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Background: Cholangiocarcinoma (CCA), a primary hepatobiliary malignancy, is characterized by a poor prognosis and a lack of effective treatments. Therefore, the need to explore novel therapeutic approaches is urgent. While the role of Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (PIN1) has been extensively studied in various tumor types, its involvement in CCA remains poorly understood. Methods: In this study, we employed tissue microarray (TMA), reverse transcription-polymerase chain reaction (RT-PCR), and The Cancer Genome Atlas (TCGA) database to assess the expression of PIN1. Through in vitro and in vivo functional experiments, we investigated the impact of PIN1 on the adhesion and metastasis of CCA. Additionally, we explored downstream molecular pathways using RNA-seq, western blotting, co-immunoprecipitation, immunofluorescence, and mass spectrometry techniques. Results: Our findings revealed a negative correlation between PIN1 overexpression and prognosis in CCA tissues. Furthermore, high PIN1 expression promoted CCA cell proliferation and migration. Mechanistically, PIN1 functioned as an oncogene by regulating ANXA2 phosphorylation, thereby promoting CCA adhesion. Notably, the interaction between PIN1 and ANXA2 was facilitated by RACK1. Importantly, pharmacological inhibition of PIN1 using the FDA-approved drug all-trans retinoic acid (ATRA) effectively suppressed the metastatic potential of CCA cells in a nude mouse lung metastasis model. Conclusion: Overall, our study emphasizes the critical role of the PIN1/RACK1/ANXA2 complex in CCA growth and functionality, highlighting the potential of targeting PIN1 as a promising therapeutic strategy for CCA. [ABSTRACT FROM AUTHOR]

Endothelins and their receptors, ETA and ETB, play vital roles in maintaining vascular homeostasis. Therapeutically targeting endothelin receptors, particularly through ETA antagonists, has shown efficacy in treating pulmonary arterial hypertension (PAH) and other cardiovascular- and renal-related diseases. Here we present cryo-electron microscopy structures of ETA in complex with two PAH drugs, macitentan and ambrisentan, along with zibotentan, a selective ETA antagonist, respectively. Notably, a specialized anti-ETA antibody facilitated the structural elucidation. These structures, together with the active-state structures of ET-1-bound ETA and ETB, and the agonist BQ3020-bound ETB, in complex with Gq, unveil the molecular basis of agonist/antagonist binding modes in endothelin receptors. Key residues that confer antagonist selectivity to endothelin receptors were identified along with the activation mechanism of ETA. Furthermore, our results suggest that ECL2 in ETA can serve as an epitope for antibody-mediated receptor antagonism. Collectively, these insights establish a robust theoretical framework for the rational design of small-molecule drugs and antibodies with selective activity against endothelin receptors. [ABSTRACT FROM AUTHOR]

A visible transparent metamaterial absorber was designed and fabricated with ultrabroadband microwave absorption and low infrared emissivity to meet the increasing demand for multispectral compatible camouflage. The absorber was fabricated with a low-infrared emissive layer at the top, a microwave-absorbing layer in the middle, and a reflective layer at the bottom, which were separated by polymethyl methacrylate plates. The absorber showed an average visible transmittance of 55%, infrared emissivity of ∼0.37, and effective microwave absorption bandwidth of 32.1 GHz with a total thickness of 3.0 mm. Furthermore, microwave absorption exhibited wide-angle stability and polarization insensitivity characteristics. The mechanism of microwave attenuation was further explored through effective electromagnetic parameters as well as surface current, electric field, magnetic field, and energy loss density distributions. The experimental results were consistent with those of the simulations and calculations, indicating the potential of the designed metamaterial absorber for future applications in multispectral compatible camouflage. [ABSTRACT FROM AUTHOR]

In this paper, a notched-wideband (NWB) bandpass filter (BPF) based on the spoof surface plasmon polaritons (SSPPs) with loaded resonator structure is proposed in microwave region. The design of the NWB BPF consists of a U-shaped SSPPs transmission line embedded with 山-shaped resonator structures, dielectric substrate, and metal ground-plane. The loaded 山-shaped resonator structure was used to generate the transmission zero in a wideband range. The dispersion and transmission properties of the designed NWB BPF are analyzed and compared with the U-shaped SSPP wideband BPF. The simulation results indicate that the operation frequency range of the designed NWB BPF is from 4.35 to 8.12 GHz, and the notched band is from 6.2 to 6.7 GHz with over − 20 dB rejection, which are agreement well with the theoretical calculation based on the equivalent LC circuit model. By adjusting the geometric parameters of the NWB BPF, the notched band position and passband cutoff frequency can be adjusted independently. To verify the effectiveness of the designed NWB BPF, a prototype is fabricated by the traditional printed circuit board (PCB) technology. Both measurements and simulations demonstrate that the design has wide passband and notch-band transmission properties. [ABSTRACT FROM AUTHOR]

The sphere decoding (SD) algorithm can provide (sub)optimal solutions with reduced computational complexity of maximum likelihood (ML) detection for multi-input multi-output (MIMO) communication systems. In this paper, we propose a novel low complexity symmetric-coded based SD algorithm for short polar codes with low rate. At the encoding stage, the first N/2 sub-channels transmit the frozen bits, while the information bits are selected from the latter N/2 sub-channels. Two symmetric codes are generated due to the mathematical structure of the generator matrix, which is well conditioned to the SD search. At the decoding stage, the presented SD algorithm computes the Euclidean distance value by the combined signals to estimate the latter N/2 input bits. Furthermore, the backtrack operation starts from the earlier (N / 2 + 1) -th bit, which can significantly reduce the average visited nodes (AVN). Simulation results show that, compared to the original SD algorithm, the presented variant of the SD algorithm can reduce the AVN to 0.9 % for the polar code P(64, 14) at SNR = 1 dB with a performance loss within 0.2 dB. The presented SD algorithm may find applications in MIMO systems where the complexity of the standar ML detection increases exponentially with the transmitting antennas. [ABSTRACT FROM AUTHOR]

Molecular variation between geographical populations and subtypes indicate potential genomic heterogeneity and novel genomic features within CCA. Here, we analyze exome-sequencing data of 87 perihilar cholangiocarcinoma (pCCA) and 261 intrahepatic cholangiocarcinoma (iCCA) cases from 3 Asian centers (including 43 pCCAs and 24 iCCAs from our center). iCCA tumours demonstrate a higher tumor mutation burden and copy number alteration burden (CNAB) than pCCA tumours, and high CNAB indicates a poorer pCCA prognosis. We identify 12 significantly mutated genes and 5 focal CNA regions, and demonstrate common mutations in post-transcriptional modification-related potential driver genes METTL14 and RBM10 in pCCA tumours. Finally we demonstrate the tumour-suppressive role of METTL14, a major RNA N6-adenosine methyltransferase (m6A), and illustrate that its loss-of-function mutation R298H may act through m6A modification on potential driver gene MACF1. Our results may be valuable for better understanding of how post-transcriptional modification can affect CCA development, and highlight both similarities and differences between pCCA and iCCA. Cholangiocarcinoma is a heterogenous group of cancers, with large genetic variation seen within subtypes. Here, the authors find 12 significantly mutated genes and 5 focal CNA regions were found in perihilar cholangiocarcinoma, and identified METTL14 to have a potential tumour suppressive role. [ABSTRACT FROM AUTHOR]

In this paper, we present an effective design of a tri-band high-efficiency circular polarization (CP) convertor based on double-split-ring resonator (DSRR) structures in the microwave region. The proposed CP convertor is composed of a periodic array of sub-wavelength tri-layered DSRR structures separated by a dielectric spacer, which can convert the normal incident CP wave to its orthogonal one at the three different resonance frequencies. Numerical simulation results indicate that the cross-polarization transmission coefficients of CP wave can achieve maximum values of 0.81 at 6.95 GHz, 0.65 at 10.55 GHz, and 0.81 at 12.85 GHz, respectively, which is in reasonable agreement with experiment. In addition, the corresponding CP conversion efficiency is over 90% at three different resonance frequencies. The simulated surface current distributions indicate that the high-efficient CP conversion properties are mainly attributed to the near field electric and magnetic dipole coupling between the adjacent DSRR layers. Due to its excellent tri-band CP properties, the proposed structure would find potential applications in the fields of remote sensing, radar, and satellite communication. [ABSTRACT FROM AUTHOR]

Background: The impact of tumor size on account of the long-term survival results in gallbladder cancer (GBC) patients has been controversial. It is urgent necessary to identify the optimal cut-off value of tumor size in resected GBC, and we attempted to integrate tumor size with other prognostic factors into a prognostic nomogram to predict the cancer-specific survival (CSS) of GBC patients. Methods: 1639 patients with resected GBC were extracted from the Surveillance, Epidemiology and End Results (SEER) database. X-tile program was used to identify the optimal cut-off value of tumor size. A nomogram including tumor size was established to predict 1-, 3- and 5-year CSS based on the independent risk factors chosen by univariate and multivariable cox analyses. The precision of the nomogram for predicting survival was validated with Harrell's concordance index (C-index), calibration curves, and receiver operating characteristic curve (ROC) internally and externally. Results: Patients with GBC were classified into 1–13 mm, 14–63 mm and 64 mm subgroup based on the optimal cut-off for tumor size in terms of CSS. The nomogram according to the independent factors was well calibrated and displayed better discrimination power than 7th tumor–node–metastasis (TNM) stage systems. Conclusions: The results demonstrated that increased tumor size is closely associated with the worse CSS. Our novel nomogram, which outperforms the conventional TNM staging system, showed satisfactory accuracy and clinically practicality for predicting the outcome of resected GBC patients. [ABSTRACT FROM AUTHOR]

A new organic template, 1,3-cyclohexanedimethanamine (1,3-CDA), is found to be effective in directing the crystallization of ZSM-11 zeolite. Phase transformation from ZSM-11 to ZSM-5 was observed when varying the molar ratios of OH−/SiO2, Na+/SiO2 and SiO2/Al2O3. ZSM-11/ZSM-5 intergrowth zeolites with ZSM-5 contents from 10 to 100% were synthesized. The structural intergrowth was evidenced by TEM, and its formation may be ascribed to the competition between ZSM-11 and ZSM-5 zeolite in the system. The morphology of zeolite varies with the change of composition of the starting gel. The particle sizes of the products decrease with the increase of 1,3-CDA/SiO2 and Na+/SiO2 ratios. With the increase the OH−/SiO2 ratio, the sizes decrease at first and then increase. Meanwhile, the morphologies change from cross-like aggregates of orthotropic rods to aggregates of nano-rods, and then to irregular bulk crystals. With the decrease of SiO2/Al2O3 ratios from 100 to 40, the particle sizes decrease from 200 to about 50 nm, resulting in the formation of nanosized ZSM-11/ZSM-5 intergrowth zeolite. [ABSTRACT FROM AUTHOR]

Due to the coarse temporal resolution of the best track databases for typhoons, some small-scale characteristics of typhoon motion have been neglected. In order to reveal the fine features of typhoon motion, the dense cloud within the radius of maximum wind (RMW) of mature typhoons, defined as a "cloud gyro" that simultaneously spins around its own rotational axis and precesses around the vertical axis, is approximated to a rigid body. Based on the principles of gyrodynamics, the derived mathematical model of a typhoon track indicates that typhoon movement is composed of translational motion governed by the steering flow and superimposed precessional motion that manifests as the inherent characteristics of typhoon tracks, especially with the external torque. High temporal resolution numerical simulation of a real case verifies the conclusion of this study, which is that the smaller the RMW, the larger the tangential wind speed or the larger the external torque, and the more obviously precessional motion manifests. [ABSTRACT FROM AUTHOR]

Designing microwave absorbers with broadband perfect absorption at high temperatures remains a challenge for researchers due to the variability of material properties with temperature. Herein, inspired by the absorption model of Papilio blumei, this work establishes a method to realize broadband metamaterial microwave blackbody using polymer ceramics and bionic metamaterial structures. The size of the high-temperature resistive film and biomimetic hole of the bionic metamaterial microwave absorber (MMA) is optimized based on the trust region framework method. The absorption rate of the MMA reached 99% across the C ~ Ku bands, which breaks the Plank-Rozanov limit by multiple absorption mechanisms (polarization loss, conductive loss, and resonance loss). It is evident from quantitative calculations and power loss density distributions that resonant losses are crucial for microwave energy absorption. Experiment results reveal that the MMA can maintain excellent absorption performance from room temperature to 1000 ℃ which guarantees the potential application for microwave absorber at evaluated temperatures. [ABSTRACT FROM AUTHOR]

The transcription factor sex determining region Y-box protein 5 (SOX5) plays important roles in various types of cancers. However, the expression and function of SOX5 in hepatocellular carcinoma (HCC) have not been elucidated. Here, we found that SOX5 is significantly up-regulated in HCC tissues and cell lines. Gain- and loss-of-function studies demonstrated that SOX5 promoted HCC cell migration and invasion. In addition, we revealed that SOX5 is linked to epithelial-mesenchymal transition (EMT) by regulation of Twist1. Our results indicate for the first time that SOX5 is a novel regulator of EMT in HCC and may be a potential therapeutic target for HCC metastasis. [ABSTRACT FROM AUTHOR]

Mesenchymal stem/progenitor cells derived from Wharton's jelly of the umbilical cord (UCMSCs/UCMPCs) are multipotent, and can be differentiated in vitro into many cell types. Much work has been done on UCMSCs/UCMPCs from humans, mice, rabbits, and other mammals, but the relatively little literature has been published about these cells in chickens. In our work, we isolated USMSCs/USMPCs from chicken embryos. We characterized the isolated cells using immunofluorescence and reverse transcription polymerase chain reaction techniques. Primary UCMSCs/UCMPCs were subcultured to passage 30 and growth curves for each passage determined. The growth curves at different passages were all typically sigmoidal. Isolated UCMSCs/UCMPCs were induced to differentiate into adipocytes, osteoblasts, myocardial cells, and neural cells, and we were able to detect characteristic CD44, CD29, CD73, and CD71 cell surface markers. Our results suggest that UCMSCs/UCMPCs isolated from chickens possess similar biological characteristics to those from other species. Their multi-lineage differentiation capabilities herald a probable application for cellular transplant therapy in tissue engineering. [ABSTRACT FROM AUTHOR]

Objectives: Costimulatory signals are essential for T-cell activation and hence play a very important role in antitumor immunity. B7 and 4-1BBL which belongs to tumor necrosis factor (TNF) family provide costimulatory interaction for T-cell activation and function. This study investigated the role of B7 and 4-1BBL in the amplification of tumor immunity by transduction of the B7-1, B7-2 and 4-1BBL into mouse hepatocellular carcinoma cell line H22. Methods: The tumorigenicity of H22 variants expressing either B7-1, B7-2 (H22/B7-1/B7-2) or 4-1BBL was compared with an H22 variant expressing B7-1, B7-2 and 4-1BBL (H22/B7-1/B7-2/4-1BBL). The study next investigated whether the combination of B7-1/B7-2 and 4-1BBL cell injection induced cytotoxic T lymphocyte (CTL) response and IL-2/IFN-γ secretion. The immune mechanisms underlying this combination treatment were then analyzed. Results: Syngeneic BALB/c mice injected with H22/B7-1/B7-2/4-1BBL cells that expressed elevated levels of B7-1, B7-2 and 4-1BBL showed a tumor development frequency of 50% compared with 100% in mice injected with the H22 parental line, H22/neo, H22/B7-1/B7-2 and H22/4-1BBL. Mice inoculated with H22 tumor cells expressing B7-1, B7-2 and 4-1BBL developed a strong cytotoxic T lymphocyte response and long-term immunity against wild-type tumor, suggesting a synergistic effect between the B7 and 4-1BBL costimulatory pathways. Results showed that H22/B7-1/B7-2/4-1BBL tumor vaccines probably protect the infiltrating lymphocytes from apoptosis and induce NF-κB activation to improve T-cell-mediated antitumor response. Conclusions: In this study, the antitumor consequences of using B7-1, B7-2 and 4-1BBL gene transfer have demonstrated the therapeutic potential of gene therapy approach for hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Fulminant hepatitis is fatal in most cases and timely liver transplantation is the only effective treatment. This study evaluates the survival outcomes of patients who underwent living-donor liver transplantation (LDLT) using right lobe liver grafts for fulminant liver failure due to hepatitis B infection. Nine cases of adult right lobe LDLT were performed in our department from September 2002 to August 2005 and the clinical and following-up data were reviewed. According to the pre-transplant Child-Pugh-Turcotte classification, the nine patients were classified as grade C. The model for end-stage liver disease (MELD) score of these patients ranged from 16 to 42. The principal complications before transplantation included abnormal renal function, hepatic coma of different degrees and alimentary tract hemorrhage. The main complications after transplantation included pulmonary infection in two cases, acute renal failure in three cases and transplantation-related encephalopathy in one case. No primary failure of vascular or biliary complications occurred. The one-year survival rate was 55.6%. There were no serious complications or deaths in donors. In general, it is extremely difficult to treat fulminant hepatitis by conservative regimen, particularly, in cases with rapid progression. Emergency adult living-donor liver transplantation is an effective treatment for fulminant hepatitis patients and is relatively safe for donors. [ABSTRACT FROM AUTHOR]

The effectiveness of liver autotransplantation for patients with partial hepatic alveolar echinococcosis was analyzed. We retrospectively studied 6 patients with hepatic alveolar echinococcosis who underwent liver autotransplantation in our hospital from 2008 to 2010. We also summarized the surgical indications of liver autotransplantation for hepatic alveolar echinococcosis and our experience in the management of postoperative complications of liver autotransplantation. Of 6 patients, 5 achieved good curative results, and one died of multiple organ failure caused by portal vein thrombosis. Main complications included postoperative bleeding, bile leak and small-for-size liver graft syndrome. Liver autotransplantation offers a new approach to cure hepatic alveolar echinococcosis with non-resectable lesions. It could be the most effective method to cure intractable hepatic alveolar echinococcosis if correct handling in operation and proper prevention of complications are performed. But the long-term outcomes are still needed to be confirmed in longer follow-up. [ABSTRACT FROM AUTHOR]