Integrative transcriptomic and genomic analyses unveil the IFI16 variants and expression as MASLD progression markers.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a broad and continuous spectrum of liver diseases ranging from fatty liver to steatohepatitis. The intricate interactions of genetic, epigenetic, and environmental factors in the development and progression of MASLD remain elusive. Here, we aimed to achieve an integrative understanding of the genomic and transcriptomic alterations throughout the progression of MASLD. APPROACH AND RESULTS: RNA-Seq profiling (n = 146) and whole-exome sequencing (n = 132) of MASLD liver tissue samples identified 3 transcriptomic subtypes (G1-G3) of MASLD, which were characterized by stepwise pathological and molecular progression of the disease. Macrophage-driven inflammatory activities were identified as a key feature for differentiating these subtypes. This subtype-discriminating macrophage interplay was significantly associated with both the expression and genetic variation of the dsDNA sensor IFI16 (rs6940, A>T, T779S), establishing it as a fundamental molecular factor in MASLD progression. The in vitro dsDNA-IFI16 binding experiments and structural modeling revealed that the IFI16 variant exhibited increased stability and stronger dsDNA binding affinity compared to the wild-type. Further downstream investigation suggested that the IFI16 variant exacerbated DNA sensing-mediated inflammatory signals through mitochondrial dysfunction-related signaling of the IFI16-PYCARD-CASP1 pathway. CONCLUSIONS: This study unveils a comprehensive understanding of MASLD progression through transcriptomic classification, highlighting the crucial roles of IFI16 variants. Targeting the IFI16-PYCARD-CASP1 pathway may pave the way for the development of novel diagnostics and therapeutics for MASLD.

LeafNet: a tool for segmenting and quantifying stomata and pavement cells.

Stomata play important roles in gas and water exchange in leaves. The morphological features of stomata and pavement cells are highly plastic and are regulated during development. However, it is very laborious and time-consuming to collect accurate quantitative data from the leaf surface by manual phenotyping. Here, we introduce LeafNet, a tool that automatically localizes stomata, segments pavement cells (to prepare them for quantification), and reports multiple morphological parameters for a variety of leaf epidermal images, especially bright-field microscopy images. LeafNet employs a hierarchical strategy to identify stomata using a deep convolutional network and then segments pavement cells on stomata-masked images using a region merging method. LeafNet achieved promising performance on test images for quantifying different phenotypes of individual stomata and pavement cells compared with six currently available tools, including StomataCounter, Cellpose, PlantSeg, and PaCeQuant. LeafNet shows great flexibility, and we improved its ability to analyze bright-field images from a broad range of species as well as confocal images using transfer learning. Large-scale images of leaves can be efficiently processed in batch mode and interactively inspected with a graphic user interface or a web server (https://leafnet.whu.edu.cn/). The functionalities of LeafNet could easily be extended and will enhance the efficiency and productivity of leaf phenotyping for many plant biologists.

PROX1 Inhibits PDGF-B Expression to Prevent Myxomatous Degeneration of Heart Valves.

BACKGROUND: Cardiac valve disease is observed in 2.5% of the general population and 10% of the elderly people. Effective pharmacological treatments are currently not available, and patients with severe cardiac valve disease require surgery. PROX1 (prospero-related homeobox transcription factor 1) and FOXC2 (Forkhead box C2 transcription factor) are transcription factors that are required for the development of lymphatic and venous valves. We found that PROX1 and FOXC2 are expressed in a subset of valvular endothelial cells (VECs) that are located on the downstream (fibrosa) side of cardiac valves. Whether PROX1 and FOXC2 regulate cardiac valve development and disease is not known. METHODS: We used histology, electron microscopy, and echocardiography to investigate the structure and functioning of heart valves from Prox1ΔVEC mice in which Prox1 was conditionally deleted from VECs. Isolated valve endothelial cells and valve interstitial cells were used to identify the molecular mechanisms in vitro, which were tested in vivo by RNAScope, additional mouse models, and pharmacological approaches. The significance of our findings was tested by evaluation of human samples of mitral valve prolapse and aortic valve insufficiency. RESULTS: Histological analysis revealed that the aortic and mitral valves of Prox1ΔVEC mice become progressively thick and myxomatous. Echocardiography revealed that the aortic valves of Prox1ΔVEC mice are stenotic. FOXC2 was downregulated and PDGF-B (platelet-derived growth factor-B) was upregulated in the VECs of Prox1ΔVEC mice. Conditional knockdown of FOXC2 and conditional overexpression of PDGF-B in VECs recapitulated the phenotype of Prox1ΔVEC mice. PDGF-B was also increased in mice lacking FOXC2 and in human mitral valve prolapse and insufficient aortic valve samples. Pharmacological inhibition of PDGF-B signaling with imatinib partially ameliorated the valve defects of Prox1ΔVEC mice. CONCLUSIONS: PROX1 antagonizes PDGF-B signaling partially via FOXC2 to maintain the extracellular matrix composition and prevent myxomatous degeneration of cardiac valves.

STAT1 modulates tissue wasting or overgrowth downstream from PDGFRß.

Platelet-derived growth factor (PDGF) acts through two conserved receptor tyrosine kinases: PDGFRα and PDGFRß. Gain-of-function mutations in human PDGFRB have been linked recently to genetic diseases characterized by connective tissue wasting (Penttinen syndrome) or overgrowth (Kosaki overgrowth syndrome), but it is unclear whether PDGFRB mutations alone are responsible. Mice with constitutive PDGFRß signaling caused by a kinase domain mutation (D849V) develop lethal autoinflammation. Here we used a genetic approach to investigate the mechanism of autoinflammation in Pdgfrb+/D849V mice and test the hypothesis that signal transducer and activator of transcription 1 (STAT1) mediates this phenotype. We show that Pdgfrb+/D849V mice with Stat1 knockout (Stat1-/-Pdgfrb+/D849V ) are rescued from autoinflammation and have improved life span compared with Stat1+/-Pdgfrb+/D849V mice. Furthermore, PDGFRß-STAT1 signaling suppresses PDGFRß itself. Thus, Stat1-/-Pdgfrb+/D849V fibroblasts exhibit increased PDGFRß signaling, and mice develop progressive overgrowth, a distinct phenotype from the wasting seen in Stat1+/-Pdgfrb+/D849V mice. Deletion of interferon receptors (Ifnar1 or Ifngr1) does not rescue wasting in Pdgfrb+/D849V mice, indicating that interferons are not required for autoinflammation. These results provide functional evidence that elevated PDGFRß signaling causes tissue wasting or overgrowth reminiscent of human genetic syndromes and that the STAT1 pathway is a crucial modulator of this phenotypic spectrum.

Skeletal stem cell fate defects caused by Pdgfrb activating mutation.

Autosomal dominant PDGFRß gain-of-function mutations in mice and humans cause a spectrum of wasting and overgrowth disorders afflicting the skeleton and other connective tissues, but the cellular origin of these disorders remains unknown. We demonstrate that skeletal stem cells (SSCs) isolated from mice with a gain-of-function D849V point mutation in PDGFRß exhibit colony formation defects that parallel the wasting or overgrowth phenotypes of the mice. Single-cell RNA transcriptomics with SSC-derived polyclonal colonies demonstrates alterations in osteogenic and chondrogenic precursors caused by PDGFRßD849V. Mutant cells undergo poor osteogenesis in vitro with increased expression of Sox9 and other chondrogenic markers. Mice with PDGFRßD849V exhibit osteopenia. Increased STAT5 phosphorylation and overexpression of Igf1 and Socs2 in PDGFRßD849V cells suggests that overgrowth in mice involves PDGFRßD849V activating the STAT5-IGF1 axis locally in the skeleton. Our study establishes that PDGFRßD849V causes osteopenic skeletal phenotypes that are associated with intrinsic changes in SSCs, promoting chondrogenesis over osteogenesis.

Unique characteristics of lung-resident neutrophils are maintained by PGE2/PKA/Tgm2-mediated signaling.

Lung-resident neutrophils need to be tightly regulated to avoid degranulation- and cytokine-associated damage to fragile alveolar structures that can lead to fatal outcomes. Here we show that lung neutrophils (LNs) express distinct surface proteins and genes that distinguish LNs from bone marrow and blood neutrophils. Functionally, LNs show impaired migratory activity toward chemoattractants and produce high levels of interleukin-6 (IL-6) at steady state and low levels of tumor necrosis factor-α in response to lipopolysaccharide (LPS) challenge. Treating bone marrow neutrophils with bronchoalveolar lavage fluid or prostaglandin E2 induces LN-associated characteristics, including the expression of transglutaminase 2 (Tgm2) and reduced production of inflammatory cytokines upon LPS challenge. Neutrophils from Tgm2-/- mice release high levels of inflammatory cytokines in response to LPS. Lung damage is significantly exacerbated in Tgm2-/- mice in an LPS-induced acute respiratory distress syndrome model. Collectively, we demonstrate that prostaglandin E2 is a key factor for the generation of LNs with unique immune suppressive characteristics, acting through protein kinase A and Tgm2, and LNs play essential roles in protection of the lungs against pathogenic inflammation.

The Inhibition Activity of Natural Methoxyflavonoid from Inula britannica on Soluble Epoxide Hydrolase and NO Production in RAW264.7 Cells.

Soluble epoxide hydrolase (sEH) is an enzyme targeted for the treatment of inflammation and cardiovascular diseases. Activated inflammatory cells produce nitric oxide (NO), which induces oxidative stress and exacerbates inflammation. We identify an inhibitor able to suppress sEH and thus NO production. Five flavonoids 1-5 isolated from Inula britannica flowers were evaluated for their abilities to inhibit sEH with IC50 values of 12.1 ± 0.1 to 62.8 ± 1.8 µM and for their effects on enzyme kinetics. A simulation study using computational chemistry was conducted as well. Furthermore, five inhibitors (1-5) were confirmed to suppress NO levels at 10 µM. The results showed that flavonoids 1-5 exhibited inhibitory activity in all tests, with compound 3 exhibiting the most significant efficacy. Thus, in the development of anti-inflammatory inhibitors, compound 3 is a promising natural candidate.

Homogenizing Zn Deposition in Hierarchical Nanoporous Cu for a High-Current, High Areal-Capacity Zn Flow Battery.

A Zn anode can offset the low energy density of a flow battery for a balanced approach toward electricity storage. Yet, when targeting inexpensive, long-duration storage, the battery demands a thick Zn deposit in a porous framework, whose heterogeneity triggers frequent dendrite formation and jeopardizes the stability of the battery. Here, Cu foam is transferred into a hierarchical nanoporous electrode to homogenize the deposition. It begins with alloying the foam with Zn to form Cu5 Zn8 , whose depth is controlled to retain the large pores for a hydraulic permeability ≈10-11  m2 . Dealloying follows to create nanoscale pores and abundant fine pits below 10 nm, where Zn can nucleate preferentially due to the Gibbs-Thomson effect, as supported by a density functional theory simulation. Morphological evolution monitored by in situ microscopy confirms uniform Zn deposition. The electrode delivers 200 h of stable cycles in a Zn-I2 flow battery at 60 mAh cm-2 and 60 mA cm-2 , performance that meets practical demands.

Effect of ß3-adrenoceptor agonist on the micromotion of bilateral major pelvic ganglion-excised rat bladder.

AIMS: Micromotion is an autonomous intramural movement of the bladder, and is believed to be an initial step in the generation of urinary urgency. Therefore, controlling micromotion may be a novel target in overactive bladder (OAB) treatment. However, developing micromotion treatment has been limited by the absence of a standardized animal model. We attempted to create a micromotion animal model and investigated the effectiveness of a ß3 -adrenoceptor agonist (CL316,243) on micromotion. METHODS: Bilateral major pelvic ganglia (MPGs) were excised in 18 male Sprague-Dawley rats, resulting in an almost completely denervated bladder. On postoperative Day 7, cystometry was performed. Rats were divided into three treatment groups: CL316,243; ß3- adrenoceptor antagonist (SR59230A) pretreated CL316,243; and a nonselective antimuscarinic agent (oxybutynin). Changes in micromotion were evaluated after the intra-arterial administration of each agent. RESULTS: Low-amplitude oscillations in intravesical pressure (micromotion) were observed 1 week after MPGs excision. Micromotion frequency significantly (p = 0.003) decreased (2.17 ± 3.54 times/5 min) with CL316,243 compared with vehicle (6.33 ± 1.97 times/5 min). Micromotion amplitude also decreased with CL316,243 (1.15 ± 1.93 cmH2 O) compared with vehicle (5.96 ± 5.12 cmH2 O), approaching conventional significance (p = 0.090). No significant decreases in frequency or amplitude were observed with oxybutynin treatment. CONCLUSIONS: Systemic administration of the ß3 -adrenoceptor agonist CL316,243 effectively controlled micromotion in bilateral MPGs-excised, almost completely denervated rat bladders. This result indicates that ß3 -adrenoceptor agonist may affect the bladder directly, suggesting that it might be effective for overall OAB, regardless of the presence or level of neurological deficits. Bilateral MPGs-excised rats are considered a plausible micromotion animal model suitable for future research.

TcPO2 Value Can Predict Wound Healing Time in Clinical Practice of CLTI Patients.

BACKGROUND: Transcutaneous oxygen pressure (TcPO2) is a noninvasive, nonradiological test to measure local oxygen released from capillaries through the skin. Since it reflects the metabolic state of the lower limb, it can predict wound healing in patients with critical limb threatening ischemia (CLTI). The purpose of this study was to determine the effectiveness of TcPO2 test in evaluating wound healing potential of patients with CLTI. METHODS: This was a retrospective, single-center, nonrandomized, and observational study. A prospectively registered database of patients who visited Vascular Surgery Department of St. Mary's Hospital for CLTI and underwent TcPO2 tests from October 1, 2015 to July 1, 2021 was reviewed. Patients were divided into 2 groups: (1) those who had amputation only; and (2) those who underwent revascularization procedures. Patients whose wound healing status could not be determined were excluded. The clinical characteristics of patients, patient characteristics related to lower TcPO2 value, treatment success rate, and time for the wound to be healed were analyzed. RESULTS: A total of 84 patients were included in this study. There was no difference in background patient characteristics between the 2 groups despite better survival within 12 months and shorter healing time in the revascularization group. A total of 76 patients survived 12 months after surgery, and 63 patients were healed. Higher HbA1c, higher serum creatinine, history of stroke, and history of coronary artery disease were related to lower TcPO2 value on multiple linear regression. The cutoff value of TcPO2 was determined to be 40 mm Hg for predicting wound healing. This value was similar to those of previous studies. In addition, there was a negative correlation between TcPO2 and wound healing time. Correlations among the anklebrachial index (ABI), toe-brachial index (TBI), and TcPO2 were not determined because ABI and TBI for some patients could not be obtained due to wound condition. CONCLUSIONS: The TcPO2 value can predict the wound healing process of ischemic lower extremity injury.

Inhibition by components of Glycyrrhiza uralensis of 3CLpro and HCoV-OC43 proliferation.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). 3CLpro is a key enzyme in coronavirus proliferation and a treatment target for COVID-19. In vitro and in silico, compounds 1-3 from Glycyrrhiza uralensis had inhibitory activity and binding affinity for 3CLpro. These compounds decreased HCoV-OC43 cytotoxicity in RD cells. Moreover, they inhibited viral growth by reducing the amounts of the necessary proteins (M, N, and RDRP). Therefore, compounds 1-3 are inhibitors of 3CLpro and HCoV-OC43 proliferation.

The neuro-protective role of telomerase via TERT/TERF-2 in the acute phase of spinal cord injury.

PURPOSE: To investigate the interaction of telomerase activity and telomere length on neuro-protection or neuro-degeneration effects after spinal cord injury (SCI). METHODS: A contusive SCI model was developed using 56 Sprague-Dawley rats. Seven rats were allocated into acute injury phase groups (1, 3, 8, 24, and 48 h), and sub-acute and chronic injury phase groups (1, 2, and 4 weeks). Telomerase activity was assessed by telomerase reverse transcriptase (TERT) and telomeric repeat binding factor-2 (TERF-2). Differentiation of activated neural stem cells was investigated by co-expression of neuronal/glial cell markers. Apoptosis expression was also investigated by caspase-3, 8, and 9 using terminal deoxynucleotidyl transferase dUTP nick end labelling staining. Immunofluorescence staining and western blotting were performed for quantitative analyses. RESULTS: Expression of TERT increased gradually until 24 h post-injury, and was decreased following SCI (P < 0.05). TERF-2 also was increased following SCI until 24 h post-injury and then decreased with time (P < 0.05). Co-localization of TERT and TERF-2 was higher at 24 h post-injury. High expression of TERT was seen in neurons (Neu N Ab), however, expression of TERT was relatively lower in astrocytes and oligodendrocytes. Apoptosis analysis showed persistent high expression of caspases-3, -9, and -8 during the observation period. CONCLUSIONS: Increased TERT and TERF-2 activity were noted 24 h post-injury in the acute phase of SCI with TERF-2 maintaining telomeric-repeat length. Our results suggest that increased activity of telomere maintenance may be related to neuro-protective mechanisms against subsequent apoptosis resulting from DNA damage after acute SCI.

Contrast enhanced duplex ultrasound for early postoperative follow-up after endovascular aneurysm repair: Relation to patient's initial risk of complications.

OBJECTIVES: Current guidelines recommend initial postoperative follow-up with computed tomography angiography (CTA) after endovascular aneurysm repair (EVAR). However, CTA has risks associated with ionizing radiations and nephrotoxic contrast agents. We investigated possibilities to replace the initial postoperative CTA with contrast enhanced duplex ultrasound (CE-DUS) in selected patients. METHODS: Out of the 273 consecutive patients who underwent EVAR, 173 were excluded and the 100 patients who underwent CTA and CE-DUS imaging concurrently (≤1 month interval between CTA and CE-DUS imaging) within 60 days after EVAR were analyzed. Patients who underwent EVAR outside the manufacturer's instructions for use or who had endoleaks discovered on intraoperative angiography were classified as the high-risk group, otherwise, they were classified as the low-risk group. Measurements of diagnostic values of CE-DUS ​​related to the detection of complications were calculated using CTA as the gold standard. McNemar's test was performed to compare these values and Pearson correlation coefficient was derived to compare CE-DUS measurements of sac diameters with CTA. RESULTS: In the low-risk group, no difference was observed between CE-DUS and CTA in the detection of EVAR-related complications (sensitivity = 0.95, specificity = 0.93). In the high-risk group, CE-DUS was not as accurate as CTA for the detection of overall EVAR-related complications (sensitivity = 0.57, specificity = 0.86, p = 0.04) and for the detection of complications other than endoleaks (p = 0.02). Regarding sac diameter measurement, there was good agreement between CE-DUS and CTA (r = 0.92, p < 0.001). CONCLUSIONS: First postoperative CE-DUS was reliable for the evaluation of EVAR-related complications compared to CTA in selected patients. Individualized EVAR follow-up strategy using CE-DUS based on the initial risk of EVAR-related complications should be considered.

The Asia-Pacific AMS800 artificial urinary sphincter consensus statement.

This Asia-Pacific (AP) AMS 800™ artificial urinary sphincter (AUS) consensus statement aims to provide a set of practical recommendations to assist surgeons with the AMS 800 device surgery. The AP consensus committee consisted of key opinion leaders with extensive experience with AMS 800 surgery across several AP countries. The panel reviewed and discussed relevant findings with emphasis on locoregional and specific clinical challenges relevant to the AP region. Recommendations were made in key areas namely (1) patient selection and informed consent process; (2) preoperative assessment; (3) dealing with co-existing urological disorders; (4) surgical principles and intraoperative troubleshooting; (5) postoperative care; (6) special populations; and (7) cost analysis and comparative review. The AMS 800 device should be offered to males with moderate to severe stress urinary incontinence (SUI). Full informed consent should be undertaken, and emphasis is placed on surgical contraindications and high-risk candidates. The presence of a surgical mentor or referral to experts is recommended in complex AUS candidates. Preoperative cystoscopy with or without multichannel urodynamic study is necessary and patients with pre-existing urological disorders should be treated adequately and clinically stable before surgery. Adherence to strict patient selection and safe surgical principles are critical to ensure excellent clinical outcomes and minimize complications. Given that InhibiZone-coated device is not available in many AP countries, the use of prophylactic antibiotics pre-and post-operatively are recommended. The AMS 800 device should be prepared according to the manufacturer's guidelines and remains a cost-effective treatment for male SUI. The AMS 800 device remains the surgical benchmark for male SUI but is associated with certain mechanical limitations and a unique set of complications.

Isocucurbic Acid Derivatives and Soluble Epoxide Hydroxylase Inhibitors from the Flowers of Chrysanthemum indicum L.

Soluble epoxide hydrolase (sEH) inhibitory activity guided fractionation and isolation of two new isocucurbic acid derivatives (1 and 2) and nine known compounds (3-11) from the flowers of Chrysanthemum indicum L. Their structures were elucidated on the basis of spectroscopic data interpretation and comparison with those reported in previous studies. Luteolin (3), acacetin-7-O-ß-D-glucopyranoside (6), and methyl 3,4-di-O-caffeoylquinate (10) displayed sEH inhibitory activities with IC50 values ranging from 13.7±3.6 to 20.8±0.4 µM. Enzyme kinetic analysis revealed that 3, 6, and 10 were non-competitive inhibitors with Ki values of 14.8±0.5, 31.2±0.8, and 3.9±0.2 µM, respectively. Additionally, molecular docking studies indicated compound 10 had the ability to form six hydrogen bonds at sEH active site, resulting binding energy as low as -9.58 Kcal/mol.

A Pneumatically Controlled Prosthetic Socket for Transfemoral Amputees.

Amputees typically experience changes in residual limb volume in their daily lives. It causes an uncomfortable fit of the socket by applying high pressure on the sensitive area of the residual limb or by loosening the socket. In this study, we developed a transfemoral prosthetic socket for above-the-knee amputees that ensures a good socket fit by maintaining uniform and constant contact pressure despite volume changes in the residual limb. The socket has two air bladders in the posterior femoral region, and the pneumatic controller is located on the tibia of the prosthesis. The pneumatic system aims to minimize unstable fitting of the socket and improve walking performance by inflating or deflating the air bladder. The developed socket autonomously maintains the air pressure inside the prosthetic socket at a steady-state error of 3 mmHg or less by adjusting the amount of air in the air bladder via closed-loop control. In the clinical trial, amputee participants walked on flat and inclined surfaces. The displacement between the residual limb and socket during the gait cycle was reduced by up to 33.4% after air injection into the socket. The inflatable bladder increased the knee flexion angle on the affected side, resulting in increased stride length and gait velocity. The pneumatic socket provides a stable and comfortable walking experience not only when walking on flat ground but also on slopes.

Salt-Assisted Selective Growth of H-phase Monolayer VSe2 with Apparent Hole Transport Behavior.

Vanadium diselenide (VSe2) exhibits versatile electronic and magnetic properties in the trigonal prismatic (H-) and octahedral (T-) phases. Compared to the metallic T-phase, the H-phase with a tunable semiconductor property is predicted to be a ferrovalley material with spontaneous valley polarization. Herein we report an epitaxial growth of the monolayer 2D VSe2 on a mica substrate via the chemical vapor deposition (CVD) method by introducing salt in the precursor. Our first-principles calculations suggest that the monolayer H-phase VSe2 with a large lateral size is thermodynamically favorable. The honeycomb-like structure and the broken symmetry are directly observed by spherical aberration-corrected scanning transmission electron microscopy (STEM) and confirmed by giant second harmonic generation (SHG) intensity. The p-type transport behavior is further evidenced by the temperature-dependent resistance and field-effect device study. The present work introduces a new phase-stable 2D transition metal dichalcogenide, opening the prospect of novel electronic and spintronics device design.

Eupatin, a Flavonoid, Inhibits Coronavirus 3CL Protease and Replication.

The coronavirus disease 2019 (COVID-19) pandemic has caused more than six million deaths worldwide since 2019. Although vaccines are available, novel variants of coronavirus are expected to appear continuously, and there is a need for a more effective remedy for coronavirus disease. In this report, we isolated eupatin from Inula japonica flowers and showed that it inhibits the coronavirus 3 chymotrypsin-like (3CL) protease as well as viral replication. We showed that eupatin treatment inhibits SARS-CoV-2 3CL-protease, and computational modeling demonstrated that it interacts with key residues of 3CL-protease. Further, the treatment decreased the number of plaques formed by human coronavirus OC43 (HCoV-OC43) infection and decreased viral protein and RNA levels in the media. These results indicate that eupatin inhibits coronavirus replication.

Inhibition of Soluble Epoxide Hydrolase Activity by Components of Glycyrrhiza uralensis.

Soluble epoxide hydrolase (sEH) is a target enzyme for the treatment of inflammation and cardiovascular disease. A Glycyrrhiza uralensis extract exhibited ~50% inhibition of sEH at 100 µg/mL, and column chromatography yielded compounds 1-11. Inhibitors 1, 4-6, 9, and 11 were non-competitive; inhibitors 3, 7, 8, and 10 were competitive. The IC50 value of inhibitor 10 was below 2 µM. Molecular simulation was used to identify the sEH binding site. Glycycoumarin (10) requires further evaluation in cells and animals.

How do carbon trading price and carbon tax rate affect power project portfolio investment and carbon emission: An analysis based on uncertainty theory.

Responding to the social, economic, and environmental call to resolve current sustainability challenges, the concern about carbon dioxide emission reduction should be incorporated into the power investment decision process. Reflecting the low carbon emission requirement, this paper proposes a new optimization model for power project portfolio selection that simultaneously considers both of carbon emission trading scheme and carbon tax imposition. In this model, the initial investment outlay, the power sale price, the carbon trading price, and carbon tax rate are treated as uncertain variables considering the fast-changing environment and complex market situation. Incorporating the constraint on whether the carbon quota is exceeded into the model, two investment strategies are proposed for investors. Using the proposed model, the impact of the rises in carbon trading price and carbon tax rate on the investor's investment strategy selection and the carbon emission is simulated and analyzed through a case study. When the expected carbon price is 203.50 RMB/tCO2-eq or less, a company should invest based on the strategy that annual emissions exceed the quota to obtain a maximum expected NPV which is larger than 408588 million RMB. When future carbon prices are 352.00, 500.50 and 649.00 RMB/tCO2-eq, the government should impose carbon tax rates of 30, 30, and 40 RMB/tCO2 on a power company, respectively, to obtain carbon emission reduction effect. At last, to see the contrast effect of the results from simultaneous implementation of both carbon trading and carbon tax, the results considering the carbon trading alone or carbon tax alone are discussed, respectively.