Transcriptome and Metabolome Analyses of Aroma Differences between Chardonnay and a Chardonnay Bud Sport.

Chardonnay is one of the most popular white grape wine varieties in the world, but this wine lacks typical aroma, considered a sensory defect. Our research group identified a Chardonnay bud sport with typical muscat characteristics. The goal of this work was to discover the key candidate genes related to muscat characteristics in this Chardonnay bud sport to reveal the mechanism of muscat formation and guide molecular design breeding. To this end, HS-SPME-GC-MS and RNA-Seq were used to analyze volatile organic compounds and the differentially expressed genes in Chardonnay and its aromatic bud sport. Forty-nine volatiles were identified as potential biomarkers, which included mainly aldehydes and terpenes. Geraniol, linalool, and phenylacetaldehyde were identified as the main aroma components of the mutant. The GO, KEGG, GSEA, and correlation analysis revealed HMGR, TPS1, TPS2, TPS5, novel.939, and CYP450 as key genes for terpene synthesis. MAO1 and MAO2 were significantly downregulated, but there was an increased content of phenylacetaldehyde. These key candidate genes provide a reference for the development of functional markers for muscat varieties and also provide insight into the formation mechanism of muscat aroma.

Homotherapy for heteropathy: therapeutic effect of Butein in NLRP3-driven diseases.

BACKGROUND: Aberrant inflammatory responses drive the initiation and progression of various diseases, and hyperactivation of NLRP3 inflammasome is a key pathogenetic mechanism. Pharmacological inhibitors of NLRP3 represent a potential therapy for treating these diseases but are not yet clinically available. The natural product butein has excellent anti-inflammatory activity, but its potential mechanisms remain to be investigated. In this study, we aimed to evaluate the ability of butein to block NLRP3 inflammasome activation and the ameliorative effects of butein on NLRP3-driven diseases. METHODS: Lipopolysaccharide (LPS)-primed bone-marrow-derived macrophages were pretreated with butein and various inflammasome stimuli. Intracellular potassium levels, ASC oligomerization and reactive oxygen species production were also detected to evaluate the regulatory mechanisms of butein. Moreover, mouse models of LPS-induced peritonitis, dextran sodium sulfate-induced colitis, and high-fat diet-induced non-alcoholic steatohepatitis were used to test whether butein has protective effects on these NLRP3-driven diseases. RESULTS: Butein blocks NLRP3 inflammasome activation in mouse macrophages by inhibiting ASC oligomerization, suppressing reactive oxygen species production, and upregulating the expression of the antioxidant pathway nuclear factor erythroid 2-related factor 2 (Nrf2). Importantly, in vivo experiments demonstrated that butein administration has a significant protective effect on the mouse models of LPS-induced peritonitis, dextran sodium sulfate-induced colitis, and high-fat diet-induced non-alcoholic steatohepatitis. CONCLUSION: Our study illustrates the connotation of homotherapy for heteropathy, i.e., the application of butein to broaden therapeutic approaches and treat multiple inflammatory diseases driven by NLRP3.

Anti-inflammatory and uric acid lowering effects of Euodiae fructus on hyperuricemia and gout mice.

The metabolic disease hyperuricemia (HUA) is caused by presence of excessive serum uric acid (UA), which leads to an increased risk of chronic kidney disease and gout. As a widely used traditional Chinese medicine, Euodiae fructus (ER) has strong anti-inflammatory and analgesic effects, however, its therapeutic effects on HUA and gout have not been investigated. To investigate the potential effects and underlying mechanisms, the effect of ER on proinflammatory cytokines and NLRP3 inflammasome activation was studied in mouse bone marrow macrophages. Moreover, a mouse model of HUA and gouty arthritis was established by coadministration of potassium oxonate (PO) and monosodium urate crystals to mice fed a high-fat diet (HFD) for 37 consecutive days. Oral administration of ER aqueous extract was given 1 hour later after the injection of PO for 10 days. Our study showed that ER is a powerful NLRP3 inhibitor in mouse macrophages. Most importantly, ER (0.75 g/kg) treatment substantially decreased the ankle joint thickness ratio, serum UA, creatinine and blood urea nitrogen levels (p < 0.05). Additionally, ER (0.75 g/kg) dramatically reversed the increases in renal urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) as well as the decreases in organic anion transporter 1 (OAT1) and ATP binding cassette subfamily G member 2 (ABCG2) levels (p < 0.05). Moreover, ER (0.75 g/kg) markedly ameliorated the production of the serum inflammatory cytokines IL-1ß and TNF-α (p < 0.01), and improved the activation of NLRP3 inflammasome signaling in the kidneys. Taken together, these data indicate that ER, a powerful and specific NLRP3 inhibitor, has multiple anti-HUA, anti-gout and anti-inflammatory effects. Our investigation is designed to experimentally support the conventional use of ER-containing classical herbal formulas in the treatment of HUA-related disorders and may add a new dimension to the clinical application of ER.

Pushing the Limit of Photo-Controlled Polymerization: Hyperchromic and Bathochromic Effects.

The photocatalyst (PC) zinc tetraphenylporphyrin (ZnTPP) is highly efficient for photoinduced electron/energy transfer reversible addition-fragmentation chain transfer (PET-RAFT) polymerization. However, ZnTPP suffers from poor absorbance of orange light by the so-called Q-band of the absorption spectrum (maximum absorption wavelength λmax = 600 nm, at which molar extinction coefficient εmax = 1.0×104 L/(mol·cm)), hindering photo-curing applications that entail long light penetration paths. Over the past decade, there has not been any competing candidate in terms of efficiency, despite a myriad of efforts in PC design. By theoretical evaluation, here we rationally introduce a peripheral benzo moiety on each of the pyrrole rings of ZnTPP, giving zinc tetraphenyl tetrabenzoporphyrin (ZnTPTBP). This modification not only enlarges the conjugation length of the system, but also alters the a1u occupied π molecular orbital energy level and breaks the accidental degeneracy between the a1u and a2u orbitals, which is responsible for the low absorption intensity of the Q-band. As a consequence, not only is there a pronounced hyperchromic and bathochromic effect (λmax = 655 nm and εmax = 5.2×104 L/(mol·cm)) of the Q-band, but the hyperchromic effect is achieved without increasing the intensity of the less useful, low wavelength absorption peaks of the PC. Remarkably, this strong 655 nm absorption takes advantage of deep-red (650-700 nm) light, a major component of solar light exhibiting good atmosphere penetration, exploited by the natural PC chlorophyll a as well. Compared with ZnTPP, ZnTPTBP displayed a 49% increase in PET-RAFT polymerization rate with good control, marking a significant leap in the area of photo-controlled polymerization.

Nucleotide and dinucleotide preference of segmented viruses are shaped more by segment: In case study of tomato spotted wilt virus.

Several studies have showed that the nucleotide and dinucleotide composition of viruses possibly follows their host species or protein coding region. Nevertheless, the influence of viral segment on viral nucleotide and dinucleotide composition is still unknown. Here, we explored through tomato spotted wilt virus (TSWV), a segmented virus that seriously threatens the production of tomatoes all over the world. Through nucleotide composition analysis, we found the same over-representation of A across all viral segments at the first and second codon position, but it exhibited distinct in segments at the third codon position. Interestingly, the protein coding regions which encoded by the same or different segments exhibit obvious distinct nucleotide preference. Then, we found that the dinucleotides UpG and CpU were overrepresented and the dinucleotides UpA, CpG and GpU were underrepresented, not only in the complete genomic sequences, but also in different segments, protein coding regions and host species. Notably, 100% of the data investigated here were predicted to the correct viral segment and protein coding region, despite the fact that only 67% of the data analyzed here were predicted to the correct viral host species. In conclusion, in case study of TSWV, nucleotide composition and dinucleotide preference of segment viruses are more strongly dependent on segment and protein coding region than on host species. This research provides a novel perspective on the molecular evolutionary mechanisms of TSWV and provides reference for future research on genetic diversity of segmented viruses.

Fast kV-switching and dual-layer flat-panel detector enabled cone-beam CT joint spectral imaging.

Purpose. Fast kV-switching (FKS) and dual-layer flat-panel detector (DL-FPD) technologies have been actively studied as promising dual-energy spectral imaging solutions for FPD-based cone-beam computed tomography (CT). However, cone-beam CT (CBCT) spectral imaging is known to face challenges in obtaining accurate and robust material discrimination performance. That is because the energy separation by either FKS or DL-FPD, alone, is still limited, along with apparently unpaired signal levels in the effective low- and high-energy projections in real applications, not to mention the x-ray scatter in cone-beam scan which will make the material decomposition almost impossible if no correction is applied. To further improve CBCT spectral imaging capability, this work aims to promote a source-detector joint multi-energy spectral imaging solution which takes advantages of both FKS and DL-FPD, and to conduct a feasibility study on the first tabletop CBCT system with the joint spectral imaging capability developed.Methods. For CBCT, development of multi-energy spectral imaging can be jointly realized by using an x-ray source with a generator whose kilo-voltages can alternate in tens of Hertz (i.e. FKS), and a DL-FPD whose top- and bottom-layer projections corresponds to different effective energy levels. Thanks to the complimentary characteristics inherent in FKS and DL-FPD, the overall energy separation will be significantly better when compared with FKS or DL-FPD alone, and the x-ray photon detection efficiency will be also improved when compared with FKS alone. In this work, a noise performance analysis using the Cramér-Rao lower bound (CRLB) method is conducted. The CRLB for basis material after a projection-domain material decomposition is derived, followed by a set of numerical calculations of CRLBs, for the FKS, the DL-FPD and the joint solution, respectively. To compensate for the slightly angular mismatch between low- and high- projections in FKS, a dual-domain projection completion scheme is implemented. Afterwards material decomposition from the complete projection data is carried out by using the maximum-likelihood method, followed by reconstruction of basis material and virtual monochromatic images (VMI). In this work, the first FKS and DL-FPD jointly enabled multi-energy tabletop CBCT system, to the best of our knowledge, has been developed in our laboratory. To evaluate its spectral imaging performance, a set of physics experiments are conducted, where the multi-energy and head phantoms are scanned using the 80/105/130 kVp switching pairs and projection data are collected using a prototype DL-FPD, whose both top and bottom layer of panels are composed of 550µm of cesium iodine (CsI) scintillators with no intermediate metal filter in-between.Results. The numerical simulations show that the joint spectral imaging solution can lead to a significant improvement in energy separation and lower noise levels in most of material decomposition cases. The physics experiments confirmed the feasibility and superiority of the joint spectral imaging, whose CNRs in the selected regions of interest of the multi-energy phantom were boosted by an average improvement of 21.9%, 20.4% for water basis images and 32.8%, 62.8% for iodine images when compared with that of the FKS and DL-FPD, respectively. For the head phantom case, the joint spectral imaging can effectively reduce the streaking artifacts as well, and the standard deviation in the selected regions of interest are reduced by an average decrement of 19.5% and 8.1% for VMI when compared with that of the FKS and DL-FPD, respectively.Conclusions. A feasibility study of the joint spectral imaging solution for CBCT by utilizing both the FKS and DL-FPD was conducted, with the first tabletop CBCT system having such a capability being developed, which exhibits improved CNR and is more effective in avoiding streaking artifacts as expected.

Multi-energy blended CBCT spectral imaging and scatter-decoupled material decomposition using a spectral modulator with flying focal spot (SMFFS).

BACKGROUND: Cone-beam CT (CBCT) has been extensively employed in industrial and medical applications, such as image-guided radiotherapy and diagnostic imaging, with a growing demand for quantitative imaging using CBCT. However, conventional CBCT can be easily compromised by scatter and beam hardening artifacts, and the entanglement of scatter and spectral effects introduces additional complexity. PURPOSE: The intertwined scatter and spectral effects within CBCT pose significant challenges to the quantitative performance of spectral imaging. In this work, we present the first attempt to develop a stationary spectral modulator with flying focal spot (SMFFS) technology as a promising, low-cost approach to accurately solving the x-ray scattering problem and physically enabling spectral imaging in a unified framework, and with no significant misalignment in data sampling of spectral projections. METHODS: To deal with the intertwined scatter-spectral challenge, we propose a novel scatter-decoupled material decomposition (SDMD) method for SMFFS, which consists of four steps in total, including (1) spatial resolution-preserved and noise-suppressed multi-energy "residual" projection generation free from scatter, based on a hypothesis of scatter similarity; (2) first-pass material decomposition from the generated multi-energy residual projections in non-penumbra regions, with a structure similarity constraint to overcome the increased noise and penumbra effect; (3) scatter estimation for complete data; and (4) second-pass material decomposition for complete data by using a multi-material spectral correction method. Monte Carlo simulations of a pure-water cylinder phantom with different focal spot deflections are conducted to validate the scatter similarity hypothesis. Both numerical simulations using a clinical abdominal CT dataset, and physics experiments on a tabletop CBCT system using a Gammex multi-energy CT phantom and an anthropomorphic chest phantom, are carried out to demonstrate the feasibility of CBCT spectral imaging with SMFFS and our proposed SDMD method. RESULTS: Monte Carlo simulations show that focal spot deflections within a range of 2 mm share quite similar scatter distributions overall. Numerical simulations demonstrate that SMFFS with SDMD method can achieve better material decomposition and CT number accuracy with fewer artifacts. In physics experiments, for the Gammex phantom, the average error of the mean values ( E RMSE ROI $E^{\text{ROI}}_{\text{RMSE}}$ ) in selected regions of interest (ROIs) of virtual monochromatic image (VMI) at 70 keV is 8 HU in SMFFS cone-beam (CB) scan, and 19 and 210 HU in sequential 80/120 kVp (dual kVp, DKV) CB scan with and without scatter correction, respectively. For the chest phantom, the E RMSE ROI $E^{\text{ROI}}_{\text{RMSE}}$ in selected ROIs of VMIs is 12 HU for SMFFS CB scan, and 15 and 438 HU for sequential 80/140 kVp CB scan with and without scatter correction, respectively. Also, the non-uniformity among selected regions of the chest phantom is 14 HU for SMFFS CB scan, and 59 and 184 HU for the DKV CB scan with and without a traditional scatter correction method, respectively. CONCLUSIONS: We propose a SDMD method for CBCT with SMFFS. Our preliminary results show that SMFFS can enable spectral imaging with simultaneous scatter correction for CBCT and effectively improve its quantitative imaging performance.

Glycyrrhizin and the Related Preparations: An Inspiring Resource for the Treatment of Liver Diseases.

Liver diseases and their related complications endanger the health of millions of people worldwide. The prevention and treatment of liver diseases are still serious challenges both in China and globally. With the improvement of living standards, the prevalence of metabolic liver diseases, including non-alcoholic fatty liver disease and alcoholic liver disease, has increased at an alarming rate, resulting in more cases of end-stage liver disease. Therefore, the discovery of novel therapeutic drugs for the treatment of liver diseases is urgently needed. Glycyrrhizin (GL), a triterpene glycoside from the roots of licorice plants, possesses a wide range of pharmacological and biological activities. Currently, GL preparations (GLPs) have certain advantages in the treatment of liver diseases, with good clinical effects and fewer adverse reactions, and have shown broad application prospects through multitargeting therapeutic mechanisms, including antisteatotic, anti-oxidative stress, anti-inflammatory, immunoregulatory, antifibrotic, anticancer, and drug interaction activities. This review summarizes the currently known biological activities of GLPs and their medical applications in the treatment of liver diseases, and highlights the potential of these preparations as promising therapeutic options and their alluring prospects for the treatment of liver diseases.

Toward the Rational Design of Organic Catalysts for Organocatalysed Atom Transfer Radical Polymerisation.

Thanks to their diversity, organic photocatalysts (PCs) have been widely used in manufacturing polymeric products with well-defined molecular weights, block sequences, and architectures. Still, however, more universal property-performance relationships are needed to enable the rational design of such PCs. That is, a set of unique descriptors ought to be identified to represent key properties of the PCs relevant for polymerisation. Previously, the redox potentials of excited PCs (PC*) were used as a good descriptor for characterising very structurally similar PCs. However, it fails to elucidate PCs with diverse chromophore cores and ligands, among which those used for polymerisation are a good representative. As showcased by model systems of organocatalysed atom transfer radical polymerisation (O-ATRP), new universal descriptors accounting for additional factors, such as the binding and density overlap between the PC* and initiator, are proposed and proved to be successful in elucidating the experimental performances of PCs in polymerisation. While O-ATRP is exemplified here, the approach adopted is general for studying other photocatalytic systems.

Circ_MAPK9 promotes STAT3 and LDHA expression by silencing miR-642b-3p and affects the progression of hepatocellular carcinoma.

BACKGROUND: Aberrant expression and activation of circular RNAs (circRNAs) are closely associated with various cancers. The role of circ_MAPK9 (hsa_circ_0001566) in cancer progression remains unknown. This study aims to investigate the function, mechanism and clinical significance of circ_MAPK9 in hepatocellular carcinoma (HCC). METHODS: Circ_MAPK9 expression on the microarray of tumor from clinical HCC patients was detected by in situ hybridization (ISH). Circ_MAPK9 knockdown was achieved with siRNAs in SMMC-7721 and SK-Hep1 HCC cell lines. The biological function of circ_MAPK9 was verified in vitro by CCK8 test, colony formation assay, transwell assay, PI-Annexin V staining, and in vivo by xenograft tumor in nude mice. Fluorescent in situ hybridization (FISH), subcellular fractionation assay, a dual-luciferase reporter assay and rescue experiments were employed for further mechanistic investigation. RESULTS: The expression of circ_MAPK9 was significantly up-regulated in HCC tissues and cells, which was found to be associated with poor prognosis. Patients with high expression of circ_MAPK9 had a shorter overall survival and disease-free survival in comparison to those with low circ_MAPK9 expression. Functional assays showed that circ_MAPK9 knockdown suppressed cellular proliferation, migration, invasion and tumor growth in vivo, and promoted apoptosis in HCC cells. Moreover, we found that circ_MAPK9 knockdown could inhibit aerobic glycolysis by decreasing the production of adenosine triphosphate (ATP) and lactic acid, which was mediated by lactate dehydrogenase (LDHA). Mechanistically, circ_MAPK9 functioned as ceRNA via sponging miR-642b-3p and alleviated the inhibitory effect of miR-642b-3p on its target signal transducer and activator of transcription 3 (STAT3) and LDHA, thereby leading to STAT3 activation and LDHA expression. CONCLUSIONS: Circ_MAPK9, as an oncogene, promotes HCC growth and metastasis through miR-642b-3p/STAT3-LDHA axis. Circ_MAPK9 could serve as a potential biomarker for HCC poor prognosis and diagnosis.