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Currently, the emergence of the endemic Coronavirus disease (COVID-19) situation still poses a serious threat to public health. However, it remains elusive about the role of fecal microbiota transplantation in treating COVID-19. We performed a randomized, double-blind, placebo-controlled clinical trial enrolling a cohort of 40 COVID-19 patients with mild-moderate symptoms. Our results showed that fecal microbiota transplantation provided an amelioration in diarrhoea (p = 0.026) of digestive system and depression (p = 0.006) of neuropsychiatric-related symptom in COVID-19 patients, respectively. Meanwhile, we found that the number of patients with diarrhoea decreased from 19 to 0 on day 7 after fecal microbiota transplantation treatment, and it was statistically changed compared to the placebo group (p = 0.047). Of note, the serum concentration of aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT, fecal microbiota transplantation, pre vs. post: 0.966 vs. 0.817), a biomarker for predicting long COVID-19, was significantly reduced by fecal microbiota transplantation. In all, our study supports that fecal microbiota transplantation could be a novel therapeutic strategy for COVID-19 patients with diarrhoea and depressive symptoms, which is potentially valuable in ameliorating long COVID-19 symptoms.
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COVID-19 , Depressão , Diarreia , Transplante de Microbiota Fecal , Humanos , Transplante de Microbiota Fecal/métodos , COVID-19/terapia , COVID-19/complicações , Diarreia/terapia , Diarreia/microbiologia , Diarreia/virologia , Masculino , Feminino , Método Duplo-Cego , Pessoa de Meia-Idade , Depressão/terapia , Estudos Prospectivos , Adulto , Idoso , Fezes/microbiologia , Fezes/virologia , SARS-CoV-2 , Resultado do Tratamento , Aspartato Aminotransferases/sangue , Microbioma GastrointestinalRESUMO
BACKGROUND: Intestinal obstruction represents a severe intestinal disease associated with higher mortality rates. However, the determinants of mortality in patients with intestinal obstruction remain inadequately understood. This study sought to elucidate the potential risk factors associated with mortality in the context of intestinal obstruction during the COVID-19 pandemic. METHODS: A retrospective analysis was performed on a cohort of 227 patients diagnosed with intestinal obstruction at the First Hospital of Hebei Medical University, spanning the period from September 7, 2022, to January 7, 2023. The primary endpoint of the study was mortality within four weeks following discharge. Univariate and multivariable logistic regression models were utilized to evaluate the risk factors associated with mortality outcomes. RESULTS: A cohort of 227 patients diagnosed with intestinal obstruction (median age, 59.02 years [IQR, 48.95-70.85 years]) was included in our study. Malignant bowel obstruction (MBO) and COVID-19 were identified as independent risk factors for mortality among these patients. Notably, the mortality rate increased significantly to 38.46% when MBO was concomitant with COVID-19. Furthermore, postoperative pulmonary complications (PPC) (OR, 54.21 [death]; 95% CI, 3.17-926.31), gastric cancer (OR, 9.71 [death]; 95% CI, 1.38-68.18), VTE (Caprini Score ≥ 5) (OR, 7.64 [death]; 95% CI, 1.37-42.51), and COVID-19 (OR, 5.72 [death]; 95% CI, 1.01-32.29) were all determined to be independent risk factors for postoperative mortality. Additionally, gastric cancer could have emerged as one of the most severe risk factors for mortality in individuals with intestinal obstruction within the cohort of cancer patients, of which gastric cancer exhibited higher mortality rates compared to individuals with other forms of cancer. CONCLUSION: The study identifies MBO, gastric cancer, COVID-19, PPC, and VTE as potential risk factors for mortality in cases of intestinal obstruction. These findings highlight the necessity for continuous monitoring of indicators related to these mortality risk factors and their associated complications, thereby offering valuable insights for the management and treatment of intestinal obstruction.
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COVID-19 , Obstrução Intestinal , Humanos , Obstrução Intestinal/mortalidade , Obstrução Intestinal/etiologia , Masculino , Pessoa de Meia-Idade , Feminino , COVID-19/complicações , COVID-19/mortalidade , Idoso , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/epidemiologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/complicaçõesRESUMO
PURPOSE: To evaluate a new non-contact instrument (OA-2000) measuring the ocular biometry parameters of silicone oil (SO)-filled aphakic eyes, as compared with IOLMaster 700. METHODS: Forty SO-filled aphakic eyes of 40 patients were enrolled in this cross-sectional clinical trial. The axial length (AL), central corneal thickness (CCT), keratometry ((flattest keratometry) Kf and (steep keratometry, 90° apart from Kf) Ks), and axis of the Kf (Ax1) were measured with OA-2000 and IOLMaster 700. The coefficient of variation (CoV) was calculated to assess the repeatability. The correlation was evaluated by the Pearson coefficient. Bland-Altman analysis and paired t test were used to analyze the agreements and differences of parameters measured by the two devices, respectively. RESULTS: The mean AL obtained with the OA-2000 was 23.57 ± 0.93 mm (range: 21.50 to 25.68 mm), and that obtained with the IOLMaster 700 was 23.69 ± 0.94 mm (range: 21.85 to 25.86 mm), resulting in a mean offset of 0.124 ± 0.125 mm (p < 0.001). The mean offset of CCT measured by OA-2000 and IOLMaster 700 was 14.6 ± 7.5 µm (p < 0.001). However, the Kf, Ks and Ax1 values from the two devices were comparable (p > 0.05). All the measured parameters of the two devices showed strong linear correlations (all r ≥ 0.966). The Bland-Altman analysis showed a narrow 95% limits of agreement (LoA) of Kf, Ks and AL, but 95%LoA of CCT and Ax1 was wide, which were - 29.3 ~ 0.1 µm and-25.9 ~ 30.7°respectively. The CoVs of the biometric parameters obtained with OA-2000 were lower than 1%. CONCLUSION: In SO-filled aphakic eyes, the ocular parameters (including AL, Kf, Ks, Ax1, and CCT) measured by the OA-2000 and IOLMaster 700 had a good correlation. Two devices had an excellent agreement on ocular biometric measurements of Kf, Ks and AL. The OA-2000 provided excellent repeatability of ocular parameters in SO-filled aphakic eyes.
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Afacia , Comprimento Axial do Olho , Óleos de Silicone , Humanos , Câmara Anterior/anatomia & histologia , Biometria , Córnea/anatomia & histologia , Estudos Transversais , Reprodutibilidade dos Testes , Doenças Retinianas , Tomografia de Coerência ÓpticaRESUMO
In this paper, we model the trajectory of the cumulative confirmed cases and deaths of COVID-19 (in log scale) via a piecewise linear trend model. The model naturally captures the phase transitions of the epidemic growth rate via change-points and further enjoys great interpretability due to its semiparametric nature. On the methodological front, we advance the nascent self-normalization (SN) technique (Shao, 2010) to testing and estimation of a single change-point in the linear trend of a nonstationary time series. We further combine the SN-based change-point test with the NOT algorithm (Baranowski et al., 2019) to achieve multiple change-point estimation. Using the proposed method, we analyze the trajectory of the cumulative COVID-19 cases and deaths for 30 major countries and discover interesting patterns with potentially relevant implications for effectiveness of the pandemic responses by different countries. Furthermore, based on the change-point detection algorithm and a flexible extrapolation function, we design a simple two-stage forecasting scheme for COVID-19 and demonstrate its promising performance in predicting cumulative deaths in the U.S.
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Luminescent cerium(III) complexes based on the d-f transition have characteristics of broad emission spectra, tunable emission colors, and short excited state lifetimes, showing potential applications in display, lighting, and other fields. Thus it is important to construct luminescent Ce(III) complexes with high photoluminescence efficiency and good stability. In this work, five Ce(III) complexes with dihydrobis(pyrazolyl)borate or diphenylbis(pyrazolyl)borate ligands, where pyrazolyl stands for pyrazolyl, 3-methylpyrazolyl, or 3,5-dimethylpyrazolyl, were designed and synthesized, showing emission colors from deep blue to yellow with a maximum wavelength in the range of 390-560 nm, short excited state lifetimes of 30-80 ns, and photoluminescence quantum yields exceeding 75% in solid powder. By comparing these complexes, it is found that higher photoluminescence efficiency and better thermal/air stability could be achieved in the complexes with dihydrobis(pyrazolyl)borate ligands.
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Rare earth europium(II) complexes based on d-f transition luminescence have characteristics of broad emission spectra, tunable emission colors and short excited state lifetimes, showing great potential in display, lighting and other fields. In this work, four complexes of Eu(II) and bis(pyrazolyl)borate ligands, where pyrazolyl stands for pyrazolyl, 3-methylpyrazolyl, 3,5-dimethylpyrazolyl or 3-trifluoromethylpyrazole, were designed and synthesized. Due to the varied steric hindrance of the ligands, different numbers of solvent molecules (tetrahydrofuran) are participated to saturate the coordination structure. These complexes showed blue-green to yellow emissions with maximum wavelength in the range of 490-560 nm, and short excited state lifetimes of 30-540 ns. Among them, the highest photoluminescence quantum yield can reach 100%. In addition, when the complexes were heated under vacuum or nitrogen atmosphere, they finally transformed into the complexes of Eu(II) and corresponding tri(pyrazolyl)borate ligands and sublimated away.
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A scheme of quarter-overlapped microlens arrays (QOMLA) is proposed to improve the display performance of integral imaging (II). The theory and the design of QOMLA is presented by the combination of geometric optics and wave optics and is verified by the optical experiments. The angular sampling density of the II system can be doubled in each dimension to further increase the spatial resolution. Multiple central depth planes can be constructed by adjusting the spacing of the multilayers, so as to expand the depth of field (DoF). Furthermore, QOMLA is easier to process when compared with the single-layer microlens array, and it reduces processing costs.
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Prolonged ER stress has been known to be one of the major drivers of impaired lipid homeostasis during the pathogenesis of non-alcoholic liver disease (NAFLD). However, the downstream mediators of ER stress pathway in promoting lipid accumulation remain poorly understood. Here, we present data showing the b-ZIP transcription factor E4BP4 in both the hepatocytes and the mouse liver is potently induced by the chemical ER stress inducer tunicamycin or by high-fat, low-methionine, and choline-deficient (HFLMCD) diet. We showed that such an induction is partially dependent on CHOP, a known mediator of ER stress and requires the E-box element of the E4bp4 promoter. Tunicamycin promotes the lipid droplet formation and alters lipid metabolic gene expression in primary mouse hepatocytes from E4bp4flox/flox but not E4bp4 liver-specific KO (E4bp4-LKO) mice. Compared with E4bp4flox/flox mice, E4bp4-LKO female mice exhibit reduced liver lipid accumulation and partially improved liver function after 10-week HFLMCD diet feeding. Mechanistically, we observed elevated AMPK activity and the AMPKß1 abundance in the liver of E4bp4-LKO mice. We have evidence supporting that E4BP4 may suppress the AMPK activity via promoting the AMPKß1 ubiquitination and degradation. Furthermore, acute depletion of the Ampkß1 subunit restores lipid droplet formation in E4bp4-LKO primary mouse hepatocytes. Our study highlighted hepatic E4BP4 as a key factor linking ER stress and lipid accumulation in the liver. Targeting E4BP4 in the liver may be a novel therapeutic avenue for treating NAFLD.
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Fatores de Transcrição de Zíper de Leucina Básica/fisiologia , Estresse do Retículo Endoplasmático , Hepatócitos , Metabolismo dos Lipídeos , Fígado , Hepatopatia Gordurosa não Alcoólica/metabolismo , Quinases Proteína-Quinases Ativadas por AMP , Animais , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Hepatócitos/metabolismo , Hepatócitos/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Quinases/metabolismo , Transdução de Sinais , Tunicamicina , UbiquitinaçãoRESUMO
A bionic-compound-eye structure (BCES), which is a substitute of a microlens array, is proposed to enhance the performance of integral imaging (II) 3D display systems. Hexagonal ocelli without gaps and barriers are predesigned to obtain a continuous image, high-resolution, and uniform parallax. A curved substrate is designed to enhance the viewing angle. In addition, ocelli are fused with the substrate to form a relief structure, BCES. When they are placed above a normal display, continuous and full-parallax 3D images with 150 µm effective resolution and a 28° horizontal, 22° vertical viewing angle could be achieved, about twice as much as that of normal systems. The weight of the BCES is 31 g, and the thickness of the whole system is 22 mm; thus, the BCES-based II (BCES-II) is very compact. In addition, this structure can be easily integrated into a cell phone or iPad for compact quasi-2D and 3D adjustable display.
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We report a novel family of lanthanide complexes Ln(DPPOP)3 (Ln = Pr, Nd, Sm, Eu, Tb, Dy, Er, and Yb) employing anionic tridentate (Oâ§Nâ§O) ligand 6-(diphenylphosphoryl)picolinate (DPPOP). Crystal structures of the complexes reveal that each lanthanide ion is nine-coordinated by three tridentate ligands. In the crystals, 1D channels are found, which can absorb and eliminate water reversibly. DPPOP possesses high triplet energy and can sensitize a series of lanthanide ions. An energy transfer mechanism is proposed through the higher excited states of the lanthanide ions. In the solid state, remarkably high quantum yields in the visible range are obtained: 81% for Eu(III), 97% for Tb(III), 13% for Dy(III), and 4% for Sm(III) complex.
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Wave optics is usually thought to be more rigorous than geometrical optics to analyze integral imaging (II) systems. However, most of the previous wave-optics investigations are directed to a certain subsystem or do not sufficiently consider the finite aperture of microlens arrays (MLAs). Therefore, a diffraction-limited model of the entire II system, which consists of pickup, image processing, and reconstruction subsystems, is proposed, and the effects of system parameters on spatial resolution are especially studied. With the help of paraxial scalar diffraction theory, the origin impulse response function of the entire II system is derived; the parameter matching condition with optimum resolution and the wave-optics principle are achieved. Besides, the modulation transfer function is then obtained and Fourier analysis is performed, which indicates that the features of MLA and the display play a critical role in spatial frequency transfer characteristics, greatly affecting the resolution. These studies might be useful for the further research and understanding of II systems, especially for the effective enhancement of resolution.
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High levels of consumption of saturated lipids have been largely associated with the increasing prevalence of metabolic diseases. In particular, saturated fatty acids such as palmitic acid (PA) have been implicated in the development of insulin resistance (IR). Scutellarin (Scu) is one of the effective traditional Chinese medicines considered beneficial for liver diseases and diabetes. In this study, we investigated the effect of Scu on IR and lipid metabolism disorders in vitro and in high fat diet (HFD)-fed mice. In vitro, we found that Scu decreased insulin-dependent lipid accumulation and the mRNA expression of CD36, Fasn, and ACC in PA-treated HepG2 cells. Additionally, Scu upregulated Akt phosphorylation and improved the insulin signalling pathway. Moreover, Scu downregulated mammalian target of rapamycin (mTOR) phosphorylation and the n-SREBP-1c protein level and also reduced lipid accumulation via the mTOR-dependent pathway, as confirmed by the molecular docking of Scu to mTOR. In HFD-fed C57BL/6 mice, Scu improved oral glucose tolerance, pyruvate tolerance and the IR index and also increased the Akt phosphorylation level. Moreover, Scu reduced hepatocyte steatosis, decreased lipid accumulation and triglyceride levels, inhibited mTOR phosphorylation, and decreased the SREBP-1c level in the liver. Taken together, these findings suggest that Scu ameliorates hepatic IR by regulating hepatocyte lipid metabolism via the mTOR-dependent pathway through SREBP-1c suppression.
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Apigenina/uso terapêutico , Glucuronatos/uso terapêutico , Hepatócitos/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Simulação de Acoplamento Molecular/métodos , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Serina-Treonina Quinases TOR/efeitos dos fármacos , Animais , Apigenina/farmacologia , Técnicas de Cultura de Células , Glucuronatos/farmacologia , Humanos , Masculino , CamundongosRESUMO
Luminescent EuII complexes with a characteristic 5d-4f transition have potential applications in many fields. However, their instability in ambient conditions impedes further exploration and application. Herein, we report two new EuII complexes, bis[hydrotris(3-trifluoromethylpyrazolyl)borate]europium(II) (Eu-1) and bis[hydrotris(3-methylpyrazolyl)borate]europium(II) (Eu-2). Intriguingly, the blue emissive Eu-1 showed high air stability arising from fluorine protection and close molecular packing, as maintaining a photoluminescence quantum yield (PLQY) of 91 % (initial 96 %) upon exposure to air over 2200 hours. While the orange emissive Eu-2 showed a maximum luminance of 30620â cd m-2 , and a maximum external quantum efficiency (EQE) of 6.5 %, corresponding to an exciton utilization efficiency around 100 % in organic light-emitting diodes (OLEDs). These results could inspire further research on stable and efficient EuII complexes and their application in OLEDs.
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As a kind of photoluminescent material, CuI complexes have many advantages such as adjustable emission, variable structures, and low cost, attracting attention in many fields. In this work, two novel two-coordinate CuI -N-heterocyclic carbene complexes were synthesized, and they exhibit unique dual emission properties, fluorescence and phosphorescence. The crystal structure, packing mode, and photophysical properties under different conditions were systematically studied, proving the emissive mechanism to be the locally excited state of the carbazole group. Based on this mechanism, ultralong room-temperature phosphorescence (RTP) with a lifetime of 140â ms is achieved by selective deuteration of the carbazole group. These results deepen the understanding of the luminescence mechanism and design strategy for two-coordinate CuI complexes, and prove their potential in applications as ultralong RTP materials.
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Four tridentate europium(III) complexes containing a diphenylphosphoryl group are prepared with strong bonding between the ligands and centered ion, convinced by crystal structures. Compared to their parent bidentate complexes, the tridentate complexes display improved and exceptionally high photoluminescence quantum yields (PLQYs) in powder (all over 80%, best 91%), as well as in a CH2Cl2 solution and poly(methyl methacrylate) films, benefiting from compact, stable, and saturated coordination.
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Two highly luminescent and water-soluble Eu(III) complexes, Eu1 and Eu2, based on novel carboxyl-functionalized 1,5-naphthyridine derivatives 8-hydroxy-1,5-naphthyridine-2-carboxylic acid (H2L1) and 7-cyano-8-hydroxy-1,5-naphthyridine-2-carboxylic acid (H2L2), respectively, are designed and synthesized. The crystal structure of Eu2 indicates that the central Eu(III) ion is nine-coordinated by three tridentate ligands (O^N^O). Both Eu1 and Eu2 show strong luminescence in aqueous solution with quantum yields (lifetimes) of 28% (1.1 ms) and 14% (0.76 ms), respectively. The chelates display unique UV-light stability in solution and remain highly emissive after 100 min of strong UV irradiation (â¼300 W·m-2 at 345 nm). Moreover, they exhibit reversible luminescence intensity changes with varied pH values, and the response mechanism is investigated. "Turn-on" of the Eu(III) emission upon increasing pH is realized by ligand structure change from keto to enol anion form, resulting in red-shifted absorption band and suppressed quenching from solvents and N-H vibration upon deprotonating. The results show that these novel Eu(III) complexes are quite intriguing for potential application as bioimaging agents and pH probes.
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Complexos de Coordenação/efeitos da radiação , Európio/efeitos da radiação , Naftiridinas/efeitos da radiação , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Európio/química , Concentração de Íons de Hidrogênio , Ligantes , Luminescência , Naftiridinas/síntese química , Naftiridinas/química , Fotodegradação , Solubilidade , Raios Ultravioleta , Água/químicaRESUMO
White organic light-emitting diodes (WOLEDs) is a new generation of lighting technology and has stimulated wide-ranging studies. Despite the advantage of simple device structure, single-emitting-layer WOLEDs (SEL-WOLEDs) still face the challenges of difficult material screening and fine energy level regulation. Herein, we report efficient SEL-WOLEDs with a sky-blue emitting cerium(III) complex Ce-TBO2Et and an orange-red emitting europium(II) complex Eu(Tp2Et)2 as the emitters, showing a maximum external quantum efficiency of 15.9% and Commission Internationale de l'Eclairage coordinates of (0.33, 0.39) at various luminances. Most importantly, the electroluminescence mechanism of direct hole capture and hindered energy transfer between the two emitters facilitate a manageable weight doping concentration of 5% for Eu(Tp2Et)2, avoiding the low concentration (<1%) of the low-energy emitter in typical SEL-WOLEDs. Our results indicate that d-f transition emitters may circumvent fine energy level regulation and provide development potential for SEL-WOLEDs.
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A new heteronuclear EuII-MnII complex [Eu(N2O6)]MnBr4 (N2O6 = 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane) is designed and synthesized, which shows an intense green emission from MnII with a near-unity photoluminescence quantum yield. Measurement of excited-state dynamics demonstrated the sensitization process from EuII to MnII, which represents the first example of f â d molecular sensitization. Due to the large optical absorption cross-section of the EuII center, [Eu(N2O6)]MnBr4 shows an emission intensity 7 to 2500 times stronger than that of the SrII-MnII control complex [Sr(N2O6)]MnBr4 upon the excitation of near ultraviolet to blue light.
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Quartz glass shows superior physicochemical properties and is used in modern high technology. Due to its hard and brittle characteristics, traditional polishing slurry mostly uses strong acid, strong alkali, and potent corrosive additives, which cause environmental pollution. Furthermore, the degree of damage reduces service performance of the parts due to the excessive corrosion. Therefore, a novel quartz glass green and efficient non-damaging chemical mechanical polishing slurry was developed, consisting of cerium oxide (CeO2), Lanthanum oxyfluoride (LaOF), potassium pyrophosphate (K4P2O7), sodium N-lauroyl sarcosinate (SNLS), and sodium polyacrylate (PAAS). Among them, LaOF abrasive showed hexahedral morphology, which increased the cutting sites and uniformed the load. The polishing slurry was maintained by two anionic dispersants, namely SNLS and PAAS, to maintain the suspension stability of the slurry, which makes the abrasive in the slurry have a more uniform particle size and a smoother sample surface after polishing. After the orthogonal test, a surface roughness (Sa) of 0.23 nm was obtained in the range of 50 × 50 µm2, which was lower than the current industry rating of 0.9 nm, and obtained a material removal rate (MRR) of 530.52 nm/min.
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BACKGROUND: The Metabolic reprogramming of tumor cells plays a vital role in the progression of hepatocellular carcinoma. Organic cation/carnitine transporter 2 (OCTN2), a sodium-ion dependent carnitine transporter and a sodium-ion independent tetraethylammonium (TEA) transporter, has been reported to contribute tumor malignancies and metabolic dysregulation in renal and esophageal carcinoma. However, the role of lipid metabolism deregulation mediated by OCTN2 in HCC cells has not been clarified. METHODS: Bioinformatics analyses and immunohistochemistry assay were employed to identify OCTN2 expression in HCC tissues. The correlation between OCTN2 expression and prognosis was elucidated through K-M survival analysis. The expression and function of OCTN2 were examined via the assays of western blotting, sphere formation, cell proliferation, migration and invasion. The mechanism of OCTN2-mediated HCC malignancies was investigated through RNA-seq and metabolomic analyses. Furthermore, xenograft tumor models based on HCC cells with different OCTN2 expression levels were conducted to analyze the tumorigenic and targetable role of OCTN2 in vivo. RESULTS: We found that gradually focused OCTN2 was significantly upregulated in HCC and tightly associated with poor prognosis. Additionally, OCTN2 upregulation promoted HCC cells proliferation and migration in vitro and augmented the growth and metastasis of HCC. Moreover, OCTN2 promoted the cancer stem-like properties of HCC by increasing fatty acid oxidation and oxidative phosphorylation. Mechanistically, PGC-1α signaling participated in the HCC cancer stem-like properties mediated by OCTN2 overexpression, which is confirmed by in vitro and in vivo analyses. Furthermore, OCTN2 upregulation may be transcriptionally activated by YY1 in HCC. Particularly, treatment with mildronate, an inhibitor of OCTN2, showed a therapeutic influence on HCC in vitro and in vivo. CONCLUSIONS: Our findings demonstrate that OCTN2 plays a critical metabolic role in HCC cancer stemness maintenance and HCC progression, providing evidence for OCTN2 as a promising target for HCC therapy.