MAGDM Method with Pythagorean 2-Tuple Linguistic Information and Applications in the HSE Performance Assessment of Laboratory

There is a significant gap between the safety management in the Chinese colleges and many renowned colleges in other countries. The subject of this study is how to assess the performance of health, safety, and environment (HSE) in Chinese college laboratories. The assessment system is established by three parts. First of all, HSE performance assessment indicators for laboratories in Chinese colleges are identified based on the previous studies. Then set valued iteration is used to calculate the weights of the various indicators. Following that, multiple attribute group decision-making (MAGDM) method with Pythagorean 2-tuple linguistic operators is used to assess the laboratory HSE performance in colleges. Finally, taking a college in Sichuan Province as an example, the proposed method is used to assess the laboratory HSE performance. The assessment result shows that the proposed method used in this study is practical and feasible

DDAH1 Protects against Acetaminophen-Induced Liver Hepatoxicity in Mice

In many developed countries, acetaminophen (APAP) overdose-induced acute liver injury is a significant therapeutic problem. Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is a critical enzyme for asymmetric dimethylarginine (ADMA) metabolism. Growing evidence suggests that liver dysfunction is associated with increased plasma ADMA levels and reduced hepatic DDAH1 activity/expression. The purpose of this study was to investigate the involvement of DDAH1 in APAP-mediated hepatotoxicity using Ddah1-/- and DDAH1 transgenic mice. After APAP challenge, Ddah1-/- mice developed more severe liver injury than wild type (WT) mice, which was associated with a greater induction of fibrosis, oxidative stress, inflammation, cell apoptosis and phosphorylation of JNK. In contrast, overexpression of DDAH1 attenuated APAP-induced liver injury. RNA-seq analysis showed that DDAH1 affects xenobiotic metabolism and glutathione metabolism pathways in APAP-treated livers. Furthermore, we found that DDAH1 knockdown aggravated APAP-induced cell death, oxidative stress, phosphorylation of JNK and p65, upregulation of CYP2E1 and downregulation of GSTA1 in HepG2 cells. Collectively, our data suggested that DDAH1 has a marked protective effect against APAP-induced liver oxidative stress, inflammation and injury. Strategies to increase hepatic DDAH1 expression/activity may be novel approaches for drug-induced acute liver injury therapy

Hepatic DDAH1 mitigates hepatic steatosis and insulin resistance in obese mice: Involvement of reduced S100A11 expression

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is an important regulator of plasma asymmetric dimethylarginine (ADMA) levels, which are associated with insulin resistance in patients with nonalcoholic fatty liver disease (NAFLD). To elucidate the role of hepatic DDAH1 in the pathogenesis of NAFLD, we used hepatocyte-specific Ddah1-knockout mice (Ddah1HKO) to examine the progress of high-fat diet (HFD)-induced NAFLD. Compared to diet-matched flox/flox littermates (Ddah1f/f), Ddah1HKO mice exhibited higher serum ADMA levels. After HFD feeding for 16 weeks, Ddah1HKO mice developed more severe liver steatosis and worse insulin resistance than Ddah1f/f mice. On the contrary, overexpression of DDAH1 attenuated the NAFLD-like phenotype in HFD-fed mice and ob/ob mice. RNA-seq analysis showed that DDAH1 affects NF-κB signaling, lipid metabolic processes, and immune system processes in fatty livers. Furthermore, DDAH1 reduces S100 calcium-binding protein A11 (S100A11) possibly via NF-κB, JNK and oxidative stress-dependent manner in fatty livers. Knockdown of hepatic S100a11 by an AAV8-shS100a11 vector alleviated hepatic steatosis and insulin resistance in HFD-fed Ddah1HKO mice. In summary, our results suggested that the liver DDAH1/S100A11 axis has a marked effect on liver lipid metabolism in obese mice. Strategies to increase liver DDAH1 activity or decrease S100A11 expression could be a valuable approach for NAFLD therapy

GCN2 deficiency ameliorates doxorubicin-induced cardiotoxicity by decreasing cardiomyocyte apoptosis and myocardial oxidative stress

The clinical use of doxorubicin for cancer therapy is limited by its cardiotoxicity, which involves cardiomyocyte apoptosis and oxidative stress. Previously, we showed that general control nonderepressible 2 (GCN2), an eukaryotic initiation factor 2α (eIF2α) kinase, impairs the ventricular adaptation to chronic pressure overload by affecting cardiomyocyte apoptosis. However, the impact of GCN2 on Dox-induced cardiotoxicity has not been investigated. In the present study, we treated wild type (WT) and Gcn2−/− mice with four intraperitoneal injections (5 mg/kg/week) to induce cardiomyopathy. After Dox treatment, Gcn2−/− mice developed less contractile dysfunction, myocardial fibrosis, apoptosis, and oxidative stress compared with WT mice. In the hearts of the Dox-treated mice, GCN2 deficiency attenuated eIF2α phosphorylation and induction of its downstream targets, activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), and preserved the expression of anti-apoptotic factor Bcl-2 and mitochondrial uncoupling protein-2(UCP2). Furthermore, we found that GCN2 knockdown attenuated, whereas GCN2 overexpression exacerbated, Dox-induced cell death, oxidative stress and reduction of Bcl-2 and UCP2 expression through the eIF2α-CHOP-dependent pathway in H9C2 cells. Collectively, our data provide solid evidence that GCN2 has a marked effect on Dox induced myocardial apoptosis and oxidative stress. Our findings suggest that strategies to inhibit GCN2 activity in cardiomyocyte may provide a novel approach to attenuate Dox-related cardiotoxicity. Keywords: GCN2, Doxorubicin, Cardiotoxicity, Oxidative stress, CHOP, UCP

Low-bandgap polymers with quinoid unit as π bridge for high-performance solar cells

To construct efficient low band gap polymers, increasing the Quinone structure of the polymer backbone could be one desirable strategy. In this work, two D–Q–A–Q polymers P1 and P2 were designed and synthesized with thiophenopyrrole diketone (TPD) and benzothiadiazole (BT) unit as the core and ester linked thieno[3,4-b]thiophene (TT) segment as π-bridging, and the main focus is to make a comparative analysis of different cores in the influence of the optical, electrochemical, photochemical and morphological properties. Compared with the reported PBDTT EH –TBTT HD−i , P1 exhibited the decreased HOMO energy level of −5.38 eV and lower bandgap of 1.48 eV. Furthermore, when replaced with BT core, P2 showed a red-shifted absorption profile of polymer but with up-shifted HOMO energy level. When fabricated the photovoltaic devices in conventional structure, just as expected, the introduction of ester substituent made an obvious increase of V OC from 0.63 to 0.74 V for P1. Besides, due to the deep HOMO energy level, higher hole mobility and excellent phase separation with PC 71 BM, a superior photovoltaic performance (PCE = 7.13%) was obtained with a short-circuit current density (J SC ) of 14.9 mA/cm 2 , significantly higher than that of P2 (PCE = 2.23%). Generally, this study highlights that the strategy of inserting quinoid moieties into D–A polymers could be optional in LBG-polymers design and presents the importance and comparison of potentially competent core groups

Genetic and Pharmacological Inhibition of GCN2 Ameliorates Hyperglycemia and Insulin Resistance in Type 2 Diabetic Mice

It is well recognized that there is a strong and complex association between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). We previously demonstrated that genetic knockout or pharmacological inhibition of general control nondepressible kinase 2 (GCN2), a well-known amino acid sensor, alleviated hepatic steatosis and insulin resistance in obese mice. However, whether GCN2 affects the development of T2D remains unclear. After a high-fat diet (HFD) plus low-dose streptozotocin (STZ) treatments, Gcn2−/− mice developed less hyperglycemia, insulin resistance, hepatic steatosis, and oxidative stress than wild-type (WT) mice. Inhibition of GCN2 by intraperitoneal injection of 3 mg/kg GCN2iB (a specific inhibitor of GCN2) every other day for 6 weeks also ameliorated hyperglycemia, insulin resistance, hepatic steatosis, and oxidative stress in HFD/STZ- and leptin receptor deletion (db/db)-induced T2D mice. Moreover, depletion of hepatic GCN2 in db/db mice by tail vein injection of an AAV8-shGcn2 vector resulted in similar improvement in those metabolic disorders. The protective mechanism of GCN2 inhibition in T2D mice was associated with regulation of the glucose metabolic pathway, repression of lipogenesis genes, and activation of the Nrf2 pathway. Together, our data provide evidence that strategies to inhibit hepatic GCN2 activity may be novel approaches for T2D therapy

Polythiophene solar cells processed from non-halogenated solvent with 15.68% efficiency

Polythiophenes (PTs) are prospective polymer donors for large-scale manufacturing and industrialization owing to their simple structures and low synthetic cost. However, the fabrication of PT solar cells depends on highly toxic chlorinated solvents, and less research has been done on the use of more environmentally friendly non-halogenated solvents. Herein, highly efficient PT solar cells based on top-performance polythiophene, P5TCN-F25, processed from a non-halogenated solvent are reported by delicate aggregation control. A power conversion efficiency of up to 15.68% was achieved by depositing the active layer from a hot o-xylene solution, which is the record efficiency of non-halogenated processed PT solar cells up to date. The appropriate solution temperature is beneficial to the formation of ordered polymer stacking and desirable phase separation size, which thereby contributes to enhanced charge transfer efficiency, more balanced hole electron mobility, and reduced trap-assisted recombination. These results provide valuable implications for improving the efficiency of PT solar cells via environmentally-friendly processing

Achieving 16% Efficiency for Polythiophene Organic Solar Cells with a Cyano-Substituted Polythiophene

Polythiophenes (PTs) are promising electron donors in organic solar cells (OSCs) due to their simple structures and excellent synthetic scalability. However, the device performance of PT-based OSCs is rather poor due mainly to large photon energy losses and an unfavorable active layer morphology. Herein, the authors report a new PT, which is abbreviated as P5TCN-2F and features cyano-group substituents for high-efficiency OSCs. The cyano-group endows P5TCN-2F with a deep-lying highest occupied molecular orbital energy level, which thereby contributed to high open-circuit voltage in OSCs as a result of reduced non-radiative recombination energy loss. Moreover, the cyano-group leads to strong interchain interaction, improved polymer crystallinity, and appropriate miscibility with the prevailing non-fullerene acceptors. Consequently, P5TCN-2F offers over 15% power conversion efficiency when blended with various Y-series non-fullerene acceptors (Y6, Y6-BO, eC9, and L8-BO). Particularly, a champion efficiency of 16.1% is obtained by the P5TCN-2F:Y6 blend, which is largely higher than that of any previous PT-based OSCs. Moreover, the average figure of merit of the active layer based on P5TCN-2F is much superior to that of benzodithiophene-based polymers. These results suggest the renaissance of PT-based OSCs and have opened an avenue to access high-performance materials for the large-scale production of OSC modules

An electron acceptor featuring a B-N covalent bond and small singlet-triplet gap for organic solar cells

BNTT2F, an electron acceptor featuring a B-N covalent bond and singlet-triplet gap as low as 0.20 eV via the multiple resonance effect, is developed for organic solar cells. The optimized device based on BNTT2F offered an efficiency of 8.3%, suggesting the great prospect of B-N covalent bond-containing π-conjugated molecules for photovoltaics

Revealing the Molecular Weight Effect on Highly Efficient Polythiophene Solar Cells

Polythiophenes (PTs) are promising electron donors inorganic solarcells (OSCs) due to their simple structures and excellent syntheticscalability. Benefiting from the rational molecular design, the powerconversion efficiency (PCE) of PT solar cells has been greatly improved.Herein, five batches of the champion PT (P5TCN-F25) with molecularweights ranging from 30 to 87 kg mol(-1) were prepared,and the effect of the molecular weight on the blend film morphologyand photovoltaic performance of PT solar cells was systematicallyinvestigated. The results showed that the PCEs of the devices improvedfirst and then maintained a high value with the increase of molecularweight, and the highest PCE of 16.7% in binary PT solar cells wasobtained. Further characterizations revealed that the promotion inphotovoltaic performance mainly comes from finer phase separationstructures and more compact molecular packing in the blend film. Thebest device stabilities were also achieved by polymers with high molecularweights. Overall, this study highlights the importance of optimizingthe molecular weight for PTs and offers directions to further improvethe PCE of PT solar cells