High-Performance Multi-Level Inverter with Symmetry and Simplification.

This paper presents a high-performance, multilevel inverter with symmetry and simplification. This inverter is a single-phase, seven-level symmetric switched-capacitor inverter based on the concept of the double voltage clamping circuit connected to the half-bridge circuit. Above all, only a single DC power supply is used to achieve a single-phase inverter with seven levels and a voltage gain of three. In addition to analyzing the operating principle of the proposed switched-capacitor multilevel inverter in detail, the stability analysis and controller design are carried out by the state-space averaging method. The feasibility and effectiveness of the proposed structure are validated by some simulated results based on the PSIM simulation tool and by some experiments using FPGA as a control kernel, respectively. However, in this study, the switches were implemented by MOSFETs to meet a high switching frequency. These MOSFETs can be replaced by IGBTs in the motor drive applications so that the used switching frequency can be reduced.

Biosynthetic production of anticoagulant heparin polysaccharides through metabolic and sulfotransferases engineering strategies.

Heparin is an important anticoagulant drug, and microbial heparin biosynthesis is a potential alternative to animal-derived heparin production. However, effectively using heparin synthesis enzymes faces challenges, especially with microbial recombinant expression of active heparan sulfate N-deacetylase/N-sulfotransferase. Here, we introduce the monosaccharide N-trifluoroacetylglucosamine into Escherichia coli K5 to facilitate sulfation modification. The Protein Repair One-Stop Service-Focused Rational Iterative Site-specific Mutagenesis (PROSS-FRISM) platform is used to enhance sulfotransferase efficiency, resulting in the engineered NST-M8 enzyme with significantly improved stability (11.32-fold) and activity (2.53-fold) compared to the wild-type N-sulfotransferase. This approach can be applied to engineering various sulfotransferases. The multienzyme cascade reaction enables the production of active heparin from bioengineered heparosan, demonstrating anti-FXa (246.09 IU/mg) and anti-FIIa (48.62 IU/mg) activities. This study offers insights into overcoming challenges in heparin synthesis and modification, paving the way for the future development of animal-free heparins using a cellular system-based semisynthetic strategy.

Brain imaging of a gamified cognitive flexibility task in young and older adults.

The study aimed to develop and validate a gamified cognitive flexibility task through brain imaging, and to investigate behavioral and brain activation differences between young and older adults during task performance. Thirty-one young adults (aged 18-35) and 31 older adults (aged 60-80) were included in the present study. All participants underwent fMRI scans while completing the gamified cognitive flexibility task. Results showed that young adults outperformed older adults on the task. The left inferior frontal junction (IFJ), a key region of cognitive flexibility, was significantly activated during the task in both older and young adults. Comparatively, the percent signal change in the left IFJ was stronger in older adults than in young adults. Moreover, older adults demonstrated more precise representations during the task in the left IFJ. Additionally, the left inferior parietal lobule (IPL) and superior parietal lobule in older adults and the left middle frontal gyrus (MFG) and inferior frontal gyrus in young adults were also activated during the task. Psychophysiological interaction analyses showed significant functional connectivity between the left IFJ and the left IPL, as well as the right precuneus in older adults. In young adults, significant functional connectivity was found between the left IFJ and the left MFG, as well as the right angular. The current study provides preliminary evidence for the validity of the gamified cognitive flexibility task through brain imaging. The findings suggest that this task could serve as a reliable tool for assessing cognitive flexibility and for exploring age-related differences of cognitive flexibility in both brain and behavior.

Analysis of spinal muscular atrophy carrier screening results in 32,416 pregnant women and 7,231 prepregnant women.

Objectives: Spinal muscular atrophy (SMA) is an autosomal recessive disease that is one of the most common in childhood neuromuscular disorders. Our screenings are more meaningful programs in preventing birth defects, providing a significant resource for healthcare professionals, genetic counselors, and policymakers involved in designing strategies to prevent and manage SMA. Method: We screened 39,647 participants from 2020 to the present by quantitative real-time PCR, including 7,231 pre-pregnancy participants and 32,416 pregnancy participants, to detect the presence of SMN1 gene EX7 and EX8 deletion in the DNA samples provided by the subjects. To validate the accuracy of our findings, we also utilized the Multiplex Ligation-dependent Probe Amplification (MLPA) to confirm the reliability of screening results obtained by quantitative real-time PCR. Result: Among the 39,647 participants who were screened, 726 participants were the carriers of SMN1. The overall carrier rate was calculated to be 1.83% (95% confidence interval: 0.86-2.8%). After undergoing screening, a total of 592 pregnancy carriers were provided with genetic counseling and only 503 of their spouses (84.97, 95% confidence interval: 82.09-87.85%) voluntarily underwent SMA screening. Conclusion: This study provides crucial insights into the prevalence and distribution of SMA carriers among the female population. The identification of 726 asymptomatic carriers highlights the necessity of comprehensive screening programs to identify at-risk individuals and ensure appropriate interventions are in place to minimize the impact of SMA-related conditions.

Advancements in heparosan production through metabolic engineering and improved fermentation.

Heparin is one of the most widely used natural drugs, and has been the preferred anticoagulant and antithrombotic agent in the clinical setting for nearly a century. Heparin also shows increasing therapeutic potential for treating inflammation, cancer, and microbial and viral diseases, including COVID-19. With advancements in synthetic biology, heparin production through microbial engineering of heparosan offers a cost-effective and scalable alternative to traditional extraction from animal tissues. Heparosan serves as the starting carbon backbone for the chemoenzymatic synthesis of bioengineered heparin, possessing a chain length that is critically important for the production of heparin-based therapeutics with specific molecular weight (MW) distributions. Recent advancements in metabolic engineering of microbial cell factories have resulted in high-yield heparosan production. This review systematically analyzes the key modules involved in microbial heparosan biosynthesis and the latest metabolic engineering strategies for enhancing production, regulating MW, and optimizing the fermentation scale-up of heparosan. It also discusses future studies, remaining challenges, and prospects in the field.

[Disease spectrum and pathogenic genes of inherited metabolic disorder in Gansu Province of China]. / ç”˜è‚ƒåœ°åŒºé—ä¼ ä»£è°¢ç— ç–¾ç— è°±åŠè‡´ç— åŸºå› åˆ†æž.

OBJECTIVES: To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder (IMD) among neonates in Gansu Province of China. METHODS: A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021. A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination. RESULTS: A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates, and the overall prevalence rate of IMD was 0.63 (1/1 593), among which phenylketonuria showed the highest prevalence rate of 0.32 (1/3 083), followed by methylmalonic acidemia (0.11, 1/8 959) and tetrahydrobiopterin deficiency (0.06, 1/15 927). In this study, 166 variants were identified in the 28 pathogenic genes, with 13 novel variants found in 9 genes. According to American College of Medical Genetics and Genomics guidelines, 5 novel variants were classified as pathogenic variants, 7 were classified as likely pathogenic variants, and 1 was classified as the variant of uncertain significance. CONCLUSIONS: This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Disease spectrum and pathogenic genes of inherited metabolic disorder in Gansu Province of China / 中国当代儿科杂志

OBJECTIVES@#To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder (IMD) among neonates in Gansu Province of China.@*METHODS@#A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021. A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.@*RESULTS@#A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates, and the overall prevalence rate of IMD was 0.63 (1/1 593), among which phenylketonuria showed the highest prevalence rate of 0.32 (1/3 083), followed by methylmalonic acidemia (0.11, 1/8 959) and tetrahydrobiopterin deficiency (0.06, 1/15 927). In this study, 166 variants were identified in the 28 pathogenic genes, with 13 novel variants found in 9 genes. According to American College of Medical Genetics and Genomics guidelines, 5 novel variants were classified as pathogenic variants, 7 were classified as likely pathogenic variants, and 1 was classified as the variant of uncertain significance.@*CONCLUSIONS@#This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Cell-Based Assay Approaches for Glycosaminoglycan Synthase High-Throughput Screening: Development and Applications.

Glycosaminoglycan synthases have immense potential in applications involving synthesis of oligosaccharides, using enzymatic approaches and construction of cell factories that produce polysaccharides as critical metabolic components. However, the use of high-throughput activity assays to screen for the evolution of these enzymes can be challenging because there are no significant changes in fluorescence or absorbance associated with glycosidic bond formation. Here, using incorporation of azido-labeled N-acetylhexosamine analogs into bacterial capsule polysaccharides via bacterial metabolism and bioorthogonal chemistry, fluorophores were specifically introduced onto cell surfaces. Furthermore, correlations between detectable fluorescence signals and the polysaccharide-synthesizing capacity of individual bacteria were established. Among 10 candidate genes, 6 members of the chondroitin synthase family were quickly identified in a recombinant Bacillus subtilis host strain. Additionally, directed evolution of heparosan synthase was successfully performed using fluorescence-activated cell sorting of recombinant Escherichia coli O10:K5(L):H4, yielding several mutants with increased activity. Cell-based approaches that selectively detect the presence or absence of synthases within an individual colony of bacterial cells, as well as their level of activity, have broad potential in the exploration and engineering of glycosaminoglycan synthases. These approaches also support the creation of novel strategies for high-throughput screening of enzyme activity based on cell systems.

Novel ß1,4 N-acetylglucosaminyltransferase in de novo enzymatic synthesis of hyaluronic acid oligosaccharides.

The efficiency of de novo synthesis of hyaluronic acid (HA) using Pasteurella multocida hyaluronate synthase (PmHAS) is limited by its low catalytic activity during the initial reaction steps when monosaccharides are the acceptor substrates. In this study, we identified and characterized a ß-1,4-N-acetylglucosaminyl-transferase (EcGnT) derived from the O-antigen gene synthesis cluster of Escherichia coli O8:K48:H9. Recombinant ß1,4 EcGnT effectively catalyzed the production of HA disaccharides when the glucuronic acid monosaccharide derivative 4-nitrophenyl-ß-D-glucuronide (GlcA-pNP) was used as the acceptor. Compared with PmHAS, ß1,4 EcGnT exhibited superior N-acetylglucosamine transfer activity (~ 12-fold) with GlcA-pNP as the acceptor, making it a better option for the initial step of de novo HA oligosaccharide synthesis. We then developed a biocatalytic approach for size-controlled HA oligosaccharide synthesis using the disaccharide produced by ß1,4 EcGnT as a starting material, followed by stepwise PmHAS-catalyzed synthesis of longer oligosaccharides. Using this approach, we produced a series of HA chains of up to 10 sugar monomers. Overall, our study identifies a novel bacterial ß1,4 N-acetylglucosaminyltransferase and establishes a more efficient process for HA oligosaccharide synthesis that enables size-controlled production of HA oligosaccharides. KEY POINTS: • A novel ß-1,4-N-acetylglucosaminyl-transferase (EcGnT) from E. coli O8:K48:H9. • EcGnT is superior to PmHAS for enabling de novo HA oligosaccharide synthesis. • Size-controlled HA oligosaccharide synthesis relay using EcGnT and PmHAS.

Machine learning algorithms for improved prediction of in-hospital outcomes after moderate-to-severe traumatic brain injury: a Chinese retrospective cohort study.

AIM: Controversy remains high over the superiority of advanced machine learning (ML) algorithms to conventional logistic regression (LR) in the prediction of prognosis after traumatic brain injury (TBI). This study aimed to compare the performance of ML and LR models in predicting in-hospital prognosis after TBI. METHOD: In a single-center retrospective cohort of adult patients hospitalized for moderate-to-severe TBI (Glasgow coma score ≤12) in our hospital from 2011 to 2020, LR and three ML algorithms (XGboost, lightGBM, and FT-transformer) were run to build prediction models for in-hospital mortality and the Glasgow Outcome Scale (GOS) functional outcomes using either all 19 clinical and laboratory features or the 10 non-laboratory ones collected at admission to the neurological intensive care unit. The Shapley (SHAP) value was used for model interpretation. RESULT: In total, 482 patients had an in-hospital mortality rate of 11.0%. A total of 23.0% of the patients had good functional scores (GOS ≥ 4) at discharge. All ML models performed better than the LR model in predicting in-hospital prognosis after TBI, among which the lightGBM model showed the best performance: When predicting mortality, the lightGBM model yielded an area under the curve (AUC) of 0.953 using all 19 features (the LR model: 0.813) and an AUC of 0.935 using 10 non-laboratory features (the LR model: 0.803); when predicting GOS functional outcomes, it yielded an AUC of 0.913 using all 19 features (the LR model: 0.832) and an AUC of 0.889 using non-laboratory data (the LR model: 0.818). The SHAP method identified key contributors to explain the lightGBM models. Finally, the integration of the lightGBM models with different prediction purposes was found to provide refined prognostic information, particularly for patients who survived moderate-to-severe TBI. CONCLUSION: The study supported the superiority of ML to LR in predicting prognosis after moderate-to-severe TBI and highlighted its potential use for clinical application.

Protection of H2S against Hypoxia/Reoxygenation Injury in Rat Hippocampal Neurons through Inhibiting Phosphorylation of ROCK2 at Thr436 and Ser575.

BACKGROUND: H2S (hydrogen sulfide) protects cerebral vasodilatation and endothelial cells against oxygen-glucose deprivation/reoxygenation injury via the inhibition of the RhoA-ROCK pathway and ROCK2 expression. However, the inhibitory mechanism of H2S on ROCK2 expression is still unclear. The study aimed to investigate the target and mechanism of H2S in inhibition of ROCK2. METHODS: His-ROCK2wild protein was constructed, expressed, and was used for phosphorylation assay in vitro. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the potential phosphorylation sites of ROCK2. Recombinant ROCK2wild-pEGFP-N1, ROCK2T436A-pEGFP-N1, and ROCK2S575F-pEGFP-N1 plasmids were constructed and transfected into rat hippocampal neurons (RHNs). ROCK2 expression, cell viability, the release of lactate dehydrogenase (LDH), nerve-specific enolase (NSE), and Ca2+ were detected to evaluate the neuroprotective mechanism of H2S. RESULTS: Phosphorylation at Thr436 and Ser575 of ROCK2 was observed by mass spectrometry when Polo-like kinase 1 (PLK1) and protein kinase A (PKA) were added in vitro, and NaHS significantly inhibited phosphorylation at Thr436 and Ser575. Additionally, NaHS significantly inhibited the expression of ROCK2 and recombinant proteins GFP-ROCK2, GFP-ROCK2T436A, and GFP-ROCK2S575F in transfected RHNs. Compared with empty plasmid, GFP-ROCK2T436A, and GFP-ROCK2S575F groups, NaHS significantly inhibited the release of LDH, NSE, and Ca2+ and promoted ROCK2 activity in the GFP-ROCK2wild group. Thr436 and Ser575 may be dominant sites that mediate NaHS inhibition of ROCK2 protein activity in RHNs. Compared with the empty plasmid, GFP-ROCK2T436A, and the GFP-ROCK2S575F group, NaHS had more significant inhibitory effects on hypoxia/reoxygenation (H/R) injury-induced cell viability reduction and increased LDH and NSE release in the GFP-ROCK2wild group. CONCLUSION: Exogenous H2S protected the RHNs against H/R injury via Thr436 and Ser575 of ROCK2. These findings suggested that Thr436 and Ser575 may be the dominant sites that mediated the effect of NaHS on protecting RHNs against H/R injury.

Imaging of Escherichia coli K5 and glycosaminoglycan precursors via targeted metabolic labeling of capsular polysaccharides in bacteria.

The introduction of unnatural chemical moieties into glycosaminoglycans (GAGs) has enormous potential to facilitate studies of the mechanism and application of these critical, widespread molecules. Unnatural N-acetylhexosamine analogs were metabolically incorporated into the capsule polysaccharides of Escherichia coli and Bacillus subtilis via bacterial metabolism. Targeted metabolic labeled hyaluronan and the precursors of heparin and chondroitin sulfate were obtained. The azido-labeled polysaccharides (purified or in capsules) were reacted with dyes, via bioorthogonal chemistry, to enable detection and imaging. Site-specific introduction of fluorophores directly onto cell surfaces affords another choice for observing and quantifying bacteria in vivo and in vitro. Furthermore, azido-polysaccharides retain similar biological properties to their natural analogs, and reliable and predictable introduction of functionalities, such as fluorophores, onto azido-N-hexosamines in the disaccharide repeat units provides chemical tools for imaging and metabolic analysis of GAGs in vivo and in vitro.

Total flavones of Rhododendron induce the transformation of A1/A2 astrocytes via promoting the release of CBS-produced H2S.

BACKGROUND: We previously found that total flavones of Rhododendron (TFR) protected against the cerebral ischemia/reperfusion (I/R) injury. But the detailed mechanism is not clear. Recent research revealed that reactive astrocytes were divided into A1 and A2 phenotypes for their morphological and functional remodeling and neurotoxic- vs-neuroprotective effect on the injury of the central nervous system (CNS). PURPOSE: The present study was undertaken to explore the role and mechanism of TFR on the phenotypic change of astrocytes following cerebral I/R in vivo and oxygen glucose deprivation/re-oxygenation (OGD/R) in vitro. STUDY DESIGN AND METHODS: We tested the expression of astrocytes marker glial fibrillary acidic protein (GFAP), A1 astrocytes marker C3 protein and A2 astrocytes marker S100a10, as well as the BrdU/GFAP-positive cells, GFAP/S100a10-positive cells and GFAP/C3-positive cells in mice hippocampal tissues to evaluate the phenotypic change of astrocytes. Besides, we assessed the change of astrocyte phenotypes following OGD/R in vitro. RESULTS: We found that mice cerebral I/R promoted the astrocytes proliferation of both A1 and A2 phenotypes in hippocampal tissues. While treatment with TFR could promote the proliferation of A2 astrocytes but inhibit the A1 astrocytes proliferation in mice hippocampal tissues, suggesting that TFR could accelerate the astrocytes transformation into A2 subtype following cerebral I/R. Whereas, in OGD/R model of astrocytes, we found that TFR inhibited the proliferation of both A1 and A2 astrocytes. Besides, we found that TFR could up-regulate the release of cystathionine ß-synthase (CBS)-produced hydrogen sulfide (H2S) and inhibit RhoA/Rho kinase pathway, and revealed that the inhibitory effect of TFR on astrocytes proliferation could be blocked by aminooxyacetic acid (AOAA), an CBS inhibitor. Furthermore, TFR could ameliorate the mice cerebral I/R injury and the OGD/R-induced astrocytic damage. CONCLUSION: These findings suggested that TFR could affect the transformation of astrocytes subtypes following cerebral I/R, which may be related to up-regulation of CBS-produced H2S and subsequent inhibition of RhoA/ROCK pathway.

Enhanced Stability and Function of Probiotic Streptococcus thermophilus with Self-Encapsulation by Increasing the Biosynthesis of Hyaluronan.

The harsh conditions of the gastrointestinal tract limit the potential health benefits of oral probiotics. It is promising that oral bioavailability is improved by strengthening the self-protection of probiotics. Here, we report the encapsulation of a probiotic strain by endogenous production of hyaluronan to enhance the effects of oral administration of the strain. The traditional probiotic Streptococcus thermophilus was engineered to produce hyaluronan shells by using traceless genetic modifications and clustered regularly interspaced short palindromic repeat interference. After oral delivery to mice in the form of fermented milk, hyaluronan-coated S. thermophilus (204.45 mg/L hyaluronan in the milk) exhibited greater survival and longer colonization time in the gut than the wild-type strain. In particular, the engineered probiotic strain could also produce hyaluronan after intestinal colonization. Importantly, S. thermophilus self-encapsulated with hyaluronan increased the number of goblet cells, mucus production, and abundance of the microorganisms related to the biosynthesis of short-chain fatty acids, resulting in the enhancement of the intestinal barrier. The coating formed by endogenous hyaluronan provides an ideal reference for the effective oral administration of probiotics.

[Ozone Sensitivity Analysis and Control Strategy in Shijiazhuang City in July 2019].

The pollution characteristics of surface ozone and its response to meteorological factors were studied based on monitoring in July 2019 in Shijiazhuang City, China. Furthermore, the WRF-CMAQ model coupled with O3 isopleths (EKMA curves) were applied to explore the non-linear response relationship of O3 to precursors VOCs and NOx, aiming to identify a suitable precursor control strategy. The results showed that the days with the maximum daily 8-hour average ozone concentration (MDA8 O3) exceeded the standard by 70.9%. The nonattainment days were usually accompanied by higher temperature, lower relative humidity, and low winds, and the south and southeast winds occurred frequently. The O3 formation was in the strong VOC-limited regime in the urban area of Shijiazhuang, whereas it was in the NOx and VOCs transition regime in suburban areas. As for the urban area, under the condition of single NOx emission reduction, O3 pollution improved when continuous NOx emission reduction was higher than 50% during the nonattainment days. By contrast, during the non-polluted days, O3 concentrations would not rebound when the reduction ratio of NOx and VOCs was higher than 1. In conclusion, VOCs reduction should be the priority for emission reduction plans in urban areas, whereas all different NOx and VOCs ratios led to a decline in O3 concentration in the suburban areas, and a VOCs:NOx of 1:2 was recommended.

The Mutation Analysis of the AMT Gene in a Chinese Family With Nonketotic Hyperglycinemia.

Background: Nonketotic hyperglycinemia is a metabolic disease with autosomal recessive inheritance due to the glycine cleavage system (GCS) defect leading to the accumulation of glycine that causes severe and fatal neurological symptoms in the neonatal period. Methods: Genomic DNA was extracted from the peripheral blood of the female proband and her family members. The AMT variation was detected in the patient by whole-exome sequencing (WES), and the variant was validated by Sanger sequencing. Results: The WES showed that there were novel compound heterozygous frameshift variations c.977delA (p.Glu326Glyfs*12) and c.982_983insG (p.Ala328Glyfs*22) in exon eight of the AMT gene (NM_000481.4) in the proband. Genetic analysis showed that the former was inherited from the mother, and the latter was inherited from the father. Conclusion: We report the novel compound heterozygous variation of the AMT gene in a Chinese girl with NKH by WES, which has never been reported previously. Our case expanded the AMT gene mutation spectrum, further strengthened the understanding of NKH, and deepened the genetic and clinical heterogeneity of the disease. However, the study of treatment and prognosis is still our future challenge and focus.

Strontium Peroxide-Loaded Composite Scaffolds Capable of Generating Oxygen and Modulating Behaviors of Osteoblasts and Osteoclasts.

The reconstruction of bone defects remains challenging. The utilization of bone autografts, although quite promising, is limited by several drawbacks, especially substantial donor site complications. Recently, strontium (Sr), a bioactive trace element with excellent osteoinductive, osteoconductive, and pro-angiogenic properties, has emerged as a potential therapeutic agent for bone repair. Herein, a strontium peroxide (SrO2)-loaded poly(lactic-co-glycolic acid) (PLGA)-gelatin scaffold system was developed as an implantable bone substitute. Gelatin sponges serve as porous osteoconductive scaffolds, while PLGA not only reinforces the mechanical strength of the gelatin but also controls the rate of water infiltration. The encapsulated SrO2 can release Sr2+ in a sustained manner upon exposure to water, thus effectively stimulating the proliferation of osteoblasts and suppressing the formation of osteoclasts. Moreover, SrO2 can generate hydrogen peroxide and subsequent oxygen molecules to increase local oxygen tension, an essential niche factor for osteogenesis. Collectively, the developed SrO2-loaded composite scaffold shows promise as a multifunctional bioactive bone graft for bone tissue engineering.

Identification and Characterization of Two Bibenzyl Glycosyltransferases from the Liverwort Marchantia polymorpha.

Liverworts are rich in bibenzyls and related O-glycosides, which show antioxidant activity. However, glycosyltransferases that catalyze the glycosylation of bibenzyls have not yet been characterized. Here, we identified two bibenzyl UDP-glucosyltransferases named MpUGT737B1 and MpUGT741A1 from the model liverwort Marchantia polymorpha. The in vitro enzymatic assay revealed that MpUGT741A1 specifically accepted the bibenzyl lunularin as substrate. MpUGT737B1 could accept bibenzyls, dihydrochalcone and phenylpropanoids as substrates, and could convert phloretin to phloretin-4-O-glucoside and phloridzin, which showed inhibitory activity against tyrosinase and antioxidant activity. The results of sugar donor selectivity showed that MpUGT737B1 and MpUGT741A1 could only accept UDP-glucose as a substrate. The expression levels of these MpUGTs were considerably increased after UV irradiation, which generally caused oxidative damage. This result indicates that MpUGT737B1 and MpUGT741A1 may play a role in plant stress adaption. Subcellular localization indicates that MpUGT737B1 and MpUGT741A1 were expressed in the cytoplasm and nucleus. These enzymes should provide candidate genes for the synthesis of bioactive bibenzyl O-glucosides and the improvement of plant antioxidant capacity.

Olfactory regulation by dopamine and DRD2 receptor in the nose.

SignificanceDespite the identification of neural circuits and circulating hormones in olfactory regulation, the peripheral targets for olfactory modulation remain relatively unexplored. Here we show that dopamine D2 receptor (DRD2) is expressed in the cilia and somata of mature olfactory sensory neurons (OSNs), while nasal dopamine (DA) is mainly released from the sympathetic nerve terminals, which innervate the mouse olfactory mucosa (OM). We further demonstrate that DA-DRD2 signaling in the nose plays important roles in regulating olfactory function using genetic and pharmacological approaches. Moreover, the local DA synthesis in mouse OM is reduced during hunger, which contributes to starvation-induced olfactory enhancement. Altogether, we demonstrate that nasal DA and DRD2 receptor can serve as the potential peripheral targets for olfactory modulation.