Aromatic and magnetic properties in a series of heavy rare earth-doped Ge6 cluster anions.

A series of pentagonal bipyramidal anionic germanium clusters doped with heavy rare earth elements, REGe 6 - (RE = Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu), have been identified at the PBE0/def2-TZVP level using density functional theory (DFT). Our findings reveal that the centrally doped pentagonal ring structure demonstrates enhanced stability and heightened aromaticity due to its uniform bonding characteristics and a larger charge transfer region. Through natural population analysis and spin density diagrams, we observed a monotonic decrease in the magnetic moment from Gd to Yb. This is attributed to the decreasing number of unpaired electrons in the 4f orbitals of the heavy rare earth atoms. Interestingly, the system doped with Er atoms showed lower stability and anti-aromaticity, likely due to the involvement of the 4f orbitals in bonding. Conversely, the systems doped with Gd and Tb atoms stood out for their high magnetism and stability, making them potential building blocks for rare earth-doped semiconductor materials.

Limited effects of xylem anatomy on embolism resistance in cycad leaves.

Drought-induced xylem embolism is a primary cause of plant mortality. Although c. 70% of cycads are threatened by extinction and extant cycads diversified during a period of increasing aridification, the vulnerability of cycads to embolism spread has been overlooked. We quantified the vulnerability to drought-induced embolism, pressure-volume curves, in situ water potentials, and a suite of xylem anatomical traits of leaf pinnae and rachises for 20 cycad species. We tested whether anatomical traits were linked to hydraulic safety in cycads. Compared with other major vascular plant clades, cycads exhibited similar embolism resistance to angiosperms and pteridophytes but were more vulnerable to embolism than noncycad gymnosperms. All 20 cycads had both tracheids and vessels, the proportions of which were unrelated to embolism resistance. Only vessel pit membrane fraction was positively correlated to embolism resistance, contrary to angiosperms. Water potential at turgor loss was significantly correlated to embolism resistance among cycads. Our results show that cycads exhibit low resistance to xylem embolism and that xylem anatomical traits - particularly vessels - may influence embolism resistance together with tracheids. This study highlights the importance of understanding the mechanisms of drought resistance in evolutionarily unique and threatened lineages like the cycads.

Application Effect of Graded Emergency Nursing in Patients with Acute Pancreatitis.

Background: Acute pancreatitis poses a significant threat in the emergency department due to its rapid and dangerous progression. Without timely and effective treatment measures, there is a heightened risk of advancing to multiple organ failure, posing a serious threat to the life safety of patients. Objective: This study aims to investigate the impact of graded emergency nursing on patients with acute pancreatitis. Design: A randomized controlled experiment was conducted to assess the effectiveness of graded emergency nursing. Setting: The study was conducted in the Emergency Department of Beijing Friendship Hospital, Capital University. Participants: A total of 112 patients diagnosed with acute pancreatitis and admitted to our hospital from June 2021 to December 2022 were randomly assigned to either the observation or control group, with 56 patients in each. Interventions: Patients in the control group received standard emergency nursing care, while those in the observation group underwent graded emergency nursing. Primary Outcome Measures: The study assessed (1) triage time, waiting time, and treatment time, (2) the correct rate of diagnosis and the success rate of rescue, (3) functional status score, and (4) patient satisfaction with nursing care. Results: Compared to the control group, patients in the observation group experienced significantly shorter triage time, waiting time, and treatment time (P < .05). Additionally, the observation group exhibited higher correct rates of diagnosis and success rates of rescue (P < .05). The functional status score in the observation group showed improvement (P < .05), and patients in the observation group reported higher satisfaction with nursing care (P < .05). Conclusions: Graded emergency nursing proves effective in reducing waiting times for diagnosis and treatment in acute pancreatitis patients, enhancing treatment success rates, and improving overall nursing quality. These findings hold valuable implications for clinical application and promotion.

Investigation of Structures, Stabilities, and Electronic and Magnetic Properties of Niobium Carbon Clusters Nb7Cn (n = 1-7).

The geometrical structures, relative stabilities, and electronic and magnetic properties of niobium carbon clusters, Nb7Cn (n = 1-7), are investigated in this study. Density functional theory (DFT) calculations, coupled with the Saunders Kick global search, are conducted to explore the structural properties of Nb7Cn (n = 1-7). The results regarding the average binding energy, second-order difference energy, dissociation energy, HOMO-LUMO gap, and chemical hardness highlight the robust stability of Nb7C3. Analysis of the density of states suggests that the molecular orbitals of Nb7Cn primarily consist of orbitals from the transition metal Nb, with minimal involvement of C atoms. Spin density and natural population analysis reveal that the total magnetic moment of Nb7Cn predominantly resides on the Nb atoms. The contribution of Nb atoms to the total magnetic moment stems mainly from the 4d orbital, followed by the 5p, 5s, and 6s orbitals.

Comprehensive Bibliometric Analysis of Stem Cell Research in Alzheimer's Disease from 2004 to 2022.

INTRODUCTION: Stem cell-based regenerative medicine has provided an excellent opportunity to investigate therapeutic strategies and innovative treatments for Alzheimer's disease (AD). However, there is an absence of visual overviews to assess the published literature systematically. METHODS: In this review, the bibliometric approach was used to estimate the searched data on stem cell research in AD from 2004 to 2022, and we also utilized CiteSpace and VOSviewer software to evaluate the contributions and co-occurrence relationships of different countries/regions, institutes, journals, and authors as well as to discover research hot spots and encouraging future trends in this field. RESULTS: From 2004 to 2022, a total of 3,428 publications were retrieved. The number of publications and citations on stem cell research in AD has increased dramatically in the last nearly 20 years, especially since 2016. North America and Asia were the top 2 highest output regions. The leading country in terms of publications and access to collaborative networks was the USA. Centrality analysis revealed that the UCL (0.05) was at the core of the network. The Journal of Alzheimer's Disease (n = 102, 2.98%) was the most productive academic journal. The analyses of keyword burst detection indicated that exosomes, risk factors, and drug delivery only had burst recently. Citations and co-citation achievements clarified that cluster #0 induced pluripotent stem cells, #2 mesenchymal stem cells, #3 microglia, and #6 adult hippocampal neurogenesis persisted to recent time. CONCLUSION: This bibliometric analysis provides a comprehensive guide for clinicians and scholars working in this field. These analysis and results hope to provide useful information and references for future understanding of the challenges behind translating underlying stem cell biology into novel clinical therapeutic potential in AD.

Coordination of intertracheid pit traits and climate effects among cycads.

Interconduit pit membranes, which are permeable regions in the primary cell wall that connect to adjacent conduits, play a crucial role in water relations and the movement of nutrients between xylem conduits. However, how pit membrane characteristics might influence water-carbon coupling remains poorly investigated in cycads. We examined pit characteristics, the anatomical and photosynthetic traits of 13 cycads from a common garden, to determine if pit traits and their coordination are related to water relations and carbon economy. We found that the pit traits of cycads were highly variable and that cycads exhibited a similar tradeoff between pit density and pit area as other plant lineages. Unlike other plant lineages (1) pit membranes, pit apertures, and pit shapes of cycads were not coordinated as in angiosperms; (2) cycads exhibited larger pit membrane areas but lower pit densities relative to ferns and angiosperms, but smaller and similar pit membrane densities to non-cycad gymnosperms; (3) cycad pit membrane areas and densities were partially coordinated with anatomical traits, with hydraulic supply of the rachis positively coordinated with photosynthesis, whereas pit aperture areas and fractions were negatively coordinated with photosynthetic traits; (4) cycad pit traits reflected adaptation to wetter habitats for Cycadaceae and drier habitats for Zamiaceae. The large variation in pit traits, the unique pit membrane size and density, and the partial coordination of pit traits with anatomical and physiological traits of the rachis and pinna among cycads may have facilitated their dominance in a variety of ecosystems from the Mesozoic to modern times.

Structural Regulation of Two Polyoxometalate-Based Metal-Organic Frameworks for the Heterogeneous Catalysis of Quinazolinones.

Two dimeric {ε-Zn4PMo12}-based metal-organic frameworks (MOFs), [ε-PMo8VMo4VIO34(OH)6Zn4][LO] (SDUT-21, LO = [5-((4'-carboxybenzyl)oxy)isophthalic acid]) and [TBA]3[ε-PMo8VMo4VIO37(OH)3Zn4][LN] (SDUT-22, TBA+ = tetrabutylammonium ion, LN = [5-((4-carboxybenzyl)imino)isophthalic acid]), combining the advantages of polyoxometalates (POMs) and MOFs, were synthesized by the one-pot assembly strategy. The dimeric {ε-Zn4PMo12} units act as nodes that are linked by the flexible ligands and extended into two- or three-dimensional frameworks. The cyclic voltammetry and proton conductivity measurements of SDUT-21 and SDUT-22 were performed and indicated the high electron and proton transfer abilities. These materials also e xhibited the catalytic performance for the synthesis of quinazolinones in the heterogeneous state, and the different binding capacities toward the substrates caused the catalytic activity of SDUT-21 to be higher than that of SDUT-22 under the same conditions. In addition, the used catalysts could be readily recovered for five successive cycles and maintained high catalytic efficiency.

Preparation of Fe/Ni-MOFs for the Adsorption of Ciprofloxacin from Wastewater.

This work studies the use of Fe/Ni-MOFs for the removal of ciprofloxacin (CIP) in wastewater. Fe/Ni-MOFs are prepared by the solvothermal method and characterized by X-ray diffraction (XRD), a scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FT-IR), and a thermal gravimetric analyzer (TG). Under the conditions of the concentration of 50 ppm, a mass of 30 mg, and a temperature of 30 °C, the maximum adsorption capacity of ciprofloxacin removal within 5 h was 232.1 mg/g. The maximum removal rate was 94.8% when 40 mg of the Fe/Ni-MOFs was added to the solution of 10 ppm ciprofloxacin. According to the pseudo-second-order (PSO) kinetic model, the R2 values were all greater than 0.99, which proved that the adsorption theory of ciprofloxacin by Fe/Ni-MOFs was consistent with the practice. The adsorption results were mainly affected by solution pH and static electricity, as well as other factors. The Freundlich isotherm model characterized the adsorption of ciprofloxacin by Fe/Ni-MOFs as multilayer adsorption. The above results indicated that Fe/Ni-MOFs were effective in the practical application of ciprofloxacin removal.

Making Sense of the Growth Behavior of Ultra-High Magnetic Gd2-Doped Silicon Clusters.

The growth behavior, stability, electronic and magnetic properties of the Gd2Sin- (n = 3-12) clusters are reported, which are investigated using density functional theory calculations combined with the Saunders 'Kick' and the Artificial Bee Colony algorithm. The lowest-lying structures of Gd2Sin- (n = 3-12) are all exohedral structures with two Gd atoms face-capping the Sin frameworks. Results show that the pentagonal bipyramid (PB) shape is the basic framework for the nascent growth process of the present clusters, and forming the PB structure begins with n = 5. The Gd2Si5- is the potential magic cluster due to significantly higher average binding energies and second order difference energies, which can also be further verified by localized orbital locator and adaptive natural density partitioning methods. Moreover, the localized f-electron can be observed by natural atomic orbital analysis, implying that these electrons are not affected by the pure silicon atoms and scarcely participate in bonding. Hence, the implantation of these elements into a silicon substrate could present a potential alternative strategy for designing and synthesizing rare earth magnetic silicon-based materials.

Phase I study of envafolimab (KN035), a novel subcutaneous single-domain anti-PD-L1 monoclonal antibody, in Japanese patients with advanced solid tumors.

Envafolimab is the first and only globally approved subcutaneously injectable PD-L1 antibody. This open-label, multicenter Phase 1 trial assessed the safety, tolerability, pharmacokinetic (PK) profile, and efficacy of envafolimab as a single agent in Japanese patients with advanced solid tumors. In the dose-escalation phase, 10 patients received subcutaneous (SC) envafolimab QW at 1.0 mg/kg, 2.5 mg/kg and 5.0 mg/kg. In the dose-expansion phase, 16 patients were treated at 2.5 or 5.0 mg/kg Q2W in part-1 and 9 patients received SC envafolimab 300 mg Q4W in part-2. No dose-limiting toxicities (DLTs) were reported. Envafolimab was well tolerated and no new safety signals were identified compared with other marketed products of the same class. Three patients reported Grade ≥ 3 envafolimab-related treatment-emergent adverse events (TEAE), including adrenal insufficiency, cerebral infarction, and immune-mediated enterocolitis. Envafolimab demonstrated dose-proportional increases in area under the time-concentration curve (AUC) and maximum serum concentration (Cmax). The overall response rate (ORR) was 11.4% (n = 4) and disease control rate (DCR) was 34.3% (n = 12). Consistent with that observed in other envafolimab Phase 1 trials and approved PD-1/PD-L1 inhibitors, the safety profile of SC envafolimab in Japanese patients with advanced solid tumors was well tolerated with efficacy comparable to IV administered treatments. Pharmacokinetics data and preliminary anti-tumor response support dose regimens with longer dosing intervals (Q2W or Q4W). As such, envafolimab offers patients a more convenient treatment option than currently available intravenously administered PD-1/PD-L1 inhibitors. CLINICALTRIALS.GOV IDENTIFIER: NCT03248843(August 14, 2017).

Entropy Sources Based on Silicon Chips: True Random Number Generator and Physical Unclonable Function.

Entropy is a measure of uncertainty or randomness. It is the foundation for almost all cryptographic systems. True random number generators (TRNGs) and physical unclonable functions (PUFs) are the silicon primitives to respectively harvest dynamic and static entropy to generate random bit streams. In this survey paper, we present a systematic and comprehensive review of different state-of-the-art methods to harvest entropy from silicon-based devices, including the implementations, applications, and the security of the designs. Furthermore, we conclude the trends of the entropy source design to point out the current spots of entropy harvesting.

Graphene Oxide Biosensors Based on Hybridization Chain Reaction Signal Amplification for Detecting Biomarkers of Radiation-Resistant Nasopharyngeal Carcinoma and Imaging in Living Cells.

Since microRNA-205 (miRNA-205) is a predictive biomarker for antiradiation of nasopharyngeal carcinoma (NPC), quantitative detection of miRNA-205 is important for developing personalized strategies for the treatment of NPC. In this investigation, based on the graphene oxide (GO) sensor and hybridization chain reaction (HCR) for fluorescence signal amplification, a highly sensitive and selective detection method for miRNA-205 was designed. A target-recycling mechanism is employed, where a single miRNA-205 target triggers the signal amplification of many DNA signal probes. The biosensor shows the ability to analyze miRNA-205 in solution, and it can detect miRNA-205 at concentrations as low as 311.96 pM. Furthermore, the method is specific in that it distinguishes between a target miRNA and a sequence with single-, double-, and three-base mismatches, as well as other miRNAs. Considering its simplicity and superior sensitivity, it was also verified in 1‰ serum with a detection limit of 111.65 pM. Importantly, the method successfully demonstrated that miRNA-205 could be imaged in living cells, which provided the possibility of localizing target molecules in live cell imaging applications. This method has great clinical application potential in the determination of miRNA-205, a biomarker for radiation-resistant NPC.

A Stereocontrolled Synthesis of a Phosphorothioate Cyclic Dinucleotide-Based STING Agonist.

We describe a stereodefined synthesis of the newly identified non-natural phosphorothioate cyclic dinucleotide (CDN) STING agonist, BMT-390025. The new route avoids the low-yielding racemic approach using P(III)-based reagents, and the stereospecific assembly of the phosphorothioate linkages are forged via the recently invented P(V)-based platform of the so-called PSI (Ψ) reagent system. This P(V) approach allows for the complete control of chirality of the P-based linkages and enabled conclusive evidence of the absolute configuration. The new approach offers robust procedures for preparing the stereodefined CDN in eight steps starting from advanced nucelosides, with late-stage direct drop isolations and telescoped steps enabling an efficient scale-up that proceeded in an overall 15% yield to produce multigram amounts of the CDN.

Substituted benzyloxytricyclic compounds as retinoic acid-related orphan receptor gamma t (RORγt) agonists.

Substituted benzyloxy aryl compound 2 was identified as an RORγt agonist. Structure based drug design efforts resulted in a potent and selective tricyclic compound 19 which, when administered orally in an MC38 mouse tumor model, demonstrated a desired pharmacokinetic profile as well as a dose-dependent pharmacodynamic response. However, no perceptible efficacy was observed in this tumor model at the doses investigated.

A Lanthanide-Containing Coordination Polymer Using Tetraphenylethene-Based Linkers with Selective Fe3+ Sensing and Efficient Iodine Adsorption Activities.

As a star ligand, the construction of coordination polymers (CPs) based on tetrakis(4-carboxyphenyl)ethylene (H4TCPE) has drawn much attention, due to not only the various coordination configurations but also the intriguing chromophore feature causing aggregation-induced emission (AIE). Herein, by the solvothermal reaction of H4TCPE as connected nodes with lanthanide La(III) salts, the first example of the La(III)-TCPE-based CP (1) has been obtained. The structural analyses indicate that 1 exhibits a 3D framework connected by the sharing carboxylate groups with two kinds of 1D rhombic channels when viewed along the c direction. The photophysical properties of 1 have been explored by luminescence, photoluminescence decay, and quantum yield in the solid state. 1 shows strong luminescence in tetrahydrofuran that was attributed to a "pseudo-AIE process" and sensitive and selective sensing activity of Fe3+ toward metal ions via the obvious luminescent quenching. The sensing mechanism has been investigated and reveals a synergetic effect of the competitive absorption and weak interactions between 1 and Fe3+. Moreover, the high porosity, multiple conjugated π-electrons within the tetrakis(4-carboxyphenyl)ethylene backbone, and the uncoordinated carboxyl oxygen sites in this material also provide the capacity for iodine adsorption. The adsorption experiments indicate that 1 could efficiently remove almost complete I2 from the cyclohexane solution after 24 h contact time with an adsorption capacity of 690 mg/g toward I2.

Diabetes downregulates peptide transporter 1 in the rat jejunum: possible involvement of cholate-induced FXR activation.

Peptide transporter 1 (PepT1), highly expressed on the apical membrane of enterocytes, is involved in energy balance and mediates intestinal absorption of peptidomimetic drugs. In this study, we investigated whether and how diabetes affected the function and expression of intestinal PepT1. Diabetes was induced in rats by combination of high-fat diet and low dose streptozocin injection. Pharmacokinetics study demonstrated that diabetes significantly decreased plasma exposures of cephalexin and acyclovir following oral administration of cephalexin and valacyclovir, respectively. Single-pass intestinal perfusion analysis showed that diabetes remarkably decreased cephalexin absorption, which was associated with decreased expression of intestinal PepT1 protein. We assessed the levels of bile acids in intestine of diabetic rats, and found that diabetic rats exhibited significantly higher levels of chenodeoxycholic acid (CDCA), cholic acid (CA) and glycocholic acid (GCA), and lower levels of lithocholic acid (LCA) and hyodeoxycholic acid (HDCA) than control rats; intestinal deoxycholic acid (DCA) levels were unaltered. In Caco-2 cells, the 6 bile acids remarkably decreased expression of PepT1 protein with CDCA causing the strongest inhibition, whereas TNF-α, LPS and insulin little affected expression of PepT1 protein; short-chain fatty acids induced rather than decreased expression of PepT1 protein. Farnesoid X receptor (FXR) inhibitor glycine-ß-muricholic acid or FXR knockdown reversed the downregulation of PepT1 expression by CDCA and GW4064 (another FXR agonist). In diabetic rats, the expression of intestinal FXR protein was markedly increased. Oral administration of CDCA (90, 180 mg·kg-1·d-1, for 3 weeks) dose-dependently decreased the expression and function of intestinal PepT1 in rats. In conclusion, diabetes impairs the expression and function of intestinal PepT1 partly via CDCA-mediated FXR activation.

A graphene oxide fluorescent sensing platform for sensitive and specific detecting biomarker of radiation-resistant nasopharyngeal carcinoma.

Since microRNA-205 (miR-205) is predictive biomarkers for radiation-resistant of nasopharyngeal carcinoma, monitoring of the dynamic variation of miR-205 is of great interest for developing a personalized strategy for the treatment of NPC. Herein, a method for detection of miR-205 was designed based on graphene oxide (GO) and fluorescent probe. The method was successfully used to sensitively and selectively assay miR-205 in aqueous solution, and a low limit of detection of 1.18 nM was obtained in the range 0-300 nM and R2 = 0.990. In addition, the designed platform is specific in that it can distinguish the target miRNA from non-target miRNAs, and even the sequences with single base, double base and three base mismatches. Considering the simplicity and superior sensitivity, it has great potential for clinical application in determining biomarker of radiation-resistant nasopharyngeal carcinoma.

RNase H amplified RNA probe and graphene oxide system for highly sensitive detection of (CAG)n DNA repeat sequences.

Huntington's disease is a chronic progressive neurodegeneration which is caused by CAG repeat sequences expanding in the huntingtin gene. There is currently no disease-modifying treatment for the disease, and its progression can only be slowed down before the onset of symptoms. A novel fluorescent platform which contains an RNA probe and graphene oxide for detection of the biomarker of Huntington's disease, CAG repeat sequences, was constructed in this investigation. In addition, RNase H was employed in the fluorescent system to enhance the sensitivity of the detection capability. The fluorescent signal was increased through the cyclic amplified reaction, which results from RNase H, specifically digestion of the RNA strand in the complement of the RNA-DNA duplex. The designed measurement method can detect CAG repeat sequences with a detection limit of 108 pM (R2 = 0.968) under which we optimized assay conditions. Furthermore, the detection limit is approximately 18 times lower than the traditional DNA and graphene oxide detection method without assistance of RNase H. Additionally, the probing platform also shows stronger ability to discriminate between the fluorescence of the target sequence and that of other non-target sequences. The results of our studies demonstrate that the RNase H amplified RNA probe and graphene oxide system exhibited excellent sensitivity and selectivity to the target of CAG repeats sequences.

Myocardium Detection by Deep SSAE Feature and Within-Class Neighborhood Preserved Support Vector Classifier and Regressor.

Automatic detection of left ventricle myocardium is essential to subsequent cardiac image registration and tissue segmentation. However, it is considered challenging mainly because of the complex and varying shape of the myocardium and surrounding tissues across slices and phases. In this study, a hybrid model is proposed to detect myocardium in cardiac magnetic resonance (MR) images combining region proposal and deep feature classification and regression. The model firstly generates candidate regions using new structural similarity-enhanced supervoxel over-segmentation plus hierarchical clustering. Then it adopts a deep stacked sparse autoencoder (SSAE) network to learn the discriminative deep feature to represent the regions. Finally, the features are fed to train a novel nonlinear within-class neighborhood preserved soft margin support vector (C-SVC) classifier and multiple-output support vector ( ε -SVR) regressor for refining the location of myocardium. To improve the stability and generalization, the model also takes hard negative sample mining strategy to fine-tune the SSAE and the classifier. The proposed model with impacts of different components were extensively evaluated and compared to related methods on public cardiac data set. Experimental results verified the effectiveness of proposed integrated components, and demonstrated that it was robust in myocardium localization and outperformed the state-of-the-art methods in terms of typical metrics. This study would be beneficial in some cardiac image processing such as region-of-interest cropping and left ventricle volume measurement.

Stearoyl-CoA Desaturase Promotes Liver Fibrosis and Tumor Development in Mice via a Wnt Positive-Signaling Loop by Stabilization of Low-Density Lipoprotein-Receptor-Related Proteins 5 and 6.

BACKGROUND & AIMS: Stearoyl-CoA desaturase (SCD) synthesizes monounsaturated fatty acids (MUFAs) and has been associated with the development of metabolic syndrome, tumorigenesis, and stem cell characteristics. We investigated whether and how SCD promotes liver fibrosis and tumor development in mice. METHODS: Rodent primary hepatic stellate cells (HSCs), mouse liver tumor-initiating stem cell-like cells (TICs), and human hepatocellular carcinoma (HCC) cell lines were exposed to Wnt signaling inhibitors and changes in gene expression patterns were analyzed. We assessed the functions of SCD by pharmacologic and conditional genetic manipulation in mice with hepatotoxic or cholestatic induction of liver fibrosis, orthotopic transplants of TICs, or liver tumors induced by administration of diethyl nitrosamine. We performed bioinformatic analyses of SCD expression in HCC vs nontumor liver samples collected from patients, and correlated levels with HCC stage and patient mortality. We performed nano-bead pull-down assays, liquid chromatography-mass spectrometry, computational modeling, and ribonucleoprotein immunoprecipitation analyses to identify MUFA-interacting proteins. We examined the effects of SCD inhibition on Wnt signaling, including the expression and stability of low-density lipoprotein-receptor-related proteins 5 and 6 (LRP5 and LRP6), by immunoblot and quantitative polymerase chain reaction analyses. RESULTS: SCD was overexpressed in activated HSC and HCC cells from patients; levels of SCD messenger RNA (mRNA) correlated with HCC stage and patient survival time. In rodent HSCs and TICs, the Wnt effector ß-catenin increased sterol regulatory element binding protein 1-dependent transcription of Scd, and ß-catenin in return was stabilized by MUFAs generated by SCD. This loop required MUFA inhibition of binding of Ras-related nuclear protein 1 (Ran1) to transportin 1 and reduced nuclear import of elav-like protein 1 (HuR), increasing cytosolic levels of HuR and HuR-mediated stabilization of mRNAs encoding LRP5 and LRP6. Genetic disruption of Scd and pharmacologic inhibitors of SCD reduced HSC activation and TIC self-renewal and attenuated liver fibrosis and tumorigenesis in mice. Conditional disruption of Scd2 in activated HSCs prevented growth of tumors from TICs and reduced the formation of diethyl nitrosamine-induced liver tumors in mice. CONCLUSIONS: In rodent HSCs and TICs, we found SCD expression to be regulated by Wnt-ß-catenin signaling, and MUFAs produced by SCD provided a forward loop to amplify Wnt signaling via stabilization of Lrp5 and Lrp6 mRNAs, contributing to liver fibrosis and tumor growth. SCD expressed by HSCs promoted liver tumor development in mice. Components of the identified loop linking HSCs and TICs might be therapeutic targets for liver fibrosis and tumors.