Macrophage AHR-TLR4 cross-talk drives p-STAT3 (Ser727)-mediated mitochondrial oxidative stress and upregulates IDO/ICAM-1 in the steatohepatitis induced by aflatoxin B1.

Aflatoxin B1 (AFB1) is a major mycotoxin contaminant showing in the environment and foods. In this study, the molecular initiating events (MIEs) of AFB1-induced steatohepatitis were explored in mice and human cell model. We observed dose-dependent steatohepatitis in the AFB1-treated mice, including triglyceride accumulation, fibrotic collagen secretion, enrichment of CD11b + and F4/80+ macrophages/Kupffer cells, cell death, lymphocytes clusters and remarkable atrophy areas. The gut barrier and gut-microbiota were also severely damaged after the AFB1 treatment and pre-conditioned colitis in the experimental mice aggravated the steatohepatitis phenotypes. We found that macrophages cells can be pro-inflammatorily activated to M1-like phenotype by AFB1 through an AHR/TLR4/p-STAT3 (Ser727)-mediated mitochondrial oxidative stress. The phenotypes can be rescued by AHR inhibitors in the mice model and human cell model. We further showed that this signaling axis is based on the cross-talk interaction between AHR and TLR4. Gene knock-up experiment found that the signaling is dependent on AFB1 ligand-binding with AHR, but not protein expressions of TLR4. The signaling elevated NLRP3 and two immune metabolic enzymes ICAM-1 and IDO that are associated with macrophage polarization. Results from intervention experiments with natural anti-oxidant and AHR inhibitor CH223191 suggest that the macrophage polarization may rely on AHR and ROS. Our study provides novel and critical references to the food safety and public health regulation of AFB1.

A Photoelectromagnetic 3D Metal-Organic Framework from Flexible Tetraarylethylene-Backboned Ligand and Dynamic Copper-Based Coordination Chemistry.

Porous frameworks that display dynamic responsiveness are of interest in the fields of smart materials, information technology, etc. In this work, a novel copper-based dynamic metal-organic framework [Cu3 TTBPE6 (H2 O)2 ] (H4 TTBPE = 1,1,2,2-tetrakis(4″-(1H-tetrazol-5-yl)-[1,1″-biphenyl]-4-yl)ethane), denoted as HNU-1, is reported which exhibits modulable photoelectromagnetic properties. Due to the synergetic effect of flexible tetraarylethylene-backboned ligands and diverse copper-tetrazole coordination chemistries, a complex 3D tunneling network is established in this MOF by the layer-by-layer staggered assembly of triplicate monolayers, showing a porosity of 59%. These features further make it possible to achieve dynamic transitions, in which the aggregate-state MOF can be transferred to different structural states by changing the chemical environment or upon heating while displaying sensitive responsiveness in terms of light absorption, photoluminescence, and magnetic properties.

Prediction of local tumor progression after microwave ablation for early-stage hepatocellular carcinoma with machine learning.

Objectives: Local tumor progression (LTP) is a major constraint for achieving technical success in microwave ablation (MWA) for the treatment of early-stage hepatocellular carcinoma (EHCC). This study aims to develop machine learning (ML)-based predictive models for LTP after initial MWA in EHCC. Materials and Methods: A total of 607 treatment-naïve EHCC patients (mean ± standard deviation [SD] age, 57.4 ± 10.8 years) with 934 tumors according to the Milan criteria who subsequently underwent MWA between August 2009 and January 2016 were enrolled. During the same period, 299 patients were assigned to the external validation datasets. To identify risk factors of LTP after MWA, clinicopathological data and ablation parameters were collected. Predictive models were developed according to 21 variables using four ML algorithms and evaluated based on the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals (CIs). Results: After a median follow-up time of 28.7 months (range, 7.6-110.5 months), 6.9% (42/607) of patients had confirmed LTP in the training dataset. The tumor size and number were significantly related to LTP. The AUCs of the four models ranged from 0.791 to 0.898. The best performance (AUC: 0.898, 95% CI: [0.842 0.954]; SD: 0.028) occurred when nine variables were introduced to the CatBoost algorithm. According to the feature selection algorithms, the top six predictors were tumor number, albumin and alpha-fetoprotein, tumor size, age, and international normalized ratio. Conclusions: Out of the four ML models, the CatBoost model performed best, and reasonable and precise ablation protocols will significantly reduce LTP.

α-Cyano Triaryl[3]radialene: Unsymmetrical Stereo-configuration, Clustering-enhanced Excimer Emission, and Radical-involved Multimodal Information Switching.

[3]Radialene has a peculiar topology and cross-conjugation system, representing a unique molecular scaffold in organic materials. Herein, we report a special class of stereoisomeric α-cyano triaryl[3]radialenes (CTRs) that show concentration-caused quenching in solution but emit red-shifted and enhanced luminescence in the crystalline state. Clustering of multiple cyano groups and their through-space interactions with the [3]radialene ring significantly extend π-electron communication meanwhile rigidifying the propeller conformation multivalently, thus playing a key role behind the state-dependent luminescence. These radialenes with a substantial electron affinity undergo a reversible electron transfer transition to anionic radicals with good stability, showing switching of photoabsorption, photoluminescence and electron spin resonance (ESR) signal. We also established proof-of-concept applications of CTRs for multimodal information encryption and chemical sensing.

Bioinspired humidity-responsive liquid crystalline materials: from adaptive soft actuators to visualized sensors and detectors.

Inspired by nature, humidity-responsive materials and devices have attracted significant interest from scientists in multiple disciplines, ranging from chemistry, physics and materials science to biomimetics. Owing to their superiorities, including harmless stimulus and untethered control, humidity-driven materials have been widely investigated for application in soft robots, smart sensors and detectors, biomimetic devices and anticounterfeiting labels. Especially, humidity-responsive liquid crystalline materials are particularly appealing due to the combination of programmable and adaptive liquid crystal matrix and humidity-controllability, enabling the fabrication of advanced self-adaptive robots and visualized sensors. In this review, we summarize the recent progress in humidity-driven liquid crystalline materials. First, a brief introduction of liquid crystal materials, including liquid crystalline polymers, cholesteric liquid crystals, blue-phase liquid crystals and cholesteric cellulose nanocrystals is provided. Subsequently, the mechanisms of humidity-responsiveness are presented, followed by the diverse strategies for the fabrication of humidity-responsive liquid crystalline materials. The applications of humidity-driven devices will be presented ranging from soft actuators to visualized sensors and detectors. Finally, we provide an outlook on the development of humidity-driven liquid crystalline materials.

Tributyltin perturbs femoral cortical architecture and polar moment of inertia in rat.

BACKGROUND: Tributyltin, a well-known endocrine disruptor, is widely used in agriculture and industry. Previous studies have shown that tributyltin could cause deleterious effects on bone health by impairing the adipo-osteogenic balance in bone marrow. METHODS: To investigate further the effects of tributyltin on bone, weaned male SD rats were treated with tributyltin (0.5, 5 or 50 µg·kg- 1) or corn oil by gavage once every 3 days for 60 days in this study. Then, we analyzed the effects of tributyltin on geometry, the polar moment of inertia, mineral content, relative abundances of mRNA from representative genes related to adipogenesis and osteogenesis, serum calcium ion and inorganic phosphate levels. RESULTS: Micro-computed tomography analysis revealed that treatment with 50 µg·kg- 1 tributyltin caused an obvious decrease in femoral cortical cross sectional area, marrow area, periosteal circumference and derived polar moment of inertia in rats. However, other test results showed that exposure to tributyltin resulted in no significant changes in the expression of genes detected, femoral cancellous architecture, ash content, as well as serum calcium ion and inorganic phosphate levels. CONCLUSIONS: Exposure to a low dose of tributyltin from the prepubertal to adult stage produced adverse effects on skeletal architecture and strength.

Multiple Anti-Counterfeiting Composite Film Based on Cholesteric Liquid Crystal and QD Materials.

A composite film with multiple anti-counterfeiting features was demonstrated by superposing quantum dots (QDs) polymer matrix (film A) and cholesteric liquid crystal film (film B) together. The first-line and second-line anti-counterfeiting characteristics were successfully implemented by employing thermochromic, angular photochromic, and circularly polarized discoloration of film B, respectively. By initiatively utilizing the different relative positions between the fluorescence emission peak (λem) of film A and the central selective reflection wavelength (λm) of film B at different temperatures, which resulted in changes in the fluorescence spectra or the different presence of latent patterns, the most important third-line anti-counterfeiting feature was successfully achieved.

[Effects of 2, 5-hexanedione on S100ß of Schwann cells in rat sciatic nerves].

OBJECTIVE: To investigate the expression of S100ß protein and mRNA of Schwann cells(SC) in sciatic nerves of 2, 5-hexanedione(HD) intoxicated rats. METHODS: Nine-week old SPF male Wistar rats were administered at daily dosing of 100 and 300 mg/kg by intraperitoneal injection for continuous 8 weeks(five times every week). Age-matched control rats received an equivalent volume of normal saline. Ten rats in each group were sacrificed and sciatic nerves were excised for S100ß determination, with excised sciatic nerves from another three rats for morphological observation through electron microscope. At the end of the exposure, the other 8-week treated animals were allowed to naturally recover for 8 weeks and sciatic nerves were excised at the end of the test. S100ß protein contents were determined by immunohistochemistry method, and mRNA expression was observed by real-time quantitative polymerase chain reaction(PCR). RESULTS: HD intoxication with 300 mg/kg was associated with severe neurological deficits of paralysis in hindlimbs, accompanied with evident movement gait abnormalities for 100 mg/kg dosage. The morphological abnormalities in myelin sheath of sciatic nerves were observed through electron microscope after HD-exposure. The S100ß contents in 100 mg/kg and 300 mg/kg groups remained relatively unaffected with 92% and 79% of the control respectively after HD-intoxication, and a increase to 149%(P<0. 05) and 119% after a recovery of 8 weeks was accompanied with. As to S100ß mRNA, HD-intoxication was associated with decreased expression to 0. 65(P<0. 05) and 0. 56 times(P<0. 05) of the control, and 1. 46 and 0. 87 times for 8-week recovery individually. CONCLUSION: The S100ß protein and mRNA levels were influenced by HD exposure, and the result suggested that S100ß might be involved in HD-induced peripheral axonopathy.

Tributyltin reduces bone mineral density by reprograming bone marrow mesenchymal stem cells in rat.

Tributyltin (TBT), a proven endocrine disrupter, was widely used in industry and agriculture. Previous research showed that TBT could alter the balance between osteogenesis and adipogenesis, which may have significant consequences for bone health. Herein, we exposed male rats to TBT chloride (TBTCl) to evaluate the deleterious effects of TBT on bone. Exposure to 50 µg kg-1 TBT resulted in a significant decrease in bone mineral density (BMD) at the femur diaphysis region in the rat. A dose-dependent increase in lipid accumulation and adipocyte number was observed in the bone marrow (BM) of the femur. Meanwhile, TBTCl treatment significantly enhanced the expression of PPARγ and attenuated the expression of Runx2 and ß-catenin in BM. In addition, serum ALP activity of TBT-exposed rats also showed a dose-dependent decrease. These results suggest that TBT could reduce BMD via inhibition of the Wnt/ß-catenin pathway and skew the adipo-osteogenic balance in the BM of rats.

One immunoassay probe makes SERS and fluorescence two readout signals: Rapid imaging and determination of intracellular glutathione levels.

In this paper, one probe (TPPA-VCh) with fluorescence and Surface-enhanced Raman Scattering (SERS) two readout signals, which has high sensitivity and specificity to glutathione in both vitro and cell image applications, is designed and synthesized. Furthermore, the quenched emissions and intensified SERS signals is obtained by loading TPPA-VCh on the surfaces of gold nanoparticles.

T-box Transcription Factor Tbx3 Contributes to Human Hepatocellular Carcinoma Cell Migration and Invasion by Repressing E-Cadherin Expression.

Tbx3, a member of the T-box family of transcription factors, contributes directly to tumor formation, migration, and invasion. However, the role of Tbx3 in the metastasis of HCC remains unclear. In the present study, Tbx3 expression was detected in HCC tissues and cells by Western blot, and Tbx3 expression was regulated by use of siRNAs or lentivirus-mediated vectors. Here we found that Tbx3 protein expression increased in HCC tissues and cell lines. Tbx3 expression was positively associated with multiple tumor nodes, venous infiltration, and advanced TNM tumor stage. Survival analysis demonstrated that Tbx3 expression was an independent prognostic factor for HCC patients. In vitro assays further validated that Tbx3 indeed prompted HCC cell migration and invasion. In addition, Tbx3 expression was negatively related with E-cadherin expression in HCC tissues. Mechanically, Tbx3 inhibited the expression of E-cadherin, and then facilitated epithelial-mesenchymal transition (EMT) of HCC cells. Furthermore, the effect of Tbx3 knockdown on HCC cells was attenuated by E-cadherin knockdown. In conclusion, Tbx3 may be a novel prognostic factor, and it contributes to HCC cell migration, invasion, and EMT by repressing E-cadherin expression. Thus, Tbx3 may be recommended as a therapeutic target for HCC patients.

Angular Photochromic LC Composite Film for an Anti-Counterfeiting Label.

In the harsh application environment, improving the mechanical properties of liquid crystal materials is a fundamental and important problem in the design of anti-counterfeit materials. In this paper, by a stepwise polymerization of first, photo-polymerization and subsequently thermal-polymerization, a coexistent polymer dispersed network was first constructed in cholesteric liquid crystal materials containing a photo-polymerizable system of urethane acrylate and a thermo-polymerizable system of isocyanate. Results revealed that the coexistent polymer dispersed network exhibited largely enhanced mechanical performance, and the networks obtained by different methods had different contributions to the enhancement of the peel strength and toughness of the composite films. Then an angular photochromic anti-fake label based on a coexistent polymer dispersed network with enhanced mechanical and apparent angular discoloration characteristics, suitable for practical applications, was successfully achieved.

Polysiloxane-Based Side Chain Liquid Crystal Polymers: From Synthesis to Structure⁻Phase Transition Behavior Relationships.

Organosilicon polymer materials play an important role in certain applications due to characteristics of much lower glass transition temperatures (Tg), viscosities, surface energy, as well as good mechanical, thermal stabilities, and insulation performance stemming from the higher bond energy and the larger bond angles of the adjacent silicon-oxygen bond. This critical review highlights developments in the synthesis, structure, and phase transition behaviors of polysiloxane-based side chain liquid crystal polymers (PSCLCPs) of linear and cyclic polysiloxanes containing homopolymers and copolymers. Detailed synthetic strategies are elaborated, and the relationship between molecular structures and liquid crystalline phase transition behaviors is systematically discussed, providing theoretical guidance on the molecular design of the materials.

Safety assessment of the fermented Phylloporia ribis (Lonicera japonica Thunb.) mycelia by oral acute toxicity study in mice and 90-day feeding study in rats.

Phylloporia ribis is an edible fungus in China. Its fermented mycelia have been approved by the National Health and Family Planning Commission (NHFPC) of PR China for use as a novel food material, but little information on its safety is available. The present research was the first to evaluate acute and subchronic toxicity in experimental animals of fermented Phylloporia ribis mycelia (FPM) following standard procedures. In acute toxicity study, FPM was orally administered to male and female mice twice a day at single dose of 10 g/kg bw. The Maximum Tolerated Dose (MTD) of FPM for mice of both sexes was over 10 g/kg bw. No death and abnormal behaviors occurred during 14 days study except for an increased locomotor activity in three animals. In 90-day feeding study, male and female Sprague-Dawley rats were fed diets containing 10.0%, 5.0%, 2.5%, 1.25% and 0% (control) FPM for 90 days. The treatment caused no effects on mortality, gross pathology, histology, hematology, and blood chemistry, no dose-dependent changes in food consumption, but caused effect on body weight gain compared with control group. The No Observed Adverse-Effect Level (NOAEL) of FPM was greater than 8.7 g/kg bw/day in both sexes of rats.

[Antitumor effect of DHA compound in vitro and in vivo and its mechanism].

OBJECTIVE: To study the anticancer effect in vitro and in vivo and mechanism of DHA compound. METHODS: Cervical cancer cell line HeLa cells, glioma cell line U251 cells and mouse hepatoma H(22) tumor were used in this study. Transmission electron microscopy and fluorescence microscopy were used to observe the morphological changes of cell apoptosis. Western blot was used to detect the expression of caspase-3. RT-PCR was used to determine the effect on Bcl-2 and Bax mRNA transcription in U251. RESULTS: Antitumor effect was observed in vivo and in vitro. Typical morphological changes were seen in cancer cells. The level of caspase-3 was significantly increased and the content of Bcl-2 mRNA was decreased significantly, while the content of Bax mRNA was significantly increased in the U251 cells after treatment with DHA compound. CONCLUSION: DHA compound can inhibit the growth of some types of tumors and the increase of caspase-3 and Bax mRNA and decrease of Bcl-2 mRNA may be involved in its mechanism of action.