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Regio-isomers are utilized to design innovative AIE luminogens (AIEgens) by regulating molecular aggregation behavior. However, relevant examples are limited, and the underlying mechanism is not fully understood. Herein, a regio-isomer strategy is used to develop AIEgens by precisely regulating the intermolecular interactions in the solid state. Among the regio-isomers it is investigated, ortho- isomer (DCM-O3-O7) exhibits enhanced AIE-activity than the para- isomer (DCM-P6), and the size of the ortho- substituents is crucial for the AIE performance. The underlying mechanism of the strategy is revealed using DFT calculations and single-crystal analysis. Dual hydrogen bonds (CâHâââπ and CâHâââN) are generated between the molecules, which contributes to form dimers, tetramers, and 1D supramolecular structures in the crystal. By restricting intramolecular motion and attenuating π-π interactions, solid-state fluorescence is significantly enhanced. This strategy's effectiveness is validated using other donor-acceptor fluorophores, with DCM-O6 and its analogues serving as efficient probes for bioimaging applications. Notably, DCM-OM, which bears a morpholinyl instead of piperidinyl group, displayed strong lysosome-targeting ability and photostability; DCM-OP, incorporated by the hydrophilic quaternary ammonium group, exhibited wash-free imaging and cell membrane-targeting capabilities; and DCM-O6 nanoparticles enabled high-fidelity in vivo tumor imaging. Therefore, this strategy affords a general method for designing bright AIEgens.
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Manipulating the local coordination environment of central metal atoms in single-atom catalysts (SACs) is a powerful strategy to exploit efficient SACs with optimal electronic structures for various applications. Herein, Co-SACs featured by Co single atoms with coordinating S atoms in the second shell dispersed in a nitrogen-doped carbon matrix have been developed toward the selective hydrogenation of halo-nitrobenzene. The location of the S atom in the model Co-SAC is verified through synchrotron-based X-ray absorption spectroscopy and theoretical calculations. The resultant Co-SACs containing second-coordination shell S atoms demonstrate excellent activity and outstanding durability for selective hydrogenation, superior to most precious metal-based catalysts. In situ characterizations and theoretical results verify that high activity and selectivity are attributed to the advantageous formation of the Co-O bond between p-chloronitrobenzene and Co atom at Co1N4-S moieties and the lower free energy and energy barriers of the reaction. Our findings unveil the correlation between the performance and second-shell coordination atom of SACs.
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Highly active nonprecious-metal single-atom catalysts (SACs) toward catalytic transfer hydrogenation (CTH) of α,ß-unsaturated aldehydes are of great significance but still are deficient. Herein, we report that Zn-N-C SACs containing Zn-N3 moieties can catalyze the conversion of cinnamaldehyde to cinnamyl alcohol with a conversion of 95.5% and selectivity of 95.4% under a mild temperature and atmospheric pressure, which is the first case of Zn-species-based heterogeneous catalysts for the CTH reaction. Isotopic labeling, in situ FT-IR spectroscopy, and DFT calculations indicate that reactants, coabsorbed at the Zn sites, proceed CTH via a "Meerwein-Ponndorf-Verley" mechanism. DFT calculations also reveal that the high activity over Zn-N3 moieties stems from the suitable adsorption energy and favorable reaction energy of the rate-determining step at the Zn active sites. Our findings demonstrate that Zn-N-C SACs hold extraordinary activity toward CTH reactions and thus provide a promising approach to explore the advanced SACs for high-value-added chemicals.
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This paper presents a fusion algorithm based on the enhanced RRT* TEB algorithm. The enhanced RRT* algorithm is utilized for generating an optimal global path. Firstly, proposing an adaptive sampling function and extending node bias to accelerate global path generation and mitigate local optimality. Secondly, eliminating path redundancy to minimize path length. Thirdly, imposing constraints on the turning angle of the path to enhance path smoothness. Conducting kinematic modeling of the mobile robot and optimizing the TEB algorithm to align the trajectory with the mobile robot's kinematics. The integration of these two algorithms culminates in the development of a fusion algorithm. Simulation and experimental results demonstrate that, in contrast to the traditional RRT* algorithm, the enhanced RRT* algorithm achieves a 5.8% reduction in path length and a 62.5% decrease in the number of turning points. Utilizing the fusion algorithm for path planning, the mobile robot generates a superior, seamlessly smooth global path, adept at circumventing obstacles. Furthermore, the local trajectory meticulously conforms to the kinematic constraints of the mobile robot.
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BACKGRUOUND: Insulin resistance (IR) is the key pathological basis of many metabolic disorders. Lack of asialoglycoprotein receptor 1 (ASGR1) decreased the serum lipid levels and reduced the risk of coronary artery disease. However, whether ASGR1 also participates in the regulatory network of insulin sensitivity and glucose metabolism remains unknown. METHODS: The constructed ASGR1 knockout mice and ASGR1-/- HepG2 cell lines were used to establish the animal model of metabolic syndrome and the IR cell model by high-fat diet (HFD) or drug induction, respectively. Then we evaluated the glucose metabolism and insulin signaling in vivo and in vitro. RESULTS: ASGR1 deficiency ameliorated systemic IR in mice fed with HFD, evidenced by improved insulin intolerance, serum insulin, and homeostasis model assessment of IR index, mainly contributed from increased insulin signaling in the liver, but not in muscle or adipose tissues. Meanwhile, the insulin signal transduction was significantly enhanced in ASGR1-/- HepG2 cells. By transcriptome analyses and comparison, those differentially expressed genes between ASGR1 null and wild type were enriched in the insulin signal pathway, particularly in phosphoinositide 3-kinase-AKT signaling. Notably, ASGR1 deficiency significantly reduced hepatic gluconeogenesis and glycogenolysis. CONCLUSION: The ASGR1 deficiency was consequentially linked with improved hepatic insulin sensitivity under metabolic stress, hepatic IR was the core factor of systemic IR, and overcoming hepatic IR significantly relieved the systemic IR. It suggests that ASGR1 is a potential intervention target for improving systemic IR in metabolic disorders.
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Receptor de Asialoglicoproteína , Dieta Hiperlipídica , Resistência à Insulina , Fígado , Camundongos Knockout , Transdução de Sinais , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Humanos , Células Hep G2 , Fígado/metabolismo , Receptor de Asialoglicoproteína/metabolismo , Masculino , Insulina/sangue , Insulina/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Síndrome Metabólica/metabolismo , Síndrome Metabólica/etiologia , GluconeogêneseRESUMO
The ongoing global warming trajectory poses extensive challenges to plant ecosystems, with rubber plantations particularly vulnerable due to their influence on not only the longevity of the growth cycle and rubber yield, but also the complex interplay of carbon, water, and energy exchanges between the forest canopy and atmosphere. However, the response mechanism of phenology in rubber plantations to climate change remains unclear. This study concentrates on sub-optimal environment rubber plantations in Yunnan province, Southwest China. Utilizing the Google Earth Engine (GEE) cloud platform, multi-source remote sensing images were synthesized at 8-day intervals with a spatial resolution of 30-meters. The Normalized Difference Vegetation Index (NDVI) time series was reconstructed using the Savitzky-Golay (S-G) filter, coupled with the application of the seasonal amplitude method to extract three crucial phenological indicators, namely the start of the growing season (SOS), the end of the growing season (EOS), and the length of the growing season (LOS). Linear regression method, Pearson correlation coefficient, multiple stepwise regression analysis were used to extract of the phenology trend and find the relationship between SOS, EOS and climate factors. The findings demonstrated that 1) the phenology of rubber plantations has undergone dynamic changes over the past two decades. Specifically, the SOS advanced by 9.4 days per decade (R2 = 0.42, p< 0.01), whereas the EOS was delayed by 3.8 days per decade (R2 = 0.35, p< 0.01). Additionally, the LOS was extended by 13.2 days per decade (R2 = 0.55, p< 0.01); 2) rubber phenology demonstrated a notable sensitivity to temperature fluctuations during the dry season and precipitation patterns during the rainy season. The SOS advanced 2.0 days (r =-0.19, p< 0.01) and the EOS advanced 2.8 days (r =-0.35, p< 0.01) for every 1°C increase in the cool-dry season. Whereas a 100 mm increase in rainy season precipitation caused the SOS to be delayed by 2.0 days (r = 0.24, p< 0.01), a 100 mm increase in hot-dry season precipitation caused the EOS to be advanced by 7.0 days (r =-0.28, p< 0.01); 3) rubber phenology displayed a legacy effect of preseason climate variations. Changes in temperature during the fourth preseason month and precipitation during the fourth and eleventh preseason months are predominantly responsible for the variation in SOS. Meanwhile, temperature changes during the second, fourth, and ninth preseason months are primarily responsible for the variation in EOS. The study aims to enhance our understanding of how rubber plantations respond to climate change in sub-optimal environments and provide valuable insights for sustainable rubber production management in the face of changing environmental conditions.
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The simultaneous determination of multi-mycotoxins in food commodities are highly desirable due to their potential toxic effects and mass consumption of foods. Herein, liquid chromatography-quadrupole exactive orbitrap mass spectrometry was proposed to analyze multi-mycotoxins in commercial vegetable oils. Specifically, the method featured a successive liquid-liquid extraction process, in which the complementary solvents consisted of acetonitrile and water were optimized. Resultantly, matrix effects were reduced greatly. External calibration approach revealed good quantification property for each analyte. Under optimal conditions, the recovery ranging from 80.8% to 109.7%, relative standard deviation less than 11.7%, and good limit of quantification (0.35 to 45.4 ng/g) were achieved. The high accuracy of proposed method was also validated. The detection of 20 commercial vegetable oils revealed that aflatoxins B1 and B2, zearalenone were observed in 10 real samples. The as-developed method is simple and low-cost, which merits the wide applications for scanning mycotoxins in oil matrices.
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Titania nanospheres have been utilized as building blocks of electron transporting layers (ETLs) for mesoscopic perovskite solar cells (PSCs). Nevertheless, the power conversion efficiencies (PCEs) reported so far for the mesoscopic PSCs containing titania nanospheres are generally lower than those of the state-of-the-art planar PSCs. Here, we have prepared Li-doped hollow titania nanospheres (Li-HTS) through a "cation-exchange" approach and used them for the first time to modify the SnO2 ETL/perovskite interfaces of planar PSCs. The Li-HTS-modified PSC delivered a PCE of 23.28% with a fill factor (FF) of over 80%, which is significantly higher than the PCE of the control device (20.51%). This is the best PCE achieved for PSCs containing titania nanospheres. Moreover, interfacial modification using Li-HTS greatly improves the stability of the PSCs. This work demonstrates the potential of interface modification using inorganic nanostructures for enhancing the efficiency and stability of planar PSCs.
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The name Striatochrista nom. n. is introduced as replacement for Striatella Volynkin & S.-Y. Huang, 2019. A new genus, Letrasilta S.-Y. Huang & Volynkin gen. n. is erected to include the Striatella cernyi species-group with the new species, L. ratnasambhava S.-Y. Huang, Volynkin & Yin sp. n. from Xizang, southwestern China designated as the type species. Based on the molecular phylogenetic analysis, the new genus is found to be sister to the clade (Aberrasine + ((Indiania + Idopterum) + Striatochrista nom. n.)) but is distinguished from all the relevant genera by the unique genitalia features. Letrasilta cernyi (Volynkin, 2018) comb. n. is also reported from India for the first time. Adults and genitalia of the aforementioned taxa are illustrated. A checklist of the genus Striatochrista is also provided.
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Mariposas , Filogenia , Animais , China , Genitália/anatomia & histologia , Mariposas/anatomia & histologia , Mariposas/classificação , Mariposas/genética , Genes de Insetos/genética , Especificidade da EspécieRESUMO
Developing cost-effective and highly efficient photocathodes toward polysulfide redox reduction is highly desirable for advanced quantum dot (QD) photovoltaics. Herein, we demonstrate nitrogen doped carbon (N-C) shell-supported iron single atom catalysts (Fe-SACs) capable of catalyzing polysulfide reduction in QD photovoltaics for the first time. Specifically, Fe-SACs with FeN4 active sites feature a power conversion efficiency of 13.7% for ZnCuInSe-QD photovoltaics (AM1.5G, 100 mW/cm2), which is the highest value for ZnCuInSe QD-based photovoltaics, outperforming those of Cu-SACs and N-C catalysts. Compared with N-C, Fe-SACs exhibit suitable energy level matching with polysulfide redox couples, revealed by the Kelvin probe force microscope, which accelerates the charge transferring at the interfaces of catalyst/polysulfide redox couple. Density functional theory calculations demonstrate that the outstanding catalytic activity of Fe-SACs originates from the preferable adsorption of S42- on the FeN4 active sites and the high activation degree of the S-S bonds in S42- initiated by the FeN4 active sites.
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In the field of AGV, a path planning algorithm is always a heated area. However, traditional path planning algorithms have many disadvantages. To solve these problems, this paper proposes a fusion algorithm that combines the kinematical constraint A* algorithm and the following dynamic window approach algorithm. The kinematical constraint A* algorithm can plan the global path. Firstly, the node optimization can reduce the number of child nodes. Secondly, improving the heuristic function can increase efficiency of path planning. Thirdly, the secondary redundancy can reduce the number of redundant nodes. Finally, the B spline curve can make the global path conform to the dynamic characteristics of AGV. The following DWA algorithm can be dynamic path planning and allow the AGV to avoidance moving obstacle. The optimization heuristic function of the local path is closer to the global optimal path. The simulation results show that, compared with the fusion algorithm of traditional A* algorithm and traditional DWA algorithm, the fusion algorithm reduces the length of path by 3.6%, time of path by 6.7% and the number of turns of final path by 25%.
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Nonalcoholic fatty liver disease (NAFLD) is prevalent worldwide; about 25% of NAFLD silently progress into steatohepatitis, in which some of them may develop into fibrosis, cirrhosis and liver failure. However, few drugs are available for NAFLD, partly because of an incomplete understanding of its pathogenic mechanisms. Here, using in vivo and in vitro gain- and loss-of-function approaches, we identified up-regulated DKK1 plays a pivotal role in high-fat diet-induced NAFLD and its progression. Mechanistic analysis reveals that DKK1 enhances the capacity of hepatocytes to uptake fatty acids through the ERK-PPARγ-CD36 axis. Moreover, DKK1 increased insulin resistance by activating the JNK signaling, which in turn exacerbates disorders of hepatic lipid metabolism. Our finding suggests that DKK1 may be a potential therapeutic and diagnosis candidate for NAFLD and metabolic disorder progression.
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Hepatopatia Gordurosa não Alcoólica , Humanos , Dieta Hiperlipídica , Hepatócitos , Peptídeos e Proteínas de Sinalização Intercelular , Metabolismo dos Lipídeos/genética , Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica/genética , Antígenos CD36/metabolismoRESUMO
AIM: Previous studies have suggested that big stick design (BSD) method can only be used in clinical trials of two treatments with equal proportion, which has good statistical performance and has become the recommended choice of randomized methods. This study expands BSD method, so that it can be applied to three groups, and provides more randomized methods for clinical trials. METHODS: On the basis of BSD method used in two treatments with equal proportion, the derivation conditional allocation probability of BSD method used in three treatments with equal proportion was carried out. BSD method was compared with simple randomization (SR) method, permuted block design (PBD) method and block urn design (BUD) method by Monte-Carlo simulation in balance and randomness. RESULTS: In terms of balance, PBD method was the best, followed by BUD method, BSD method, and SR method was the worst. In terms of randomness, SR method was the best, followed by BSD method, BUD method and PBD method. The comprehensive performance showed that BSD method was better than BUD method, PBD method and SR method. CONCLUSION: The expanded BSD method used in three treatments with equal proportion has good comprehensive performance, and it can be the recommended randomization method for clinical trials of three treatments with equal proportion.
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This study aimed to observe the effect of terpinen-4-ol(T4O) on the proliferation of vascular smooth muscle cells(VSMCs) exposed to high glucose(HG) and reveal the mechanism via the Krüppel-like factor 4(KLF4)/nuclear factor kappaB(NF-κB) signaling pathway. The VSMCs were first incubated with T4O for 2 h and then cultured with HG for 48 h to establish the model of inflammatory injury. The proliferation, cell cycle, and migration rate of VSMCs were examined by MTT method, flow cytometry, and wound healing assay, respectively. The content of inflammatory cytokines including interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α) in the supernatant of VSMCs was measured by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to determine the protein levels of proliferating cell nuclear antigen(PCNA), Cyclin D1, KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. The KLF4 expression in VSMCs was silenced by the siRNA technology, and then the effects of T4O on the cell cycle and protein expression of the HG-induced VSMCs were observed. The results showed that different doses of T4O inhibited the HG-induced proliferation and migration of VSMCs, increased the percentage of cells in G_1 phase, and decreased the percentage of cells in S phase, and down-regulated the protein levels of PCNA and Cyclin D1. In addition, T4O reduced the HG-induced secretion and release of the inflammatory cytokines IL-6 and TNF-α and down-regulated the expression of KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. Compared with si-NC+HG, siKLF4+HG increased the percentage of cells in G_1 phase, decreased the percentage of cells in S phase, down-regulated the expression of PCNA, Cyclin D1, and KLF4, and inhibited the activation of NF-κB signaling pathway. Notably, the combination of silencing KLF4 with T4O treatment further promoted the changes in the above indicators. The results indicate that T4O may inhibit the HG-induced proliferation and migration of VSMCs by down-regulating the level of KLF4 and inhibiting the activation of NF-κB signaling pathway.
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NF-kappa B/metabolismo , Interleucina-18/metabolismo , Antígeno Nuclear de Célula em Proliferação/genética , Ciclina D1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Músculo Liso Vascular , Proliferação de Células , Transdução de Sinais , Citocinas/metabolismo , Glucose/metabolismoRESUMO
Aflatoxin B1 (AFB1) solution certified reference materials (CRMs) have been widely utilized in the measurements of AFB1 contaminations in foods and agricultural products. It is of great importance to evaluate the stability of AFB1 solution CRMs in different matrices for their practical applications. In this study, the stability of AFB1 solution CRM was investigated and its degradation products under various conditions were elucidated using ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry for the first time. Exposure to high temperatures and UV light irradiation accelerated the degradation of AFB1 solution significantly, and the degradation products were largely dependent on the solvents. Two degradation pathways were proposed based on the degradation products. The addition reaction, oxidation reaction, and modification of the methoxy group are the major processes involved in the degradation of the AFB1 solution. The results of this study indicate that the property value of the acetonitrile solution of AFB1 can be well retained when it is stored at temperatures lower than 60 °C, and the exposure to UV light irradiation is avoided.
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This study investigates the possibility of supporting tourists in a foreign land intelligently by using the Tourism Cloud Management System (TCMS) to enhance and better their tourism experience. Some technologies allow tourists to highlight popular tourist routes and circuits through the visualisation of data and sensor clustering approaches. With this, a tourist can access the shared data on a specific location to know the sites of famous local attractions, how other tourists feel about them, and how to participate in local festivities through a smart tourism model. This study surveyed the potential of smart tourism among tourists and how such technologies have developed over time while proposing a TCMS. Its goals were to make physical/paper tickets redundant via the introduction of a mobile app with eTickets that can be validated using camera and QR code technologies and to enhance the transport network using Bluetooth and GPS for real-time identification of tourists' presence. The results show that a significant number of participants engage in tourist travels, hence the need for smart tourism and tourist management. It was concluded that smart tourism is very appealing to tourists and can improve the appeal of the destination if smart solutions are implemented. This study gives a first-hand review of the preference of tourists and the potential of smart tourism.
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Multiple endocrine neoplasia type 1 (MEN1) is an inherited disease caused by mutations in the MEN1 gene encoding a nuclear protein menin. Among those different endocrine tumors of MEN1, the pancreatic neuroendocrine tumors (PNETs) are life-threatening and frequently implicated. Since there are uncertainties in genotype and phenotype relationship and there are species differences between humans and mice, it is worth it to replenish the mice model with human cell resources. Here, we tested whether the patient-origin induced pluripotent stem cell (iPSC) lines could phenocopy some defects of MEN1. In vitro ß-cell differentiation revealed that the percentage of insulin-positive cells and insulin secretion were increased by at least two-fold in MEN1-iPSC derived cells, which was mainly resulted from significantly higher proliferative activities in the pancreatic progenitor stage (Day 7-13). This scenario was paralleled with increased expressions of prohormone convertase1/3 (PC1/3), glucagon-like peptide-1 (GLP-1), GLP-1R, and factors in the phosphatidylinositol 3-kinase (PI3K)/AKT signal pathway, and the GLP-1R was mainly expressed in ß-like cells. Blockages of either GLP-1R or PI3K significantly reduced the percentages of insulin-positive cells and hypersecretion of insulin in MEN1-derived cells. Furthermore, in transplantation of different stages of MEN1-derived cells into immune-deficient mice, only those ß-like cells produced tumors that mimicked the features of the PNETs from the original patient. To the best of our knowledge, this was the first case using patient-origin iPSCs modeling most phenotypes of MEN1, and the results suggested that GLP-1R may be a potential therapeutic target for MEN1-related hyperinsulinemia.
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Células-Tronco Pluripotentes Induzidas , Neoplasia Endócrina Múltipla Tipo 1 , Tumores Neuroectodérmicos Primitivos , Animais , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Insulina/metabolismo , Insulina Regular Humana , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-OncogênicasRESUMO
We designed a novel ratiometric fluorescent probe P1-Leu with a donor-acceptor-donor fluorophore for the detection of leucine aminopeptidase in lysosomes. P1-Leu exhibits a lower detection limit than the ratiometric donor-π-acceptor probe, due to the low ratiometric background. Besides, P1-Leu has good lysosome-targeting ability and realizes the distinction of LAP levels in different cells.
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Corantes Fluorescentes , Leucil Aminopeptidase , Lisossomos , Espectrometria de FluorescênciaRESUMO
Well dispersible and stable single atom catalysts (SACs) with hydrophilic features are highly desirable for selective hydrogenation reactions in hydrophilic solvents towards important chemicals and pharmaceutical intermediates. A general strategy is reported for the fabrication of hydrophilic SACs by cation-exchange approach. The cation-exchange between metal ions (M = Ni, Fe, Co, Cu) and Na+ ions introduced in the skeleton of metal oxide (TiO2 or ZrO2 ) nanoshells plays the key role in forming M1 /TiO2 and M1 /ZrO2 SACs, which efficiently prevents the aggregation of the exchanged metal ions. The as-obtained SACs are highly dispersible and stable in hydrophilic solvents including alcohol and water, which greatly facilitates the catalysis reaction in alcohol. The Ni1 /TiO2 SACs have been successfully utilized as catalysts for the selective C=C hydrogenation of cinnamaldehyde to produce phenylpropanal with 98% conversion, over 90% selectivity, good recyclability, and a turnover frequency (TOF) of 102 h-1 , overwhelming most reported catalysts including noble metal catalysts.
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Álcoois , Óxidos , Catálise , Hidrogenação , SolventesRESUMO
BACKGROUND: Various methods have been developed to generate hepatic cells from human pluripotent stem cells (hPSCs) that rely on the combined use of multiple expensive growth factors, limiting industrial-scale production and widespread applications. Small molecules offer an attractive alternative to growth factors for producing hepatic cells since they are more economical and relatively stable. METHODS: We dissect small-molecule combinations and identify the ideal cocktails to achieve an optimally efficient and cost-effective strategy for hepatic cells differentiation, expansion, and maturation. RESULTS: We demonstrated that small-molecule cocktail CIP (including CHIR99021, IDE1, and PD0332991) efficiently induced definitive endoderm (DE) formation via increased endogenous TGF-ß/Nodal signaling. Furthermore, we identified that combining Vitamin C, Dihexa, and Forskolin (VDF) could substitute growth factors to induce hepatic specification. The obtained hepatoblasts (HBs) could subsequently expand and mature into functional hepatocyte-like cells (HLCs) by the established chemical formulas. Thus, we established a stepwise strategy with complete small molecules for efficiently producing scalable HBs and functionally matured HLCs. The small-molecule-derived HLCs displayed typical functional characteristics as mature hepatocytes in vitro and repopulating injured liver in vivo. CONCLUSION: Our current small-molecule-based hepatic generation protocol presents an efficient and cost-effective platform for the large-scale production of functional human hepatic cells for cell-based therapy and drug discovery using.