CLCF1 signaling restrains thermogenesis and disrupts metabolic homeostasis by inhibiting mitochondrial biogenesis in brown adipocytes.

Great progress has been made in identifying positive regulators that activate adipocyte thermogenesis, but negative regulatory signaling of thermogenesis remains poorly understood. Here, we found that cardiotrophin-like cytokine factor 1 (CLCF1) signaling led to loss of brown fat identity, which impaired thermogenic capacity. CLCF1 levels decreased during thermogenic stimulation but were considerably increased in obesity. Adipocyte-specific CLCF1 transgenic (CLCF1-ATG) mice showed impaired energy expenditure and severe cold intolerance. Elevated CLCF1 triggered whitening of brown adipose tissue by suppressing mitochondrial biogenesis. Mechanistically, CLCF1 bound and activated ciliary neurotrophic factor receptor (CNTFR) and augmented signal transducer and activator of transcription 3 (STAT3) signaling. STAT3 transcriptionally inhibited both peroxisome proliferator-activated receptor-γ coactivator (PGC) 1α and 1ß, which thereafter restrained mitochondrial biogenesis in adipocytes. Inhibition of CNTFR or STAT3 could diminish the inhibitory effects of CLCF1 on mitochondrial biogenesis and thermogenesis. As a result, CLCF1-TG mice were predisposed to develop metabolic dysfunction even without external metabolic stress. Our findings revealed a brake signal on nonshivering thermogenesis and suggested that targeting this pathway could be used to restore brown fat activity and systemic metabolic homeostasis in obesity.

Targeting Follistatin like 1 ameliorates liver fibrosis induced by carbon tetrachloride through TGF-ß1-miR29a in mice.

BACKGROUND: Hepatic fibrosis is a pathological response of the liver to a variety of chronic stimuli. Hepatic stellate cells (HSCs) are the major source of myofibroblasts in the liver. Follistatin like 1 (Fstl1) is a secreted glycoprotein induced by transforming growth factor-ß1 (TGF-ß1). However, the precise functions and regulation mechanisms of Fstl1 in liver fibrogenesis remains unclear. METHODS: Hepatic stellate cell (HSC) line LX-2 stimulated by TGF-ß1, primary culture of mouse HSCs and a model of liver fibrosis induced by CCl4 in mice was used to assess the effect of Fstl1 in vitro and in vivo. RESULTS: Here, we found that Fstl1 was significantly up regulated in human and mouse fibrotic livers, as well as activated HSCs. Haplodeficiency of Fstl1 or blockage of Fstl1 with a neutralizing antibody 22B6 attenuated CCl4-induced liver fibrosis in vivo. Fstl1 modulates TGF-ß1 classic Samd2 and non-classic JNK signaling pathways. Knockdown of Fstl1 in HSCs significantly ameliorated cell activation, cell migration, chemokines C-C Motif Chemokine Ligand 2 (CCL2) and C-X-C Motif Chemokine Ligand 8 (CXCL8) secretion and extracellular matrix (ECM) production, and also modulated microRNA-29a (miR29a) expression. Furthermore, we identified that Fstl1 was a target gene of miR29a. And TGF-ß1 induction of Fstl1 expression was partially through down regulation of miR29a in HSCs. CONCLUSIONS: Our data suggests TGF-ß1-miR29a-Fstl1 regulatory circuit plays a key role in regulation the HSC activation and ECM production, and targeting Fstl1 may be a strategy for the treatment of liver fibrosis. Video Abstract.

Comparative evaluation of epidural bupivacaine alone and bupivacaine combined with magnesium sulfate in providing postoperative analgesia: a meta-analysis of randomized controlled trials.

BACKGROUND: The comparative efficacy of epidural bupivacaine alone and bupivacaine combined with magnesium sulfate in providing postoperative analgesia remains controversial. METHODS: We searched Mediline (OvidSP), EMBASE (OvidSP) and Cochrane Central Register of Controlled Trials (CENTRAL) to identify trials that compared epidural bupivacaine and magnesium sulfate combination (intervention) with bupivacaine alone (control). Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework was used to assess the quality of evidence. RESULTS: Eleven studies fulfilled our inclusion criteria after screening. We found that epidural bupivacaine combined with magnesium sulfate could prolong the time for first rescue analgesics (SMD 4.96; 95% CI [2.75, 7.17], P < 0.00001, I2 = 98%), reduce the number of patients who need rescue analgesics (RR 0.38; 95% CI [0.20, 0.74], P = 0.004, I2 = 75%) and requirement for rescue analgesics (SMD -2.65; 95% CI [- 4.23, - 1.06], P = 0.001, I2 = 96%). CONCLUSIONS: Magnesium suifate as an adjuvant of epidural bupivacaine improved postoperative analgesia. However, we rated the quality of evidence to be very low because of high heterogeneity, imprecise of results and small sample sizes. Furthermore, further large high-quality trials are still needed to confirm the effects of magnesium sulfate on postoperative analgesia.

Effects of dexamethasone on post-operative cognitive dysfunction and delirium in adults following general anaesthesia: a meta-analysis of randomised controlled trials.

BACKGROUND: Several studies have investigated the effects of dexamethasone on post-operative cognitive dysfunction (POCD) or post-operative delirium (POD); however, their conclusions have been inconsistent. Thus, we conducted a meta-analysis to determine the effects of dexamethasone on POCD and POD in adults following general anaesthesia. METHODS: The Cochrane Central Register of Controlled Trials (2018, Issue 11 of 12) in the Cochrane Library (searched 17 November 2018), MEDLINE OvidSP (1946 to 16 November 2018) and Embase OvidSP (1974 to 16 November 2018) were searched for randomised controlled trials that evaluated the incidence of POCD and POD following dexamethasone administration in adults (age ≥ 18 years) under general anaesthesia. We used the Grading of Recommendations, Assessment, Development and Evaluations framework to assess the quality of the evidence. RESULTS: Five studies were included (three studies with 855 participants in the dexamethasone group and 538 participants in the placebo group for the incidence of POCD, and two studies with 410 participants in the dexamethasone group and 420 participants in the placebo group for the incidence of POD). There was no significant difference between the dexamethasone group and the placebo group in terms of the incidence of POCD 30 days after surgery (RR [relative risk] 1.00; 95% CI [confidence interval: 0.51, 1.96], P = 1.00, I2 = 77%) or the incidence of POD (RR 0.96; 95% CI [0.68, 1.35], P = 0.80, I2 = 0%). However, both analyses had some limitations because of limited evidence and clinical heterogeneity, and we considered the quality of the evidence for the post-operative incidence of POCD and POD to be very low. CONCLUSIONS: This meta-analysis revealed that prophylactic dexamethasone did not reduce the incidence of POCD and POD. Trials of alternative preventive strategies for POCD and POD, as well as a better understanding of the pathophysiology of those complex syndromes, are still needed to make progress in this field. TRIAL REGISTRATIONR: This study is registered with PROSPERO, 23 October 2018, number CRD42018114552. Available from  https://www.crd.york.ac.uk/PROSPERO/#recordDetails .

MicroRNA29a Reverts the Activated Hepatic Stellate Cells in the Regression of Hepatic Fibrosis through Regulation of ATPase H⁺ Transporting V1 Subunit C1.

Activated hepatic stellate cells (aHSCs) play a key role in liver fibrosis. During the regression of fibrosis, aHSCs are transformed into inactivated cells (iHSCs), which are quiescent lipid-containing cells and express higher levels of lipid-related genes, such as peroxisome proliferators-activated receptors gamma (PPARγ). Here, we investigated the role of MicroRNA29a (Mir29a) in the resolution of liver fibrosis. Mir29a and lipid-related genes were up-regulated after the recovery of CCl4-induced liver fibrosis in mice. PPARγ agonist rosiglitazone (RSG) promoted de-differentiation of aHSCs to iHSCs and up-regulated MIR29a expression in a human HSC cell line LX-2. MIR29a mimics in vitro promoted the expression of lipid-related genes, while decreased the expression of fibrosis-related genes. MIR29a inhibitor showed the reverse effects. ATPase H⁺ transporting V1 subunit C1 (Atp6v1c1) was increased in liver fibrosis, while down-regulated after the recovery in mice, and negatively regulated by MIR29a in LX-2 cells. Knockdown of ATP6V1C1 by siRNA decreased alpha-smooth muscle actin (α-SMA) and increased lipid-related genes expression. Simultaneous addition of MIR29a mimics and ATP6V1C1 siRNA further increased RSG promoted expression of lipid-related proteins in vitro. Collectively, MIR29a plays an important role during the trans-differentiation of aHSCs in the resolution of liver fibrosis, in part, through regulation of ATP6V1C1.

Lithiophilic Faceted Cu(100) Surfaces: High Utilization of Host Surface and Cavities for Lithium Metal Anodes.

Lithium metal anodes suffer from poor cycling stability and potential safety hazards. To alleviate these problems, Li thin-film anodes prepared on current collectors (CCs) and Li-free types of anodes that involve direct Li plating on CCs have received increasing attention. In this study, the atomic-scale design of Cu-CC surface lithiophilicity based on surface lattice matching of the bcc Li(110) and fcc Cu(100) faces as well as electrochemical achievement of Cu(100)-preferred surfaces for smooth Li deposition with a low nucleation barrier is reported. Additionally, a purposely designed solid-electrolyte interphase is created for Li anodes prepared on CCs. Not only is a smooth planar Li thin film prepared, but a uniform Li plating/stripping on the skeleton of 3D CCs is achieved as well by high utilization of the surface and cavities of the 3D CCs. This work demonstrates surface electrochemistry approaches to construct stable Li metal-electrolyte interphases towards practical applications of Li anodes prepared on CCs.

Simulated Microgravity Promotes Angiogenesis through RhoA-Dependent Rearrangement of the Actin Cytoskeleton.

BACKGROUND/AIMS: Microgravity leads to hydrodynamic alterations in the cardiovascular system and is associated with increased angiogenesis, an important aspect of endothelial cell behavior to initiate new vessel growth. Given the critical role of Rho GTPase-dependent cytoskeleton rearrangement in cell migration, small GTPase RhoA might play a potential role in microgravity-induced angiogenesis. METHODS: We examined the organization of actin filaments by FITC-conjugated phalloidin staining, as well as the expression and activity of RhoA by quantitative PCR and Western blot, in human umbilical vein endothelial cells (HUVECs) under normal gravity and simulated microgravity. Effect of simulated microgravity on the wound closure and tube formation in HUVECs, and their dependence on RhoA, were also analyzed by cell migration and tube formation assays. RESULTS: We show that in HUVECs actin filaments are disorganized and RhoA activity is reduced by simulated microgravity. Blocking RhoA activity either by C3 transferase Rho inhibitor or siRNA knockdown mimicked the effect of simulated microgravity on inducing actin filament disassembly, followed by enhanced wound closure and tube formation in HUVECs, which closely resembled effects seen on microgravity-treated cells. In contrast, overexpressing RhoA in microgravity-treated HUVECs restored the actin filaments, and decreased wound closure and tube formation abilities. CONCLUSION: These results suggest that RhoA inactivation is involved in the actin rearrangement-associated angiogenic responses in HUVECs during simulated microgravity.

Identification of antrodin B from Antrodia camphorata as a new anti-hepatofibrotic compound using a rapid cell screening method and biological evaluation.

AIM: Liver fibrosis is the excessive accumulation of extracellular matrix (ECM) resulting from chronic liver diseases. Efficient and well-tolerated drugs for its treatment are urgently needed. This study aims to identify the active ingredients of Antrodia camphorata by a bioassay-guided fractionation approach and explore the acting mechanism by using a hepatic stellate cell (HSC) line CFSC-8B stimulated by transforming growth factor-ß1 (TGF-ß1). METHODS: The accumulation of collagens was evaluated using chromogenic precipitation reaction with picro-sirius red (PSR) dye solution and quantified by spectrophotometric analysis of the dissolved stain. MTT assay, cell migration assay, quantitative polymerase chain reaction and western blotting analysis were used to determine the cell viability, cell migration and gene expression. RESULTS: We established a rapid colorimetric assay suitable for screening of anti-hepatofibrotic reagents. Stimulation with 10 ng/mL TGF-ß1 for 48 h and 200 µL PSR dye solution were optimal for the colorimetric assay in CFSC-8B cells. We used SB431542, silybin and another 11 antifibrotic reagents to verify the cellular model. Within the safe doses, they attenuated ECM production induced by TGF-ß1. Bioactivity-guided fractionation led to the identification of antrodin B from A. camphorata. Antrodin B significantly ameliorated cell proliferation, cell migration, suppressed HSC activation marker α-smooth muscle actin expression and ECM components Col1, Col3 and Fn expression, and blocked the phosphorylation of Smad2/3 induced by TGF-ß1 in CFSC-8B cells in a dose-dependent manner. CONCLUSION: We developed a simple assay based on TGF-ß1-induced total collagen accumulation in CFSC-8B cells and identified antrodin B which may serve as a potential candidate for treatment of liver fibrosis.

NR2F6 is essential for brown adipocyte differentiation and systemic metabolic homeostasis.

OBJECTIVE: Brown adipose tissue (BAT) development and function are essential for maintaining energy balance. However, the key factors that specifically regulate brown adipogenesis require further identification. Here, we demonstrated that the nuclear receptor subfamily 2 group F member 6 (NR2F6) played a pivotal role in brown adipogenesis and energy homeostasis. METHODS: We examined the differentiation of immortalized brown adipocytes and primary brown adipocytes when NR2F6 were deleted, and explored the mechanism through which NR2F6 regulated adipogenesis using ChIP-qPCR in vitro. Male wild type (WT) and Pdgfra-Cre-mediated deletion of Nr2f6 in preadipocytes (NR2F6-PKO) mice were fed with high fat diet (HFD) for 12 weeks, and adiposity, glucose intolerance, insulin resistance and inflammation were assessed. RESULTS: NR2F6 exhibited abundant expression in BAT, while its expression was minimal in white adipose tissue (WAT). Within BAT, NR2F6 was highly expressed in preadipocytes, experienced a transient increase in the early stage of brown adipocyte differentiation, and significantly decreased in the mature adipocytes. Depletion of NR2F6 in preadipocytes inhibited brown adipogenesis, caused hypertrophy of brown adipocytes, and impaired thermogenic function of BAT, but without affecting WAT development. NR2F6 transcriptionally regulated PPARγ expression to promote adipogenic process in brown adipocytes. Loss of NR2F6 in preadipocytes led to increased susceptibility to diet-induced metabolic disorders. CONCLUSIONS: Our findings unveiled NR2F6 as a novel key regulator of brown adipogenesis, potentially opening up new avenues for maintaining metabolic homeostasis by targeting NR2F6.

Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction.

Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia through suppression of ovarian androgen synthesis. Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction. Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation. Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins. Our data suggest that artemisinin application is a promising approach for treating PCOS and highlight the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.

Antrodia camphorata ATCC 200183 sporulates asexually in submerged culture.

Antrodia camphorata is a well-known Chinese medicinal mushroom that protects against diverse health-related conditions. Submerged fermentation of A. camphorata is an alternative choice for the effective production of bioactive metabolites, but the effects of nutrition and environment on mycelial morphology are largely unknown. In this study, we show that A. camphorata American Type Culture Collection 200183 can form arthrospores in the end of liquid fermentation. Different morphologies of A. camphorata in submerged culture were analyzed using scanning electron microscopy. The optimal carbon and nitrogen sources for sporulation were soluble starch and yeast extract. We found that a carbon-to-nitrogen ratio (C/N) of 40:1, MgSO4 (0.5 g/l), KH2PO4 (3.0 g/l), an initial pH 5.0, and an inoculum size of 1.5×10(5) spores/ml led to maximum production of arthroconidia. Our results will be useful in the regulation and optimization of A. camphorata cultures for efficient production of arthroconidia in submerged culture, which can be used as inocula in subsequent fermentation processes.

Bioassay-guided isolation of DPP-4 inhibitory fractions from extracts of submerged cultured of Inonotus obliquus.

Inonotus obliquus is a medicinal mushroom used in Russian and Eastern European folk medicine for the treatment of gastrointestinal cancer, cardiovascular disease and diabetes. Previous studies in our laboratory have demonstrated that the mycelium powders of I. obliquus possess significant antihyperglycemic effects in a mouse model of diabetic disease induced by alloxan. However, the active ingredients of mycelium powders responsible for the diabetes activity have not been identified. This study aims to identify the active ingredients of I. obliquus mycelium powders by a bioassay-guided fractionation approach and explore the mechanism of action of these active ingredients by using a well-established DPP-4 (an important enzyme as a new therapeutic target for diabetes) inhibitory assay model. The results showed the chloroform extract of mycelium was potential inhibitory against DPP-4. Bioactivity guided fractionation led to the identification of 19 compounds using UPLC-Q-TOF-MS. Molecular docking between the compounds and DPP-4 revealed that compounds 5, 8, 9, 14, 15 may be the active components responsible for the DPP-4 inhibitory activity.

[2-Acet-oxy-3-(naphthalen-1-yl-oxy)prop-yl](propan-2-yl)aza-nium chloride monohydrate.

The title compound, C18H24NO3 (+)·Cl(-)·H2O, was synthesized by the reaction of propranolol hydro-chloride with acetyl chloride in chloro-form followed by slow evaporation in air. In the cation, the dihedral angle between the planes of the naphthalene ring system and the acetate group is 71.1 (2)°. An intra-molecular N-H⋯O hydrogen bond results in the formation of a non-planar pseudo-ring, with the ether O and the H atom displaced by -1.328 (2) and 0.65 Å, respectively, from the plane of the other ring atoms. The cation and anion are linked by an N-H⋯Cl hydrogen bond. The water molecule is linked to a methyl H atom by C-H⋯O hydrogen bond.

[Changes in Ozone Pollution Trend Characteristics and Sensitivity in Jinan from 2015 to 2020].

The surface ozone (O3) spatiotemporal distribution, variations, and its causes in Ji'nan from 2015 to 2020 were revealed based on the air quality monitoring network data and satellite retrievals from the Ozone Monitoring Instrument (OMI). The results showed that the ozone concentration in Ji'nan gradually increased from 2015 to 2020. The annual 90th percentile of the daily maximum 8-h average (MDA8) O3(namely the annual evaluation value) and the MDA8 O3(April-September) increased by 4.8 µg·(m3·a)-1 and 3.8 µg·(m3·a)-1, respectively. The trend of the ozone levels in the high-concentration range increased faster than that in the low-concentration range. The MDA8 in June increased by 7.4 µg·(m3·a)-1, and the rate range of increases was 2.6-3.9 µg·(m3·a)-1 in the cool seasons (December-February); thus, the O3 control in winter cannot be ignored. It is apparent from the diurnal variations in ozone from 2015 to 2020 in April-September that the average ozone levels have risen in recent years. The growth rate in the daytime was higher than that at night. The capacity of photochemical production has been increasing, especially in recent years. Additionally, it is noteworthy that the peak time for ozone levels occurred approximately 1-2 h earlier. The disparity of ozone concentrations among different stations gradually decreased in recent years. Compared with that in 2015, the range of areas with high O3 concentrations in 2019-2020 was further expanded. The significant positive trends in MDA8-90th and MDA8 (April-September) were observed in 16.1% and 22.6% of the monitoring sites in Ji'nan (P<0.05), most of which were located in urban areas and the suburbs close to urban areas. The temporal and spatial changes in ozone in Jinan had been affected by the changes in VOCs and NOx emissions since 2015. Satellite remote sensing data from 2015 to 2020 revealed that the NO2 tropospheric columns (April-September) showed reductions of 20.6%, with a decreasing rate of 0.3×1015 mole·(cm2·a)-1, especially in the urban areas and suburbs. The detected variation trends of tropospheric HCHO were weak and insignificant, which suggested that the decrease in NOx emissions was much greater than the decrease in VOCs emissions, and the gap had become more obvious in the urban areas. With responses to precursor emissions, the chemical sensitivity of O3 formation had been changing. The VOCs-limited regimes continuously decreased, and the mixed NOx/VOCs-sensitive regimes and NOx-limited regimes increased. In general, such an extremely inappropriate control ratio of ozone precursor NOx/VOCs led to an overall trend of slow increasing fluctuations of O3 in Ji'nan. The findings clearly indicate that the reduction of VOCs in Ji'nan was far from sufficient, and strengthening the current control of VOCs emissions is an effective measure to control the growth trend of O3 pollution in Ji'nan in the near future, especially in urban and surrounding suburban areas.

Diagnosis of Middle Cerebral Artery Stenosis Using Transcranial Doppler Images Based on Convolutional Neural Network.

BACKGROUND: The purpose of this study was to explore the diagnostic value of convolutional neural networks (CNNs) in middle cerebral artery (MCA) stenosis by analyzing transcranial Doppler (TCD) images. METHODS: Overall, 278 patients who underwent cerebral vascular TCD and cerebral angiography were enrolled and classified into stenosis and non-stenosis groups based on cerebral angiography findings. Manual measurements were performed on TCD images. The patients were divided into a training set and a test set, and the CNN architecture was used to classify TCD images. The diagnostic accuracies of manual measurements, CNNs, and TCD parameters for MCA stenosis were calculated and compared. RESULTS: Overall, 203 patients without stenosis and 75 patients with stenosis were evaluated. The sensitivity, specificity, and area under the curve (AUC) for manual measurements of MCA stenosis were 0.80, 0.83, and 0.81, respectively. After 24 iterations of the running model in the training set, the sensitivity, specificity, and AUC of the CNNs in the test set were 0.84, 0.86, and 0.80, respectively. The diagnostic value of CNNs differed minimally from that of manual measurements. Two parameters of TCD, peak systolic velocity and mean flow velocity, were higher in patients with stenosis than in those without stenosis; however, their diagnostic values were significantly lower than those of CNNs (P < 0.05). CONCLUSIONS: The diagnostic value of CNNs for MCA stenosis based on TCD images paralleled that of manual measurements. CNNs could be used as an auxiliary diagnostic tool to improve the diagnosis of MCA stenosis.

The complete chloroplast genome of Bothriochloa ischaemum.

Bothriochloa ischaemum (Linn.) 1936 is a high-quality perennial forage in Loess Plateau of China. In this study, we sequenced and characterized the complete chloroplast genome of B. ischaemum, which was a circular DNA of 138,316 bp in length, including a large single copy (LSC) region of 80,226 bp, a small single copy (SSC) region of 12,526 bp, and the circular DNA was separated by a pair of identical inverted repeat regions (IRs) of 22,782 bp each. A total of 134 genes were identified, including 87 protein-coding genes, 39 tRNA genes, and eight rRNA genes. Phylogenetic tree showed that B. ischaemum was closer to B. decipiens and B. alta, genus Bothriochloa was closely related to genus Pseudanthistiria. Our findings will be helpful for better understanding of genetic diversity of Bothriochloa plants.

Dietary Goji Shapes the Gut Microbiota to Prevent the Liver Injury Induced by Acute Alcohol Intake.

Diet is a major driver of the structure and function of the gut microbiota, which influences the host physiology. Alcohol abuse can induce liver disease and gut microbiota dysbiosis. Here, we aim to elucidate whether the well-known traditional health food Goji berry targets gut microbiota to prevent liver injury induced by acute alcohol intake. The results showed that Goji supplementation for 14 days alleviated acute liver injury as indicated by lowering serum aspartate aminotransferase, alanine aminotransferase, pro-inflammatory cytokines, as well as lipopolysaccharide content in the liver tissue. Goji maintained the integrity of the epithelial barrier and increased the levels of butyric acid in cecum contents. Furthermore, we established the causal relationship between gut microbiota and liver protection effects of Goji with the help of antibiotics treatment and fecal microbiota transplantation (FMT) experiments. Both Goji and FMT-Goji increased glutathione (GSH) in the liver and selectively enriched the butyric acid-producing gut bacterium Akkermansia and Ruminococcaceae by using 16S rRNA gene sequencing. Metabolomics analysis of cecum samples revealed that Goji and its trained microbiota could regulate retinoyl ß-glucuronide, vanillic acid, and increase the level of glutamate and pyroglutamic acid, which are involved in GSH metabolism. Our study highlights the communication among Goji, gut microbiota, and liver homeostasis.

[Ozone Formation and Key VOCs of a Continuous Summertime O3 Pollution Event in Ji'nan].

In the summer of 2019, field measurements of ozone (O3) and its precursors[volatile organic compounds (VOCs) and nitrogen oxides (NOx)] were carried out at an urban site in Ji'nan. We found that the daily maximum 8-hour averages φ(O3) were (103.0±14.5)×10-9. The average φ(NOx) and φ(VOCs), which are ozone precursors, were (16.7±11.3)×10-9and (22.4±9.4)×10-9, respectively. The ·OH reactivity of VOCs was determined (9.6±3.8) s-1. Ji'nan suffered from serious O3 pollution. An observation-constrained chemical box model was deployed to evaluate in situ photochemical O3 production, which indicated that chemical reactions made positive contributions to O3 production rates between 07:00 and 19:00 LT, with the average hourly O3 production rate of 35.6×10-9 h-1. To evaluate the effectiveness of various ozone precursor control strategies in reducing ozone pollution, we combined the observation-based model (OBM) with the relative incremental reactivity (RIR) method. The key indicators that affect the local ozone production rate were identified. Ji'nan was under VOC-limited conditions and the key VOC precursors were alkenes. The O3 formation mechanism changed from the VOC-limited regime in the morning to the transitional regime in the afternoon. Correspondingly, the simulated local O3 production rate was increased from 18.3×10-9 h-1 to 29.6×10-9 h-1. To further explore the role of anthropogenic emissions in ozone pollution, we used the positive matrix factorization (PMF) model to identify the major sources contributing to VOCs. The major sources in Ji'nan were vehicular exhaust and gasoline evaporation, accounting for more than 50% of the observed VOCs. Therefore, constraints on vehicular emissions is the most effective strategy to control O3 pollution in Ji'nan.

Optimization of fermentation medium for triterpenoid production from Antrodia camphorata ATCC 200183 using artificial intelligence-based techniques.

In this study, alteration in morphology of submergedly cultured Antrodia camphorata ATCC 200183 including arthroconidia, mycelia, external and internal structures of pellets was investigated. Two optimization models namely response surface methodology (RSM) and artificial neural network (ANN) were built to optimize the inoculum size and medium components for intracellular triterpenoid production from A. camphorata. Root mean squares error, R (2), and standard error of prediction given by ANN model were 0.31%, 0.99%, and 0.63%, respectively, while RSM model gave 1.02%, 0.98%, and 2.08%, which indicated that fitness and prediction accuracy of ANN model was higher when compared to RSM model. Furthermore, using genetic algorithm (GA), the input space of ANN model was optimized, and maximum triterpenoid production of 62.84 mg l(-1) was obtained at the GA-optimized concentrations of arthroconidia (1.78 × 105 ml(-1)) and medium components (glucose, 25.25 g l(-1); peptone, 4.48 g l(-1); and soybean flour, 2.74 g l(-1)). The triterpenoid production experimentally obtained using the ANN-GA designed medium was 64.79 ± 2.32 mg l(-1) which was in agreement with the predicted value. The same optimization process may be used to optimize many environmental and genetic factors such as temperature and agitation that can also affect the triterpenoid production from A. camphorata and to improve the production of bioactive metabolites from potent medicinal fungi by changing the fermentation parameters.

[Analyze on volatile compounds of Antrodia camphorata using HS-SPME-GC-MS].

OBJECTIVE: To analyze the volatile compounds of Antrodia camphorata in solid-state and submerged cultures. METHODS: A headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry(GC-MS) were used to evaluate the profile of the volatile compounds. RESULTS: 49 volatile compounds were identified in A. camphorata mycelia in submerged culture, while 43 volatile compounds were identified in mycelia in solid-state culture. 1-octen-3-ol, 3-octanone, 1-octen-3-ylacetate, acetic acid octyl ester and ethanol were the main volatile compounds in A. camphorata mycelia in submerged culture, while 1-octen-3-ol, 3-octanone, 3-methyl-butyraldenhyde, gamma-podecalactone and methyl 2-furozte were the most potent key volatile compounds in mycelia in solid-state culture. CONCLUSION: The volatile compounds in the mycelia of A. camphorata in solid-state and submerged cultures are similar but their relative contents are different.