Construction of Thiadiazole-Bridged sp2-Carbon-Conjugated Covalent Organic Frameworks with Diminished Excitation Binding Energy Toward Superior Photocatalysis.

Sp2-carbon-conjugated covalent organic frameworks (sp2c-COFs) have emerged as promising platforms for phototo-chemical energy conversion due to their tailorable optoelectronic properties, in-plane π-conjugations, and robust structures. However, the development of sp2c-COFs in photocatalysis is still highly hindered by their limited linkage chemistry. Herein, we report a novel thiadiazole-bridged sp2c-COF (sp2c-COF-ST) synthesized by thiadiazole-mediated aldol-type polycondensation. The resultant sp2c-COF-ST demonstrates high chemical stability under strong acids and bases (12 M HCl or 12 M NaOH). The electro-deficient thiadiazole together with fully conjugated and planar skeleton endows sp2c-COF-ST with superior photoelectrochemical performance and charge-carrier separation and migration ability. As a result, when employed as a photocathode, sp2c-COF-ST exhibits a significant photocurrent up to ∼14.5 µA cm-2 at 0.3 V vs reversible hydrogen electrode (RHE) under visible-light irradiation (>420 nm), which is much higher than those analogous COFs with partial imine linkages (mix-COF-SNT ∼ 9.5 µA cm-2) and full imine linkages (imi-COF-SNNT ∼ 4.9 µA cm-2), emphasizing the importance of the structure-property relationships. Further temperature-dependent photoluminescence spectra and density functional theory calculations demonstrate that the sp2c-COF-ST has smaller exciton binding energy as well as effective mass in comparison to mix-COF-SNT and imi-COF-SNNT, which suggests that the sp2c-conjugated skeleton enhances the exciton dissociation and carrier migration under light irradiation. This work highlights the design and preparation of thiadiazole-bridged sp2c-COFs with promising photocatalytic performance.

Short-chain fatty acids mitigate Methamphetamine-induced hepatic injuries in a Sigma-1 receptor-dependent manner.

Methamphetamine (Meth) is a potent psychostimulant with well-established hepatotoxicity. Gut microbiota-derived short-chain fatty acids (SCFAs) have been reported to yield beneficial effects on the liver. In this study, we aim to further reveal the mechanisms of Meth-induced hepatic injuries and investigate the potential protective effects of SCFAs. Herein, mice were intraperitoneally injected with 15 mg/kg Meth to induce hepatic injuries. The composition of fecal microbiota and SCFAs was profiled using 16 S rRNA sequencing and Gas Chromatography/Mass Spectrometry (GC/MS) analysis, respectively. Subsequently, SCFAs supplementation was performed to evaluate the protective effects against hepatic injuries. Additionally, Sigma-1 receptor knockout (S1R-/-) mice and fluvoxamine (Flu), an agonist of S1R, were introduced to investigate the mechanisms underlying the protective effects of SCFAs. Our results showed that Meth activated S1R and induced hepatic autophagy, inflammation, and oxidative stress by stimulating the MAPK/ERK pathway. Meanwhile, Meth disrupted SCFAs product-related microbiota, leading to a reduction in fecal SCFAs (especially Acetic acid and Propanoic acid). Accompanied by the optimization of gut microbiota, SCFAs supplementation normalized S1R expression and ameliorated Meth-induced hepatic injuries by repressing the MAPK/ERK pathway. Effectively, S1R knockout repressed Meth-induced activation of the MAPK/ERK pathway and further ameliorated hepatic injuries. Finally, the overexpression of S1R stimulated the MAPK/ERK pathway and yielded comparable adverse phenotypes to Meth administration. These findings suggest that Meth-induced hepatic injuries relied on the activation of S1R, which could be alleviated by SCFAs supplementation. Our study confirms the crucial role of S1R in Meth-induced hepatic injuries for the first time and provides a potential preemptive therapy.

Structure-Property Relationship of Cyano-Functionalized Conjugated Polymers for Photocatalytic Hydrogen Production.

Conjugated polymers (CPs) have garnered increasing attention in the field of photocatalysis due to their stability and molecular tunability. Understanding the structure-property relationship in CPs and addressing appropriate molecular design strategies are pivotal to improving the photocatalytic performance of CPs. Herein, a new efficient cyano (CN) engineering approach was proposed to promote the photocatalytic performance of CPs, and three representative CP-based photocatalysts with different CN contents were tailor-made to investigate the relationship between CN functionalization and photocatalytic activity. A series of systematically experimental and theoretical studies reveal that CN functionalization contributes to strengthening the donor-acceptor (D-A) interaction, enhancing the light absorption ability, charge separation/transfer efficiency, and hydrophilicity of CPs, and also facilitating the output of separated photoinduced electrons from CPs to Pt cocatalyst. Thus, the dicyano-functionalized polymer (P-2CN) manifests an attractive photocatalytic performance in hydrogen production. This study provides a facile strategy to develop excellent CP-based photocatalysts for solar fuel production.

Design and synthesis of photoaffinity-based probes for labeling ß-glucuronidase.

ß-Glucuronidase (GUSB) plays an important role in human physiological and pathological activities. The activity level of GUSB is closely related to human health and diseases. It is imperative to detect the activity of GUSB for related disease diagnosis and treatment. However, exactly evaluating the activity of GUSB in complicated biological system remains a challenge. In this study, we developed photoaffinity-based probes (AfBPs) equipped with photosensitive benzophenone group for labeling active GUSB. Through molecule docking, we predicted the binding model of the AfBPs and GUSB, and the obtained results suggested thermodynamically favorable binding. The AfBPs indicated high efficiency and showed dose-/time-dependent labeling of Escherichia coli (E. coli) GUSB. The application of AfBPs toward GUSB provides a powerful tool to study the activity of target enzymes and contributes to huge potential of enzyme inhibitor discovery and biomedical diagnostics.

An Autophagy-Associated Prognostic Gene Signature for Breast Cancer.

Autophagy is closely related to breast cancer and has the dual role of promoting and inhibiting the progression of breast cancer. In this study, we aimed to establish an autophagy-related gene signature for the prognosis of breast cancer. A gene signature composed of the eight most survival-relevant autophagy-associated genes was identified by least absolute shrinkage and selection operator (LASSO) regression analysis. A risk score was calculated based on the gene signature, which divided breast cancer patients into low- or high-risk groups and showed good and poor prognosis, respectively. The risk score displayed good prognostic performance in both the training cohort (TCGA, 1-10-year AUC > 0.63) and the validation cohort (GEO, 1-10-year AUC > 0.66). The multivariate Cox regression and stratified analysis revealed that the risk score was an independent prognostic factor for breast cancer patients. Moreover, the high-risk score was associated with higher infiltration of neutrophils and M2-polarized macrophages, and lower infiltration of resting memory CD4+ T cells, CD8+ T cells, and NK cells. Finally, the high-risk score was associated with myc target, glycolysis, and mTORC1 signaling. The risk score developed based on the autophagy-associated gene signature was an independent prognostic biomarker for breast cancer.

Electronic Transmission Channels Promoting Charge Separation of Conjugated Polymers for Photocatalytic CO2 Reduction with Controllable Selectivity.

Conjugated polymers (CPs) represent a promising platform for photocatalytic CO2 fixation owing to their suitable band structures that meet the requirements of the reduction potential of CO2 to value-added fuels. However, the photocatalytic performance of CPs is rather restrained by the low charge transfer efficiency. Herein, we rationally designed three CPs with a more delocalized electronic transmission channel and planar molecular structure, which are regarded to evidently reduce the exciton binding energy (Eb ) and accelerate the internal charge transfer process. Besides, the assembly of suitable electron-output "tentacles" and cocatalysts on the surface of CPs could effectively facilitate interfacial electron delivery. Accordingly, the optimal P-2CN exhibits an apparent quantum yield of 4.6 % at 420 nm for photocatalytic CO2 to CO. Further adjusting the amounts of cyano groups and cocatalysts, the CO selectivity could be obtained in the range of 0-80.5 %.

Molecular Design of Covalent Triazine Frameworks with Anisotropic Charge Migration for Photocatalytic Hydrogen Production.

Covalent triazine frameworks (CTFs) represent promising polymeric photocatalysts for photocatalytic hydrogen production with visible light. However, the separation and transfer of charges in CTFs are isotropic because of the uniform distribution of donor-acceptor motifs in the skeleton. Herein, to achieve the anisotropic charge carrier separation and migration, thiophene (Th) or benzothiadiazole (BT) unit is selected as the dopant to modify the molecular structure of CTF-based photocatalysts. Both theoretical and experimental studies reveal that the incorporation of Th or BT units induces the anisotropic charge carrier separation and migration at the interface of CTFs. The optimized polymer manifests a much enhanced photocatalytic activity for photocatalytic hydrogen production with visible light, and thus this study provides a useful tool to design conjugated polymer photocatalysts at the molecular level for solar energy conversion.

Ionothermal Synthesis of Covalent Triazine Frameworks in a NaCl-KCl-ZnCl2 Eutectic Salt for the Hydrogen Evolution Reaction.

Covalent triazine-based frameworks (CTFs) are typically produced by the salt-melt polycondensation of aromatic nitriles in the presence of ZnCl2 . In this reaction, molten ZnCl2 salt acts as both a solvent and Lewis acid catalyst. However, when cyclotrimerization takes place at temperatures above 300 °C, undesired carbonization occurs. In this study, an ionothermal synthesis method for CTF-based photocatalysts was developed using a ternary NaCl-KCl-ZnCl2 eutectic salt (ES) mixture with a melting point of approximately 200 °C. This temperature is lower than the melting point of pure ZnCl2 (318 °C), thus providing milder salt-melt conditions. These conditions facilitated the polycondensation process, while avoiding carbonization of the polymeric backbone. The resulting CTF-ES200 exhibited enhanced optical and electronic properties, and displayed remarkable photocatalytic performance in the hydrogen evolution reaction.

Genetic diversity and evolutionary dynamics of Ebola virus in Sierra Leone.

A novel Ebola virus (EBOV) first identified in March 2014 has infected more than 25,000 people in West Africa, resulting in more than 10,000 deaths. Preliminary analyses of genome sequences of 81 EBOV collected from March to June 2014 from Guinea and Sierra Leone suggest that the 2014 EBOV originated from an independent transmission event from its natural reservoir followed by sustained human-to-human infections. It has been reported that the EBOV genome variation might have an effect on the efficacy of sequence-based virus detection and candidate therapeutics. However, only limited viral information has been available since July 2014, when the outbreak entered a rapid growth phase. Here we describe 175 full-length EBOV genome sequences from five severely stricken districts in Sierra Leone from 28 September to 11 November 2014. We found that the 2014 EBOV has become more phylogenetically and genetically diverse from July to November 2014, characterized by the emergence of multiple novel lineages. The substitution rate for the 2014 EBOV was estimated to be 1.23 × 10(-3) substitutions per site per year (95% highest posterior density interval, 1.04 × 10(-3) to 1.41 × 10(-3) substitutions per site per year), approximating to that observed between previous EBOV outbreaks. The sharp increase in genetic diversity of the 2014 EBOV warrants extensive EBOV surveillance in Sierra Leone, Guinea and Liberia to better understand the viral evolution and transmission dynamics of the ongoing outbreak. These data will facilitate the international efforts to develop vaccines and therapeutics.

A Fully Coplanar Donor-Acceptor Polymeric Semiconductor with Promoted Charge Separation Kinetics for Photochemistry.

Charge generation and separation are regarded as the major constraints limiting the photocatalytic activity of polymeric photocatalysts. Herein, two new linear polyarylether-based polymers (PAE-CPs) with distinct linking patterns between their donor and acceptor motifs were tailor-made to investigate the influence of different linking patterns on the charge generation and separation process. Theoretical and experimental results revealed that compared to the traditional single-stranded linker, the double-stranded linking pattern strengthens donor-acceptor interactions in PAE-CPs and generates a coplanar structure, facilitating charge generation and separation, and enabling red-shifted light absorption. With these prominent advantages, the PAE-CP interlinked with a double-stranded linker exhibits markedly enhanced photocatalytic activity compared to that of its single-strand-linked analogue. Such findings can facilitate the rational design and modification of organic semiconductors for charge-induced reactions.

Identification and functional analysis of transforming growth factor-ß type III receptor (TßR3) from Scylla paramamosain: The first evidence of TßR3 involved in development and innate immunity in invertebrates.

Transforming growth factor-ß type III receptor (TßR3), as a co-receptor of TGF-ß superfamily, plays critical roles in development and growth as well as some disease pathogeneses by presenting ligands to other receptors in vertebrates. However, the identification and functional characterization of TßR3 had not been reported yet in invertebrates. In the present study, TßR3 was first identified and characterized in mud crab Scylla paramamosain. The obtained cDNA length of SpTßR3 was 2, 424 bp with a 1, 854 bp open reading frame, which encoded a putative peptide of 617 amino acids containing a typical transmembrane region and a Zona pellucida (ZP) domain. Real-time PCR results showed that SpTßR3 was predominantly expressed at early embryonic development stage and early postmolt stage, suggesting its participation in development and growth. We report, for the first time in invertebrates, the challenge of both Vibro alginolyticus and Poly (I:C) could alter the expression patterns of SpTßR3. Notably, the expression levels of SpIKK, two NF-κB members (SpRelish and SpDorsal), and five antimicrobial peptide genes (SpCrustin and SpALF1-4) were significantly suppressed when SpTßR3 was interfered in vivo. Secondly, the overexpression of SpTßR3 in vitro could activate NF-κB signaling through the dual-luciferase reporter assays. Furthermore, the bacterial clearance assay after SpTßR3 was silenced in vivo highlighted the potential of SpTßR3 in activating the innate immune responses. These results implied the involvement of SpTßR3 in the innate immune responses by regulating the NF-κB pathway. This study first indicated that TßR3 was present in invertebrate, and it participated in not only the development and growth but also the innate immunity of S. paramamosain. It also provided new insights into the origin or evolution of TGF-ß receptors in crustacean species and even in invertebrates.

Transforming growth factor-ß-activating kinase 1 and its binding protein 1 participate in the innate immune responses via modulating the IMDNFκB signaling in mud crab (Scylla paramamosain).

Transforming growth factor-ß-activating kinase 1 (TAK1) is essential for diverse important biological functions, such as innate immunity, development and cell survival. In the present study, the homologs of TAK1 and TAK1-binding protein 1 (TAB1) were identified and characterized from mud crab Scylla paramamosain for the first time. The full-length cDNAs of SpTAK1 and SpTAB1 were 2, 226 bp and 2, 433 bp with 1, 782 bp and 1, 533 bp open reading frame (ORF), respectively. The deduced SpTAK1 protein contained a conserved S_TKc (Serine/threonine protein kinases, catalytic) domain, and the putative SpTAB1 protein possessed a typical PP2Cc (Serine/threonine phosphatases, family 2C, catalytic) domain and a potential TAK1 docking motif. Real-time PCR analysis showed that SpTAK1 and SpTAB1 were highly expressed at early development stages, suggesting their participation in crab's development process. Moreover, the expression levels of SpTAK1 and SpTAB1 in hepatopancreas were positively stimulated after challenge with Vibro alginolyticus and Poly (I:C), implying the involvement of SpTAK1 and SpTAB1 in innate immune responses against both bacterial and viral infections. When SpTAK1 or SpTAB1 were silenced in vivo, the expression levels of two IMDNFκB signaling components (SpIKKß and SpRelish) and six antimicrobial peptide (AMP) genes (SpALF1-5 and SpCrustin) were significantly reduced, and the bacteria clearance capacity of crabs was also markedly impaired in SpTAK1 or SpTAB1 silenced crabs. Additionally, overexpression of SpTAK1 and SpTAB1 in HEK293T cells could markedly activate the mammalian NF-κB signaling. Collectively, our results suggested that TAK1 and TAB1 regulated crab's innate immunity via modulating the IMDNFκB signaling. These findings may provide new insights into the TAK1/TAB1-mediated signaling cascades in crustaceans and pave the way for a better understanding of crustacean innate immune system.

A catalyst-free four-component domino reaction for the synthesis of functionalized 3-acyl-1,5-benzodiazepines.

Various functional 3-acyl-1,5-benzodiazepines containing carboxyl, ester and acyl groups at the 2-position were synthesized via an efficient, sustainable and catalyst-free domino reaction. During the synthesis process, one new cycle and four new bonds (one C-C, two C-N and one C[double bond, length as m-dash]C) were constructed by the nucleophilic substitution, nucleophilic addition, dehydration and cyclization reaction by the H+ shift. Furthermore, a total of 26 examples were examined by reacting inexpensive starting materials of N,N-dimethylformamide dimethyl acetal, aromatic ketones, 1,2-phenylenediamine compounds and aldehyde derivatives. Therefore, it displayed a broad substrate scope, good functional group tolerance, high yields (77-97%) and the ease of obtaining target compounds without the involvement of toxic solvents and column chromatography, which provided a novel method for the synthesis of a wide variety of biologically relevant 1,5-benzodiazepines.

Reducing the Exciton Binding Energy of Donor-Acceptor-Based Conjugated Polymers to Promote Charge-Induced Reactions.

Exciton binding energy has been regarded as a crucial parameter for mediating charge separation in polymeric photocatalysts. Minimizing the exciton binding energy of the polymers can increase the yield of charge-carrier generation and thus improve the photocatalytic activities, but the realization of this approach remains a great challenge. Herein, a series of linear donor-acceptor conjugated polymers has been developed to minimize the exciton binding energy by modulating the charge-transfer pathway. The results reveal that the reduced energy loss of the charge-transfer state can facilitate the electron transfer from donor to acceptor, and thus, more electrons are ready for subsequent reduction reactions. The optimized polymer, FSO-FS, exhibits a remarkable photochemical performance under visible light irradiation.

Effects of both cold and heat stress on the liver of the giant spiny frog (Quasipaa spinosa): stress response and histological changes.

Ambient temperature-associated stress can affect normal physiological functions in ectotherms. To assess the effects of cold or heat stress on amphibians, giant spiny frogs (Quasipaa spinosa) were acclimated at 22°C followed by exposure to 5°C or 30°C for 0, 3, 6, 12, 24 and 48 h, respectively. Histological alterations, apoptotic index, generation of mitochondrial reactive oxygen species (ROS), antioxidant activity indices and stress-response gene expression in frog livers were subsequently determined. Results showed that many fat droplets appeared after 12 h of heat stress and the percentage of melanomacrophage centres significantly changed after 48 h at both stress conditions. Furthermore, the mitochondrial ROS levels were elevated in a time-dependent manner up to 6 h and 12 h in the cold and heat stress groups, respectively. The activities of superoxide dismutase, glutathione peroxidase and catalase were successively increased with increasing periods of cold or heat exposure, and their gene expression levels showed similar changes in both stress conditions. Most tested heat shock protein (HSP) genes were sensitive to temperature exposure, and the expression profiles of most apoptosis-related genes was significantly upregulated at 3 and 48 h under cold and heat stress, respectively. Apoptotic index at 48 h under cold stress was significantly higher than that under heat stress. Notably, lipid droplets, HSP30, HSP70 and HSP110 might be suitable bioindicators of heat stress. The results of these alterations at physiological, biochemical and molecular levels might contribute to a better understanding of the stress response of Q. spinosa, and perhaps amphibians more generally, under thermal stress.

Identification and functional analysis of immune deficiency (IMD) from Scylla paramamosain: The first evidence of IMD signaling pathway involved in immune defense against bacterial infection in crab species.

Immune deficiency (IMD) pathway, one of the most essential pattern recognition receptor signaling pathways, plays vital roles in innate immune responses to eliminate pathogen infection in invertebrates. In the present study, an immune deficiency (IMD) gene and two NF-κB family members, Relish and Dorsal, were identified and characterized in mud crab Scylla paramamosain for the first time. The deduced SpIMD, SpRelish and SpDorsal protein contained conserved death domain and classical NF-κB domains, respectively. Phylogenetic analysis suggested that SpIMD was classified into the invertebrate IMD branch, and SpRelish could be classified into the type I NF-κB class while SpDorsal could be grouped into the type II NF-κB class. Tissue distribution results showed these three genes were ubiquitously expressed in all tested tissues. The expression patterns of IMD signaling pathway and NF-κB genes, including SpIMD, SpIKKß, SpIKKε, SpRelish and SpDorsal, were distinct when crabs were stimulated with Vibro alginolyticus, indicating that they might be involved in responding to bacterial infection. When SpIMD was silenced by in vivo RNA interference assay, the expression levels of IMD pathway and antimicrobial peptides (AMPs) genes, including SpIKKß, SpRelish, SpALF1-6 and SpCrustin, were significantly down-regulated (p < 0.05). Correspondingly, the bacteria clearance ability of hemolymph was extremely impaired in IMD silenced crabs. Overall, the IMD played vital roles in innate immune response by regulating the expressions of its down-stream signaling genes and AMPs in S. paramamosain. These findings might pave the way for a better understanding of innate immune system and establish a fundamental network for the IMD signaling pathway in crustaceans.

Effects of heat stress on the liver of the Chinese giant salamander Andrias davidianus: Histopathological changes and expression characterization of Nrf2-mediated antioxidant pathway genes.

Nuclear factor E2-related factor 2 (Nrf2) is a crucial transcription factor that regulates the basal and inducible expression of many antioxidant-relevant genes, and the Nrf2-mediated antioxidant pathway has been regarded as a critical switch in the initiation of cellular defence systems against oxidative damages. In this study, Nrf2 was first identified and characterized in the Chinese giant salamander (Andrias davidianus). A. davidianus was exposed to a high ambient temperature of 30 °C for various periods of time (0, 3, 6, 12, 24, 48 and 72 h). We investigated the effects of heat stress on alterations of the hepatic malondialdehyde (MDA) concentration, the activities of lactic acid dehydrogenase (LDH), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), the histology of the liver, and the mRNA expression patterns of 11 genes involved in the Nrf2-mediated antioxidant pathway in A. davidianus. The results showed that both the hepatic LDH activity and MDA content significantly increased after heat exposure, indicating that heat stress could induce cell injury and oxidative damage. Histological analysis of the liver showed that heat stress caused hepatocyte abnormalities, fat accumulation and ultrastructural alterations of the hepatocytes, endoplasmic reticulum and nuclei. The expression patterns of genes involved in the Nrf2-mediated antioxidant pathway in the liver were distinct when A. davidianus was exposed to heat stress. To the best of our knowledge, this study is the first on the characterization of Nrf2 in A. davidianus and even in amphibians. The results indicated that heat stress could induce oxidative damage, and the Nrf2 antioxidant pathway might play a critical role in the resistance against heat stress in A. davidianus. These findings will deepen and enrich the current knowledge on the evolutionary conserved antioxidant roles and mechanisms of Nrf2 in A. davidianus, or even in amphibians, in the antioxidant defence against heat stress.

Microhemorrhage identified on 3.0 T MR susceptibility-weighted imaging for prognosis of viral encephalitis.

OBJECTIVE: To evaluate the relationship of microhemorrhage on susceptibility-weighted imaging (SWI) with the severity of clinical symptoms and the prognosis of viral encephalitis. MATERIALS AND METHODS: Thirty patients with clinically diagnosed viral encephalitis were divided into three groups according to the Glasgow Coma Scale (GCS) and the condition of recovery namely, Group I (n = 12): Glasgow Coma Scale (GCS)≥13 and recovered with no sequelae; Group II (n = 11): GCS 9-12 and recovered with some sequelae; Group III (n = 7): GCS 3-8 and recovered with more severe sequelae. The microhemorrhage detectability on SWI and conventional MR imaging in these three groups was compared and their correlations with different seriousness of clinical symptoms and prognosis were analyzed. RESULTS: There was a significant difference in microhemorrhage volume among different MR sequences (p < 0.05). SWI was more sensitive to detect microhemorrhage than conventional MR imaging techniques. Microhemorrhages on SWI were significantly different among the three groups (p < 0.01). The volume of microhemorrhage on SWI was well correlated with the degree of clinical symptoms and the prognosis of viral encephalitis. CONCLUSION: SWI can be used to detect microhemorrhage in patients with viral encephalitis. Assessment of microhemorrhage with SWI can provide useful information for the prognosis evaluation of viral encephalitis.

Photocatalytic Oxygen Evolution from Functional Triazine-Based Polymers with Tunable Band Structures.

Conjugated polymers (CPs) are emerging and appealing light harvesters for photocatalytic water splitting owing to their adjustable band gap and facile processing. Herein, we report an advanced mild synthesis of three conjugated triazine-based polymers (CTPs) with different chain lengths by increasing the quantity of electron-donating benzyl units in the backbone. Varying the chain length of the CTPs modulates their electronic, optical, and redox properties, resulting in an enhanced performance for photocatalytic oxygen evolution, which is the more challenging half-reaction of water splitting owing to the sluggish reaction kinetics. Our results could stimulate interest in these functional polymers where a molecular engineering strategy enables the production of suitable semiconductor redox energetics for oxygenic photosynthesis.

Cis-stilbene glucoside in Polygonum multiflorum induces immunological idiosyncratic hepatotoxicity in LPS-treated rats by suppressing PPAR-γ.

The root of Polygonum multiflorum Thunb (PM) has been used in China to treat a variety of diseases, such as constipation, early graying of the hair and hyperlipemia. Recent evidence shows that PM causes idiosyncratic drug-induced liver injury (IDILI) in humans. In this study, we investigated the molecular basis of PM-induced liver injury in a rat model of IDILI based on a non-hepatotoxic dose of LPS. SD rats were orally administered 3 potentially hepatotoxic compounds of PM: cis-stilbene glucoside (cis-SG, 50 mg/kg), trans-SG (50 mg/kg) or emodin (5 mg/kg), followed by injection of LPS (2.8 mg/kg, iv). Serum and liver histology were evaluated 7 h after LPS injection. Among the 3 compounds tested, cis-SG, but not emodin or trans-SG, induced severe liver injury in rats when combined with LPS. The levels of AST and ALT in plasma and inflammatory cytokines in both plasma and liver tissues were markedly elevated. The liver tissues showed increased injury, hepatocyte apoptosis, and macrophage infiltration, and decreased cell proliferation. Microarray analysis revealed a negative correlation between peroxisome proliferator-activated receptor-γ (PPAR-γ) and LPS/cis-SG-induced liver injury. Immunohistochemical staining and RT-PCR results further confirmed that cis-SG significantly inhibited activation of the PPAR-γ pathway in the liver tissues of LPS/cis-SG-treated rats. Pre-treatment with a PPAR-γ agonist pioglitazone (500 g/kg, ig) reversed LPS/cis-SG-induced liver injury, which was associated with inhibiting the nuclear factor kappa B (NF-κB) pathway. These data demonstrate that cis-stilbene glucoside induces immunological idiosyncratic hepatotoxicity through suppressing PPAR-γ in a rat model of IDILI.