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Due to soared obesity population worldwide, hepatosteatosis is becoming a major risk factor for hepatocellular carcinoma (HCC). Undertaken molecular events during the progression of steatosis to liver cancer are thus under intensive investigation. In this study, we demonstrated that high-fat diet potentiated mouse liver AKT2. Hepatic AKT2 hyperactivation through gain-of-function mutation of Akt2 (Akt2E17K) caused spontaneous hepatosteatosis, injury, inflammation, fibrosis, and eventually HCC in mice. AKT2 activation also exacerbated lipopolysaccharide and D-galactosamine hydrochloride-induced injury/inflammation and N-Nitrosodiethylamine (DEN)-induced HCC. A positive correlation between AKT2 activity and SCD1 expression was observed in human HCC samples. Activated AKT2 enhanced the production of monounsaturated fatty acid which was dependent on SREBP1 upregulation of SCD1. Blockage of active SREBP1 and ablation of SCD1 reduced steatosis, inflammation, and tumor burden in DEN-treated Akt2E17K mice. Therefore, AKT2 activation is crucial for the development of steatosis-associated HCC which can be treated with blockage of AKT2-SREBP1-SCD1 signaling cascade. [ABSTRACT FROM AUTHOR]

A closed-form equation was developed in this work to quantify the stress intensity factor (SIF) along an arbitrarily shaped planar crack under mode-I loading by substituting the ellipse-related parameters in Irwin's solution with geometry-related parameters f i of the crack. This allowed incorporation of the local crack curvature effect on SIF at each discrete point along the crack front and its relative weighted contribution to SIF of the neighboring crack point i , where either stress concentration or shielding took place, into computation of the SIF distribution along the crack front. Good agreement was obtained between the K I values derived in the current work and previous numerical simulation-based studies. The current method could capture the K I distributions for surface and embedded cracks having the same shape, with their maximum values being consistent with Murakami's area method. This solution of K I allows for highly efficient calculation of Δ K I for quantification of the 3D growth behaviors of a fatigue crack with a complex shape, paving the way for studying the statistical nature of short fatigue crack growth. [ABSTRACT FROM AUTHOR]

Abstract The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A novel family of donepezil-butylated hydroxytoluene (BHT) hybrids were designed, synthesized and evaluated as multifunctional ligands against AD. The optimal compound 7d displayed a balanced multifunctional profile covering an intriguing acetylcholinesterase (AChE) inhibition (IC 50, 0.075 μM for ee AChE and 0.75 μM for h AChE) and Monoamine oxidase B (MAO-B) inhibition (IC 50 , 7.4 μM for h MAO-B), excellent antioxidant activity (71.7 μM of IC 50 by DPPH method, 0.82 and 1.62 trolox equivalent by ABTS method and ORAC method respectively), and inhibitory effects on self-induced, h AChE-induced A β aggregation. Moreover, 7d possessed neuroprotective potency against H 2 O 2 -induced oxidative damage on PC12 cells and Lipopolysaccharides (LPS)-stimulated inflammation on BV2 cells. Compound 7d was capable of penetrating BBB and presented good liver microsomal metabolic stability. Importantly, compound 7d could dose-dependently reverse scopolamine-induced memory deficit in mice without acute toxicity. Taken together, those outstanding results highlight the donepezil-BHT hybrid 7d as a promising prototype in the research of innovative compound for AD. Graphical abstract Image 1 Highlights • A series of donepezil-BHT derivatives through two modifications were rational designed, synthesized and evaluated. • Most of the compounds showed good inhibitory activities against AChE and MAO-B as well as remarkable antioxidant activities. • 7d displayed a balanced multifunctional profile covering an intriguing AChE and MAO-B inhibition, antioxidant activity. • 7d possessed neuroprotection against H 2 O 2 -induced oxidative damage and LPS-stimulated inflammation on cell level. • 7d could dose-dependently reverse scopolamine-induced memory deficit in mice without acute toxicity and hepatotoxicity. [ABSTRACT FROM AUTHOR]

A series of multitargeted 8-hydroxyquinoline derivatives were designed and synthesized for the treatment of Alzheimer’s disease (AD). In vitro studies indicated that most of the prepared compounds exhibited significant inhibitory effects against self-induced A β 1−42 aggregation and potential antioxidant properties especially compound 5b (IC 50  = 5.64 μM for self-induced A β aggregation; the oxygen radical absorbance capacity using fluorescein (ORAC-FL) value is 2.63 Trolox equivalents). Notably, 5b can chelate biometals and inhibit Cu 2+ /Zn 2+ -induced A β 1−42 aggregation. The cell assays showed that 5b had excellent protective effects against oxidative toxin H 2 O 2 and presented low neurotoxicity in PC12 cells. Furthermore, 5b could penetrate the blood–brain barrier (BBB) in vitro and did not show any acute toxicity in mice at doses up to 2000 mg/kg in vivo . Our findings provide a rationale for the potential application of compound 5b as a lead compound in AD therapy. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are a subset of cancer cells which have self-renewal ability and exist in various tumors. Inhibition of CSCs self-renewal is considered as a new method for tumor therapy. A novel semi-synthetic taxane analogue, Lx2-32c, could overcome drug resistance in various cancer cell lines. In this study, it was found that Lx2-32c inhibited the proliferation and mammosphere formation of MDA-MB-231-derived cancer stem cell-like cells (MCSCLCs) and induced apoptosis, as well as down-regulated the expression of FoxM1 and CD44 in MCSCLCs. Simultaneously, it was proved that Lx2-32c combined with thiostreption, a FoxM1 inhibitor inhibited proliferation and mammosphere formation of MCSCLCs and induced apoptosis to a more extent than Lx2-32c alone; thiostreption could also enhance the effect of Lx2-32c of reduction of the expression of FoxM1 and CD44. All of these results indicated that Lx2-32c is a novel semi-synthetic taxane analogue which inhibits the self-renewal of MCSCLCs cells and induces apoptosis involving in down-regulating FoxM1. [ABSTRACT FROM AUTHOR]

A series of salicyladimine derivatives were designed, synthesized and evaluated as multi-target-directed ligands for the treatment of Alzheimer’s disease (AD). Biological activity results demonstrated that some derivatives possessed significant inhibitory activities against amyloid- β (A β ) aggregation and human monoamine oxidase B ( h MAO-B) as well as remarkable antioxidant effects and low cell toxicity. The optimal compound, 5 , exhibited excellent potency for inhibition of self-induced A β 1–42 aggregation (91.3 ± 2.1%, 25 μM), inhibition of h MAO-B (IC 50 , 1.73 ± 0.39 μM), antioxidant effects (43.4 ± 2.6 μM of IC 50 by DPPH method, 0.67 ± 0.06 trolox equivalent by ABTS method), metal chelation and BBB penetration. Furthermore, compound 5 had neuroprotective effects against ROS generation, H 2 O 2 -induced apoptosis, 6-OHDA-induced cell injury, and a significant in vitro anti-inflammatory activity. Collectively, these findings highlighted that compound 5 was a potential balanced multifunctional neuroprotective agent for the development of anti-AD drugs. [ABSTRACT FROM AUTHOR]

By using fragments endowed with interesting and complementary properties for the treatment of Alzheimer's disease (AD), a novel series of cinnamamide-dibenzylamine hybrids have been designed, synthesized, and evaluated biologically. In vitro assay indicated that most of the target compounds exhibited a significant ability to inhibit ChEs, strong potency inhibitory of self-induced β -amyloid (A β ) aggregation and to act as potential antioxidants and biometal chelators. A Lineweaver-Burk plot and molecular modeling study showed that compound 7f targeted both the CAS and PAS of AChE. In addition, compound 7f could chelate metal ions, reduce PC12 cells death induced by oxidative stress and penetrate the blood–brain barrier (BBB). Overall, all of these outstanding in vitro results in combination with promising in vivo outcomes highlighted derivative 7f as the lead structure worthy of further investigation. [ABSTRACT FROM AUTHOR]

A series of coumarin-pargyline hybrids ( 4a-x ) have been designed, synthesized and evaluated as novel dual inhibitors of Alzheimer's disease (AD). Most of the compounds exhibited a potent ability to inhibit amyloid- β (A β ) aggregation and monoamine oxidases. In particular, compound 4x exhibited remarkable inhibitory activities against monoamine oxidases (IC 50 , 0.027 ± 0.004 μ M for MAO-B; 3.275 ± 0.040 μ M for MAO-A) and A β 1-42 aggregation (54.0 ± 1.1%, 25 μ M). Moreover, compound 4x showed low toxicity according to in vitro cell toxicity test. The results of the parallel artificial membrane permeability assay for blood-brain barrier indicated that compound 4x would be potent to cross the blood-brain barrier. Collectively, these findings demonstrate that compound 4x was an effective and promising candidate for AD therapy. [ABSTRACT FROM AUTHOR]

A quantitative model which took into account the 3-D effects of pores on the local stress/strain fields was developed to quantify the fatigue weak-link density and strength distribution in an A713 Al alloy. In the model, a digital pore structure was first constructed using single-sized pores (15 μm in diameter) that had a total volume fraction same as that of the pores measured experimentally in the alloy. In the surface randomly selected by cross-sectioning through the simulated pore structure, the stress and strain fields around each pore in the surface were quantified using a 3-D finite element model under an applied cyclic stress, and the fatigue crack incubation life at the pore was estimated with a micro-scale Manson-Coffin equation. The quantified rate of fatigue crack initiation at these pores was found to be a Weibull function of the applied stress, which was consistent with the experimental result measured in the alloy. The density and strength distribution of fatigue weak-links could then be derived and used to evaluate the fatigue crack initiation properties of the alloy. By matching to the experimentally measured fatigue weak-links, the minimum critical pore size for fatigue crack initiation was determined to be 11 μm in diameter at the cyclic maximum stress of 100% yield strength of the alloy. [ABSTRACT FROM AUTHOR]

A series of novel donepezil derivatives was designed, synthesized and evaluated as multifunctional acetylcholinesterase (AChE) inhibitors for the treatment of Alzheimer's disease (AD). The screening results indicated that most of the compounds exhibited potent inhibition of AChE with IC 50 values in the nanomolar range. Moreover, these derivatives displayed good antioxidant, A β interaction, blood-brain barrier penetration (PAMPA-BBB+) and ADMET properties ( in silico ). Among them, 5c demonstrated excellent AChE inhibition (IC 50 : 85 nM for eeAChE, 73 nM for hAChE), metal chelation, and inhibitory effects on self-induced, hAChE-induced and Cu 2+ -induced A β 1-42 aggregation (18.5%, 72.4% and 46.3%, at 20 μ M). Kinetic analysis and molecular modeling studies suggested that 5c could bind simultaneously to the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. More importantly, 5c exhibited significant neuroprotective potency against A β 1-42 -induced PC12 cell injury. Furthermore, the step-through passive avoidance test showed 5c significantly reversed scopolamine-induced memory deficit and no hepatotoxicity in mice. These results indicated that 5c might be a promising drug candidate for AD therapy. [ABSTRACT FROM AUTHOR]

Two thin-film microextractions (TFME), octadecylsilane (ODS)-polyacrylonitrile (PAN)-TFME and polar enhanced phase (PEP)-PAN-TFME have been proposed for the analysis of bisphenol-A, diethylstilbestrol and 17β-estradiol in aqueous tea extract and environmental water samples followed by high performance liquid chromatography-ultraviolet detection. Both thin-films were prepared by spraying. The influencing factors including pH, extraction time, desorption solvent, desorption volume, desorption time, ion strength and reusability were investigated. Under the optimal conditions, the two TFME methods are similar in terms of the analytical performance evaluated by standard addition method. The limits of detection for three estrogens in environmental water and aqueous tea extract matrix ranged from 1.3 to 1.6 and 2.8 to 7.1 ng mL −1 by the two TFME methods, respectively. Both approaches were applied for the analysis of analytes in real aqueous tea extract and environmental water samples, presenting satisfactory recoveries ranged from 87.3% to 109.4% for the spiked samples. [ABSTRACT FROM AUTHOR]

• The n-octadecane contents in TRTSF should be less than 30 w.t.% to avoid leakage issue. • Comparing between OCT10%, OCT20% and OCT30%, the higher n-octadecane content in TRTSF the more significant switching effect. • The OCT20% showed a good phase change stability and optical switching effect. • The switching effect of TRTSF samples is enhanced by the thickness of the switch film. • Temperature switching of TRTSF resulted by the decreased transmittance of PCM from 97% to 3.7% after solidification. To overcome the problem of unable automatic turn on and off response to the ambient temperature of current static radiative cooling systems, we prepared a series of temperature-responsive transmission switch film (TRTSF) samples using n-octadecane as phase change material (PCM) and polydimethylsiloxane (PDMS) as carrier material. The phase change cycle permeability analysis showed that the TRTSF samples with PCM content above 30.0 w.t.% exhibit a serious leakage problem due to a large number of holes on surface. The TRTSF samples with 10.0–30.0 w.t.% PCM content were further analysed by Differential scanning calorimetry (DSC) and Thermogravimetry (TG), and compared with the theoretical PCM contents, which verified the reliability of the curing results of PCM in TRTSF from various aspects. The ultraviolet–visible light-near-infrared (UV–VIS-NIR) and mid-infrared (MIR) transmittance characterization of TRTSF revealed that the switching effect was obvious during solid–liquid phase change process. TRTSF microstructure analysis revealed that the particle size distribution of PCM microspheres was between 1 μm and 6 μm. The UV–VIS-NIR band (wavelength at 0.25–1.1 μm) transmittance of PCM decreased to less than 3.7% after solidification due to the interfacial reflectance of solid PCM particles increased to more than 66.8% even in monolayer, thus the solid PCM particles would produce Mie scattering and isolate the internal and external radiation heat transfer. However, the TRTSF can be used as the radiative cooling emission layer since its optical properties were similar to the PDMS when the PCM is in liquid phase. Overall, the TRTSF film prepared in this study successfully adapted the temperature switching properties, also, is expected to be further used for the development of self-adaptive radiative cooling systems. [ABSTRACT FROM AUTHOR]

Tumor resistance, especially that mediated by P-glycoprotein (P-gp) and β-III tubulin, is a major obstacle to the efficacy of most microtubule-targeting anticancer drugs in clinics. A novel semisynthetic taxane, 2-debenzoyl-2-(3-azidobenzyl)-10-propionyldocetaxel (Yg-3-46a) was shown to be highly cytotoxic to breast cancer cell lines MCF-7 and MCF/ADR which overexpressed P-gp via long term culture with doxorubicin, and cervical cancer cell lines Hela and Hela/βIII which overexpressed βIII-tubulin via stable transfection with TUBB3 gene. siRNA transfection experiments also confirmed that Yg-3-46a can circumvent P-gp and β-III tubulin mediated drug resistance. In addition, its cytotoxicity was lower than that of paclitaxel in the human mammary cell line HBL-100 and the human telomerase-immortalized retinal pigment epithelium cell line (hTERT-RPE1), suggesting a better safety margin for this compound in vivo. It exhibited more potent microtubule polymerization ability than paclitaxel in vitro, and also induced G2/M phase arrest in MCF-7/ADR cells. Moreover, it was found to induce apoptosis in MCF-7/ADR cells through the caspase-dependent death-receptor pathway by enhancing levels of Fas and FasL, and activating caspase-8 and 3. Yg-3-46a was found to be a poorer substrate of P-gp compared to paclitaxel, in both binding and ATPase experiments, which is likely responsible for its ability to circumvent P-gp mediated multidrug resistance (MDR). All of these results indicate that Yg-3-46a is a novel microtubule-stabilizing agent that has the potential to evade drug resistance mediated by P-gp and β-III tubulin overexpression. [ABSTRACT FROM AUTHOR]

Abstract: Metal-free (5+2) cycloadditions of homopyrrole and homofuran with dienophiles of N-phenylmaleimide, dimethyl acetylenedicarboxylate (DMAD), and maleic anhydride have been investigated by DFT calculations at the (U)B3LYP/6-31+G(d) level. Homopyrrole and homofuran act as 4-electron 1,5-dipoles in these (5+2) reactions. These 1,5-dipoles can exist only in the transition states and undergo competitive concerted or stepwise (5+2) cycloadditions. The (5+2) cycloadditions of homopyrrole with dienophiles are stepwise involving generation of diradical intermediates, and its concerted pathways are disfavored marginally. In contrast, the (5+2) cycloaddition of homofuran with maleic anhydride occurs in a concerted fashion, which is preferred over the stepwise diradical pathway slightly. The distortion energies from homopyrrole and homofuran to their respective 1,5-dipoles in the transition states are not high and this is the main reason why homopyrrole and homofuran can undergo metal-free (5+2) cycloadditions with dienophiles. [Copyright &y& Elsevier]

Aim: To investigate the radiological findings of head and neck radiation-induced sarcomas (RISs) following radiotherapy for nasopharyngeal carcinoma (NPC). Materials and methods: Fifty-nine patients with RISs were identified. Imaging characteristics on computed tomography (CT) and magnetic resonance imaging (MRI), including lesion location, extent, size, margin, internal architecture, pattern, and degree of enhancement, together with patient characteristics at NPC diagnosis and latency periods, were reviewed. Results: The study included 20 women and 39 men, with a median age of 49 years (range 30–71 years). The median latency was 9 years (range 3–37 years). The median radiation dose at the site of RIS was 66 Gy (range 44–78 Gy). The most common histological RIS types were fibrosarcoma (44.1%) and osteosarcoma (30.5%). The most common RIS sites were the paranasal sinuses and the nasal cavity (39%), the neck (16.9%), and the mandible (15.3%). The mean size was 5.1 cm (range 1.2–8.6 cm). Overall, 78% of lesions extended to adjacent spaces and 66.1% were accompanied by bone destruction. Heterogeneous density/signal intensity before and after enhancement was seen in all lesions on imaging. Marked lesion enhancement was noted in 49 cases (76.3%). Conclusions: The radiologist should be aware of the different sites at which RISs occur and the radiological appearance of the wide variety of RIS subtypes. Careful imaging follow-up is necessary for early detection of RISs in patients with NPC after radiotherapy. [ABSTRACT FROM AUTHOR]

Abstract: One current major hurdle to practical implementation of aerobic granule technology is the frequent occurrence of granule disintegration during long-term operation. However, the mechanism behind this is largely unclear today. Here, 2-decenoic acid, which has been previously demonstrated to be released by Pseudomonas aeruginosa and disperse biofilms, was found to also induce the disintegration of aerobic granules. A comparison of the solution compositions from samples of only trans-2-decenoic acid, only aerobic granules, and granules added with trans-2-decenoic acid shows that bacteria and extracellular polymeric substances (EPS) were stripped from granule surface upon trans-2-decenoic acid dosing. Due to the possible toxicity of trans-2-decenoic acid at a saturation concentration, the disintegrated granules and the milky suspension in the disintegration test showed a significantly lower oxygen uptake rate than the un-integrated granules. This work suggests that trans-2-decenoic acid released by microbes might play a critical role in regulating the disintegration of aerobic granules. [Copyright &y& Elsevier]

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) induces the unfolded protein response (UPR), which acts through various mechanisms to reduce ER stress. While the UPR has been well studied for its effects on the ER, its impact on the Golgi is less understood. The Golgi complex receives transport vesicles from the endosome through two types of tethering factors: long coiled-coil golgin and the multisubunit Golgi-associated retrograde protein (GARP) complex. Here, we report that ER stress increases the phosphorylation of golgin Imh1 to maintain the GARP-mediated recycling of the SNAREs Snc1 and Tlg1. We also identify a specific function of the Golgi affected by ER stress and elucidate a homeostatic response to restore this function, which involves both an Ire1-dependent and a MAP kinase Slt2/ERK2-dependent mechanism. Furthermore, our findings advance a general understanding of how two different types of tethers act cooperatively to mediate a transport pathway. [Display omitted] • Tunicamycin (TM)-induced ER stress partially impairs GARP function on the Golgi • Imh1 is necessary for GARP-mediated Snc1/Tlg1 recycling under TM-induced stress • TM induces Slt2/ERK2-dependent Imh1 phosphorylation to maintain Snc1/Tlg1 recycling • Defects in N-linked glycosylation govern post-ER stress response at the late Golgi Wang et al. present the cooperative action of two different classes of tethers, golgin Imh1 and GARP complex, in mediating proper recycling of SNAREs Snc1/Tlg1 under ER stress. They show that ER stress induces an Ire1-independent response mechanism, which involves the MAP kinase Slt2/ERK2-dependent Imh1 phosphorylation to maintain Snc1/Tlg1 transport. [ABSTRACT FROM AUTHOR]

Objective: To introduce a new technique of 1-stage reconstruction for thumb loss complicated by thumb–index web space contracture and to report its clinical effectiveness. Methods: From November 1994 to September 2004 there were 11 patients with thumb loss and contracture in the thumb–index web space who had a combined transplantation of free tissues to reconstruct the missing thumb and to rebuild the web space. The reconstructive procedure used the second toe and the anterolateral thigh flap in 5 patients, the second toe and the scapular flap in 2, the big toe wraparound flap and the anterolateral thigh flap in 3, and the big toe wrapround flap and the scapular flap in 1. The 2 independent free tissues were connected together by a vascular combination to form an assembly with 1 common vascular pedicle, which then was anastomosed to the selected vessels in the recipient hand. In this vascular series the dorsalis pedis artery and the greater saphenous vein served as the common vascular pedicle of the flap transfers and the radial artery and the cephalic vein provided the recipient vessels. The outcomes of the reconstructions were evaluated using the Michigan Hand Outcomes Questionnaire. Results: The flaps survived completely in all patients except 1. In this patient a small area in the distal part of the transplanted anterolateral thigh flap became necrotic but healed after dressing changes without the need for further surgical intervention. A mean follow-up period of 3.6 years showed a mean increase of 4.3 cm in the width of the thumb–index web space and a considerable improvement in overall hand function was noted on the Michigan Hand Outcomes Questionnaire with effect sizes of greater than 3 (large effect) in all domains. Conclusions: Combined transplantation of the second toe or the big toe wraparound flap and a free skin flap is suitable to reconstruct a missing thumb and repair the associated skin defect in the adjacent thumb–index web space. We found good functional recovery and an acceptable appearance in this series of patients.Type of study/level of evidence: Therapeutic, Level IV. Type of study/level of evidence: Therapeutic, Level IV. [Copyright &y& Elsevier]

• A 4-steps molecular simulation method is developed to generate Compact oil/water interface generation by a 4-steps molecular simulation method. • Analysis on dissolution and mass transfer for water/fluorobenzene interfaces. • Impacts on mass transfer caused by ion and alcohol additives in the aqueous phase. • Combination of microscopic simulation and macroscopic modelling for W/O interface. Understanding the dissolution and diffusion process of water molecules across the oil/water interface is helpful to fabricate polymer shells with high surface quality. In this work, microscopic fluorobenzene/water, fluorobenzene/NaCl(aq) and fluorobenzene/1,3-butanediol(aq) systems are constructed by molecular simulation. The solubility of water in fluorobenzene and interfacial diffusion resistances is calculated by fitting the simulated dissolving curves to a one-dimensional surface evaporation continuum model. The equilibrium solubility, interfacial diffusion resistances and component diffusivities are calculated for the oil/water systems. The simulated water solubility and diffusivity in fluorobenzene at 320 K are 305 ppm and (8.38 ± 0.29) × 10−9 m2/s, respectively. The density distribution near the oil/water interface is statistical averaged and the solution microstructures are analyzed. Both the ions and alcohol molecules added in the aqueous phase can slow down the water dissolving process, by reducing the equilibrium solubility and interfacial mass transfer rate of water in fluorobenzene. Applying the properties provided by microscopic simulations to the macroscopic mass transfer model, the characteristic time t ∞ (0.05–1.34 s) when the dissolved water mass reaches 95% of the equilibrium solubility is calculated for fluorobenzene membranes with a width range of 50–200 μm, which provides a time reference for double emulsions treatment process in polymer shell fabrication. [ABSTRACT FROM AUTHOR]

Supported ionic liquid membranes (SILMs) prepared with inorganic supports are more stable under high temperatures and differential pressures for gas separation than those based on organic membranes. In this study, a hot coating method was used to modify commercial α-Al 2 O 3 tubular substrates to prepare high-quality membrane supports. Following impregnation of an ionic liquid (IL; [BMIM][BF 4 ] or [BMIM][Ac]) into the supports over a short time, the as-prepared SILMs were used for separation of N 2 and CO 2 . The effects of preparation parameters, including impregnation time (0–1800 s) and impregnation temperature (18–59 °C) on SILM performance and IL loading were systematically investigated to gain a better understanding of the SILM preparation process. The optimum impregnation time was determined by considering both the permeance and the selectivity. Further, a high temperature was found to be beneficial for the preparation process because the viscosity of ILs is usually low at higher temperatures. However, when the viscosities of the two ILs ([BMIM][BF 4 ] and [BMIM][Ac]) were maintained at the same value by controlling the impregnation temperature, the qualities of the as-prepared SILMs were different, which may be due to the different surface tensions of these ILs. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Tuberculosis is uncommon in the nasopharynx. The purpose of this study was to investigate the CT and MRI features of 36 cases of tuberculosis in this area. Materials and methods: CT (n =15) and MRI (n =21) scans from 36 patients with histologically proved tuberculosis of the nasopharynx were reviewed by two experienced radiologists, paying particular attention to the lesions’ distribution, location, extent, size, internal architecture, pattern, and degree of enhancement, and cervical lymphadenopathy. Results: Twenty-nine patients exhibited a polypoid mass pattern and seven had diffuse mucosal thickening. The roof of the nasopharynx was involved in all cases. The mean size of the lesions was 11.4mm. Striped pattern was detected in 19 cases. Adjacent muscle invasion or bone destruction was not detected. Heterogeneous enhancement was detected in all patients, and necrosis in the nasopharyngeal lesions was detected in 16 cases. Poor, moderate, and marked enhancement was detected in one, 27, and eight cases, respectively. Thirty-four patients had involvement of the cervical lymph nodes. Twenty-two and 28 cases were associated with bilateral lymphadenopathy or necrosis, respectively. The retropharyngeal lymph node was the most commonly involved site (94.1%). Conclusion: The presence of necrosis and striped pattern in nasopharyngeal lesions, site predilection, no invasion of regional structures, and central necrosis with peripheral rim enhancement of cervical lymphadenopathy may suggest the diagnosis of nasopharyngeal tuberculosis. [Copyright &y& Elsevier]

Abstract: Purpose: To evaluate patterns of skull base invasion and its possible impact on tumor (T)-staging in nasopharyngeal carcinoma (NPC) using magnetic resonance imaging (MRI). Materials and methods: 838 consecutive newly diagnosed by biopsy proven and untreated patients with NPC underwent MRI. The skull-base invasion of NPC was classified according to their incidence from proximal sites to more distant sites surrounding the nasopharynx as: high (≥35%), medium (≥5–35%), and low (<5%) groups. A retrospective analysis of data consisting of a 5-year follow-up was carried out. The skull base invasion was related to their tumor (T) staging and prognosis at the 5-year follow-up after treatment with definitive radiation therapy. In addition, a survival health-related quality of life (QOL), overall survival (OS), local relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) were also assessed among the three groups. Results: The total incidence of skull-base invasion was 65.51% (549/838). The differences in T-stage distribution, and the total survival health-related QOL, among the three groups were statistically significant (χ 2 =160.45, p <0.005; χ 2 =38.43, p <0.005, respectively). The differences between any two of the three groups were also significant, except when the medium grade was compared to the low grade. Significant differences were observed with regard to 5-year OS (83.2%, 74.7%, 59.2%, p =0.000) and DMFS (95.0%, 88.0%, 88.0%, p =0.016); no significant difference was observed in LRFS (95.3%, 95.6%, 91.23%, p =0.450). Conclusions: The results indicate that medium and low group displayed similar findings of skull base invasion, and survival status. We, therefore, propose that patients in these two groups be grouped under T4 in the TNM classification that might have a bearing in implementing optimum treatment. [Copyright &y& Elsevier]

Objective Romidepsin (FK228), a Histone Deacetylase (HDAC) inhibitor, has been used for anti-cancer therapies. However, the anti-cancer effect of FK228 and its underlying mechanism in endometrial carcinoma (EC) have not been studied. The aime of this study was to investigate the anti-cancer effects of FK228 and the associated mechanism(s) in EC. Methods Ishikawa and HEC-1-A endometrial cancer cells were treated with 8 nM concentration of FK228 and cell growth was measured by XTT assay. The cell cycle distribution and cell death were measured by flow cytometry, immunofluorescence, respectively. The mNRA and protein expressions were analyzed by quantitative RT-PCR and western blot, respectively. Results Based on assays carried out in EC cell lines, it was observed that FK228 inhibited EC cell proliferation in a dose and time-dependent manner. Furthermore, following treatment with FK228 for 48 h, there were significant induction of apoptosis and cell cycle arrest at G 0 /G 1 phase in EC cells. Moreover, FK228 treatment significantly increased the mRNA and protein expressions of p53, p21, cleaved caspases such as 3, 7 and 8 and PARP. Further, FK228 treatment increased the levels of acetylated histone H3 and H4 that confirms the HDAC inhibition. Conclusion In conclusion, FK228 inhibits EC tumor cell proliferation and induces apoptosis by activation caspase/PARP via the induction of p53/p21 signaling cascades, suggesting that FK228 is a potential therapeutic agent for EC. [ABSTRACT FROM AUTHOR]

In this study, conventional thin-film microextraction (TFME) was endowed with magnetic by introducing superparamagnetic SiO 2 @Fe 3 O 4 nanoparticles in thin-films. Novel magnetic octadecylsilane (ODS)-polyacrylonitrile (PAN) thin-films were prepared by spraying, and used for the microextraction of quetiapine and clozapine in plasma and urine samples, followed by the detection of HPLC-UV. The influencing factors on the extraction efficiency of magnetic ODS-PAN TFME, including pH, extraction time, desorption solvent, desorption time, and ion strength were investigated systematically. Under the optimal conditions, both analytes showed good linearity over ranges of 0.070–9.000 μg mL −1 and 0.012–9.000 μg mL −1 in plasma and urine samples, respectively, with correlation coefficients ( R 2 ) above 0.9990. Limits of detection (LODs) for quetiapine in plasma and urine samples were 0.013 and 0.003 μg mL −1 , respectively. LODs for clozapine in plasma and urine samples were 0.015 and 0.003 μg mL −1 , respectively. The relative standard deviations (RSDs) for quetiapine and clozapine were less than 9.23%. After the validation, the protocol was successfully applied for the determination of quetiapine and clozapine in patients’ plasma and urine samples with satisfactory recoveries between 99–110%. The proposed magnetic ODS-PAN TFME was very simple, fast and easy to handle. It showed high potential as a powerful pretreatment technology for routine therapeutic drug monitoring (TDM) in plasma and urine samples. [ABSTRACT FROM AUTHOR]

Geopolymer concrete reinforced with Glass fiber-reinforced polymer (GFRP) bar presents a novel, durable, eco-friendly strengthening system with significant promise for practical engineering. To employ this strengthening system, a clear understanding of the bond performance between GFRP bars and geopolymer concrete under bending conditions is essential. Interface behaviors of GFRP bars-geopolymer concrete was investigated using hinged beam tests, considering the following parameters: concrete type(geopolymer and ordinary), concrete strength(C30, C50, C70), surface treatment of bars(shallow thread, spiral wrap ribs, and sandblasted), bar diameters(6 mm, 10 mm, and 16 mm), and bond lengths(2, 4, and 8 times the bar diameter). Results indicate a consistent bond mechanism between geopolymer and ordinary concrete. The bond strength increases with higher concrete strength, and the initial bond stiffness is improved by spiral wrap ribs. Moreover, the mBPE model was used to describe the local bond-slip relationship, and the effects of different parameters on interface shear stress distribution were discussed. The development length of GFRP bars in concrete was evaluated and compared with existing codes. These findings provide valuable references for the performance assessment and optimization of GFRP bar-reinforced geopolymer concrete structures in engineering applications. • GFRP bars-geopolymer concrete bond behavior was investigated using hinged beam tests. • Geopolymer concrete exhibits similar bonding mechanisms to ordinary concrete. • The mBPE model was used to describe the local bond-slip relationship. • Developed stress versus bonded length is compared with existing codes formula. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins. In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patients were randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell death protein 1 (PD-1) antibody sintilimab. As the primary endpoint, the total complete response (CR) rate is 26.9% (18/67, 95% confidence interval [CI] 16.0%–37.8%) and 44.8% (30/67, 95% CI 32.6%–57.0%) in the control and experimental arm, respectively, with significant difference (p = 0.031 for chi-squared test). Response ratio is 1.667 (95% CI 1.035–2.683). Immunohistochemistry shows PD-1 ligand 1 (PD-L1) combined positive score is associated with the synergistic effect. The safety profile is similar between the arms. Adding the PD-1 antibody sintilimab to NACRT significantly increases the CR rate in pMMR LARC, with a manageable safety profile. PD-L1 positivity may help identify patients who might benefit most from the combination therapy. [Display omitted] • Combination of sintilimab and NACRT increases CR rate for pMMR LARC patients • The combination therapy shows a manageable safety profile • CPS may serve as a biomarker for the synergistic effect In a phase 2 randomized clinical trial, Xiao et al. demonstrate the efficacy and safety of adding sintilimab to neoadjuvant chemoradiotherapy for patients with pMMR locally advanced rectal cancer. Compared with neoadjuvant chemoradiotherapy, combination of sintilimab and neoadjuvant chemoradiotherapy significantly increases complete response rate, with a manageable safety profile. [ABSTRACT FROM AUTHOR]