PpHY5 is involved in anthocyanin coloration in the peach flesh surrounding the stone.

Red coloration around the stone (Cs) is an important trait of canned peaches (Prunus persica). In this study, an elongated hypocotyl 5 gene in peach termed PpHY5 was identified to participate in the regulation of the Cs trait. The E3 ubiquitin ligase PpCOP1 was expressed in the flesh around the stone and could interact with PpHY5. Although HY5 is known to be degraded by COP1 in darkness, the PpHY5 gene was activated in the flesh tissue surrounding the stone at the ripening stages and its expression was consistent with anthocyanin accumulation. PpHY5 was able to promote the transcription of PpMYB10.1 through interacting with its partner PpBBX10. Silencing of PpHY5 in the flesh around the stone caused a reduction in anthocyanin pigmentation, while transient overexpression of PpHY5 and PpBBX10 resulted in anthocyanin accumulation in peach fruits. Moreover, transgenic Arabidopsis seedlings overexpressing PpHY5 showed increased anthocyanin accumulation in leaves. Our results improve our understanding of the mechanisms of anthocyanin coloration in plants.

High expression of NOTCH2 in gastric adenocarcinoma: A novel early diagnostic target.

BACKGROUND AND AIM: NOTCH2 is overexpressed in gastric cancer (GC), and its enhanced activity is significantly correlated with worse tumor characteristics. We aim to analyze the clinicopathologic correlation between NOTCH2 and the molecular typing of GC by immunohistochemistry and by transcriptional sequencing. METHODS: In this immunohistochemical study, we detected NOTCH2, EBER, P53, HER2, MLH1, MSH2, PMS2, and MSH6 and evaluated the association of NOTCH2 with clinical and histopathological features in a large single-institutional series of gastric adenocarcinomas (n = 488). The correlation was also investigated between immunohistochemical results and survival outcomes. RESULTS: High NOTCH2 expression (2+/3+) was found in 139/488 (27.5%) samples analyzed. NOTCH2 expression was correlated with early stage T1 (P < 0.0001), GC in the fundus (P = 0.0364), and positive P53 status (P = 0.0019). We did not find an association between NOTCH2 and HER2, microsatellite instability, EBER, and overall survival. Through RNA sequencing, it was revealed that NOTCH2 plays an important biological function in the pathogenesis and development of GC. CONCLUSIONS: Our findings suggested that NOTCH2 may be a potential diagnostic target for GC due to the fact that its high expression is closely associated with the early stages of cancer.

Integrated transcriptomics and metabolomics reveal the mechanism of intestinal damage upon acute patulin exposure in mice.

Mycotoxin contamination has become a major food safety issue and greatly threatens human and animal health. Patulin (PAT), a common mycotoxin in the environment, is exposed through the food chain and damages the gastrointestinal tract. However, its mechanism of enterotoxicity at the genetic and metabolic levels remains to be elucidated. Herein, the intestinal histopathological and biochemical indices, transcriptome, and metabolome of C57BL/6 J mice exposed to different doses of PAT were successively assessed, as well as the toxicokinetics of PAT in vivo. The results showed that acute PAT exposure induced damaged villi and crypts, reduced mucus secretion, decreased SOD and GSH-Px activities, and enhanced MPO activity in the small intestine and mild damage in the colon. At the transcriptional level, the genes affected by PAT were dose-dependently altered in the small intestine and fluctuated in the colon. PAT primarily affected inflammation-related signaling pathways and oxidative phosphorylation in the small intestine and immune responses in the colon. At the metabolic level, amino acids decreased, and extensive lipids accumulated in the small intestine and colon. Seven metabolic pathways were jointly affected by PAT in two intestinal sites. Moreover, changes in PAT products and GST activity were detected in the small intestinal tissue but not in the colonic tissue, explaining the different damage degrees of the two sites. Finally, the integrated results collectively explained the toxicological mechanism of PAT, which damaged the small intestine directly and the colon indirectly. These results paint a clear panorama of intestinal changes after PAT exposure and provide valuable information on the exposure risk and toxic mechanism of PAT.

Gas chromatography-ion mobility spectrometry (GC-IMS) technique and its recent applications in grain research.

Grains are the primary source of food for most people worldwide and constitute a major source of carbohydrates. Many novel technologies are being employed to ensure the safety and reliability of grain supply and production. Gas chromatography-ion mobility spectrometry (GC-IMS) can effectively separate and sensitively detect volatile organic compounds. It possesses advantages such as speed, convenience, high sensitivity, no pretreatment, and wide applicability. In recent years, many studies have shown that the application of GC-IMS technology for grain flavor analysis can play a crucial role in grains. This article elucidates the working principle of GC-IMS technology, reviews the application of GC-IMS in grains in the past 5 years. GC-IMS technology is mainly applied in four aspects in grains. In grain classification, it distinguishes varieties, quality, origin, production year, and processing methods based on the trace differences in volatile organic compounds, thereby fulfilling various grain classification requirements such as origin tracing, geographical indication product recognition, variety identification, production year identification, and detection of counterfeit and inferior grain samples. In optimizing the processing technology of grains and their products, it can improve food flavor, reduce undesirable flavors, and identify better processing parameters. In grain storage, it can determine the storage time, detect spoilage phenomena such as mold and discoloration during storage, eliminate pests affecting storage, and predict the vitality of seeds after storage. In aroma evaluation of grains and their processed products, it can assess the impact of new raw materials, new technologies, fermentation processes, and even oral processing on the quality of grain products. This article also summarizes the characteristics of GC-IMS technology, compiles typical grain flavor compounds, and provides prospects for the future application of GC-IMS. © 2024 Society of Chemical Industry.

XPO1 is a new target of homoharringtonine (HHT): Making NPMc+ AML cells much more sensitive to HHT treatment.

Acute myeloid leukemia (AML) is a heterogeneous disease and about one third of AML patients carry nucleophosmin (NPM1) mutation. Because 95% mutations give NPM1 an additional nuclear export signaling (NES) and dislocate NPM1 in cytoplasm (NPMc+), relocating NPM1 in nucleus provide an innovative strategy for treating this type of AML. The nuclear export of NPM1 depends on the nuclear protein export receptor XPO1, which recognizes the NES sequence on NPM1. Homoharringtonine (HHT) is a first-line chemotherapy drug of AML, yet the exact mechanism of its anti-AML activity is elusive. In this study, we found that HHT can directly target XPO1 to its NES-binding cleft, bind to Cys528 of XPO1, and inhibits its nuclear transport function. In addition, HHT can block NPMc+ proteins nuclear export and thus make NPMc+ AML cells much more sensitive to HHT treatment. Furthermore, the sensitivity of NPMc+ AML cells to HHT is a universal phenomenon irrespective of the different genetic lesions of AML. Taken together, our findings suggest that XPO1 is a new target of HHT and provide a novel strategy for NPMc+ AML treatment.

Visible-Light-Induced Diradical-Mediated ipso-Cyclization towards Double Dearomative [2+2]-Cycloaddition or Smiles-Type Rearrangement.

When mono-radical ipso-cyclization of aryl sulfonamides tend to undergo Smiles-type rearrangement through aromatization-driven C-S bond cleavage, diradical-mediated cyclization must perform in a distinct reaction pathway. It is interesting meanwhile challenging to tune the rate of C-S bond cleavage to achieve a chemically divergent reaction of (hetero) aryl sulfonamides in a visible-light induced energy transfer (EnT) reaction pathway involving diradical species. Herein a chemically divergent reaction based on the designed indole-tethered (hetero)arylsulfonamides is reported which involves a diradical-mediated ipso-cyclization and a controllable cleavage of an inherent C-S bond. The combined experimental and computational results have revealed that the cleavage of the C-S bond in these substrates can be controlled by tuning the heteroaryl moieties: a) If the (hetero)aryl is thienyl, furyl, phenanthryl, etc., the radical coupling of double dearomative diradicals (DDDR) precedes over C-S bond cleavage to afford cyclobutene fused indolines by double dearomative [2+2]-cycloaddition; b) if the (hetero)aryl is phenyl, naphthyl, pyridyl, indolyl etc., the cleavage of C-S bond in DDDR is favored over radical coupling to afford biaryl products.

A 6-month prognostic nomogram incorporating hemoglobin level for intracerebral hemorrhage in younger adults.

OBJECTIVE: Intracerebral hemorrhage (ICH) is the second most common subtype of stroke, with high mortality and morbidity. At present, there are no effective 6-month prognostic markers, particularly for younger patients. The aim of this research was to construct a new valuable prognostic nomogram model incorporating haemoglobin levels for adult patients with ICH. METHODS: Patients aged between 18 and 50 presenting with intracerebral haemorrhage at the Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology between January 1st 2012 and December 31st 2018 were included in this retrospective study. Independent factors of prognosis were identified by univariate and multivariate logistic regression analyses, and a new nomogram model was constructed and validated. The clinical value of the nomogram model was subsequently explored utilizing decision curve analysis and clinical impact curves. RESULTS: In total, 565 patients were enrolled in this study, 117 (20.7%) of whom developed an unfavourable prognosis. Infratentorial lesion (adjusted odds ratio [aOR] = 3.708, 95% confidence interval [CI], 1.490-9.227; P = 0.005) was the most significant unfavourable outcome. Age ([aOR] = 1.054; 95% CI, 1.014-1.096; P = 0.008), hematoma volume (aOR = 1.014, 95% CI, 1.002-1.027; P = 0.024), haemoglobin (aOR = 0.981, 95% CI, 0.969-0.993; P = 0.002), blood glucose (aOR = 1.135, 95% CI, 1.037-1.241; P = 0.005) and NIHSS (aOR = 1.105, 95% CI, 1.069-1.141; P < 0.001) were independent risk factors. Based on these 6 factors, the nomogram can be employed to predict early functional prognosis with high accuracy (AUC 0.791). Decision curve analysis and clinical impact curves showed an increased net benefit for utilizing the nomogram. CONCLUSION: The haemoglobin level at admission may be an easily overlooked factor in clinical work. This new nomogram model could be a promising and convenient tool to predict the early functional prognosis of adults with ICH. More prospective multicentre studies are needed to validate these findings.

COVID-19 vaccination for patients with epilepsy: A Chinese expert consensus.

Coronavirus disease-2019 (COVID-19) first emerged in late 2019 and has since spread worldwide. More than 600 million people have been diagnosed with COVID-19, and over 6 million have died. Vaccination against COVID-19 is one of the best ways to protect humans. Epilepsy is a common disease, and there are approximately 10 million patients with epilepsy (PWE) in China. However, China has listed "uncontrolled epilepsy" as a contraindication for COVID-19 vaccination, which makes many PWE reluctant to get COVID-19 vaccination, greatly affecting the health of these patients in the COVID-19 epidemic. However, recent clinical practice has shown that although a small percentage of PWE may experience an increased frequency of seizures after COVID-19 vaccination, the benefits of COVID-19 vaccination for PWE far outweigh the risks, suggesting that COVID-19 vaccination is safe and recommended for PWE. Nonetheless, vaccination strategies vary for different PWE, and this consensus provides specific recommendations for PWE to be vaccinated against COVID-19.

Functional characterization of a cold related flavanone 3-hydroxylase from Tetrastigma hemsleyanum: an in vitro, in silico and in vivo study.

Tetrastigma hemsleyanum Diels et Gilg, a traditional Chinese medicine, frequently suffers from cold damage in the winter, leading to lower yields. There is a pressing need to improve cold resistance; however, the mechanisms underlying T. hemsleyanum responses to cold stress are still not clearly understood. Here, we explored the function of the flavanone 3-hydroxylase gene (ThF3H) in T. hemsleyanum under cold treatment. The open reading frame of ThF3H is 1092 bp and encodes 363 amino acid residues. In vitro, the ThF3H enzyme was expressed in E. coli and successfully catalyzed naringenin and eriodictyol into dihydrokaempferol and dihydroquercetin, respectively. ThF3H exhibited a higher affinity for naringenin than for eriodictyol, which was in accordance with an in silico molecular docking analysis. The optimal pH and temperature for ThF3H activity were 7.0 and 30 °C, respectively. In vivo, overexpression of the ThF3H gene enhanced the cold tolerance of transgenic Arabidopsis lines, which was likely due to the increase in flavonoids. Collectively, the function of a cold-related ThF3H in the flavonoid biosynthesis pathway may be helpful for improving the cold tolerance of T. hemsleyanum through molecular breeding techniques.

Good functional outcome following bilateral external capsule hemorrhage mimicking bilateral basal ganglia hemorrhage in a coma patient.

Simultaneous spontaneous bilateral external capsule hemorrhage is a rare clinical entity with extremely poor outcome. However, knowledge on the effective management of this fatal disease is limited. Herein,we described a case of a 42-year-old man with acute coma and quadriplegia as well as respiratory failure related to the disease. The patient underwent minimally invasive surgery plus local thrombolysis. Consequently, he recovered with satisfactory neurological function recovery on the 180th day of follow-up.

Comparative study on acute management of intracerebral haematoma using local thrombolysis in moyamoya and non-moyamoya patients: a single institution experience.

PURPOSE: Spontaneous intracerebral haemorrhage (ICH) is the main presentation in adults with moyamoya disease (MMD), an unusual clinical entity with a poor prognosis. However, optimal management in the acute stage of ICH in patients with MMD remains a challenge. Since minimally invasive surgery (MIS) plus local thrombolysis has emerged as a promising strategy for ICH, we aimed to describe our experience of performing this procedure in this special population in the acute phase, while focusing on its efficacy and safety. MATERIALS AND METHODS: The medical data of patients with ICH treated with MIS and local thrombolysis between November 2013 and December 2017 were retrospectively reviewed at our institution. MMD was identified based on the angiographic images. The primary outcome was postoperative intracranial rebleeding. The secondary outcomes were 30-day mortality and 6-month outcome graded using the modified Rankin scale (mRS). Logistic regression was applied to explore independent risk factors for the above outcomes. RESULTS: A cohort of consecutive 337 ICH patients was analysed, of whom 14 (4.15%) were diagnosed with MMD. In total, 36 (11.46%) patients experienced postoperative intracranial rehaemorrhage, of which one patient had MMD. No significant difference was found between the patients with and without MMD regarding postoperative rebleeding (9.09% vs. 11.55%, p = 1.000). Additionally, the 30-day mortality of patients with MMD was 21.42% (3/14), which was not significantly different from that of non-MMD patients (10.83%; p = 0.201). Moreover, 53.8% of patients had poor outcomes at the 6-month follow-up among MMD patients, similar to 43.9% of patients without MMD (p = 0.573). The coexistence of MMD failed to show a significant association with postoperative intracranial rebleeding (p = 0.348), 30-day mortality (p = 0.211), or poor outcome at the 6-month follow-up (p = 0.450). CONCLUSION: Our findings suggest that coexistent MMD is not associated with an increased risk of postoperative rebleeding or poor outcome after local thrombolysis for ICH.

Genome-Wide Characterization and Functional Analysis of ABCG Subfamily Reveal Its Role in Cutin Formation in Cotton.

ATP-binding cassette transporter G (ABCG) has been shown to be engaged in export of broad-spectrum compounds with structural differences, but little is known concerning its role in cutin formation of cotton (Gossypium spp.). In this study, we conduct a genome-wide survey and detected 69, 71, 124 and 131 ABCG genes within G. arboretum, G. raimondii, G. hirsutum and G. barbadense, separately. The above ABCGs could be divided into four groups (Ia, Ib, Ic, II). Some ABCG genes such as GhABCG15, whose homologous gene transports cuticular lipid in Arabidopsis, was preferentially expressed in the development of fiber. A weighted gene co-expression network analysis (WGCNA) demonstrated that GhABCG expression was significantly associated with the amount of 16-Hydroxypalmitate (a main component of cutin precursor) in cotton fibers. Further, silencing of GhABCG15 by virus-induced gene silencing (VIGS) in cotton generated brightened and crinkled leaves as well as reduced thickness of cuticle and increased permeability. Chemical composition analysis showed the cutin content in GhABCG15-silenced leaves had decreased while the wax content had increased. Our results provide an insight for better understanding of the role of the Gossypium ABCG family and revealed the essential role of GhABCGs in cotton cutin formation.

TFEB in Alzheimer's disease: From molecular mechanisms to therapeutic implications.

Alzheimer's disease (AD), an age-dependent neurodegenerative disorder, is the most prevalent neurodegenerative disease worldwide. The primary pathological hallmarks of AD are the deposition of ß-amyloid plaques and neurofibrillary tangles. Autophagy, a pathway of clearing damaged organelles, macromolecular aggregates, and long-lived proteins via lysosomal degradation, has emerged as critical for proteostasis in the central nervous system (CNS). Studies have demonstrated that defective autophagy is strongly implicated in AD pathogenesis. Transcription factor EB (TFEB), a master transcriptional regulator of autophagy, enhances the expression of related genes that control autophagosome formation, lysosome function, and autophagic flux. The study of TFEB has greatly increased over the last decade, and the dysfunction of TFEB has been reported to be strongly associated with the pathogenesis of many neurodegenerative disorders, including AD. Here, we delineate the basic understanding of TFEB dysregulation involved in AD pathogenesis, highlighting the existing work that has been conducted on TFEB-mediated autophagy in neurons and other nonneuronal cells in the CNS. Additionally, we summarize the small molecule compounds that target TFEB-regulated autophagy involved in AD therapy. Our review may yield new insights into therapeutic approaches by targeting TFEB and provide a broadly applicable basis for the clinical treatment of AD.

Identification of a novel HOOK3-FGFR1 fusion gene involved in activation of the NF-kappaB pathway.

BACKGROUND: Rearrangements involving the fibroblast growth factor receptor 1 (FGFR1) gene result in 8p11 myeloproliferative syndrome (EMS), which is a rare and aggressive hematological malignancy that is often initially diagnosed as myelodysplastic syndrome (MDS). Clinical outcomes are typically poor due to relative resistance to tyrosine kinase inhibitors (TKIs) and rapid transformation to acute leukemia. Deciphering the transcriptomic signature of FGFR1 fusions may open new treatment strategies for FGFR1 rearrangement patients. METHODS: DNA sequencing (DNA-seq) was performed for 20 MDS patients and whole exome sequencing (WES) was performed for one HOOK3-FGFR1 fusion positive patient. RNA sequencing (RNA-seq) was performed for 20 MDS patients and 8 healthy donors. Fusion genes were detected using the STAR-Fusion tool. Fluorescence in situ hybridization (FISH), quantitative real-time PCR (qRT-PCR), and Sanger sequencing were used to confirm the HOOK3-FGFR1 fusion gene. The phosphorylation antibody array was performed to validate the activation of nuclear factor-kappaB (NF-kappaB) signaling. RESULTS: We identified frequently recurrent mutations of ASXL1 and U2AF1 in the MDS cohort, which is consistent with previous reports. We also identified a novel in-frame HOOK3-FGFR1 fusion gene in one MDS case with abnormal monoclonal B-cell lymphocytosis and ring chromosome 8. FISH analysis detected the FGFR1 break-apart signal in myeloid blasts only. qRT-PCR and Sanger sequencing confirmed the HOOK3-FGFR1 fusion transcript with breakpoints located at the 11th exon of HOOK3 and 10th exon of FGFR1, and Western blot detected the chimeric HOOK3-FGFR1 fusion protein that is presumed to retain the entire tyrosine kinase domain of FGFR1. The transcriptional feature of HOOK3-FGFR1 fusion was characterized by the significant enrichment of the NF-kappaB pathway by comparing the expression profiling of FGFR1 fusion positive MDS with 8 healthy donors and FGFR1 fusion negative MDS patients. Further validation by phosphorylation antibody array also showed NF-kappaB activation, as evidenced by increased phosphorylation of p65 (Ser 536) and of IKBalpha (Ser 32). CONCLUSIONS: The HOOK3-FGFR1 fusion gene may contribute to the pathogenesis of MDS and activate the NF-kappaB pathway. These findings highlight a potential novel approach for combination therapy for FGFR1 rearrangement patients.

Genome-wide association study reveals novel quantitative trait loci and candidate genes of lint percentage in upland cotton based on the CottonSNP80K array.

KEY MESSAGE: Thirty-four SNPs corresponding with 22 QTLs for lint percentage, including 13 novel QTLs, was detected via GWAS. Two candidate genes underlying this trait were also identified. Cotton (Gossypium spp.) is an important natural textile fiber and oilseed crop cultivated worldwide. Lint percentage (LP, %) is one of the important yield components, and increasing LP is a core goal of cotton breeding improvement. However, the genetic and molecular mechanisms underlying LP in upland cotton remain unclear. Here, we performed a genome-wide association study (GWAS) for LP based on 254 upland cotton accessions in four environments as well as the best linear unbiased predictors using the high-density CottonSNP80K array. In total, 41,413 high-quality single-nucleotide polymorphisms (SNPs) were screened, and 34 SNPs within 22 quantitative trait loci (QTLs) were significantly associated with LP. In total, 175 candidate genes were identified from two major genomic loci (GR1 and GR2), and 50 hub genes were identified through GO enrichment and weighted gene co-expression network analysis. Two candidate genes (Gh_D01G0162 and Gh_D07G0463), which may participate in early fiber development to affect the number of fiber protrusions and LP, were also identified. Their genetic variation and expression were verified by linkage disequilibrium blocks, haplotypes, and quantitative real-time polymerase chain reaction, respectively. The weighted gene interaction network analysis showed that the expression of Gh_D07G0463 was significantly correlated with that of Gh_D01G0162. These identified SNPs, QTLs and candidate genes provide important insights into the genetic and molecular mechanisms underlying variations in LP and serve as a foundation for LP improvement via marker-assisted breeding.

Design, synthesis and evaluation of a series of novel long-acting dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is one of the most popular chronic diseases around the whole world. To improve the compliance of patients, long-acting antidiabetic drugs needed to be developed. Dipeptidyl peptidase-4 (DPP-4) inhibitors are becoming increasingly important in the T2DM treatment due to the favorable properties. In the present study, a series of new substituted dihydropyrido [4',3':3,4] pyrazolo [1,5-a] pyrimidin-9(10H)-yl)-2-(2,5-difluorophenyl)tetrahydro-2H-pyran-3-amine were designed and synthesized as potent DPP-4 inhibitors. All compounds were characterized by 1H NMR, 13C NMR and HRMS and were evaluated in vitro. The inhibitory activity ranged from 0.43 to 12.70 µM while the inhibitory activity of positive control (omarigliptin) was 3.63 µM on DPP-4 in Caco-2 cells. Then pharmacokinetic studies were carried out in rats and compound 6c was finally selected for the further study because of its better pharmacokinetic profile. Additionally, preclinical pharmacological study of compound 6c exhibited extraordinary efficacy in vivo and good safety profile. In conclusion, compound 6c was considered as a promising DPP-4 inhibitor, which could be taken once a week or once every two weeks for the treatment of T2DM. More comprehensive researches will be carried out in the future for the further development of compound 6c.

A candidate PpRPH gene of the D locus controlling fruit acidity in peach.

KEY MESSAGE: A candidate gene, designate PpRPH, in the D locus was identified to control fruit acidity in peach. Fruit acidity has a strong impact on organoleptic quality of fruit. Peach fruit acidity is controlled by a large-effect D locus on chromosome 5. In this study, the D locus was mapped to a 509-kb interval, with two markers, 5dC720 and 5C1019, co-segregating with the non-acid/acid trait of peach fruit. Within this interval, a candidate gene encoding a putative small protein, designated PpRPH, showed a consistency between gene expression and fruit acidity, with up- and down-regulation in non-acidic and acidic fruits, respectively. Transient ectopic expression of PpRPH in tobacco leaves caused an increase of pH by approximately 40% compared to the control transformed with empty vector. Whereas, the concentrations of citrate and malate decreased significantly by 22% and 37%, respectively, with respect to the empty vector control. All these results suggest that PpRPH is a strong candidate gene of the D locus. These findings contribute to our overall understanding of the complex mechanism underlying fruit acidity in peach as well as that in other fruit crops.

Obacunone Attenuates Liver Fibrosis with Enhancing Anti-Oxidant Effects of GPx-4 and Inhibition of EMT.

Obacunone, a limonin triterpenoid extracted from Phellodendronchinense Schneid or Dictamnus dasycarpusb Turcz plant, elicits a variety of pharmacological effects such as anti-inflammatory, anti-neoplastic, anti-oxidation, and anti-lung-fibrosis ones. However, the anti-fibrotic effect of obacunone and the detailed underlying mechanism in liver fibrosis remain unclear. Liver fibrosis is a debilitating disease threatening human health. Transforming growth factor (TGF)-ß/P-Smad is a major pathway of fibrosis featured with epithelia mesenchymal transformations (EMT) and collagen depositions, accompanying with excessive oxygen-free radicals. Nrf-2 acts as a key anti-oxidative regulator driving the expressions of various antioxidant-related genes. Glutathionperoxidase-4 (GPx-4) is a member of the glutathione peroxidase family that directly inhibits phospholipid oxidation to alleviate oxidative stress. In the present study, we aimed to explore the role of obacunone in mouse liver fibrosis model induced by carbon tetrachloride (CCl4) and in hepatic stellate cells (LX2 cell line) challenging with TGF-ß. Obacunone demonstrated potent ameliorative effects on liver fibrosis both in activated LX2 and in mice liver tissues with reduced levels of α-SMA, collagen1, and vimentin. Obacunone also remarkably suppressed the TGF-ß/P-Smad signals and EMT process. Meanwhile, obacunone exerted a potent anti-oxidation effect by reducing the levels of reactive oxygen species (ROS) in both models. The antioxidant effect of obacunone was attributed to the activation of GPx-4 and Nrf-2. In addition, the therapeutic effect of obacunone on LX2 cells was significantly removed in vitro plus with GPx-4 antagonist RSL3, in parallel with the re-elevated levels of ROS. Thus, we demonstrate that obacunone is able to attenuate liver fibrosis via enhancing GPx-4 signal and inhibition of the TGF-ß/P-Smad pathway and EMT process.

Mitigation effects of phlorizin immersion on acrylamide formation in fried potato strips.

BACKGROUND: Several researches reported that natural polyphenols affected acrylamide formation of fried products. However, the effects of different variety of polyphenols on acrylamide formation were distinct. In this study, we isolated and purified phlorizin from apples and identified the influence of phlorizin immersion on acrylamide formation and sensory properties of fried potato strips with regard to the immersion concentration, time and temperature. RESULTS: The acrylamide formation of fried samples decreased as the phlorizin concentration increased from 0 to 0.3 g kg-1 , and 0.14 g kg-1 could be selected as the suitable immersion concentration to dramatically inhibit acrylamide formation with considering the cost of industrial production. Additionally, the acrylamide formation significantly reduced from 8.71 × 10-3 to 2.13 × 10-3 g kg-1 lyophilized weight (LW) with immersion time from 0 to 120 min, and 60 min could be selected to significantly reduce acrylamide formation in consideration of efficiency of the large-scale industrial processing. However, the effect of phlorizin immersion temperature on acrylamide formation of fried samples was not significant. Compared to the fried samples without immersion, the phlorizin immersion improved the color properties and the change of texture parameters was slight. CONCLUSION: The fresh potato strips immersed in the phlorizin solution of 0.14 g kg-1 at 40 °C for 60 min before frying could significantly decrease acrylamide formation of fried samples and retain the majority of fresh sensorial properties. The significant correlations obtained between sensory properties and acrylamide content indicated the sensory properties could be used as the indicator of acrylamide levels during industrial processing. © 2020 Society of Chemical Industry.

Hydroxychloroquine inhibiting neutrophil extracellular trap formation alleviates hepatic ischemia/reperfusion injury by blocking TLR9 in mice.

Hepatic ischemia/reperfusion (I/R) injury may arise after partial hepatectomy and liver transplantation. Neutrophil extracellular traps (NETs) were involved in hepatic I/R injury. This study tested the hypothesis that blocking NETs formation could be a potential therapeutic target against hepatic I/R injury. NETs were excessively formed within liver and in serum of I/R mice models and were testified to be an independent contributor to hepatic I/R injury. Hydroxychloroquine (HCQ) alleviated hepatic I/R injury by inhibiting NETs formation in SCID and c57BL/6 mice models. In vitro, HCQ inhibited neutrophils to form NETs at a concentration of 100 µg/ml. CpG-ODN reversed the effect of HCQ inhibiting NETs formation. HCQ inhibited PAD4 and Rac2 expressions by blocking TLR9. NETs are essential contributors to hepatic I/R injury. HCQ blocking TLR9 protects against hepatic I/R injury by inhibiting NETs formation, which may suggest utility of HCQ or other TLR9 agonists for preventing hepatic I/R injury in clinical practices.