TNF-α Mediated the Disruption of Hepatic Tight Junction Expression in Blood-Biliary Barrier of Colitis via Downregulating PI3K/AKT Signaling Pathway.

Hepatocyte tight junctions (TJ) constituted blood-biliary barrier is the most important hepatic barrier for separating bile from the bloodstream, disruption or dysfunction of TJ barrier is involved in hepatobiliary manifestations of colitis, but the underlying mechanism is still not clear. This study aims to investigate the effect and underlying mechanism of tumor necrosis factor alpha (TNF-α) on hepatic TJ protein expression in blood-biliary barrier and identify its role in the pathogenesis of acute colitis-related cholestasis. Acute colitis rat model was induced by trinitrobenzene sulfonic acid (TNBS) intra-colonic administration. TJs expression of blood-biliary barrier was tested in colitis rats, the serum TNF-α level was also determined in order to elucidate the correlation of TNF-α and TJs. HepaRG cells were used to investigate the effect of TNF-α on TJs, and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway were also evaluated in rats and TNF-α treated HepaRG cells. Acute colitis was induced in rats at 5 d post TNBS, which is accompanied with cholestasis-like alteration. Serum TNF-α level was increased in colitis rats and positively correlated with the alteration of total bile acids and bilirubin, marked decrease in TJs was found in TNF-α treated HepaRG cells and the rats, down-regulated PI3K/AKT signaling pathway were also identified in TNF-α treated HepaRG cells and the rats. The study concluded that serum TNF-α mediated the down-regulation of PI3K/AKT signaling pathway, which contributed to the reduction of TJ protein expression in acute colitis-related intrahepatic cholestasis. These findings suggest that TNF-α plays an important role in the pathogenesis of intrahepatic cholestasis of colitis.

[Comparison of clinical efficacy between percutaneous endoscopic transforaminal discectomy and coblation nucleoplasty in the treatment of inclusive lumbar disc herniation].

OBJECTIVE: To observe clinical efficacy of percutaneous endoscopic transforaminal discectomy (PETD) and target radioffrequency thermal coblation nucleoplasty(CN) on inclusive lumbar disc herniation(LDH) in different age groups, and provide a basis for clinical formulation of precise and individualized treatments. METHODS: A retrospective analysis of 219 patients with lumbar disc herniation treated with PETD and CN between January 2018 and June 2021 was performed, in which 107 patients were treated with PETD and 112 with CN. Patients were stratified by age into young group(≤45 years old), middle-aged group(>45 years old and <60 years old) and older group(≥60 years old). Before treatment, 3 days, 1 month and 6 months after treatment, visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) score, infrared thermal imaging temperature difference (△T) and lumbar range of motion (ROM) were evaluated and clinical efficacy were compared in the different age groups between two treatment methods. RESULTS: ①VAS and JOA score outcomes, in the same age group and the same treatment method, the VAS and JOA scores at different time points postoperatively were obviously improved (P<0.05). For the same age group and the different treatment methods, the older group had lower VAS and higher JOA scores after PETD than after CN (P<0.05), and there was no significant difference between the young group and middle-aged group (P>0.05). There was no significant difference in VAS and JOA scores at the same time between age groups by PETD treatment (P>0.05). The VAS was higher and the JOA score was lower in older group than in young group and middle-aged group at 1, 6 months after CN treatment(P<0.05). ②△T and ROM outcomes, in the same age group and same treatment method, postoperative △T and ROM at different time points were obviously improved(P<0.05). There was no significant difference in △T between two methods of PETD and CN at the same age(P>0.05), there was no significant difference in ROM between young group and middle-aged group(P>0.05), ROM was higher after PETD treatment than after CN treatment(P<0.05). There was no significant difference in △T and ROM at the same time between age groups by PETD treatment(P>0.05). There was no significant difference in △T between age groups by CN treatment, but the ROM was smaller in older group than in young group and middle-aged group after CN treatment(P<0.05). CONCLUSION: Both PETD and CN for inclusive LDH have good efficacy, the curative benefit for older patients receiving PETD within 6 months after surgery more than CN, and CN is more appropriate for young and middle-aged patients.

SYTL5 Promotes Papillary Thyroid Carcinoma Progression by Enhancing Activation of the NF-κB Signaling Pathway.

The function and mechanism of SYTL5 in papillary thyroid carcinoma (PTC) are still unclear. In this research, we found that SYTL5 was significantly overexpressed in PTC tissues compared with normal thyroid tissues. SYTL5 downregulation significantly weakened the proliferative, migratory, and invasive abilities of PTC cells. In addition, upregulated SYTL5 could promote cancer progression by activating the NF-κB signaling pathway. RAC1b expression is positively associated with SYTL5, and overexpressed RAC1b abrogated the antitumor effect after SYTL5 inhibition. In conclusion, our findings identify the oncogenic role of SYTL5 in PTC by activation of the NF-κB signaling pathway, thus facilitating PTC development and progression.

Enhanced piezotronics by single-crystalline ferroelectrics for uniformly strengthening the piezo-photocatalysis of electrospun BaTiO3@TiO2 nanofibers.

Turning the built-in electric field by modulating the morphology and microstructure of ferroelectric materials is considered a viable approach to enhancing the piezo-photocatalytic activity of the ferroelectric/oxide semiconductor heterojunctions. Here, hydrothermally synthesized single-crystalline BaTiO3 nanoparticles are employed to construct BaTiO3@TiO2 hybrid nanofibers by sol-gel assisted electrospinning of TiO2 nanofibers and annealing. Because of the obvious enhancement of the synergetic piezo-photocatalytic effect under both ultrasonic and ultraviolet (UV) light irradiation, the piezo-photocatalytic degradation rate constant (k) of BaTiO3@TiO2 hybrid nanofibers on methyl orange (MO) reaches 14.84 × 10-2 min-1, which is approximately seven fold that for piezocatalysis and six fold that for photocatalysis. Moreover, BaTiO3@TiO2 core-shell nanoparticles are also synthesized for comparison purposes to assess the influence of microstructure on the piezo-photocatalysis by a wet-chemical coating of TiO2 on BaTiO3 nanoparticles. Such a high piezo-photocatalytic activity is attributed to the enhancement of the piezotronic effect by the single-crystalline ferroelectric nanoparticles and the nanoconfinement effect caused by the one-dimensional boundary of nanofibers with high specific surface areas. The mechanically induced uniform local built-in electric fields originated from the single-crystalline ferroelectric nanoparticles can enhance the separation of photogenerated electron and hole pairs and promote the formation of free hydroxyl radicals, resulting in a strong piezotronic effect boosted photochemical degradation of organic dye. This work introduces the single-crystalline ferroelectrics to construct ferroelectric/oxide semiconductor heterojunctions, and the enhanced local piezotronic effect uniformly strengthens the photochemical reactivity, which offers a new option to design high-efficiency piezo-photocatalysts for pollutant treatment.

Enhanced and Robust Directional Propulsion of Light-Activated Janus Micromotors by Magnetic Spinning and the Magnus Effect.

Advances in the versatile design and synthesis of nanomaterials have imparted diverse functionalities to Janus micromotors as autonomous vehicles. However, a significant challenge remains in maneuvering Janus micromotors by following desired trajectories for on-demand motility and intelligent control due to the inherent rotational Brownian motion. Here, we present the enhanced and robust directional propulsion of light-activated Fe3O4@TiO2/Pt Janus micromotors by magnetic spinning and the Magnus effect. Once exposed to a low-intensity rotating magnetic field, the micromotors become physically actuated, and their rotational Brownian diffusion is quenched by the magnetic rotation. Photocatalytic propulsion can be triggered by unidirectional irradiation based on a self-electrophoretic mechanism. Thus, a transverse Magnus force can be generated due to the rotational motion and ballistic motion (photocatalytic propulsion) of the micromotors. Both the self-electrophoretic propulsion and the Magnus force are periodically changed due to the magnetic rotation, which results in an overall directed motion moving toward a trajectory with a deflection angle from the direction of incident light with enhanced speed, maneuverability, and steering robustness. Our study illustrates the admirable directional motion capabilities of light-driven Janus micromotors based on magnetic spinning and the Magnus effect, which unfolds a new paradigm for addressing the limitations of directionality control in the current asymmetric micromotors.

Transfer RNA-Derived Small RNAs: Novel Regulators and Biomarkers of Cancers.

Transfer RNA-derived small RNAs (tsRNAs) are conventional non-coding RNAs (ncRNAs) with a length between18 and 40 nucleotides (nt) playing a crucial role in treating various human diseases including tumours. Nowadays, with the use of high-throughput sequencing technologies, it has been proven that certain tsRNAs are dysregulated in multiple tumour tissues as well as in the blood serum of cancer patients. Meanwhile, data retrieved from the literature show that tsRNAs are correlated with the regulation of the hallmarks of cancer, modification of tumour microenvironment, and modulation of drug resistance. On the other side, the emerging role of tsRNAs as biomarkers for cancer diagnosis and prognosis is promising. In this review, we focus on the specific characteristics and biological functions of tsRNAs with a focus on their impact on various tumours and discuss the possibility of tsRNAs as novel potential biomarkers for cancer diagnosis and prognosis.

Highly Ordered SnO2 Nanopillar Array as Binder-Free Anodes for Long-Life and High-Rate Li-Ion Batteries.

SnO2, a typical transition metal oxide, is a promising conversion-type electrode material with an ultrahigh theoretical specific capacity of 1494 mAh g-1. Nevertheless, the electrochemical performance of SnO2 electrode is limited by large volumetric changes (~300%) during the charge/discharge process, leading to rapid capacity decay, poor cyclic performance, and inferior rate capability. In order to overcome these bottlenecks, we develop highly ordered SnO2 nanopillar array as binder-free anodes for LIBs, which are realized by anodic aluminum oxide-assisted pulsed laser deposition. The as-synthesized SnO2 nanopillar exhibit an ultrahigh initial specific capacity of 1082 mAh g-1 and maintain a high specific capacity of 524/313 mAh g-1 after 1100/6500 cycles, outperforming SnO2 thin film-based anodes and other reported binder-free SnO2 anodes. Moreover, SnO2 nanopillar demonstrate excellent rate performance under high current density of 64 C (1 C = 782 mA g-1), delivering a specific capacity of 278 mAh g-1, which can be restored to 670 mAh g-1 after high-rate cycling. The superior electrochemical performance of SnO2 nanoarray can be attributed to the unique architecture of SnO2, where highly ordered SnO2 nanopillar array provided adequate room for volumetric expansion and ensured structural integrity during the lithiation/delithiation process. The current study presents an effective approach to mitigate the inferior cyclic performance of SnO2-based electrodes, offering a realistic prospect for its applications as next-generation energy storage devices.

Dipole-Moment Induced Phototaxis and Fuel-Free Propulsion of ZnO/Pt Janus Micromotors.

Light-driven micromotors have stimulated considerate interests due to their potentials in biomedicine, environmental remediation, or serving as the model system for non-equilibrium physics of active matter. Simultaneous control over the motion direction and speed of micro/nanomotors is crucial for their functionality but still difficult since Brownian motion always randomizes the orientations. Here, a highly efficient light-driven ZnO/Pt Janus micromotor capable of aligning itself to illumination direction and exhibiting negative phototaxis at high speeds (up to 32 µm s-1 ) without the addition of any chemical fuels is developed. A light-triggered self-built electric field parallel to the light illumination exists due to asymmetrical surface chemical reactions induced by the limited penetration depth of light along the illumination. The phototactic motion of the motor is achieved through electrophoretic rotation induced by the asymmetrical distribution of zeta potential on the two hemispheres of the Janus micromotor, into alignment with the electric field. Notably, similar phototactic propulsion is also achieved on TiO2 /Pt and CdS/Pt micromotors, which presents explicit proof of extending the mechanism of dipole-moment induced phototactic propulsion in other light-driven Janus micromotors. Finally, active transportation of yeast cells are achieved by the motor, proving its capability in performing complex tasks.

NK-/T-cell lymphomas.

Natural killer/T-cell lymphoma (NKTL) is a sub-type of Epstein-Barr virus (EBV)-related non-Hodgkin lymphomas common in Asia and Latin America but rare elsewhere. Its pathogenesis is complex and incompletely understood. Lymphoma cells are transformed from NK- or T-cells, sometimes both. EBV-infection and subsequent genetic alterations in infected cells are central to NKTL development. Hemophagocytic syndrome is a common complication. Accurate staging is important to predict outcomes but there is controversy which system is best. More than two-thirds of NKTL lympohmas are localized at diagnosis, are frequently treated with radiation therapy only and have 5-year survival of about 70 percent. Persons with advanced NKTLs receive radiation therapy synchronously or metachronously with diverse multi-drug chemotherapy typically including L-asparginase with 5-year survival of about 40 percent. Some persons with widespread NKTL receive chemotherapy only. There are few data on safety and efficacy of high-dose therapy and a haematopoietic cell autotransplant. Immune therapies, histone deacetylase (HDAC)-inhibitors and other drugs are in early clinical trials. There are few randomized controlled clinical trials in NKTLs and no therapy strategy is clearly best; more effective therapy(ies) are needed. Some consensus recommendations are not convincingly evidence-based. Mechanisms of multi-drug resistance are considered. We discuss these issues including recent advances in our understanding of and therapy of NKTLs.

Isotropic Hedgehog-Shaped-TiO2/Functional-Multiwall-Carbon-Nanotube Micromotors with Phototactic Motility in Fuel-Free Environments.

Directional motion in response to specific signals is critically important for micro/nanomotors in precise cargo transport, obstacle avoidance, collective control, and complex maneuvers. In this work, a kind of isotropic light-driven micromotor that is made of hedgehog-shaped TiO2 and functional multiwall carbon nanotubes (Hs-TiO2@FCNTs) has been developed. The FCNTs are closely entangled with Hs-TiO2 and form a close-knit matrix on the surface of Hs-TiO2, which facilitates the transfer of electrons from Hs-TiO2 to FCNTs. Due to the high redox potential of Hs-TiO2, excellent electron-hole separation efficiency by the addition of FCNTs, and isotropic morphology of the micromotor, these Hs-TiO2@FCNT micromotors show phototactic and fuel-free propulsion under unidirectional irradiation of UV light. It is the first time to demonstrate isotropic micromotors that are propelled by self-electrophoresis. The isotropy of Hs-TiO2@FCNT micromotors makes them immune to the rotational Brownian diffusion and local flows, exhibiting superior directionality. The motion direction of our micromotors can be precisely tuned by light and a velocity of 8.9 µm/s is achieved under 160 mW/cm2 UV light illumination. Photodegradation of methylene blue and active transportation of polystyrene beads are demonstrated for a proof-of-concept application of our micromotors. The isotropic design of the Hs-TiO2@FCNT micromotors with enhanced photocatalytic properties unfolds a new paradigm for addressing the limitations of directionality control and chemical fuels in the current asymmetric light-driven micromotors.

Three-dimensional mesoporous γ-Fe2O3@carbon nanofiber network as high performance anode material for lithium- and sodium-ion batteries.

Electrode materials that can function well in both lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs) are desirable for electrochemical energy storage applications, especially under high rate. In this work, a three-dimensional (3D) mesoporous γ-Fe2O3@carbon nanofiber (γ-Fe2O3@CNF) mat has been successfully synthesized by sol-gel based electrospinning and carbonization. It delivers a specific capacity of 820 mAh g-1 at 0.5 C after 250 cycles, 430 mAh g-1 at 6 C after 1000 cycles, and 222 mAh g-1 at ultrahigh rate of 60 C for LIBs, while for SIBs it delivers a specific capacity of 360 mAh g-1 at 1 C after 1000 cycles and 130 mAh g-1 at 60 C. Besides, the result of ex situ microstructure examination shows the polycrystalline nature of γ-Fe2O3 nanoparticle still exists in LIB even after 1000 cycles, while it vanishes in SIB, suggesting that the relatively larger volume expansion occurred during Na+ insertion/deinsertion, resulting in pulverization of the particles. The CNFs maintained their pristine 3D network structure after the charge/discharge, which demonstrated the critical role of a robust conductive electrode in promoting fast Li+/Na+ transportation. More importantly, they act as an electrical bridge between Li+/Na+ and γ-Fe2O3 nanoparticles, therefore suppressing the cell impedance growth and γ-Fe2O3 volume expansion, resulting in the enhancement in both cyclic and rate capability.

Evaluation of Early Gadolinium Enhancement (EGE) and Cardiac Functional Parameters in Cine-Magnetic Resonance Imaging (MRI) on Artificial Intelligence in Patients with Acute Myocarditis: A Case-Controlled Observational Study.

BACKGROUND The diagnosis of myocarditis is challenging, and the treatment is generally delayed due to misdiagnosis or missed diagnosis. Endomyocardial biopsy (EMB) is not a specific or sensitive method. A case-controlled observational study was conducted to evaluate early gadolinium enhancement (EGE) and left ventricular functional parameters on Artificial Intelligence in cine-MRI in patients with acute myocarditis. MATERIAL AND METHODS We selected 21 patients with pathologically proven acute myocarditis. We analyzed the EGE findings (total/serial number and location of positive-segments using the 17-segment model according to the American Heart Association) and clinical characteristics (symptoms, arrhythmias in ECG, coronary angiography, and EMB). All patients were divided into positive EGE and negative EGE groups to analyze left ventricular functional parameters (LVEF, FS, LVEDD, LVEDV, LVESV, LVMM, LVSV, CO, and CI) on Artificial Intelligence. RESULTS We enrolled 21 patients (11 males) with a mean age of 32.6±9.8 years (range, 16 to 51 years). Abnormalities on EGE were found in 2/3 of patients, involving 41 segments among multiple locations on the myocardium. The differences in LVEF (40.2±10.2% vs. 51.3±3.6%), LVESV (69.0±16.1ml vs. 52.5±10.6ml) and LVSV (42.6±11.4 vs. 52.8±2.8 ml) on Artificial Intelligence was statistically significant between the positive EGE and negative EGE groups (p<0.05). CONCLUSIONS Our results suggest a significant role of EGE on the basis of Lake Louise criteria in evaluating patients with clinical suspicion of acute myocarditis. Parameters, including LVEF, LVESV, and LVSV, on Artificial Intelligence, may be useful independent predictors for capillary leakage and microcirculatory disturbance in myocarditis.

Correction: Huang, F.-C., et al. Arabidopsis RETICULON-LIKE3 (RTNLB3) and RTNLB8 Participate in Agrobacterium-Mediated Plant Transformation. Int. J. Mol. Sci. 2018, 19, 638.

The authors would like to make a correction to their published paper [...].

Using Tree Shrews (Tupaia belangeri) as a Novel Animal Model of Liver Transplantation.

Liver transplantation (LT) is most effective and promising approach for end-stage liver disease. However, there remains room for further improvement and innovation, for example, to reduce ischemic reperfusion injury, transplant rejection and immune tolerance. A good animal model of LT is essential for such innovation in transplant research. Although rat LT model has been used since the last century, it has never been an ideal model because the results observed in rat may not be applied to human because these two species are genetically distinct from each other. In this study, we for the first time performed LT using the tree shrew (Tupaia belangeri), a species in the Order Scandentia which is closely related with primates, and evaluated the possibility to adopt this species as a new model of LT. We performed LT on 30 animals using the two-cuff technique, examining the success rate, the survival rate and the immunological reaction. The recipient operation time was 60 min averagely, and we limited the time of the anhepatic phase within 20 min. Twenty-seven (90%) of the animals survived for at least 3 days after the transplantation. Thirteen animals that did not receive any immunosuppressive drug died in 8 days mostly because of acute rejection effect (n=9), similar to the reaction in human but not in experimental rat. The rest 14 animals that were given rapamycin survived significantly longer (38 days) and half of them survived for 60 days until the end of the study. Our results suggest that performing LT in tree shrews can yield high success rate and high survival rate. More importantly, the tree shrews share similar immunological reaction with human. In addition, previous genomics study found that the tree shrews share more proteins with human. In sum, the tree shrews may outperform the experimental rats and could be used as a better and cost-effective animal model for LT.

Sirtuin3 protects aged human mesenchymal stem cells against oxidative stress and enhances efficacy of cell therapy for ischaemic heart diseases.

Sirtuin3 (SIRT3) is associated with oxidative stress and lifespan. However, the possible mechanisms underlying its influence are unknown. We hypothesized that SIRT3 increases the antioxidant capacity of aged cells and improves the efficacy of human mesenchymal stem cell (hMSC) therapy for ischaemic heart diseases in aged patients. In vitro, the antioxidant capacity of old hMSCs (O-hMSCs) was increased after SIRT3 overexpression using a gene transfection technique, while the antioxidant capacity of young hMSCs (Y-hMSCs) was decreased by SIRT3 silencing. The levels of forkhead box O3a (FoxO3a) in the nucleus, and antioxidant enzymes Mn-superoxide dismutase (MnSOD) and catalase (CAT) increased in SIRT3-overexpressed O-hMSCs while they decreased in SIRT3-silenced Y-hMSCs after oxidative stress. Following myocardial infarction in adult rats in vivo, infarct size decreased and cardiac function was significantly enhanced after cell transplantation with SIRT3 overexpressed O-hMSCs. The number of apoptotic cells decreased and the survival rate of transplanted cells increased following SIRT3 overexpression in O-hMSCs. SIRT3 protects aged hMSCs against oxidative stress by positively regulating antioxidant enzymes (MnSOD and CAT) via increasing the expression of FoxO3a in the nucleus. The efficacy of aged hMSC transplantation therapy for ischaemic heart diseases can be improved by SIRT3 overexpression.

Multifield Control of Domains in a Room-Temperature Multiferroic 0.85BiTi0.1Fe0.8Mg0.1O3-0.15CaTiO3 Thin Film.

Single-phase materials that combine electric polarization and magnetization are promising for applications in multifunctional sensors, information storage, spintronic devices, etc. Following the idea of a percolating network of magnetic ions (e.g., Fe) with strong superexchange interactions within a structural scaffold with a polar lattice, a solid solution thin film with perovskite structure at a morphotropic phase boundary with a high level of Fe atoms on the B site of perovskite structure is deposited to combine both ferroelectric and ferromagnetic ordering at room temperature with magnetoelectric coupling. In this work, a 0.85BiTi0.1Fe0.8Mg0.1O3-0.15CaTiO3 thin film has been deposited by pulsed laser deposition (PLD). Both the ferroelectricity and the magnetism were characterized at room temperature. Large polarization and a large piezoelectric effective coefficient d33 were obtained. Multifield coupling of the thin film has been characterized by scanning force microscopy. Ferroelectric domains and magnetic domains could be switched by magnetic field ( H), electric field ( E), mechanical force ( F), and, indicating that complex cross-coupling exists among the electric polarization, magnetic ordering and elastic deformation in 0.85BiTi0.1Fe0.8Mg0.1O3-0.15CaTiO3 thin film at room temperature. This work also shows the possibility of writing information with electric field, magnetic field, and mechanical force and then reading data by magnetic field. We expect that this work will benefit information applications.

Arabidopsis RETICULON-LIKE3 (RTNLB3) and RTNLB8 Participate in Agrobacterium-Mediated Plant Transformation.

Agrobacterium tumefaciens can genetically transform various eukaryotic cells because of the presence of a resident tumor-inducing (Ti) plasmid. During infection, a defined region of the Ti plasmid, transfer DNA (T-DNA), is transferred from bacteria into plant cells and causes plant cells to abnormally synthesize auxin and cytokinin, which results in crown gall disease. T-DNA and several virulence (Vir) proteins are secreted through a type IV secretion system (T4SS) composed of T-pilus and a transmembrane protein complex. Three members of Arabidopsis reticulon-like B (RTNLB) proteins, RTNLB1, 2, and 4, interact with VirB2, the major component of T-pilus. Here, we have identified that other RTNLB proteins, RTNLB3 and 8, interact with VirB2 in vitro. Root-based A. tumefaciens transformation assays with Arabidopsis rtnlb3, or rtnlb5-10 single mutants showed that the rtnlb8 mutant was resistant to A. tumefaciens infection. In addition, rtnlb3 and rtnlb8 mutants showed reduced transient transformation efficiency in seedlings. RTNLB3- or 8 overexpression transgenic plants showed increased susceptibility to A. tumefaciens and Pseudomonas syringae infection. RTNLB1-4 and 8 transcript levels differed in roots, rosette leaves, cauline leaves, inflorescence, flowers, and siliques of wild-type plants. Taken together, RTNLB3 and 8 may participate in A. tumefaciens infection but may have different roles in plants.

Upregulation of B7-H4 promotes tumor progression of intrahepatic cholangiocarcinoma.

Recent reports show that B7-H4 is highly expressed in a variety of tumor cells, functions as a negative regulator of T cells and then promotes tumor progression. However, its expression and role in intrahepatic cholangiocarcinoma (ICC) remain unclear. In present study, B7-H4 expression in ICC and peritumoral tissues was determined at the level of mRNA and protein, and its bioactivity in ICC cells was studied after modification of B7-H4 expression. Then, the mechanism related to tumor progression induced by B7-H4 expression in ICC cells was explored. Finally, clinical significance of B7-H4 expression in ICC patients was further analyzed. The results showed that B7-H4 expression in ICC was much higher than that in peritumoral tissues at the level of both mRNA and protein. The high level of B7-H4 in ICC cells induced epithelial-to-mesenchymal transitions and promoted invasion and metastasis of tumor cells through activation of ERK1/2 signaling. The elevated B7-H4 expression was associated with the downregulated Bax, upregulated Bcl-2 expression, and activation of caspase-3. Clinically, high B7-H4 expression in tumor samples was significantly related to malignant phenotype, such as lymph node metastasis, high tumor stage, and poor differentiation. ICC patients with high expression of B7-H4 had shorter overall survival (OS) and disease-free survival. Moreover, the B7-H4 expression was an independent prognostic factor for predicting OS and tumor recurrence of ICC patients after operation. In conclusion, high expression of B7-H4 promotes tumor progression of ICC and may be a novel therapeutic target for ICC patients.