Flux regulation through glycolysis and respiration is balanced by inositol pyrophosphates in yeast.

Although many prokaryotes have glycolysis alternatives, it's considered as the only energy-generating glucose catabolic pathway in eukaryotes. Here, we managed to create a hybrid-glycolysis yeast. Subsequently, we identified an inositol pyrophosphatase encoded by OCA5 that could regulate glycolysis and respiration by adjusting 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate (5-InsP7) levels. 5-InsP7 levels could regulate the expression of genes involved in glycolysis and respiration, representing a global mechanism that could sense ATP levels and regulate central carbon metabolism. The hybrid-glycolysis yeast did not produce ethanol during growth under excess glucose and could produce 2.68 g/L free fatty acids, which is the highest reported production in shake flask of Saccharomyces cerevisiae. This study demonstrated the significance of hybrid-glycolysis yeast and determined Oca5 as an inositol pyrophosphatase controlling the balance between glycolysis and respiration, which may shed light on the role of inositol pyrophosphates in regulating eukaryotic metabolism.

Assessment of nonylphenol exposure based on global urinary concentration data and its risk analysis.

Nonylphenol (NP) has been recognized as a priority hazardous substance because of its estrogenic activity and ubiquity in the environment. Therefore, it is important to understand the daily intake of NP in humans and evaluate the potential health risks of NP. The median or average estimated daily intake (EDI) of NP was estimated based on urinary NP or alkyl-chain-oxidized NP metabolites concentration data from published epidemiological studies. In brief, we acquired 34 peer-reviewed publications, which contained 14235 samples from twelve countries or regions. The global average estimated daily intake of NP was 1.003 µg/(kg bw·day), which was lower than the tolerable daily intake recommended by the Danish Veterinary and Food Authority [5 µg/(kg bw·day)]. Korea had the highest exposure level [3.471 µg/(kg bw·day)] among different countries or regions. Compared with the adult [0.743 µg/(kg bw·day)] and pregnant women [0.806 µg/(kg bw·day)] groups, the children group had the highest estimated daily intake of NP at 2.368 µg/(kg bw·day). Besides, the global NP risk hazard quotient was 0.201, and the risk hazard quotients of all countries or regions were less than 1. However, the global HQ value of the 95th quantile population was 2.299, which was much higher than 1, the potential health risk cannot be ignored and needs to be confirmed by more research. To our knowledge, this is the first study to assess the overall NP exposure levels based on published biomonitoring data, and has important implications for assessing the potential effects of NP exposure on human health. In addition, OH-NP is a robust and sensitive novel biomarker for NP, there are fewer studies on the application of this biomarker, and more studies are needed in the future for quantitative exposure and risk assessment of NP.

Association between medication literacy and blood pressure control among hypertensive patients.

AIM: This study aimed to explore the association between medication literacy and blood pressure control among hypertensive patients. BACKGROUND: Blood pressure control is a challenge for global health systems. Medication literacy is essential for medication self-management in hypertensive patients and a basis for managers to develop comprehensive intervention strategies for hypertension medication use. DESIGN: A cross-sectional observational study was conducted. METHODS: A total of 378 hypertensive patients was selected by convenience sampling from two tertiary hospitals and four community health service centres from December 2021 to January 2022 in Changsha, China. Associations between medication literacy and blood pressure control were identified with chi-square, independent samples t-tests and logistic regression analyses. RESULTS: The average medication literacy score of the hypertensive patients investigated was low. Over a third of patients had uncontrolled blood pressure. Logistic regression analysis showed that medication literacy was an influencing factor for blood pressure control rate in hypertensive patients. CONCLUSIONS: Medication literacy and blood pressure control among hypertensive patients was poor. Medication literacy was a facilitator of blood pressure control so improving medication literacy may be of value to improve blood pressure control in hypertensive patients.

Microbial production of odd-chain fatty acids.

Odd-chain fatty acids (OcFAs) and their derivatives have attracted much attention due to their beneficial physiological effects and their potential to be alternatives to advanced fuels. However, cells naturally produce even-chain fatty acids (EcFAs) with negligible OcFAs. In the process of biosynthesis of fatty acids (FAs), the acetyl-CoA serves as the starter unit for EcFAs, and propionyl-CoA works as the starter unit for OcFAs. The lack of sufficient propionyl-CoA, the precursor, is usually regarded as the main restriction for large-scale bioproduction of OcFAs. In recent years, synthetic biology strategies have been used to modify several microorganisms to produce more propionyl-CoA that would enable an efficient biosynthesis of OcFAs. This review discusses several reported and potential metabolic pathways for propionyl-CoA biosynthesis, followed by advances in engineering several cell factories for OcFAs production. Finally, trends and challenges of synthetic biology driven OcFAs production are discussed.

Associations of serum cortisol and inflammatory marker features with depression and anxiety in young women with gynecologic cancer.

PURPOSE: Serum cortisol and inflammatory markers may play a role in depression and anxiety, but little is known about whether various features of serum cortisol and inflammatory markers have different associations with depression and anxiety. This study examines the associations of serum cortisol and inflammatory marker features with depression and anxiety in young women with gynecologic cancer. METHODS: Sixty-four young women with gynecologic cancer, aged 15-39 years, were recruited in a tertiary general hospital and a tertiary hospital specializing in oncology in China from May to December 2021. The Hospital Anxiety and Depression Scale was used to evaluate depression and anxiety. Blood samples were taken at 8 am, 4 pm, and 10 pm on the same day to examine the various features (average, variability, and diurnal patterns) of serum cortisol and inflammatory markers, namely C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). RESULTS: Young women with gynecologic cancer who reported depression/anxiety had significantly higher average levels of serum cortisol, IL-6 and TNF-α than those who did not. The dysregulations in the diurnal patterns of serum cortisol and IL-6 were associated with depression and anxiety. Serum cortisol levels were significantly higher in the depression/anxiety group at 10 pm. Depression and anxiety were associated with elevated levels of IL-6 and TNF-α at each time point. CONCLUSION: This study revealed various associations of serum cortisol and inflammatory marker features with depression and anxiety in young women with gynecologic cancer. Further research is needed to understand the role of serum cortisol and inflammatory marker features in the progression of depression and anxiety.

The role of sleep quality and perceived stress on depressive symptoms among tertiary hospital nurses: a cross-sectional study.

BACKGROUND: Nurses in tertiary hospitals are at high risk for depression. Understanding sleep quality and perceived stress may contribute to nurses' mental health and health-related nursing productivity. The aim of this study was to investigate the role of sleep quality and perceived stress on depressive symptoms among nurses in tertiary hospitals. METHODS: A total of 2,780 nurses (overall response rate = 91.1%) were recruited through a cross-sectional survey in 23 tertiary hospitals in China. Questionnaires included the Self-Rating Depression Scale, the Pittsburgh Sleep Quality Index, and the Chinese Perceived Stress Scale. Variables that were significant in Chi-square tests were further entered into binary logistic stepwise regression. RESULTS: The prevalence of depressive symptoms was 60.3% (n = 1,676), of which 97.4% (n = 1,633) were female, and 77.8% were younger than 35 years (n = 1,304). Nurses who had moderate, poor, severe sleep quality and poor perceived pressure were more likely to be depressed. Master's degree, 6-10 years of work, and physical activity were protective factors, while the opposite was the case for shift work and high dissatisfaction. CONCLUSIONS: More than half of nurses working in tertiary care hospitals reported depressive symptoms, and lower sleep quality and higher perceived stress were more associated with this. Perceived stress is an interesting concept, which may provide a new entry point for the well-known idea that there is a relationship between poor sleep quality and depression. It is possible to reduce depressive symptoms among public hospital nurses by providing information on sleep health and stress relief.

The role of bidirectional associations between depression, anxiety, and emotional exhaustion on turnover intention among nurses: a multicenter cross-sectional study in China.

BACKGROUND: A high turnover rate in nursing has become a global concern. Mental health issues may increase the turnover intention of nurses and lead to turnover behaviors. However, very little is known about the role of bidirectional associations between emotional exhaustion and depression/anxiety on turnover intention. This study aimed to examine the associations among depression, anxiety, emotional exhaustion and turnover intention, and to test the role of bidirectional associations between depression, anxiety, and emotional exhaustion on turnover intention among nurses. METHODS: An online multicenter cross-sectional study was conducted in Hunan Province, China, from December 2021 to February 2022. The questionnaire collected data from the Turnover Intention Scale, the Emotional Exhaustion Scale, the Patient Health Questionnaire-2, and the Generalized Anxiety Disorder Scale-2, as well as sociodemographic information. Data analysis was performed by univariate analysis, Pearson correlation analysis, multiple linear regression analysis, and structural equation modeling. RESULTS: The average turnover intention score among Chinese nurses was 14.34 ± 3.75. The prevalence of depression and anxiety was 25.9% and 22.3%, respectively. Depression (r = 0.378, P < 0.001), anxiety (r = 0.391, P < 0.001), and emotional exhaustion (r = 0.532, P < 0.001) were positively associated with turnover intention. Emotional exhaustion partially mediated the associations between depression/anxiety and turnover intention, with both mediating effects accounting for 60.7%. The mediating ratios of depression/anxiety on the associations between emotional exhaustion and turnover intentions were 17.6% and 16.5%, respectively. CONCLUSIONS: Depression, anxiety, and emotional exhaustion showed significant positive effects on turnover intention among nurses. Emotional exhaustion played a partial mediation role between depression/anxiety and turnover intention, while depression/anxiety played no significant mediation role between emotional exhaustion and turnover intention.

Effects of rational emotive behavior therapy on alexithymia, anxiety, depression and sleep quality of older people in nursing homes: a quasi-experimental study.

BACKGROUND: Alexithymia, a subclinical cognitive-affective impairment, is prevalent in older people and increases the risk of mental disorders. There is a vast alexithymia treatment gap, with majority of older people in nursing homes lacking access to adequate mental health care. The study aimed to evaluate the effects of rational emotive behavior therapy (REBT) on alexithymia, anxiety, depression and sleep quality of older people in nursing homes. METHODS: This quasi-experimental study was conducted with two groups (the control group and intervention) from March to November 2021. This study enrolled 86 participants, two of whom were lost to follow-up; 42 received usual care (control group) and 42 received REBT based on usual care (intervention group) in nursing homes. The older people in both groups were evaluated at baseline (T0), within one-week post-intervention (T1), and at 3-month follow-up (T3). Generalized estimating equations were used by SPSS version 26 to assess the differential change in the outcomes between the two groups. RESULTS: The intervention group shows significantly greater improvement in alexithymia than the control group at both T1 (ß = -8.167, 95%CI= -10.965, -5.368, P < 0.001) and T2 (ß=-4.119, 95%CI= -7.171, -1.067, P = 0.008). The two groups showed significant differences at both T1 and T2 in both difficulty identifying feelings and difficulty describing feelings. Compared to the control group, the intervention group shows a significant improvement in sleep quality at T2 (ß = -2.048, 95%CI=-4.004, -0.091, P = 0.040). The two groups showed significant differences at both T1 and T2 in both sleep disturbance and daytime dysfunction. For depression and anxiety, no significant differences were found between the intervention and control groups. CONCLUSIONS: REBT showed to be an effective method for improving alexithymia and sleep quality of older people in nursing homes. However, it failed to significantly alleviate anxiety and depression at least in a short-term trial. Refining this intervention may have a broader, more substantial impact on future research.

Two-Step Redox in Polyimide: Witness by In Situ Electron Paramagnetic Resonance in Lithium-ion Batteries.

Organic materials are promising candidates for future rechargeable batteries, owing to their high natural abundance and rapidly redox reaction. Elaborating the charge/discharge process of organic electrode is critical to unveil the fundamental redox mechanism of lithium-ion batteries (LIBs), but monitoring of this process is still challenging. Here, we report a nondestructive electron paramagnetic resonance (EPR) technique to real-time detect the electron migration step within polyimide cathode. From in situ EPR tests, we vividly observe a classical redox reaction along with two-electron transfer which only shows one pair of peaks in the cyclic voltammetry curve. The radical anion and dianion intermediates are detailed delineation at redox sites in EPR spectra, which can be further confirmed through density functional theory calculations. This approach is especially crucial to elaborate the correlation behind electrochemical and molecular structure for multistep organic-based LIBs.

Health risk assessment of As due to rice ingestion based on iAs distribution and actual consumption patterns for the residents in Beijing: a cross-sectional study.

As a well-known human carcinogen, arsenic (As) could pose various detrimental health effects to humans mainly through the exposure pathway of food ingestion. In comparison with other foods, rice can accumulate more arsenic due to its tissue specificity. Thus, it is of great significance to assess the health risk of As due to rice ingestion. However, the study on risk assessment from exposure to As in rice is still in an early stage and lack accuracy to date. In this study, after obtaining the rice exposure behavior patterns based on a questionnaire survey, a total of 160 rice samples, which consisted of 4 types (i.e., japonica, indica, glutinous and brown rice), rice from 4 areas and consumed by most of the population in Beijing, were collected. On the basis of the actual intake rate and the species weighted average concentration of consumed rice, average daily exposure dose and health risks of inorganic As (iAs) from rice ingestion were assessed for the population among different genders and ages in Beijing. The results show that japonica rice and rice from Northeast China had higher As content, with the same value of 0.064 mg kg-1. And, they were the most popular rice consumed by people, with the intake rates of 75.50 g d-1, and 67.91 g d-1, respectively. The proportion of iAs to total As (tAs) was 58.34%, with a range of 43.18-71.88%. The average daily dose of iAs for the population was 1.15 × 10-4, which mainly came from japonica rice and the rice from Northeast China ingestion. In comparison with the acceptable non-cancer risk, which had a HQ value of 0.38, the carcinogenic risk of the population in Beijing was 1.73 × 10-4 on average. Furthermore, males had higher carcinogenic risk (1.88 × 10-4) than females (1.62 × 10-4), and the people in the age of 45-55 suffered from the highest carcinogenic risk (2.22 × 10-4), which mainly was attributed to the japonica rice and the rice from Northeast China. This study strengthened that appropriate dietary patterns should be paid more attention in order to control the health risk due to As exposure.

Status of knowledge, attitude, and practice of SARS-CoV-2 vaccine inoculation among college students and the influencing factors. / å¤§å­¦ç”Ÿæ–°å† ç— æ¯’ç–«è‹—æŽ¥ç§çŸ¥ä¿¡è¡ŒçŽ°çŠ¶åŠå½±å“å› ç´ .

OBJECTIVES: During the outbreak of coronavirus disease 2019 (COVID-19), vaccine is an important way to build and improve the immune barrier of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in the population. The purpose of this study is to understand the current situation of knowledge, attitude, and practice (KAP) of SARS-CoV-2 vaccine inoculation among Chinese college students during the epidemic of COVID-19, and analyze the influencing factors. METHODS: Using the convenient sampling method, we selected the college students from a comprehensive university in Hunan Province in May 2021 and designed KAP questionnaire about SARS-CoV-2 vaccine inoculation for offline and online survey to analyze the current situation of college students' KAP of SARS-CoV-2 vaccine inoculation and the influenting factors. RESULTS: The total score of KAP of SARS-CoV-2 vaccine inoculation of Chinese college students was 43.72±5.60. The total score of knowledge was 16.28 ±3.09, and the score of each item was 3.26±0.62. The correct rate of the 5 questions in knowledge was 80.34%, 93.18%, 94.64%, 99.60% and 39.18%, respectively. The total score of attitude was 13.56±2.39, and the score of each item was 3.39±0.60. The total score of behavior was 13.88±2.51, and the score of each item was 3.47±0.63. The total scores of better health status, girls, and medical majors were relatively higher; those of medical majors, older students, and girls had higher scores on vaccination knowledge; those with better health and younger age had higher scores on attitude; those of better health status and girls had higher behavior scores (all P<0.05). CONCLUSIONS: College students' KAP about SARS-CoV-2 vaccine inoculation is generally high, but the knowledge level is relatively low. We should strengthen the propaganda and education for SARS-CoV-2 vaccine inoculation related knowledge, and strengthen the SARS-CoV-2 vaccine inoculation attitude and behavior of college students. Special attention should be paid to the education of vaccination knowledge for non-medical majors, younger, and male students, the guidance of vaccination attitude for those with poor health and older age, and encouragement of vaccination behavior for those with poor health and boys.

Transcriptome comparative analysis of ovarian follicles reveals the key genes and signaling pathways implicated in hen egg production.

BACKGROUND: Ovarian follicle development plays an important role in determination of poultry egg production. The follicles at the various developmental stages possess their own distinct molecular genetic characteristics and have different biological roles in chicken ovary development and function. In the each stage, several genes of follicle-specific expression and biological pathways are involved in the vary-sized follicular development and physiological events. Identification of the pivotal genes and signaling pathways that control the follicular development is helpful for understanding their exact regulatory functions and molecular mechanisms underlying egg-laying traits of laying hens. RESULTS: The comparative mRNA transcriptomic analysis of ovarian follicles at three key developmental stages including slow growing white follicles (GWF), small yellow follicles (SYF) of recruitment into the hierarchy, and differentiated large yellow follicles (LYF), was accomplished in the layers with lower and higher egg production. Totally, 137, 447, and 229 of up-regulated differentially expressed genes (DEGs), and 99, 97, and 157 of down-regulated DEGs in the GWF, SYF and LYF follicles, including VIPR1, VIPR2, ADRB2, and HSD17B1 were identified, respectively. Moreover, NDUFAB1 and GABRA1 genes, two most promising candidates potentially associated with egg-laying performance were screened out from the 13 co-expressed DEGs in the GWF, SYF and LYF samples. We further investigated the biological effects of NDUFAB1 and GABRA1 on ovarian follicular development and found that NDUFAB1 promotes follicle development by stimulating granulosa cell (GC) proliferation and decreasing cell apoptosis, increases the expression of CCND1 and BCL-2 but attenuates the expression of caspase-3, and facilitates steroidogenesis by enhancing the expression of STAR and CYP11A1. In contrast, GABRA1 inhibits GC proliferation and stimulates cell apoptosis, decreases the expression of CCND1, BCL-2, STAR, and CYP11A1 but elevates the expression of caspase-3. Furthermore, the three crucial signaling pathways such as PPAR signaling pathway, cAMP signaling pathway and neuroactive ligand-receptor interaction were significantly enriched, which may play essential roles in ovarian follicle growth, differentiation, follicle selection, and maturation. CONCLUSIONS: The current study provided new molecular data for insight into the regulatory mechanism underlying ovarian follicle development associated with egg production in chicken.

Decoupled Redox Catalytic Hydrogen Production with a Robust Electrolyte-Borne Electron and Proton Carrier.

Electrolytic water splitting is an effective approach for H2 mass production. A conventional water electrolyzer concurrently generates H2 and O2 in neighboring electrode compartments separated by a membrane, which brings about compromised purity, energy efficiency, and system durability. On the basis of distinct redox electrochemistry, here, we report a system that enables the decoupling of both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) from the electrodes to two spatially separated catalyst bed reactors in alkaline solutions. Through a pair of close-loop electrochemical-chemical cycles, the system operates upon 7,8-dihydroxy-2-phenazinesulfonic acid (DHPS) and ferricyanide-mediated HER and OER, respectively, on Pt/Ni(OH)2 and NiFe(OH)2 catalysts. Near unity faradaic efficiency and sustained production of hydrogen has been demonstrated at a current density up to 100 mA/cm2. The superior reaction kinetics, particularly the HER reaction mechanism of DHPS as a robust electrolyte-borne electron and proton carriers, were scrutinized both computationally and experimentally. We anticipate the system demonstrated here would provide an intriguing alternative to the conventional water electrolytic hydrogen production.

Discovery of a Novel Respiratory Syncytial Virus Replication Inhibitor.

A high-throughput screen of a Roche internal chemical library based on inhibition of the respiratory syncytial virus (RSV)-induced cytopathic effect (CPE) on HEp-2 cells was performed to identify RSV inhibitors. Over 2,000 hits were identified and confirmed to be efficacious against RSV infection in vitro Here, we report the discovery of a triazole-oxadiazole derivative, designated triazole-1, as an RSV replication inhibitor, and we characterize its mechanism of action. Triazole-1 inhibited the replication of both RSV A and B subtypes with 50% inhibitory concentration (IC50) values of approximately 1 µM, but it was not effective against other viruses, including influenza virus A, human enterovirus 71 (EV71), and vaccinia virus. Triazole-1 was shown to inhibit RSV replication when added at up to 8 h after viral entry, suggesting that it inhibits RSV after viral entry. In a minigenome reporter assay in which RSV transcription regulatory sequences flanking a luciferase gene were cotransfected with RSV N/P/L/M2-1 genes into HEp-2 cells, triazole-1 demonstrated specific and dose-dependent RSV transcription inhibitory effects. Consistent with these findings, deep sequencing of the genomes of triazole-1-resistant mutants revealed a single point mutation (A to G) at nucleotide 13546 of the RSV genome, leading to a T-to-A change at amino acid position 1684 of the L protein, which is the RSV RNA polymerase for both viral transcription and replication. The effect of triazole-1 on minigenome transcription, which was mediated by the L protein containing the T1684A mutation, was significantly reduced, suggesting that the T1684A mutation alone conferred viral resistance to triazole-1.

GhGASA10-1 promotes the cell elongation in fiber development through the phytohormones IAA-induced.

BACKGROUND: Cotton is an important cash crop. The fiber length has always been a hot spot, but multi-factor control of fiber quality makes it complex to understand its genetic basis. Previous reports suggested that OsGASR9 promotes germination, width, and thickness by GAs in rice, while the overexpression of AtGASA10 leads to reduced silique length, which is likely to reduce cell wall expansion. Therefore, this study aimed to explore the function of GhGASA10 in cotton fibers development. RESULTS: To explore the molecular mechanisms underlying fiber elongation regulation concerning GhGASA10-1, we revealed an evolutionary basis, gene structure, and expression. Our results emphasized the conservative nature of GASA family with its origin in lower fern plants S. moellendorffii. GhGASA10-1 was localized in the cell membrane, which may synthesize and transport secreted proteins to the cell wall. Besides, GhGASA10-1 promoted seedling germination and root extension in transgenic Arabidopsis, indicating that GhGASA10-1 promotes cell elongation. Interestingly, GhGASA10-1 was upregulated by IAA at fiber elongation stages. CONCLUSION: We propose that GhGASA10-1 may promote fiber elongation by regulating the synthesis of cellulose induced by IAA, to lay the foundation for future research on the regulation networks of GASA10-1 in cotton fiber development.

Anxiety and depression-like behaviours are more frequent in aged male mice conceived by ART compared with natural conception.

The number of children born after assisted reproductive technology (ART) is accumulating rapidly, and the health problems of the children are extensively concerned. This study aims to evaluate whether ART procedures alter behaviours in male offspring. Mouse models were utilized to establish three groups of offspring conceived by natural conception (NC), in vitro fertilization and embryo transfer (IVF-ET), and frozen-thawed embryo transfer (IVF-FET), respectively. A battery of behaviour experiments for evaluating anxiety and depression levels, including the open field test (OFT), elevated plus maze (EPM) test, light/dark transition test (L/DTT), tail suspension test (TST), forced swimming test (FST), and sucrose preference test (SPT) was carried out. Aged (18 months old), but not young (3 months old), male offspring in the IVF-ET and IVF-FET groups, compared with those in the NC group, exhibited increased anxiety and depression-like behaviours. The protein expression levels of three neurotrophins in PFC or hippocampus in aged male offspring from the IVF-ET and IVF-FET groups reduced at different extent, in comparison to NC group. RNA sequencing (RNA-Seq) was performed in the hippocampus of 18 months old offspring to further explore the gene expression profile changes in the three groups. KEGG analyses revealed the coexisted pathways, such as PI3K-Akt signalling pathway, which potentially reflected the similarity and divergence in anxiety and depression between the offspring conceived by IVF-ET and IVF-FET. Our research suggested the adverse effects of advanced age on the psychological health of children born after ART should be highlighted in the future.

Single copper sites dispersed on defective TiO2-x as a synergistic oxygen reduction reaction catalyst.

Catalysts containing isolated single atoms have attracted much interest due to their good catalytic behavior, bridging the gap between homogeneous and heterogeneous catalysts. Here, we report an efficient oxygen reduction reaction (ORR) catalyst that consists of atomically dispersed single copper sites confined by defective mixed-phased TiO2-x. This synergistic catalyst was produced by introducing Cu2+ to a metal organic framework (MOF) using the Mannich reaction, occurring between the carbonyl group in Cu(acac)2 and the amino group on the skeleton of the MOF. The embedding of single copper atoms was confirmed by atomic-resolution high-angle annular dark-field scanning transmission electron microscopy and x-ray absorption fine structure spectroscopy. Electronic structure modulation of the single copper sites coupling with oxygen vacancies was further established by electron paramagnetic resonance spectroscopy and first-principles calculations. Significantly enhanced ORR activity and stability were achieved on this special Cu single site. The promising application of this novel electrocatalyst was demonstrated in a prototype Zn-air battery. This strategy of the stabilization of single-atom active sites by optimization of the atomic and electronic structure on a mixed matrix support sheds light on the development of highly efficient electrocatalysts.

Theoretical Exploring of a Molecular Mechanism for Melanin Inhibitory Activity of Calycosin in Zebrafish.

Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin in the human body. Overproduction of melanin can lead to a variety of skin disorders. Calycosin is an isoflavone from Astragali Radix, which is a traditional Chinese medicine that exhibits several pharmacological activities including skin whitening. In our study, the inhibitory effect of calycosin on melanin production is confirmed in a zebrafish in vivo model by comparing with hydroquinone, kojic acid, and arbutin, known as tyrosinase inhibitors. Moreover, the inhibitory kinetics of calycosin on tyrosinase and their binding mechanisms are determined using molecular docking techniques, molecular dynamic simulations, and free energy analysis. The results indicate that calycosin has an obvious inhibitory effect on zebrafish pigmentation at the concentration of 7.5 µM, 15 µM, and 30 µM. The IC50 of calycosin is 30.35 µM, which is lower than hydroquinone (37.35 µM), kojic acid (6.51 × 103 µM), and arbutin (3.67 × 104 µM). Furthermore, all the results of molecular docking, molecular dynamics simulations, and free energy analysis suggest that calycosin can directly bind to the active site of tyrosinase with very good binding affinity. The study indicates that the combination of computer molecular modeling and zebrafish in vivo assay would be feasible in confirming the result of the in vitro test and illustrating the target-binding information.

Continuous Electrochemical Synthesis of Iso-Coumarin Derivatives from o-(1-Alkynyl) Benzoates under Metal- and Oxidant-Free.

A non-oxidant and metal-free strategy for synthesizing iso-coumarin by using a continuous electrochemical microreactor to initiate an oxidative cyclization reaction of o-(1-alkynyl) benzoate and radicals. This efficient and clean continuous electrosynthesis method not only avoids the complicated gas protection operation and production of by-products in the batch processes, but also help to overcome the difficulty that batch metal catalysis and electrocatalysis are difficult to scale up, and has the potential for pilot-scale experiment.

Expressing a cytosolic pyruvate dehydrogenase complex to increase free fatty acid production in Saccharomyces cerevisiae.

BACKGROUND: Saccharomyces cerevisiae is being exploited as a cell factory to produce fatty acids and their derivatives as biofuels. Previous studies found that both precursor supply and fatty acid metabolism deregulation are essential for enhanced fatty acid synthesis. A bacterial pyruvate dehydrogenase (PDH) complex expressed in the yeast cytosol was reported to enable production of cytosolic acetyl-CoA with lower energy cost and no toxic intermediate. RESULTS: Overexpression of the PDH complex significantly increased cell growth, ethanol consumption and reduced glycerol accumulation. Furthermore, to optimize the redox imbalance in production of fatty acids from glucose, two endogenous NAD+-dependent glycerol-3-phosphate dehydrogenases were deleted, and a heterologous NADP+-dependent glyceraldehyde-3-phosphate dehydrogenase was introduced. The best fatty acid producing strain PDH7 with engineering of precursor and co-factor metabolism could produce 840.5 mg/L free fatty acids (FFAs) in shake flask, which was 83.2% higher than the control strain YJZ08. Profile analysis of free fatty acid suggested the cytosolic PDH complex mainly resulted in the increases of unsaturated fatty acids (C16:1 and C18:1). CONCLUSIONS: We demonstrated that cytosolic PDH pathway enabled more efficient acetyl-CoA provision with the lower ATP cost, and improved FFA production. Together with engineering of the redox factor rebalance, the cytosolic PDH pathway could achieve high level of FFA production at similar levels of other best acetyl-CoA producing pathways.