. Several latest studies suggest that curcumin's health benefits may rely on its positive gastrointestinal effects rather than its poor bioavailability solely. Microbial antigens, metabolites, and bile acids regulate metabolism and immune responses in the intestine and liver, suggesting the possibility that the liver-gut axis bidirectional crosstalk controls gastrointestinal health and diseases. Accordingly, these pieces of evidence have evoked great interest in the curcumin-mediated crosstalk among liver-gut system diseases. The present study discussed the beneficial effects of curcumin against common liver and gut diseases and explored the underlying molecular targets, as well as collected evidence from human clinical studies. Moreover, this study summarized the roles of curcumin in complex metabolic interactions in liver and intestine diseases supporting the application of curcumin in the liver-gut system as a potential therapeutic option, which opens an avenue for clinical use in the future.

The role and mechanism of unfolded protein response signaling pathway in methylmercury-induced apoptosis of mouse spermatocytes germ cell-2 cells.

The study aimed to explore the role and mechanism of unfolded protein response (UPR) in methylmercury (MeHg)-induced Mouse Spermatocytes (GC-2spd[ts]) apoptosis. Methods such as MTT, flow cytometry, and Western Blot were used to evaluate the cell viability, membrane potential (MMP), reactive oxygen species (ROS), calcium ion (Ca2+ ), rate of cell apoptosis, and the expression of apoptosis-related and UPR-related protein. The results showed that with the increase of MeHg concentration, cell viability and MMP decreased, ROS, Ca2+ , rate of cell apoptosis, and the expression of apoptosis-related protein and UPR-related protein increased. To further explore the effect of ROS-induced oxidative damage on it, the ROS inhibitor N-acetyl-L-cysteine (NAC) was used. The effects of MeHg on germ cell (GC-2) cells were partially inhibited after NAC pretreatment. Our present study proved that MeHg might induce cell apoptosis by activating the UPR signaling pathway in GC-2 cells and affect normal reproductive function.

Clinical utiliy of a model-based piperacillin dose in neonates with early-onset sepsis.

AIMS: Early-onset sepsis (EOS) is a common disease in neonates with a high morbidity and mortality rate. Piperacillin/tazobactam has been used extensively and empirically for EOS treatment without clinically validated dosing regimens, although the population pharmacokinetics (PPK) of piperacillin in neonates has been reported. Therefore, we wanted to study the effectiveness and tolerance of a PPK model-based dosing regimen of piperacillin/tazobactam in EOS patients. METHODS: A prospective, single-centre, phase II clinical study of piperacillin/tazobactam in neonates with EOS was conducted. The dosing regimen (90 mg·kg-1 , q8h) was determined based on a previous piperacillin PPK model in young infants using NONMEM v7.4. The pharmacodynamics (PD) target (70%fT > MIC, free drug concentration above MIC during 70% of the dosing interval) attainment was calculated using NONMEM combined with an opportunistic sampling design. The clinical treatment data were collected. RESULTS: A total of 52 neonates were screened and 49 neonates completed their piperacillin/tazobactam treatment course and were included in this analysis. The median (range) values of postmenstrual age were 33.57 (range 26.14-41.29) weeks. Forty-seven (96%) neonates reached their PD target. Eight (16%) neonates experienced treatment failure clinically. The mean (SD, range) duration of treatment and length of hospitalization were 100.1 (62.2, 36.2-305.8) hours and 31 (30, 5-123) days. There were no obvious adverse events and no infection-related deaths occurred in the first month of life. CONCLUSIONS: A model-based dosing regimen of piperacillin/tazobactam was evaluated clinically, was tolerated well and was determined to be effective for EOS treatment.

Methylmercury induced apoptosis of human neuroblastoma cells through the reactive oxygen species mediated caspase and poly ADP-ribose polymerase/apoptosis-inducing factor dependent pathways.

Methylmercury (MeHg) is an environmental neurotoxic substance, which can easily cross the blood-brain barrier, causing irreversible damage to the human central nervous system. Reactive oxygen species (ROS) are involved in various ways of intracellular physiological or pathological processes including neuronal apoptosis. This study attempted to explore the role of ROS-mediated poly ADP-ribose polymerase (PARP)/apoptosis-inducing factor (AIF) apoptosis signaling pathway in the process of MeHg-induced cell death of human neuroblastoma cells (SH-SY5Y). Here, we found that SH-SY5Y cells underwent apoptosis in response to MeHg, which was accompanied by the increased levels of ROS and calcium ion, and the activation of caspase cascades and PARP. Inhibiting the production of ROS can reduce the apoptosis rate to a certain extent. PARP/AIF apoptotic pathway is independent of caspase dependent signaling pathway and regulates it. In conclusion, these results suggest that ROS mediated activation of caspase pathway and PARP/AIF signaling pathway are involved in MeHg induced apoptosis, and these two pathways interact with each other.

Enhancing microbial fuel cell performance using anode modified with Fe3O4 nanoparticles.

Low electricity generation efficiency is one of the key issues that must be addressed for the practical application of microbial fuel cells (MFCs). Modification of microbial electrode materials is an effective method to enhance electron transfer. In this study, magnetite (Fe3O4) nanoparticles synthesized by co-precipitation were added to anode chambers in different doses to explore its effect on the performance of MFCs. The maximum power density of the MFCs doped with 4.5 g/L Fe3O4 (391.11 ± 9.4 mW/m2) was significantly increased compared to that of the undoped MFCs (255.15 ± 24.8 mW/m2). The COD removal efficiency of the MFCs increased from 85.8 ± 2.8% to 95.0 ± 2.1%. Electrochemical impedance spectroscopy and cyclic voltammetry tests revealed that the addition of Fe3O4 nanoparticles enhanced the biocatalytic activity of the anode. High-throughput sequencing results indicated that 4.5 g/L Fe3O4 modified anodes enriched the exoelectrogen Geobacter (31.5%), while control MFCs had less Geobacter (17.4%). Magnetite is widely distributed worldwide, which provides an inexpensive means to improve the electrochemical performance of MFCs.

Coenzyme Q10 Attenuates Human Platelet Aggregation Induced by SARS-CoV-2 Spike Protein via Reducing Oxidative Stress In Vitro.

Platelet hyperreactivity and oxidative stress are the important causes of thrombotic disorders in patients with COVID-19. Oxidative stress, induced by the excessive generation of reactive oxygen species (ROS), could increase platelet function and the risk of thrombus formation. Coenzyme Q10 (CoQ10), exhibits strong antioxidative activity and anti-platelet effect. However, the effects and mechanisms of CoQ10 on attenuating platelet aggregation induced by spike protein have never been studied. This study aims to investigate whether the SARS-CoV-2 spike protein potentiates human platelet function via ROS signaling and the protective effect of CoQ10 in vitro. Using a series of platelet function assays, we found that spike protein potentiated platelet aggregation and oxidative stress, such as ROS level, mitochondrial membrane potential depolarization, and lipid damage level (MDA and 8-iso-PGF2α) in vitro. Furthermore, CoQ10 attenuated platelet aggregation induced by spike protein. As an anti-platelet mechanism, we showed that CoQ10 significantly decreased the excess production of ROS induced by spike protein. Our findings show that the protective effect of CoQ10 on spike protein-potentiated platelet aggregation is probably associated with its strong antioxidative ability.

Activation of Nrf2/HO-1 signaling pathway attenuates ROS-mediated autophagy induced by silica nanoparticles in H9c2 cells.

Silica nanoparticles (SiNPs) as one of the most productive nano-powder, has been extensively applied in various fields. There has been increasing concern about the adverse effects of SiNPs on the health of ecological organisms and human. The potential cardiovascular toxicity of SiNPs and involved mechanisms remain elusive. Hence, in this study, we investigated the cardiovascular toxicity of SiNPs (60 nm) and explored the underlying mechanisms using H9c2 cardiomyocytes. Results showed that SiNPs induced oxidative stress and activated the Nrf2/HO-1 antioxidant pathway. Autophagy was also activated by SiNPs. Interestingly, N-acetyl-L-cysteine (NAC）attenuated autophagy after inhibiting reactive oxygen species (ROS). Meanwhile, down-regulation of Nrf2 enhanced autophagy. In summary, these data indicated that SiNPs induce autophagy in H9c2 cardiomyocytes through oxidative stress, and the Nrf2/HO-1 pathway has a negative regulatory effect on autophagy. This study provides new evidence for the cardiovascular toxicity of SiNPs and provides a reference for the safe use of nanomaterials in the future.

Silica nanoparticles induce mitochondrial pathway-dependent apoptosis by activating unfolded protein response in human neuroblastoma cells.

The application of silica nanoparticles (SiNPs) in areas of agriculture and medicine has raised great concerns for the potential adverse effects of SiNPs. The increasing toxicological studies focused mainly on the lung and cardiovascular system, but the adverse effects of SiNPs on nervous system have not been well explored. This study aimed to evaluate the role and mechanism of unfolded protein reaction (UPR) in SiNPs-induced cell injury on nerve cells in vitro. We investigated the UPR-mediated apoptosis caused by SiNPs in human neuroblastoma (SH-SY5Y) cell line. The size of SiNPs and its effect on cell ultrastructure were observed by transmission electron microscopy (TEM). Cell growth, mitochondrial membrane potential (MMP), calcium ion (Ca2+ ), apoptosis rate, and the expression level of related proteins were evaluated using MTT, flow cytometry, and western blot in SH-SY5Y cells exposed to SiNPs. The results showed that with the increase of SiNPs concentration, cell viability decreased, MMP decreased, active oxygen (ROS), and Ca2+ levels increased in a dose-dependent manner. In addition, protein expression of PERK, GRP78, and other related proteins in the unfolded protein response increased in a dose-response manner together with the expression of apoptosis proteins. Conclusively, this study confirmed that SiNPs can affect the neural system by interfering structure and functional and inducing apoptosis in nerve cells through unfolded protein response.

Sequentially recover heavy metals from smelting wastewater using bioelectrochemical system coupled with thermoelectric generators.

Smelting wastewater is characterized with high concentration of toxic heavy metals and high acidity, which must be properly treated before discharge. Here, bioelectrochemical system (BES) coupled with thermoelectric generator (TEG) was first demonstrated to simultaneously treat organic wastewater and smelting wastewater by utilizing the simulated waste heat that was abundant in smelting factories. By modulating the input voltage generated from simulated waste heat via TEG to 0, 1.0 and 2.0 V, almost all the Cu2+, Cd2+ and Co2+ in smelting wastewater were sequentially recovered with a respective rate of 121.17, 158.20 and 193.87 mg L-1 d-1. Cu2+ was bioelectrochemically recovered as Cu0. While, Cd2+ and Co2+ were recovered by electrodeposition as Cd(OH)2, CdCO3 or Co(OH)2 on cathodic surface. High throughput sequencing analysis showed that the microbial community of anodic biofilm was greatly shifted after successive treatment by batch-mode. Desulfovibrio (17.00%), Megasphaera (11.81%), Geobacter (10.36%) and Propionibacterium (8.64%) were predominant genera in anodic biofilm enriched from activated sludge in BES before treatment. After successive treatment by batch-mode, Geobacter (34.76%), Microbacter (8.60%) and Desulfovibrio (5.33%) were shifted as the major genera. Economic analysis revealed that it was feasible to use TEG to substitute electrical grid energy to integrate with BES for wastewater treatment. In addition, literature review indicated that it was not uncommon for the coexistence of waste heat with typical pollutants (e.g. heavy metal ions and various biodegradation-resistant organic wastes) that could be treated by BES in different kinds of factories or geothermal sites. This study provides novel insights to expand the application potentials of BES by integrating with TEG to utilize widespread waste heat.

Functionalized carbon quantum dots as fluorescent nanoprobe for determination of tetracyclines and cell imaging.

Nitrogen and sulfur co-doped carbon dots (N, S-CQDs) with high fluorescent, water-soluble, low-toxicity properties were synthesized by microwave-assisted hydrothermal approach. The prepared N, S-CDs exhibited high selectivity in detection of tetracyclines (TCs) and displayed a fast-responsive fluorescence quenching signal in the mixture, which are mainly attributed to the inner filter effect (IFE). The synthesized N, S-CQDs are successfully used as a fluorescent nanoprobe for the determination of CTC in milk samples (with excitation/emission maxima at 373/424 nm). The limit of detection (LOD) is 71 ng mL-1, and the recoveries of spiked samples range from 96 to 104% with a relative standard deviations (RSDs) less than 2.7% (n = 3). Additionally, the cytotoxicity and optical imaging performance of N, S-CQDs were preliminarily evaluated. The results indicate the low-toxicity and good biocompatibility of the N, S-CQDs and their promising future as fluorescent-imaging agents in pharmaceutical analysis. Graphical Abstract Synthesis flowchart and application of nitrogen and sulfur dual-doped carbon quantum dots.

Crucial Roles of 5-HT and 5-HT2 Receptor in Diabetes-Related Lipid Accumulation and Pro-Inflammatory Cytokine Generation in Hepatocytes.

BACKGROUND/AIMS: Previously, we confirmed that liver-synthesized 5-HT rather than non-liver 5-HT, acting on the 5-HT2 receptor (5-HT2R), modulates lipid-induced excessive lipid synthesis (ELS). Here, we further revealed the effects of the hepatocellular 5-HT system in diabetes-related disorders. METHODS: Studies were conducted in male ICR mice, human HepG2 cells, and primary mouse hepatocytes (PMHs) under gene or chemical inhibition of the 5-HT system, key lipid metabolism, and inflammation-related factors. Protein and messenger RNA expression and levels of the factors were determined via western blotting, reverse transcription PCR, and quantitative assay kits, respectively. Hepatic steatosis with inflammation and fibrosis, intracellular lipid droplet accumulation (LDA), and reactive oxygen species (ROS) location were determined via hematoxylin and eosin, Masson's trichrome, Oil red O, and fluorescent-specific staining, respectively. RESULTS: Palmitic acid induced the activation of the 5-HT system: the activation of 5-HT2R, primarily 5-HT2AR, in addition to upregulating monoamine oxidase A (MAO-A) expression and 5-HT synthesis, by activating the G protein/ phospholipase C pathway modulated PKCε activation, resulting in ELS with LDA; the activation of NF-κB, which mediates the generation of pro-inflammatory cytokines, was primarily due to ROS generation in the mitochondria induced by MAO-A-catalyzed 5-HT degradation, and secondarily due to the activation of PKCε. These effects of the 5-HT system were also detected in palmitic acid- or high glucose-treated PMHs and regulated multiple inflammatory signaling pathways. In diabetic mice, co-treatment with antagonists of both 5-HT synthesis and 5-HT2R significantly abolished hepatic steatosis, inflammation, and fibrosis as well as hyperglycemia and dyslipidemia. CONCLUSION: Activation of the hepatocellular 5-HT system plays a crucial role in inducing diabetes-related hepatic dysfunction and is a potential therapeutic target.

Discovery of thinopyrimidine-triazole conjugates as c-Met targeting and apoptosis inducing agents.

Five series of N-methylpicolinamide moiety and thienopyrimidine moiety bearing triazole (21-26, 27-34, 35-41, 42-47 and 48-54) were designed and synthesized. And all the target compounds were evaluated for the IC50 values against three cancer cell lines (A549, HepG2 and MCF-7) and some selected compounds (43, 49 and 52) were further evaluated for the activity against c-Met, Flt-3, VEGFR-2, c-Kit and EGFR kinases. Moreover, SARs and docking studies indicated that thieno[3,2-d]pyrimidine bearing triazole moiety was privileged structure for the activity. Especially, the Cl atom on the 4-C position of aryl group showed the best activity. The most promising compound 49 showed 3.7-5.4-fold more activity than the lead drug Foretinib against A549, HepG2 and MCF-7 cell lines, with the IC50 values of 0.9 ±â€¯0.1 µM, 0.5 ±â€¯0.1 µM and 1.1 ±â€¯0.2 µM, respectively. And The experiments of enzyme-based showed that 49 inhibitor the c-Met selectively, with the IC50 values of 16 nM, which showed equal activity to Foretinib (14 nM). What's more, According to the result of AO single staining and Annexin V/PI staining, it's claimed that the 49 could induce late apoptosis of HepG2 cells and by a concentration-dependent manner.

Anti-ICAM-1 antibody-modified nanostructured lipid carriers: a pulmonary vascular endothelium-targeted device for acute lung injury therapy.

BACKGROUND: Acute lung injury (ALI) is a life-threatening clinical syndrome without effective treatment. Targeting delivery of glucocorticoid to lung shows potential efficacy for ALI based on their anti-inflammatory and anti-fibrotic properties, breaking through their clinical application limitation due to systemic side effects. This work was aimed to establish lung-targeted dexamethasone (DEX) loaded nanostructured lipid carriers (NLCs) with opposite surface charge and investigate their therapeutic effects on lipopolysaccharide (LPS)-induced ALI mice. RESULTS: The diameter of anionic anti-intercellular adhesion molecule 1 (anti-ICAM-1) antibody-conjugated DEX-loaded NLCs (ICAM/DEX/NLCs) and the cationic ones with octadecylamine (ODA) modification (ICAM/DEX/ODA-NLCs) was about 249.9 and 235.9 nm. The zeta potential of ICAM/DEX/NLCs and ICAM/DEX/ODA-NLCs was about - 30.3 and 37.4 mV, respectively. Relative to the non-targeted control and ICAM/DEX/ODA-NLCs, ICAM/DEX/NLCs exhibited higher in vitro cellular uptake in LPS-activated human vascular endothelial cell line EAhy926 after CAM-mediated endocytosis, and stronger in vivo pulmonary distribution in the ALI model mice. In vivo i.v. administration of ICAM/DEX/NLCs significantly attenuated pulmonary inflammatory cells infiltration, and the production of pro-inflammatory cytokine TNF-α and IL-6 in ALI mice. H&E stain also revealed positive histological improvements by ICAM/DEX/NLCs. CONCLUSIONS: ICAM/DEX/NLCs may represent a potential pulmonary endothelium targeted device, which facilitate translation of DEX into clinical ALI treatment.

A sensitive, high-throughput, and ecofriendly method for the determination of lumefantrine, artemether, and its active metabolite dihydroartemisinin by supercritical fluid chromatography and tandem mass spectrometry.

A quick and sensitive supercritical fluid chromatography with tandem mass spectrometry method for the simultaneous determination of lumefantrine, artemether, and its active metabolite dihydroartemisinin in rat plasma was developed and validated. The chromatographic separation was performed on an ACQUITY UPC2 ™ BEH 2-EP column within 2.5 min by gradient elution using compressed CO2 and methanol containing 2 mM ammonium acetate as the mobile phases. Detection was achieved by multiple reaction monitoring using electrospray ionization in the positive ionization mode. For sample preparation, 50 µL of the sample was processed by modified high-throughput, one-step protein precipitation using hydrogen peroxide as a stabilizer to protect the endoperoxide-containing artemisinin derivatives from degradation. The calibration curves were linear over the concentration range of 2.0-1000 ng/mL for both artemether and dihydroartemisinin, and 1.0-5000 ng/mL for lumefantrine. The values of selectivity, lower limit of quantification, linearity, accuracy, precision, matrix effects, stability, and recovery met the acceptable range according to the Food and Drug Administration guidelines. The developed method enables high resolution and speed as well as low cost, low solvent consumption, and short time and was successfully applied to pharmacokinetic studies through the intravenous administration of an artemether-lumefantrine lipid emulsion in rats.

Nematodes avoid and are killed by Bacillus mycoides-produced styrene.

Root-knot nematodes are obligate parasites that feed on plant roots and cause serious crop losses worldwide. Bacillus species (Bacilliaceae) can produce nematicidal metabolites and have shown good potential for biological control of nematodes. In this study, Bacillus mycoides strain R2 isolated from rhizosphere soil of tomato plants exhibited high nematicidal activity against the free-living nematode Caenorhabditis elegans and the root-knot nematode Meloidogyne incognita. In a pot experiment, control efficiency of B. mycoides R2 on M. incognita was as high as 90.94%. The nematicidal compound was isolated and identified as styrene. The median lethal concentration of styrene against M. incognita was 4.55 µg/ml (m/v). The volatile styrene caused avoidance and killed nematodes primarily by the olfactory neuron and G protein signal pathway. C. elegans detected styrene with the AWB neuron; the signal was then transmitted to the downstream G protein coupled receptors CHE-3, DOP-3, and STR-2. Then signal activated G protein GPA-3 and GPA-7. The signal was then transmitted to ion channels (CNGs channel and TRPV channel), causing calcium ion internal flow and a stress response towards the increased concentration of intracellular calcium. Styrene should be registered as a nematode repellent and biocontrol agent for protection of crops against root-knot nematode attack.

A mutant in the CsDET2 gene leads to a systemic brassinosteriod deficiency and super compact phenotype in cucumber (Cucumis sativus L.).

KEY MESSAGE: A novel dwarf cucumber mutant, scp-2, displays a typical BR biosynthesis-deficient phenotype, which is due to a mutation in CsDET2 for a steroid 5-alpha-reductase. Brassinosteroids (BRs) are a group of plant hormones that play important roles in the development of plant architecture, and extreme dwarfism is a typical outcome of BR-deficiency. Most cucumber (Cucumis sativus L.) varieties have an indeterminate growth habit, and dwarfism may have its value in manipulation of plant architecture and improve production in certain production systems. In this study, we identified a spontaneous dwarf mutant, super compact-2 (scp-2), that also has dark green, wrinkle leaves. Genetic analyses indicated that scp-2 was different from two previously reported dwarf mutants: compact (cp) and super compact-1 (scp-1). Map-based cloning revealed that the mutant phenotype was due to two single nucleotide polymorphism and a single-base insertion in the CsDET2 gene that resulted in a missense mutation in a conserved amino acid and thus a truncated protein lacking the conserved catalytic domains in the predicted steroid 5α-reductase protein. Measurement of endogenous hormone levels indicated a reduced level of brassinolide (BL, a bioactive BR) in scp-2, and the mutant phenotype could be partially rescued by the application of epibrassinolide (EBR). In addition, scp-2 mutant seedlings exhibited dark-grown de-etiolation, and defects in cell elongation and vascular development. These data support that scp-2 is a BR biosynthesis-deficient mutant, and that the CsDET2 gene plays a key role in BR biosynthesis in cucumber. We also described the systemic BR responses and discussed the specific BR-related phenotypes in cucumber plants.

Indole-TEMPO conjugates alleviate ischemia-reperfusion injury via attenuation of oxidative stress and preservation of mitochondrial function.

Mitochondrial oxidative damage contributes to a wide range of pathologies including ischemia/reperfusion injury. Accordingly, protecting mitochondria from oxidative damage should possess therapeutic relevance. In the present study, we have designed and synthesized a series of novel indole-TEMPO conjugates that manifested good anti-inflammatory properties in a murine model of xylene-induced ear edema. We have demonstrated that these compounds can protect cells from simulated ischemia/reperfusion (s-I/R)-induced reactive oxygen species (ROS) overproduction and mitochondrial dysfunction. Furthermore, we have demonstrated that indole-TEMPO conjugates can attenuate organ damage induced in rodents via intestinal I/R injury. We therefore propose that the pharmacological profile and mechanism of action of these indole-TEMPO conjugates involve convergent roles, including the ability to decrease free radical production via lipid peroxidation which couples to an associated decrease in ROS-mediated activation of the inflammatory process. We further hypothesize that the protective effects of indole-TEMPO conjugates partially reside in maintaining optimal mitochondrial function.

The Association between the Diversity of Coenzyme Q10 Intake from Dietary Sources and the Risk of New-Onset Hypertension: A Nationwide Cohort Study.

Coenzyme Q10 (CoQ10) is a food active component with blood-pressure-improving properties. However, the association between the variety and quantity of different sources of dietary CoQ10 and new-onset hypertension remains uncertain. We aimed to investigate the associations between the diversity and quantity of CoQ10 intake from eight major food sources and new-onset hypertension risk. A total of 11,489 participants were included. Dietary intake was evaluated via three consecutive 24 h recalls and household food inventory. The diversity score of CoQ10 sources was calculated by the sum of food groups consumed in the ideal range. Cox proportional hazard models were used for evaluating their associations with hypertension. Model performance was assessed by ROC analyses and 200-times ten-fold cross-validation. The relationships between CoQ10 and hypertension were U-shaped for meat, egg, vegetable, and fruit sources, inverse J-shaped for fish, and nut sources, and L-shaped for dairy products sources (all p-values < 0.001). A higher diversity score was associated with lower hypertension risk (HR (95% CI): 0.66 (0.64, 0.69)). The mean areas under the ROC curves for 6, 12 and 18 years were 0.81, 0.80 and 0.78, respectively. There is a negative correlation between the diversity of CoQ10 with moderate intake from different sources and new-onset hypertension. One diversity score based on CoQ10 was developed.