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Aim: To identify distinct profiles of fear of cancer recurrence (FCR) among breast cancer patients of reproductive age, investigate the relationship between these profiles and reproductive concerns and explore potential risk factors encompassing sociodemographic, clinical and reproductive characteristics., Design: A cross-sectional study was conducted from January 2022 to September 2022., Methods: A convenience sample of 210 reproductive-aged breast cancer patients completed a questionnaire that included a general information section, the Fear of Progression Questionnaire-Short Form (FoP-Q-SF) and the Reproductive Concerns After Cancer Scale (RCAC). Latent profile analysis was conducted using the scores of the 12 items from the FoP-Q-SF as explicit variables, while univariate and multiple logistic regression analyses were employed for statistical analysis., Results: Three latent variables were identified: low FCR-stable group (27.6%), moderate FCR-uneasy group (17.2%) and high FCR-intense group (55.2%). This study found that FCR was predicted by age, education level, cancer stage, chemotherapy and fertility intention. Furthermore, patients with heightened reproductive concerns exhibited a higher likelihood of belonging to the high FCR-intense group., Conclusion: These findings indicate that FCR varies among breast cancer patients of reproductive age and demonstrates individual differences., Implication: Early identification of FCR patterns in patients is crucial for medical professionals, with particular attention given to those in the high-intensity FCR group. Tailored prevention and care strategies should be implemented based on the unique characteristics and influencing factors associated with different potential categories of FCR among patients of childbearing age with breast cancer., Patient or Public Contribution: No patient or public contribution., (© 2024 John Wiley & Sons Ltd.)

Diaphorina citri is a serious citrus pest. Dinotefuran is highly insecticidal against D. citri . To analyze the sublethal effects of dinotefuran on D. citri adults, an indoor toxicity test was performed, which revealed that the lethal concentration 50 (LC 50 ) values were 4.23 and 0.50 μg/mL for 24 and 48 h treatments, respectively. RNA-Seq led to the identification of 71 and 231 differentially expressed genes (DEGs) after dinotefuran treatments with LC 20 and LC 50 doses, respectively. Many of the DEGs are significantly enriched in the apoptosis pathway. Dinotefuran-induced apoptosis in the gut cells was confirmed through independent assays of 4',6-diamidino-2-phenylindole (DAPI) and TdT-mediated dUTP nick end labeling (TUNEL) staining. Increased levels of reactive oxygen species (ROS) and a loss of mitochondrial membrane potential were observed. Four caspase genes were identified, and dinotefuran treatments resulted in increased mRNA levels of DcCasp1 and DcCasp3a . These findings shed light on the sublethal effects of dinotefuran on D. citri .

Aberrant activation of the Wnt/β-catenin signaling is associated with tumor development, and blocking β-catenin/BCL9 is a novel strategy for oncogenic Wnt/β-catenin signaling. Herein, we presented two novel β-catenin variations and exposed conformational dynamics in several β-catenin crystal structures at the BCL9 binding site. Furthermore, we identified a class of novel urea-containing compounds targeting β-catenin/BCL9 interaction. Notably, the binding modalities of inhibitors were greatly affected by the conformational dynamics of β-catenin. Among them, 28 had a strong affinity for β-catenin ( K d = 82 nM), the most potent inhibitor reported. In addition, 13 and 35 not only activate T cells but also promote the antigen presentation of cDC1, showing robust antitumor efficacy in the CT26 model. Collectively, our study demonstrated a series of potent small-molecule inhibitors targeting β-catenin/BCL9, which can enhance antigen presentation and activate cDC1 cells, delivering a potential strategy for boosting innate and adaptive immunity to overcome immunotherapy resistance.

Purpose: This study aimed to investigate reproductive concerns among breast cancer patients of reproductive age, analyze the influencing factors, explore the relationship between coping styles, fear of progression (FOP), and reproductive concerns, and identify the multiple effects of coping styles on the relationship between FOP and reproductive concerns among Chinese breast cancer patients., Methods: A cross-sectional, descriptive study was conducted among breast cancer patients in four tertiary grade A hospitals in Fujian, China, from January 2022 to September 2022. A total of 210 patients were recruited to complete paper-based questionnaires, which included the general data questionnaires, the Reproductive Concerns After Cancer Scale (RCACS), the Fear of Progression Questionnaire-Short Form (FOP-Q-SF), and the Medical Coping Modes Questionnaire (MCMQ). Structural equation models were utilized to evaluate the multiple effects of coping styles on FOP and reproductive concerns., Results: Reproductive concerns in breast cancer patients had a mean score of 53.02 (SD, 10.69), out of a total score of 90, and coping styles for cancer (confrontation, avoidance) were closely associated with FOP and reproductive concerns. FOP showed a significant positive correlation with reproductive concerns (r = .52, p < .01). At the same time, confrontation was significantly negatively correlated with both FOP (r = -.28, p < .01) and reproductive concerns (r = -.39, p < .01). Avoidance was positively correlated to both FOP (r = .25, p < .01) and reproductive concerns (r = .34, p < .01). The impact of FOP on reproductive concerns is partially mediated by confrontation and avoidance, with effect sizes of .07 and .04, respectively. These mediating factors account for 22.0% of the total effect., Conclusions: The FOP directly impacted reproductive concerns, while coping styles could partially mediate the association between FOP and reproductive concerns. This study illustrates the role of confrontation and avoidance in alleviating reproductive concerns, suggesting that it is necessary to focus on the changes in reproductive concerns among reproductive-age breast cancer patients. Healthcare professionals can improve disease awareness and reduce patients' FOP, thereby promoting positive psychological and coping behaviors and ultimately alleviating reproductive concerns., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

During diabetic kidney disease (DKD), ectopic ceramide (CER) accumulation in renal tubular epithelial cells (RTECs) is associated with interstitial fibrosis and albuminuria. As RTECs are primarily responsible for renal energy metabolism, their function is intimately linked to mitochondrial quality control. The role of CER synthesis in the progression of diabetic renal fibrosis has not been thoroughly investigated. In this study, we observed a significant upregulation of ceramide synthase 6 ( Cers6 ) expression in the renal cortex of db/db mice, coinciding with increased production of CER (d18:1/14:0) and CER (d18:1/16:0) by Cer6. Concurrently, the number of damaged mitochondria in RTECs rose. Cers6 deficiency reduced the abnormal accumulation of CER (d18:1/14:0) and CER (d18:1/16:0) in the kidney cortex, restoring the PTEN-induced kinase 1 (PINK1)-mediated mitophagy in RTECs, and resulting in a decrease in damaged mitochondria and attenuation of interstitial fibrosis in DKD. Automated docking analysis suggested that both CER (d18:1/14:0) and CER (d18:1/16:0) could bind to the PINK1 protein. Furthermore, inhibiting PINK1 expression in CERS6 knockdown HK-2 cells diminished the therapeutic effect of CERS6 deficiency on DKD. In summary, CERS6-derived CER (d18:1/14:0) and CER (d18:1/16:0) inhibit PINK1-regulated mitophagy by possibly binding to the PINK1 protein, thereby exacerbating the progression of renal interstitial fibrosis in DKD. NEW & NOTEWORTHY This article addresses the roles of ceramide synthase 6 ( CERS6 ) and CERS6-derived ceramides in renal tubular epithelial cells of diabetic kidney disease (DKD) associated interstitial fibrosis. Results from knockdown of CERS6 adjusted the ceramide pool in kidney cortex and markedly protected from diabetic-induced kidney fibrosis in vivo and in vitro. Mechanically, CERS6-derived ceramides might interact with PINK1 to inhibit PINK1/Parkin-mediated mitophagy and aggravate renal interstitial fibrosis in DKD.

Ethnopharmacological Relevance: Huanglian Jiedu Decoction (HLJDD) is a traditional heat-dissipating and detoxicating prescription used in Chinese medicine and has been extensively applied in the clinical treatment of ischemic stroke. Preliminary research confirmed that HLJDD exerts a neuroprotective effect on brain tissue injury caused by cerebral ischemia by promoting angiogenesis. However, the components of HLJDD responsible for its medicinal activity in ischemic injury remain unclear., Aim of the Study: The aim of this study was to identify the active components of HLJDD that could promote angiogenesis and investigate its underlying mechanism, as well as Hypoxia-inducible factor-1α (HIF-1α)/Vascular endothelial growth factor (VEGF) signalings in human umbilical vein endothelial cells (HUVECs)., Materials and Methods: The specific binding components of HLJDD with HUVECs were isolated and identified through a combination of live cell biospecific extraction, solid-phase extraction, and ultra performance liquid chromatography (UPLC)-Orbitrap Fusion Tribrid mass spectrometry (MS). Their pharmacological activity against oxygen-glucose deprivation-reperfusion (OGD/R) injury and in vitro pro-angiogenesis was validated using Cell Counting Kit-8 (CCK-8) and tube formation analysis, respectively. Finally, we explored the effect of active ingredients on the expression levels of HIF-1α and VEGF using enzyme-linked immunosorbent assay. Molecular docking was used to predict the potential binding of six active components to phosphoinositide 3-kinase (PI3K), serine/threonine-specific protein kinase (AKT) and Von Hippel-Lindau (VHL) proteins, which are involved in the regulation of HIF-1α and are highly associated with angiogenesis., Results: A total of 13 HUVECs-specific HLJDD components were identified, and 10 of them were shown to protect against OGD/R injury. We were the first to demonstrate that two of these components have a protective role in OGD/R-induced HUVECs injury. Additionally, seven of these 10 components exhibited angiogenesis-promoting activity, and two of these components were shown, for the first time, to promote angiogenesis in HUVECs. These effects might occur through the HIF-1α/VEGF pathway. Molecular docking results showed that all six active ingredients could stably bind to PI3K and AKT proteins, suggesting that these two proteins may be potential targets for six active ingredients., Conclusions: The approach employed in this study effectively identified proangiogenic components in HLJDD that might act via PI3K/AKT/HIF-1α/VEGF pathways and other mechanisms involved in angiogenesis. In conclusion, this study was the first to demonstrate four compounds with new bioactivities and could also provide insight into the isolation and discovery of new bioactive compounds existing in Chinese medicine with potential clinical value., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Lipid dysregulation plays a fundamental role in nonalcoholic steatohepatitis (NASH), which is an emerging critical risk factor that aggravates hepatic ischemia/reperfusion (I/R) injury. However, the specific lipids that mediate the aggressive I/R injury in NASH livers have not yet been identified., Methods: The mouse model of hepatic I/R injury on NASH was established on C56B/6J mice by first feeding the mice with a Western-style diet to induce NASH, then the NASH mice were subjected to surgical procedures to induce hepatic I/R injury. Untargeted lipidomics were performed to determine hepatic lipids in NASH livers with I/R injury through ultra-high performance liquid chromatography coupled with mass spectrometry. The pathology associated with the dysregulated lipids was examined., Results: Lipidomics analyses identified cardiolipins (CL) and sphingolipids (SL), including ceramides (CER), glycosphingolipids, sphingosines, and sphingomyelins, as the most relevant lipid classes that characterized the lipid dysregulation in NASH livers with I/R injury. CER were increased in normal livers with I/R injury, and the I/R-induced increase of CER was further augmented in NASH livers. Metabolic pathway analysis revealed that the enzymes involved in the synthesis and degradation of CER were highly upregulated in NASH livers with I/R injury, including serine palmitoyltransferase 3 ( Sptlc3 ), ceramide synthase 2 ( Cers2 ), neutral sphingomyelinase 2 ( Smpd3 ), and glucosylceramidase beta 2 ( Gba2 ) that produced CER, and alkaline ceramidase 2 ( Acer2 ), alkaline ceramidase 3 ( Acer3 ), sphingosine kinase 1 ( Sphk1 ), sphingosine-1-phosphate lyase ( Sgpl1 ), and sphingosine-1-phosphate phosphatase 1 ( Sgpp1 ) that catalyzed the degradation of CER. CL were not affected by I/R challenge in normal livers, but CL was dramatically reduced in NASH livers with I/R injury. Consistently, metabolic pathway analyses revealed that the enzymes catalyzing the generation of CL were downregulated in NASH-I/R injury, including cardiolipin synthase ( Crls1 ) and tafazzin (Taz ). Notably, the I/R-induced oxidative stress and cell death were found to be aggravated in NASH livers, which were possibly mediated by the reduction of CL and accumulation of CER., Conclusions: The I/R-induced dysregulation of CL and SL were critically rewired by NASH, which might potentially mediate the aggressive I/R injury in NASH livers., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-21-133/coif). The authors have no conflicts of interest to declare., (2023 Hepatobiliary Surgery and Nutrition. All rights reserved.)

Background & Aims: The machinery that prevents colorectal cancer liver metastasis (CRLM) in the context of liver regeneration (LR) remains elusive. Ceramide (CER) is a potent anti-cancer lipid involved in intercellular interaction. Here, we investigated the role of CER metabolism in mediating the interaction between hepatocytes and metastatic colorectal cancer (CRC) cells to regulate CRLM in the context of LR., Methods: Mice were intrasplenically injected with CRC cells. LR was induced by 2/3 partial hepatectomy (PH) to mimic the CRLM in the context of LR. The alteration of corresponding CER-metabolizing genes was examined. The biological roles of CER metabolism in vitro and in vivo were examined by performing a series of functional experiments., Results: Induction of LR augmented apoptosis but promoted matrix metalloproteinase 2 (MMP2) expression and epithelial-mesenchymal transition (EMT) to increase the invasiveness of metastatic CRC cells, resulting in aggressive CRLM. Up-regulation of sphingomyelin phosphodiesterase 3 (SMPD3) was determined in the regenerating hepatocytes after LR induction and persisted in the CRLM-adjacent hepatocytes after CRLM formation. Hepatic Smpd3 knockdown was found to further promote CRLM in the context of LR by abolishing mitochondrial apoptosis and augmenting the invasiveness in metastatic CRC cells by up-regulating MMP2 and EMT through promoting the nuclear translocation of β-catenin. Mechanistically, we found that hepatic SMPD3 controlled the generation of exosomal CER in the regenerating hepatocytes and the CRLM-adjacent hepatocytes. The SMPD3-produced exosomal CER critically conducted the intercellular transfer of CER from the hepatocytes to metastatic CRC cells and impeded CRLM by inducing mitochondrial apoptosis and restricting the invasiveness in metastatic CRC cells. The administration of nanoliposomal CER was found to suppress CRLM in the context of LR substantially., Conclusions: SMPD3-produced exosomal CER constitutes a critical anti-CRLM mechanism in LR to impede CRLM, offering the promise of using CER as a therapeutic agent to prevent the recurrence of CRLM after PH., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Sepsis is an infection-induced severe inflammatory disorder leading to multiple organ dysfunction. It remains a highly lethal condition for which early diagnosis and therapy achieve unsatisfactory results. Circulating exosomes containing biomarkers and mediators of sepsis have recently received attention, but the progress has been far from optimal., Objectives: The present study focuses on the profiles of molecular dynamics in serum exosomes and explores the potential molecular mechanisms on serum exosomes during the process of sepsis., Methods: We used high-performance liquid chromatography-tandem mass spectrometry and RNA-seq to detect the dynamic profiles of exosome proteins and RNAs (including mRNAs, lncRNAs and miRNAs) in serum exosomes from 3 healthy individuals and 9 septic patients at the different stages. Then integrative multiomics analyses were performed and the results were validated by qRT-PCR, LiquiChip assay and metabolomics analysis on mice subjected to cecal ligation and puncture (CLP) modeling., Results: A total of 354 proteins, 195 mRNAs, 82 lncRNAs and 55 miRNAs were identified as differentially expressed molecules in serum exosomes from septic patients. Integrative multiomics analysis showed that exosome components were associated with cytokine storm, complement and clotting cascades, the endothelial barrier, 20S proteasome-dependent protein degradation and vitamin metabolism. Importantly, pretreatment with serum exosomes derived from mice subjected to CLP significantly restrained proinflammatory cytokine expression and alleviated tissue injury in septic mice. Further metabolomics analysis demonstrated that pretreatment with septic serum exosomes significantly affected the metabolites associated with vitamin digestion and absorption in CLP mice., Conclusion: Our study for the first time describes the landscape of the molecular dynamics of serum exosomes during the development of sepsis and proposes some hypothetical molecular mechanisms by integrative multiomics analysis, which may provide helpful diagnostic and therapeutic insights for the ongoing battle against sepsis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Production and hosting by Elsevier B.V.)

Post-hepatectomy liver dysfunction is a life-threatening morbidity that lacks efficient therapy. Bioactive lipids involved in macrophage polarization crucially regulate tissue injury and regeneration. Herein, we investigate the key bioactive lipids that mediate the cytotherapeutic potential of polarized-macrophage for post-hepatectomy liver dysfunction. Untargeted lipidomics identified elevation of ceramide (CER) metabolites as signature lipid species relevant to M1/M2 polarization in mouse bone-marrow-derived-macrophages (BMDMs). M1 BMDMs expressed a CER-generation-metabolic pattern, leading to elevation of CER; M2 BMDMs expressed a CER-breakdown-metabolic pattern, resulting in upregulation of sphingosine-1-phosphate (S1P). After infusing M1- or M2-polarized BMDMs into the mouse liver after hepatectomy, we found that M1-BMDM infusion increased M1 polarization and CER accumulation, resulting in exaggeration of hepatocyte apoptosis and liver dysfunction. Conversely, M2-BMDM infusion enhanced M2 polarization and S1P generation, leading to alleviation of liver dysfunction with improved hepatocyte proliferation. Treatment of exogenous CER and S1P or inhibition CER and S1P synthesis by siRNA targeting relevant enzymes further revealed that CER induced apoptosis while S1P promoted proliferation in post-hepatectomy primary hepatocytes. In conclusion, CER and S1P are uncovered as critical lipid mediators for M1- and M2-polarized BMDMs to promote injury and regeneration in the liver after hepatectomy, respectively. Notably, the upregulation of hepatic S1P induced by M2-BMDM infusion may have therapeutic potential for post-hepatectomy liver dysfunction.

Recently, inclusion complexes formed from cyclodextrins (CDs) and surfactants have been found to play complex and important roles in supramolecular self-assembly. In this work, the self-assembly of perfluorononanoic acid (PFNA)/γ-cyclodextrin (γ-CD) in aqueous solution was investigated. The sole PFNA solution assembled into spherical uni-lamellar vesicles under certain concentrations as revealed by freeze-fracture transmission electron microscopy (FF-TEM) images. Interestingly, when γ-CD was added into the PFNA solution, one novel kind of cyclodextrin-based hydrogel with a crystal-like structure was obtained. The morphology of the hydrogels was inerratic parallel hexahedron or regular hexahedron as revealed by optical microscopy and scanning electron microscopy (SEM) measurements. Furthermore, the hydrogels were transformed into crystalline precipitates, which were composed of highly uniform tetragonal sheets with excellent crystallinity and homogeneous size distribution just by changing the γ-CD concentration. More amazingly, the crystal-like hydrogels were sensitive to shear and switched to solutions in their morphology with bar-like and rod-like aggregates and smaller square sheets under different shear rates, and the hydrogel-solution transition behavior was a reversable process. 1H NMR, Fourier transform infrared (FT-IR) and wide-angle X-ray diffraction (WXRD) measurements were performed to lead us to propose the formation mechanism of the above aggregates. Hopefully, our studies will cast new light on the fundamental investigations into the self-assembly of supramolecular systems of fluorinated surfactants and CD molecules and provide a new idea for smart material design.

Background: Nonalcoholic fatty liver (NAFL) is emerging as a leading risk factor of hepatic ischemia/reperfusion (I/R) injury lacking of effective therapy. Lipid dyshomeostasis has been implicated in the hepatopathy of NAFL. Herein, we investigate the bioactive lipids that critically regulate I/R injury in NAFL., Methods: Lipidomics were performed to identify dysregulated lipids in mouse and human NAFL with I/R injury. The alteration of corresponding lipid-metabolizing genes was examined. The effects of the dysregulated lipid metabolism on I/R injury in NAFL were evaluated in mice and primary hepatocytes., Results: Sphingolipid metabolic pathways responsible for the generation of sphingosine-1-phosphate (S1P) were uncovered to be substantially activated by I/R in mouse NAFL. Sphingosine kinase 1 (Sphk1) was found to be essential for hepatic S1P generation in response to I/R in hepatocytes of NAFL mice. Sphk1 knockdown inhibited the hepatic S1P rise while accumulating ceramides in hepatocytes of NAFL mice, leading to aggressive hepatic I/R injury with upregulation of oxidative stress and increase of reactive oxygen species (ROS). In contrast, administration of exogenous S1P protected hepatocytes of NAFL mice from hepatic I/R injury. Clinical study revealed a significant activation of S1P generation by I/R in liver specimens of NAFL patients. In vitro studies on the L02 human hepatocytes consolidated that inhibiting the generation of S1P by knocking down SPHK1 exaggerated I/R-induced damage and oxidative stress in human hepatocytes of NAFL., Conclusions: Generation of S1P by SPHK1 is important for protecting NAFL from I/R injury, which may serve as therapeutic targets for hepatic I/R injury in NAFL., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Radiation enteritis (RE) is a common complication in cancer patients receiving radiotherapy. Although studies have shown the changes of this disease at clinical, pathological and other levels, the dynamic characteristics of local microbiome and metabolomics are hitherto unknown. We aimed to examine the multi-omics features of the gut microecosystem, determining the functional correlation between microbiome and lipid metabolites during RE activity. By delivering single high-dose irradiation, a RE mouse model was established. High-throughput 16S rDNA sequencing and global lipidomics analysis were performed to examine microbial and lipidomic profile changes in the gut microecosystem. Spearman correlation analysis was used to determine the functional correlation between bacteria and metabolites. Clinical samples were collected to validate the above observations. During RE activity, the intestinal inflammation of the mice was confirmed by typical signs, symptoms, imaging findings and pathological evidences. 16S datasets revealed that localized irradiation dramatically altered the gut microbial composition, resulting in a decrease ratio of Bacteroidetes to Firmicutes . Lipidomics analysis indicated the remarkable lipidomic profile changes in enteric epithelial barrier, determining that glycerophospholipids metabolism was correlated to RE progression with the highest relevance. Spearman correlation analysis identified that five bacteria-metabolite pairs showed the most significant functional correlation in RE, including Alistipes -PC(36:0e), Bacteroides -DG(18:0/20:4), Dubosiella -PC(35:2), Eggerthellaceae -PC(35:6), and Escherichia-Shigella -TG(18:2/18:2/20:4). These observations were partly confirmed in human specimens. Our study provided a comprehensive description of microbiota dysbiosis and lipid metabolic disorders in RE, suggesting strategies to change local microecosystem to relieve radiation injury and maintain homeostasis., (Copyright © 2020 Li, Yan, Zhang, Li, Yu, Li, Liu, Xie, Chen, Ye, Wang, Chen and Ding.)

Overload of palmitic acids is linked to the dysregulation of ceramide metabolism in nonalcoholic steatohepatitis (NASH), and ceramides are important bioactive lipids mediating the lipotoxicity of palmitic acid in NASH. However, much remains unclear about the role of ceramidases that catalyze the hydrolysis of ceramides in NASH. By analyzing the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, we found that alkaline ceramidase 3 (ACER3) is upregulated in livers of patients with NASH. Consistently, we found that Acer3 mRNA levels and its enzymatic activity were also upregulated in mouse livers with NASH induced by a palmitate-enriched Western diet (PEWD). Moreover, we demonstrated that palmitate treatment also elevated Acer3 mRNA levels and its enzymatic activity in mouse primary hepatocytes. In order to investigate the function of Acer3 in NASH, Acer3 null mice and their wild-type littermates were fed a PEWD to induce NASH. Knocking out Acer3 was found to augment PEWD-induced elevation of C 18:1 -ceramide and alleviate early inflammation and fibrosis but not steatosis in mouse livers with NASH. In addition, Acer3 deficiency attenuated hepatocyte apoptosis in livers with NASH. These protective effects of Acer3 deficiency were found to be associated with suppression of hepatocellular oxidative stress in NASH liver. In vitro studies further revealed that loss of ACER3/Acer3 increased C 18:1 -ceramide and inhibited apoptosis and oxidative stress in mouse primary hepatocytes and immortalized human hepatocytes induced by palmitic-acid treatment. These results suggest that ACER3 plays an important pathological role in NASH by mediating palmitic-acid-induced oxidative stress.

Understanding of the molecular regulatory mechanisms underlying the inflammatory response is incomplete. The present study focuses on characterizing the proteome in a model of inflammation in macrophages treated with lipopolysaccharide (LPS). A total of 3597 proteins are identified in macrophages with the data-independent acquisition (DIA) method. Bioinformatic analyses reveal discrete modules and the underlying molecular mechanisms, as well as the signaling network that modulates the development of inflammation. It is found that a total of 87 differentially expressed proteins are shared by all stages of LPS-induced inflammation in macrophages and that 18 of these proteins participate in metabolic processes by forming a tight interaction network. Data support the hypothesis that ribosome proteins play a key role in regulating the macrophage response to LPS. Interestingly, conjoint analyses of the transcriptome and proteome in macrophages treated with LPS reveal that the genes upregulated at both the mRNA and protein levels are mainly involved in inflammation and the immune response, whereas the genes downregulated are significantly enriched in metabolism-related processes. These results not only provide a more comprehensive understanding of the molecular mechanisms of inflammation mediated by bacterial infection but also provide a dynamic proteomic resource for further studies., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The self-assembly of α-cyclodextrin (α-CD) mixed with a fluorocarbon surfactant, perfluorononanoic acid (PFNA), in aqueous solution was studied. Interestingly, the 1:1 inclusion complex, PFNA@α-CD, was verified to form by 1 H nuclear magnetic resonance measurement. Also as the building block, the PFNA@α-CD complex was further self-assembled into worm-like micelles under lower concentrations while hydrogels were self-assembled under higher concentrations. The hydrogels were composed of unilamellar vesicles with polydisperse size, which were clearly detected by freeze-fracture transmission electron microscopy measurements. Besides, the vesicle hydrogels showed high viscoelasticities and a substantial elastic characteristic. Also as revealed by the results of Fourier transform infrared measurements, the driving force for the vesicle and worm-like micelle formation was the hydrogen bonding between α-CD molecules. Then, these vesicles were densely packed to form hydrogels. As far as we know, the self-assembly of CDs and fluorocarbon surfactants based on host-guest inclusion in aqueous solution has been limitedly reported. Our work successfully constructed hydrogels consisting of vesicles through the self-assembly of the α-CD/PFNA complex for the first time and will also provide a better understanding and enrich the fundamental research of the self-assembly behavior of the CD/fluorosurfactant complex.

Reported herein is an inverse-electron-demand oxa-Diels-Alder reaction that is remotely β,γ-regioselective with β,γ-unsaturated amides and β,γ-unsaturated-α-ketoesters using a bifunctional catalyst. It can provide different kinds of dihydropyrans bearing three subsequent chiral carbon centers in good to high yield (61-99%) and with complete enantioselectivity (99 to >99% ee). Furthermore, a larger-scale experiment confirmed the reliability of the current reaction, and further effective transformation of the product has been realized.

Herein, we report a novel Fe foil-guided, in situ etching strategy for the preparation of highly uniform Ag@AgX (X = Cl, Br) nanowires (NWs) and applied the photoelectric-responsive materials for sensitive photoelectrochemical (PEC) detection of leukemia DNA. The Ag@AgX NW formation process was discussed from the redox potential and K sp value. The fabricated PEC platform for sensing leukemia DNA showed good assay performance with a wide linear range (0.1 pM to 50 nM) and low detection limit of 0.033 pM. We envision that our Fe foil-guided synthetic method could be applied to synthesize more photoactive materials for sensitive PEC detections.

Background: More than 2,000 chemicals have been used in the tannery industry. Although some tannery chemicals have been reported to have harmful effects on both human health and the environment, only a few have been subjected to genotoxicity and cytotoxicity evaluations., Objective: This study focused on cytotoxicity and genotoxicity of ten tannery chemicals widely used in China., Materials and Methods: DNA-damaging effects were measured using the SOS/umu test with Salmonella typhimurium TA1535/pSK1002. Chromosome-damaging and cytotoxic effects were determined with the high-content in vitro Micronucleus test (MN test) using the human-derived cell lines MGC-803 and A549., Conclusion: The cytotoxicity of the ten tannery chemicals differed somewhat between the two cell assays, with A549 cells being more sensitive than MGC-803 cells. None of the chemicals induced DNA damage before metabolism, but one was found to have DNA-damaging effects on metabolism. Four of the chemicals, DY64, SB1, DB71 and RR120, were found to have chromosome-damaging effects. A Quantitative Structure-Activity Relationship (QSAR) analysis indicated that one structural feature favouring chemical genotoxicity, Hacceptor-path3-Hacceptor, may contribute to the chromosome-damaging effects of the four MN-test-positive chemicals., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Craniofacial reconstruction is to estimate an individual's face model from its skull. It has a widespread application in forensic medicine, archeology, medical cosmetic surgery, and so forth. However, little attention is paid to the evaluation of craniofacial reconstruction. This paper proposes an objective method to evaluate globally and locally the reconstructed craniofacial faces based on the geodesic network. Firstly, the geodesic networks of the reconstructed craniofacial face and the original face are built, respectively, by geodesics and isogeodesics, whose intersections are network vertices. Then, the absolute value of the correlation coefficient of the features of all corresponding geodesic network vertices between two models is taken as the holistic similarity, where the weighted average of the shape index values in a neighborhood is defined as the feature of each network vertex. Moreover, the geodesic network vertices of each model are divided into six subareas, that is, forehead, eyes, nose, mouth, cheeks, and chin, and the local similarity is measured for each subarea. Experiments using 100 pairs of reconstructed craniofacial faces and their corresponding original faces show that the evaluation by our method is roughly consistent with the subjective evaluation derived from thirty-five persons in five groups.