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Cholangiocarcinoma represents the second most frequent type of primary liver cancer that develops through a multistep histopathologic sequence. Dysplasia in the biliary tract epithelium is a precursor lesion of cholangiocarcinoma. This review provides a practical overview of bile duct dysplasia in relation to invasive carcinoma, covering clinicopathological features, diagnostic criteria, differential diagnosis, useful testing modalities, and challenges in daily practice. The key features of biliary intraepithelial neoplasia, intraductal papillary neoplasm, intraductal tubulopapillary neoplasm, and mucinous cystic neoplasm are described. Important differential diagnoses are included. Common pitfalls in histopathologic interpretation of bile duct biopsies and frozen sections are discussed.

Background aims Cell-based regenerative medicine is an innovative field that can potentially alter the overall survival and quality of life of patients with devastating diseases. Several cell therapy products (CTPs) have been approved within the last two decades, and more are under development. The establishment of an effective developmental strategy in accordance with the regulatory bodies of each country/region is crucial for fast delivery of each respective CTP. In particular, facilitating investigational new drug (IND) approval is important for accelerating the transition from non-clinical to clinical research/trial phases. Methods Here the authors compared the non-clinical prerequisites for initiating clinical studies in five Asian countries/regions (India, China, Korea, Taiwan and Japan) from an industry viewpoint. The authors first identified the differences and tried to clarify the perspectives/considerations underpinning the different requirements. Results The authors’ findings revealed that differences in regulations and development experiences, especially with CTPs, have led to clear differences in the non-clinical study package and its corresponding study design. Conclusions By sharing experiences of the research and development of CTPs among Asian countries/regions and including not only industry but also regulatory authorities, we will be able to expedite cross-border IND approval and eventually contribute to the early delivery of innovative CTPs to many Asian patients.

A series of Ce modified La-Mn perovskite catalysts are synthesized by sol-gel method and systematically characterized. The results showed that Ce doping can improve catalytic activity of La-Mn perovskite catalyst for NOx removal with NH3. When the Ce/Mn ratio is 0.2, the catalyst exhibits the best SCR activity and achieves 90% NOx conversion at 135 °C, above 70% N2 selectivity in the testing temperature, and 95% NOx conversion at 200 °C in the presence of SO2 and H2O. Ce modified La-Mn catalysts are porous and have perovskite structure of LaMnO3.15. However, the doped Ce ions do not completely enter the perovskite framework, while some of them form Ce oxides on the catalyst surface. Moreover, some of Mn ions do not participate into the formation of La-Mn perovskite structure but deposit on the catalyst surface with a form of Mn3O4 to maintain the perovskite structure stability and charge balance. The Ce doped La-Mn perovskite catalysts provide larger specific surface area, more acidic sites, more chemically adsorbed oxygen and better redox performance than the undoped sample, which is conducive to the de-NOx performance. SO2 is oxidized into SO3 and forms some sulfates, but Ce doping increases the tolerance of catalyst to SO2.

Immune checkpoint antibodies have emerged as novel therapeutics, while many patients are refractory. Researchers had identified tumor-associated macrophages (TAMs) is the pivotal factor involved in immune resistance and that manipulation of TAMs functions would improve the immunotherapies effectively. NF-κB pathway was one of the master regulators in TAMs manipulation. Inhibition of NF-κB pathway could achieve both re-polarization M2 TAMs and downregulation the expression of programmed cell death protein 1 (PD-1) ligand 1 (PD-L1) on TAMs to improve the effect of immunotherapies. Here, IMD-0354, inhibitor of NF-κB pathway was loaded in mannose modified lipid nanoparticles (M-IMD-LNP). Then, PD-1 antibody and M-IMD-LNP were co-loaded in matrix metalloproteinase 2 (MMP2) responsive and tumor target nanogels (P/ML-NNG). P/ML-NNG could co-deliver drugs to tumor site, disintegrated by MMP2 and release drugs to different targets. Evaluation of PD-1 expression, inhibition of NF-κB pathway, expression of PD-L1 on M2 TAMs and M2 TAMs re-polarization demonstrated that P/ML-NNG could block the PD-1/PD-L1 and NF-κB pathways simultaneously. Evaluation of CD4 + T cells, CD8 + T cells, Tregs, cytokines and antitumor immunity confirmed that IMD-0354 could improve the immunotherapies effectively. Those results provided forceful references for tumor immunetherapy.

This research reveals biochemical and genetic changes for enhanced lipid production in Desmodesmus sp. mutated using atmospheric and room temperature plasma. Three lipid-rich mutant strains were selected by the special screening method, decided by the specific growth rate, relative fluorescence and the combination. There were no significant differences in genetic stability under 3-generation cultivation (p > 0.05). The highest lipid production and biomass increased by >100% and >15% compared to original strain, respectively. The activities of lipid enzymes, including acetyl-CoA carboxylase and diacylglycerol acyltransferases, responded to similar trends with lipid accumulation. Functional genes classification of mutant strains showed a great ratio in genetic information process (33.51%) and metabolism pathway (28.74%). More than 80% genes were not significant in lipid-related metabolisms and total 27 significant genes were analyzed, signifying similar genetic changes in mutant strains. Finally the establishing simplified diagram explained high lipid accumulation based on typical enzymes for fatty acid synthesis by upregulated genes, ACACA, fabF, fabG, ACSL, as well as triacylglycerol synthesis by upregulated genes, glpk, GPAT1_2, plsC, PDAT, dgat 1 and MGAT2. Lipid-rich strains performed a positive effect on lipid accumulation. These relative regulated genes and analysis might provide the control points for high lipid production in energy consumption.

To overcome the shortcomings of single component carrier supported platinum (Pt)-based catalysts, herein, we demonstrate the fabrication of alumina combined mesoporous carbon to prepare a series of alumina-carbon composites and their corresponding Pt-based catalysts. The alumina-carbon composites Al@PhFC are synthesized by using phloroglucinol-formaldehyde resin as carbon source and aluminum acetylacetone as the aluminum source. Further, the effect of alumina content on the properties of the composites is investigated. The composites and catalysts are characterized by using XRD, XPS, N2 sorption, and TEM. The Pt/Al@PhFC-1.8 composite with appropriate amounts of alumina, pore diameter, and moderate Pt nanoparticle size, resulted in 99.5% of conversion efficiency and 77.4% of optical selectivity in the asymmetric hydrogenation of ethyl 2-oxo-4-phenylbutanoate (EOPB). Interestingly, this composite can be used more than 20 times without a significant decrease in its performance.

Listeria ivanovii is one of the two pathogenic species within the genus Listeria, the other being L. monocytogenes. In this study, we generated a stable pediocin resistant mutant Liv-r1 of a L. ivanovii strain, compared phenotypic differences between the wild-type and the mutant, localised the pediocin-induced mutations in the chromosome, and analysed the mechanisms behind the bacteriocin resistance. In addition to pediocin resistance, Liv-r1 was also less sensitive to nisin. The growth of Liv-r1 was significantly reduced with glucose and mannose, but less with cellobiose. The cells of Liv-r1 adsorbed less pediocin than the wild-type cells. Consequently, with less pediocin on the cell surface, the mutant was also less leaky, as shown as the release of intracellular lactate dehydrogenase to the supernatant. The surface of the mutant cells was more hydrophobic than that of the wild-type. Whole genome sequencing revealed numerous changes in the Liv-r1 chromosome. The mutations were found e.g., in genes encoding sigma-54-dependent transcription regulator and internalin B, as well as in genes involved in metabolism of carbohydrates such as glucose and cellobiose. Genetic differences observed in the mutant may be responsible for resistance to pediocin but no direct evidence is provided.

In this study, the metabolic fates and response strategies of microorganisms to aromatic compounds with different structures (phenol, naphthalene, phenanthrene, and pyrene) were comparatively studied. The results indicated that the phenol (90.9%), naphthalene (68.4%), phenanthrene (69.5%), and pyrene (67.1%) could be mineralized, and the biotoxicity also has been drastically reduced. The degradation characteristics and toxic effects were closely related to their chemical structure. The microorganisms showed different response strategies to aromatic compounds with different structures. Phenol had a simple structure and low toxicity, the microbial community structure was simple, and the rapid expression of key enzymes enabled it to be rapidly degraded. For the hydrophobic and complex naphthalene, phenanthrene, and pyrene, the more complex the structure, the higher the microbial diversity, the EPS showed different response for the purpose of improving their bioavailability, and the activity of key enzymes was positively correlated with their structural complexity.

Sedum alfredii Hance is a cadmium (Cd)/zinc (Zn) hyperaccumulator native to China. However, its relatively low biomass restricted the large-scale application for heavy metal contamination remediation. The chromosome set doubling of S. alfredii in vitro was achieved by 0.1%-0.2% (W/V) colchicine treatment. The plant DNA ploidy was analyzed by flow cytometry and chromosome set doubling plants (CSD) were identified based on the obvious different sharp peak. A tissue culture experiment with different Cd treated levels and a field trial with natural polluted mined soil were conducted to study the effects of chromosome doubling on plant biomass and Cd accumulation in shoots. The results suggested that S. alfredii is a mixoploid. Compared with the wild type plants (WT), CSD exhibited typical "gigas" characteristics in morphology including stem thickness, root hair production, number of leaves and size of stoma guard cell. Fresh weight and dry weight of CSD were increased to 1.62-2.03-fold and 2.26-3.25-fold of WT. And Cd content of CSD showed a 17.49%-42.82% increase and 59% increase under tissue culture and field condition, accordingly. In addition, the TF and in BCF of CSD were 2.37- and 1.59-fold of WT, respectively. These results proved that it is feasible to promote phytoextraction efficiency of S. alfredii in Cd contaminated soils through chromosomal engineering, which provides a novel approach for hyperaccumulator application in phytoremediation.

Three compounds constructed by homopiperazine with 1,5-naphthalenedisulfonic acid, 4,5-dichlorophthalic acid and 2,2′,5,5′-biphenyltetracarboxylic acid have been analyzed with respect to hydrogen bonds appeared in the crystal structures. Single crystal X-ray diffraction studies showed that partial protons were transferred to homopiperazine, which made it possible to form N–H⋯O hydrogen bonds in all three compounds. Moreover, O–H⋯O and C–H⋯O hydrogen bonds are founded in 2 and 3 respectively. All of the three compounds displayed 3D supramolecular network structures for the effect of various hydrogen bonds interactions. In addition solvent water molecules and ethanol molecules played an indispensable role in the construction of compounds 2 and 3 . Some main supramolecular synthons observed in three compounds were shown to construct most of these hydrogen bonding networks. These new multi-component molecular solids of homopiperazine were characterized by powder X-ray diffraction, infrared spectroscopy, 1 H nuclear magnetic resonance and thermogravimetric analysis.

Interests in securing alternatives to oil have been intensified in recent years. This work provides a conceptual design of a highly efficient Biomass-to-Liquid (BTL) fuels process that produces gasoline and diesel. It incorporated the configuration of biomass pre-pyrolysis followed by entrained flow gasification, which avoided separate torrefaction of feedstock and provided more syngas with a higher cold gas efficiency. The application of Fe-based slurry-phase Fischer-Tropsch synthesis further improved the gasoline/diesel yield to 10.2 GJ/t dry biomass with an overall energy efficiency of 58%, which is higher than current reports. However, the water consumption of BTL was much more than that of conventional petroleum refinery. A CO2 cycling scheme was developed in this design to reduce water consumption. The value-added of these features and performance of this BTL system are revealed. The production cost of this BTL was approximately 5,115∼5,683 CNY/t with a breakeven crude oil price of 83∼93 $/bbl.

The potential of arbuscular mycorrhizal (AM) fungi in ecological restoration has been appreciated increasingly, yet the successional patterns of AM fungal community and their relatedness with plants and ecosystem functions during the recovery of degraded lands remain poorly understood. Here, we examined synchronously the root-associated AM fungal and plant communities as well as the ecosystem multifunctionality (EMF) in paired historically disturbed (topsoil was removed in the early 1980s) and undisturbed habitats of eight Tibetan grasslands. We found that, after three decades of natural recovery, AM fungal richness and community composition were similar in disturbed and undisturbed habitats, whereas vegetation coverage and plant species richness were still lower in disturbed habitat than that in undisturbed habitat. Higher abundance of AM plants was established in disturbed habitat, while the undisturbed habitat was dominated by less- or non-AM plant species. AM fungal species composition showed tight relationship with the species composition of all plants only in the disturbed habitat, while it was always correlated with the species composition of AM plants regardless of the historical disturbance. The EMF index was lower in disturbed habitat compared to that in undisturbed habitat, and it correlated positively with AM fungal richness in disturbed habitat. Our study shows that AM fungal community is more resilient to disturbance than plant community in Tibetan grasslands, and the findings suggest that rapid recovery of AM fungal community in degraded lands may potentially drive vegetation development and enhance ecosystem functions in the early stages of ecosystem recovery.

Three novel metal-organic complexes, formulated as [Cu2(2-HBA)2(bimb)4] (1), {[Cd(CEDA)(bimb)]·H2O}n (2), and {[Ag2(bimb)2]·(1,4-CDA)·13H2O} (3) (bimb = 1,2-bis((1H-imidazole-1-yl)methyl)benzene; 2-HBA = 2-hydroxybenzoic acid; CEDA = cyclohex-4-ene-1,2-dicarboxylic acid; 1,4-CDA = cyclohexane-1,4-dicarboxylic acid), were synthesized by self-assembly of mixed ligands with Cu(II), Cd(II), and Ag(I) under hydrothermal conditions and characterized by means of single-crystal X-ray diffraction, X-ray powder diffraction, infrared spectra, thermogravimetric analysis, fluorescence spectra and UV–vis absorption spectra. 1 is shown as a 0D structure, which is formed by Cu2+, 2-HBA ligands and bimb ligands. 2 displays a 1D ladder structure, which is built by Cd2+, CEDA ligands and bimb ligands, and it is assembled into 2D structure by hydrogen bonding. 3 possesses a 0D [Ag(bimb)]2 dimer which is assembled into 3D structure by the Ag O weak interaction and hydrogen bonding. Interestingly, a rare 13-core water cluster participates in forming the network of 3. The UV–vis spectrum and luminescence properties were also studied and discussed.

The introduction of metal atom or heteroatom into transition metal phosphide is an effective strategy to enhance the electrochemical activity for hydrogen evolution reaction, while the controllable synthesis and purposeful design of efficient and stable transition metal phosphide based electrocatalyst with typical structural morphology is still a big challenge. Here, we investigated the relationship among the variety of the doped metal element (Fe and Mn), the corresponding morphology and electrocatalytic performance of the obtained sample for hydrogen evolution reaction. We found that with the doping of Fe and Mn, the cylinder-like CoP has transformed into microflower-like CoP-FeP and rambutan-like CoP-MnP, respectively. Meanwhile, the obtained CoP-FeP exhibits the excellent electrocatalytic activity hydrogen evolution reaction (HER) over a wide pH range (0–14), followed by CoP-MnP and CoP, resulting from the typical nanostructure and the moderately optimized electronic structure of P and Co center.

CuMn mixed oxides catalysts doped with La were prepared following a co-precipitation method and used for the catalytic oxidation of toluene. Catalysts properties of the catalysts were investigated by X-ray diffraction, N2 adsorption/desorption, scanning electron microscopy, H2-temperature-programmed reduction (H2-TPR), O2-temperature-programmed desorption (O2-TPD) and X-ray photoelectron spectroscopy techniques. Characterization data reveal that the phase change and decrease in crystallinity of the La-doped catalysts increase the number of oxygen vacancies. Improvements in reducibility and an increase in the amount of chemisorbed oxygen of the La-doped catalysts were also verified by H2-TPR and O2-TPD. The activity of the CuMn mixed oxides catalysts is significantly improved by the addition of a nominal amount of La. The CuMn/La-4 mol% catalyst exhibits the best catalytic activity, with a 90% conversion temperature of 255 °C, attributed to a high Mn3+ratio, superficial chemisorbed oxygen, and high surface area. This study indicates La to be a promising dopant for Cu Mn catalysts toward toluene oxidation.

Background Current literature shows a variable degree of concordance between endoscopic and histopathologic findings in gastric mucosal biopsies. Most prior studies have focused on specific gastric entities such as gastritis in patients with high prevalence of Helicobacter pylori (H. pylori). In this study, we assess concordance between histologic and endoscopic findings in a wide spectrum of targeted as well as non-targeted gastric endoscopic biopsies. Methods We retrospectively reviewed pathology database and slides at Hershey Medical Center to identify 630 gastric mucosal biopsies obtained from 525 consecutive patients. The corresponding clinical and endoscopic findings were retrieved from the electronic medical record. Results The rate of abnormal endoscopic and histologic findings was 72.9% and 74.4%, respectively, with Cohen's ĸ coefficient of 0.24. There were 444 (70.5%) concordant cases and 186 (29.5%) discordant cases (88 cases with abnormal endoscopy but normal histology, and 98 cases with normal endoscopy but abnormal histology). Some endoscopic findings, in particular, mass, polyp, ulcer, and nodule/papule were highly concordant with abnormal histopathologic findings; while other endoscopic findings such as inflammatory changes, normal and prominent folds were associated with normal and a variety of abnormal histopathology. Multivariate analysis showed no significant association between intestinal metaplasia and H. pylori in this study. Conclusions Histopathologic-endoscopic correlation in gastric biopsies varies depending on endoscopic mucosal patterns. Intestinal metaplasia may not have a significant association with H. pylori infection in populations with low prevalence of H. pylori.