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Converting checkpoint inhibitor (CPI) resistant patients to responsive requires identifying novel suppressive mechanisms. We identified TREM2 + tumor associated macrophages (TAMs) as being correlated with exhausted CD8 + tumor infiltrating lymphocytes (TILs) in both mouse syngeneic tumor models and human solid tumors of multiple histological types. Fc-domain enhanced anti-TREM2 monoclonal antibody (mAb) therapy promoted anti-tumor immunity by elimination and modulation of TAM populations which led to enhanced CD8 + TIL infiltration and effector function. TREM2 + TAMs were most enriched in human ovarian cancer patients, where TREM2 expression corresponded to disease grade accompanied by worse recurrence-free survival. In an aggressive orthotopic ovarian cancer model, anti-TREM2 mAb therapy drove potent anti-tumor immunity. Together, these results highlight TREM2 as a highly attractive target for immunotherapeutic modulation in patients who are refractory to CPI therapy and likely have a TAM-rich tumor microenvironment.

Background. Cardiomyocyte apoptosis functions essentially in ischemia/reperfusion- (I/R-) induced myocardial injury. It is suggested that autophagy is widely implicated in the regulation of cell survival and death. Sevoflurane, as a largely used inhalational general anesthetic, has been shown to have a protective effect on cardiomyocytes. However, it was yet elusive on the underlying mechanisms. Aim. The objective of this study is to investigate the association of sevoflurane-mediated cardioprotective effects with autophagy regulation. Methods. An in vitro hypoxia model was established in primary cardiomyocytes from fresh myocardial tissue of the rats. The apoptosis rate of myocardial cells treated with hypoxia and treated with sevoflurane was measured. Western blot and immunocytochemical assay were used to measure the protein expression. The cell proliferation rate and cell apoptosis were measured using the MTT assay and flow cytometry, respectively. Results. The expression of apoptotic proteins including B cell lymphoma-2 (Bcl-2), CCAAT/enhancer-binding protein homologous protein (CHOP), glucose-regulated protein 78 (GRP78), and Bcl-2-associated X protein (BAX) in myocardium treated with sevoflurane was significantly lower than that in myocardium treated with hypoxia. The expression of adhesion proteins such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in myocardium treated with sevoflurane was higher than that in myocardium treated with hypoxia, suggesting better connectivity of the myocardium. Conclusion. Sevoflurane treatment reduced the apoptosis of myocardial cells after hypoxia treatment.

Lots of people are at the risk of arsenic-contaminated drinking water. Arsenic exposure was confirmed to be closely linked to neurocognitive deficits, particularly during childhood. The multi-omics approaches are known be well suitable for toxicological research. Thus, this study aimed to explore the molecular mechanisms of arsenic-induced learning and memory function impairments through the integrative proteome and metabolome analysis of cortex in rats. The weaned rats were exposed to arsenic-contaminated drinking water for six months to mimic the developmental exposure. 220 differential proteins and 19 differential metabolites were identified in the cortex, and nine potential biomarkers were found to be related to impaired Morris water maze (MWM) indicators. Chronic arsenic exposure affected the cognitive function by inducing the overproduction of amyloid-β (Aβ) peptides and the redox imbalance in the mitochondria. Glycolysis and tricarboxylic acid (TCA) cycle enhancement driven by the increased heterogeneous nuclear ribonucleoprotein L (hnRNP L) is a low-dose protective mechanism against arsenic-induced ATP deficiency and oxidative stress. Moreover, apoptosis is another important pathway of arsenic-induced neurotoxicity. This study provides new evidence about the alterations of proteins and metabolites in the cortex of the exposed rats under arsenic toxicity. These findings suggest hnRNP L could be a potential target for the treatment of arsenic-induced neurotoxicity.

Unmanned aerial vehicle (UAV) has been extensively studied and widely adopted in practical systems owing to its effectiveness and flexibility. Although heterogeneous UAVs have an enormous advantage in improving performance and conserving energy with respect to homogeneous ones, they give rise to a complex path planning problem. Especially in large-scale cooperative search systems with multiple separated regions, coverage path planning which seeks optimal paths for UAVs to completely visit and search all of regions of interest, has a NP-hard computation complexity and is difficult to settle. In this work, we focus on the coverage path planning problem of heterogeneous UAVs, and present an ant colony system (ACS)-based algorithm to obtain good enough paths for UAVs and fully cover all regions efficiently. First, models of UAVs and regions are built, and a linear programming-based formulation is presented to exactly provide the best point-to-point flight path for each UAV. Then, inspired by the foraging behaviour of ants that they can obtain the shortest path between their nest and food, an ACS-based heuristic is presented to seek approximately optimal solutions and minimize the time consumption of tasks in the cooperative search system. Experiments on randomly generated regions have been organized to evaluate the performance of the new heuristic in terms of execution time, task completion time and deviation ratio.

Helicobacter pylori is designated as a class I carcinogen of human gastric cancer following long-term infection. During this process, H. pylori bacteria persist in proliferation and death, and release bacterial components that come into contact with gastric epithelial cells and regulate host cell function. However, the impact of long-term exposure to H. pylori lysate on the pathological changes of gastric cells is not clear. In this study, we aimed to investigate the regulation and mechanisms involved in gastric cell dysfunction following continuous exposure to H. pylori lysate. We co-cultured gastric cell lines GES-1 and MKN-45 with H. pylori lysate for 30 generations, and we found that sustained exposure to H. pylori lysate inhibited GES-1 cell invasion, migration, autophagy, and apoptosis, while it did not inhibit MKN-45 cell invasion or migration. Furthermore, Mongolian gerbils infected with H. pylori ATCC 43504 strains for 90 weeks confirmed the in vitro results. The clinical and in vitro data indicated that sustained exposure to H. pylori lysate inhibited cell apoptosis and autophagy through the Nod1-NF-κB/MAPK-ERK/FOXO4 signaling pathway. In conclusion, sustained exposure to H. pylori lysate promoted proliferation of gastric epithelial cells and inhibited autophagy and apoptosis via Nod1-NF-κB/MAPK-ERK/FOXO4 signaling pathway. In the process of H. pylori-induced gastric lesions, H. pylori lysate plays as an “accomplice” to carcinogenesis.

Many studies have linked airborne fine particulate matter (PM2.5) exposure to cardiovascular diseases. We performed a time-series analysis to investigate whether the disruption of lipid metabolism recovered or lasted after acute PM2.5 exposure in mice. Targeted lipidomic analysis showed that four major plasma membrane phospholipids along with cholesterol esters (CE) were significantly altered on 7th post-exposure day (PED7), and the alteration reached a peak on PED14. On PED21, the phosphatidylcholine (PC) decrease was more marked than on PED14, and its resurgence was indirectly linked to triglyceride (TG) increase. Homocysteine (HCY), lactate dehydrogenase (LDH), and α-hydroxybutyrate dehydrogenase (α-HBDH) levels increased but glucose levels decreased markedly in a dose- and time-dependent manner throughout the experimental period. Network analysis showed that the lasting lipid deregulation on PED21 correlated to myocardial markers and glucose interruption, during which high-density lipoprotein cholesterol (HDL-C) decreased. The present data implied that the constructional membrane lipids were initially interrupted by PM2.5, and the subsequent rehabilitation resulted in the deregulation of storage lipids; the parallel myocardial and glucose effects may be enhanced by the lasting HDL-C lipid deregulation on PED21. These myocardial and lipidomic events were early indicators of cardiovascular risk, resulting from subsequent exposure to and accumulation of PM2.5.

BACKGROUND With the prevalence of cardiovascular diseases increasing worldwide, early prediction and accurate assessment of heart failure (HF) risk are crucial to meet the clinical demand. OBJECTIVE Our study objective was to develop machine learning (ML) models based on real-world electronic health records to predict 1-year in-hospital mortality, use of positive inotropic agents, and 1-year all-cause readmission rate. METHODS For this single-center study, we recruited patients with newly diagnosed HF hospitalized between December 2010 and August 2018 at the First Affiliated Hospital of Dalian Medical University (Liaoning Province, China). The models were constructed for a population set (90:10 split of data set into training and test sets) using 79 variables during the first hospitalization. Logistic regression, support vector machine, artificial neural network, random forest, and extreme gradient boosting models were investigated for outcome predictions. RESULTS Of the 13,602 patients with HF enrolled in the study, 537 (3.95%) died within 1 year and 2779 patients (20.43%) had a history of use of positive inotropic agents. ML algorithms improved the performance of predictive models for 1-year in-hospital mortality (areas under the curve [AUCs] 0.92-1.00), use of positive inotropic medication (AUCs 0.85-0.96), and 1-year readmission rates (AUCs 0.63-0.96). A decision tree of mortality risk was created and stratified by single variables at levels of high-sensitivity cardiac troponin I (9/L). CONCLUSIONS ML techniques based on a large scale of clinical variables can improve outcome predictions for patients with HF. The mortality decision tree may contribute to guiding better clinical risk assessment and decision making.

In non-fullerene organic solar cells (OSCs), the long-range structure ordering induced by end group π–π stacking of fused-ring non-fullerene acceptors is considered as the critical factor in realizing efficient charge transport and high power conversion efficiency. Here, we demonstrate that side-chain engineering of non-fullerene acceptors could drive the fused-ring backbone assembly from a π–π stacking mode to an intermixed packing mode, and to a non-stacking mode to refine its solid-state properties. Different from the above-mentioned understanding, we find that close atom contacts in a non-stacking mode can form efficient charge transport pathway through close side atom interactions. The intermixed solid-state packing motif in active layers could enable OSCs with superior efficiency and reduced non-radiative recombination loss compared with devices based on molecules with the classic end-group π–π stacking mode. Our observations provide new insights into the influence of non-fullerene acceptor molecular packing on exciton dissociation, charge transport, and recombination losses, and open a new avenue in material design that endows better photovoltaic performance.

Poultries including chickens, ducks, geese, and pigeons are widely used in the biological and medical research in many aspects. The genetic quality of experimental poultries directly affects the results of the research. In this study, following electrophoresis analysis and short tandem repeat (STR) scanning, we screened out the microsatellite loci for determining the genetic characteristics of Chinese experimental chickens, ducks, geese, and pigeons. The panels of loci selected in our research provide a good choice for genetic monitoring of the population genetic diversity of Chinese native experimental chickens, ducks, geese, and ducks.

Stability of perovskite-based photovoltaics remains a topic requiring further attention. Cation engineering influences perovskite stability, with the present-day understanding of the impact of cations based on accelerated ageing tests at higher-than-operating temperatures (e.g. 140°C). By coupling high-throughput experimentation with machine learning, we discover a weak correlation between high/low-temperature stability with a stability-reversal behavior. At high ageing temperatures, increasing organic cation (e.g. methylammonium) or decreasing inorganic cation (e.g. cesium) in multi-cation perovskites has detrimental impact on photo/thermal-stability; but below 100°C, the impact is reversed. The underlying mechanism is revealed by calculating the kinetic activation energy in perovskite decomposition. We further identify that incorporating at least 10 mol.% MA and up to 5 mol.% Cs/Rb to maximize the device stability at device-operating temperature (, Current view of the impact of A-site cation on the stability of perovskite materials and devices is derived from accelerated ageing tests at high temperature, which is beyond normal operation range. Here, the authors reveal the great impact of ageing condition on assessing the photothermal stability of mixed-cation perovskites using high-throughput robot system coupled with machine learning.

Objective: The aim of this study was to explore the effects of NINJ2 polymorphisms on susceptibility of coronary heart disease (CHD).Methods: We conducted a case-control study with 499 CHD cases and 505 age- and sex- matched controls. Five single nucleotide polymorphisms (SNP) in NINJ2 (rs118050317, rs75750647, rs7307242, rs10849390 and rs11610368) were genotyped by Agena MassARRAY platform. Odd ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression to assess the association of NINJ2 polymorphism and CHD risk adjusting for age and gender..Results: NINJ2 rs118050317 significantly increased the risk of CHD in people over 60 years old (allele: P = 0.010; heterozygote: P = 0.016; dominant: P = 0.015; additive: P = 0.021) and women (allele: P = 0.026; heterozygote: P = 0.015; dominant: P = 0.018; additive: P = 0.030). Rs118050317 and rs7307242 were closely related to the risk of hypertension in CHD patients. Additionally, rs75750647 significantly increased diabetes risk in multiple models among CHD cases (allele: P = 0.014; homozygote: P = 0.037; heterozygote: P = 0.044; dominant: P = 0.019; additive: P = 0.013), whereas rs10849390 could protect CHD patients from diabetes in allele (P = 0.035), homozygote (P = 0.047) and additive (P = 0.037) models. We also observed two block (block 1: rs118050317 and rs75750647; block 2: rs7307242, rs10849390 and rs11610368) in NINJ2.Conclusion: Our results suggested that the relationships of NINJ2 polymorphisms and CHD risk were dependent on age, sex or complications.

Long noncoding RNAs (lncRNAs) regulate gene expression at different levels in various diseases, including type 1 diabetes (T1D). However, the expression of circulating lncRNAs in leukocytes in T1D has not been well documented. To identify differentially expressed lncRNAs between T1D patients and healthy controls, RNA sequencing was performed on samples of leukocytes collected from both healthy persons and T1D patients. The categories, enriched pathways, coexpression networks, and the characteristics of novel lncRNAs were analyzed to provide an extensive profile. qPCR was adopted to validate the differential expression of lncRNAs in the validation cohort. A total of 14,930 lncRNAs and 16,063 mRNAs were identified in the peripheral blood leukocyte of T1D patients. After optimization using an adjusted p value (threshold of

Milk casein and triglyceride content are important production traits in goats. Studies on mechanisms in milk casein secretion and mammary gland development is essential for milk goat breeding. miRNAs play an important role in goat lactation. While novel-miR-3880 is highly expressed at goat peak lactation stage, its molecular mechanism has not been studied. The purpose of the present study was to explore the relationship between novel-miR-3880 and lactation, as well as to construct a network among novel-miR-3880, ciRNA13761, and E74 like ETS transcription factor 2 (ELF2), thus further exploring their potential roles in milk components and mammary gland development. ELF2 was previously proven to be important in cell survival and proliferation, and 3'-UTR of ELF2 was predicted to have binding sites of novel-miR-3880. Our study found that the overexpression of novel-miR-3880 exerted anti-apoptotic and proliferative roles in GMEC, induced a boost in triglyceride synthesis, and caused a decrease in α s1-, α s2-, and β-casein, but an increase in κ-casein secretion. Furthermore, treatment in mice indicated that novel-miR-3880 could promote mammary gland development and extend the lactation period, while novel-miR-3880 expression was found to be suppressed by ciRNA13761 as a miRNA sponge. The present study explores a mechanism of triglyceride synthesis and casein secretion, and reveals a crosstalk between ciRNA13761/novel-miR-3880/ELF2 axis and PI3K/AKT/mTOR/S6K1 pathway, to gain a better understanding of lactation traits in dairy goats.

In non-fullerene organic solar cells, the long-range structure ordering induced by end-group π–π stacking of fused-ring non-fullerene acceptors is considered as the critical factor in realizing efficient charge transport and high power conversion efficiency. Here, we demonstrate that side-chain engineering of non-fullerene acceptors could drive the fused-ring backbone assembly from a π–π stacking mode to an intermixed packing mode, and to a non-stacking mode to refine its solid-state properties. Different from the above-mentioned understanding, we find that close atom contacts in a non-stacking mode can form efficient charge transport pathway through close side atom interactions. The intermixed solid-state packing motif in active layers could enable organic solar cells with superior efficiency and reduced non-radiative recombination loss compared with devices based on molecules with the classic end-group π–π stacking mode. Our observations open a new avenue in material design that endows better photovoltaic performance., Non-fullerene acceptors are crucial for realising efficient charge transport and high power conversion in organic solar cells, yet the relationship of molecular packing and carrier transport is not well-understood. Here, the authors study the effect of side-chain engineering on the backbone assembly and the corresponding charge transport pathway.

The performance of tandem organic solar cells (OSCs) is directly related to the functionality and reliability of the interconnecting layer (ICL). However, it is a challenge to develop a fully functional ICL for reliable and reproducible fabrication of solution-processed tandem OSCs with minimized optical and electrical losses, in particular for being compatible with various state- of-the-art photoactive materials. Although various ICLs have been developed to realize tandem OSCs with impressively high performance, their reliability, reproducibility, and generic applicability are rarely analyzed and reported so far, which restricts the progress and widespread adoption of tandem OSCs. In this work, a robust and fully functional ICL is developed by incorporating a hydrolyzed silane crosslinker, (3-glycidyloxypropyl)trimethoxysilane (GOPS), into poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS), and its functionality for reliable and reproducible fabrication of tandem OSCs based on various photoactive materials is validated. The cross-linked ICL can successfully protect the bottom active layer against penetration of high boiling point solvents during device fabrication, which widely broadens the solvent selection for processing photoactive materials with high quality and reliability, providing a great opportunity to continuously develop the tandem OSCs towards future large-scale production and commercialization.

Triple negative breast cancer (TNBC) is the most aggressive subtype with the worst prognosis. The role of profilin 2 (PFN2) in TNBC is very controversial. The current study is to explore the role of PFN2 in TNBC. PFN2 expression in TNBC and normal breast tissues were evaluated by immunohistochemical analysis. The association between PFN2 expression and prognosis in TNBC patients was analyzed from the TCGA database. A cell counting kit-8 (CCK8) assay was employed to investigate the effects of PFN2 in TNBC cell proliferations. The migration and invasion capability of TNBC cells was evaluated by transwell assays. Western blot was performed to assess the related protein expression of TGF-β/Smad signaling and epithelial to mesenchymal transition. Finally, TNBC xenografts were established to determine the tumorigenicity in vivo using female Nod/Scid mice. PFN2 is upregulated in TNBC and the higher expression was associated with worse survival. CCK8 assays and Transwell assays demonstrated that PFN2 promoted the proliferation, migration and invasion of TNBC cells. Smad2 and Smad3 were upregulated in PFN2 overexpressing TNBC cells, which further induced the process of epithelial‑to‑mesenchymal transition. Similarly, the overexpressing PFN2 TNBC cells exhibited stronger tumorigenicity in vivo. Higher PFN2 expression is associated with a worse 10-year overall survival and relapse-free survival in breast cancer patients, as well as worse 10-year relapse-free survival in TNBC patients. PFN2 promotes the proliferation, migration and invasion of TNBC cells by regulating epithelial-to-mesenchymal transition.

Great attention has been paid to developing low bandgap non-fullerene acceptors (NFAs) for matching wide bandgap donor polymers to increase the photocurrent and therefore the power conversion efficiencies (PCEs) of NFA organic solar cells, while pyrene-core based acceptor–donor–acceptor (A–D–A) NFAs have been mainly reported via the 2,9-position connection due to their bisthieno[30,20-b']thienyl[a,h]pyrene fused via a five-membered ring bridge at the ortho-position of pyrene as the representative one named FPIC5, which has prohibited further narrowing their energy gap. Herein, an acceptor FPIC6 was exploited by creating the 1,8-position connection through fusing as bisthieno[30,20-b0]thienyl[f-g,m-n]pyrene linked at the bay-position via a six-membered bridge, with enhanced push–pull characteristics within such A–D–A structure. As a structural isomer of FPIC5, FPIC6 exhibited a much lower bandgap of 1.42 eV (1.63 eV for FPIC5). Therefore, the photocurrent and PCE of PTB7-Th:FPIC6 cells were improved to 21.50 mA cm2 and 11.55%, respectively, due to the balanced mobilities, better photoluminescence quenching efficiency and optimized morphology, which are both40% better than those of PTB7-Th:FPIC5 cells. Our results clearly proved that a pyrene fused core with 1,8-position connection with electron-withdrawing end groups instead of 2,9-position connection is an efficient molecular design strategy to narrow the optical bandgap and improve the photovoltaic performance of NFA based OSCs.

Objective: The aim of this study was to explore the effects of NINJ2 polymorphisms on susceptibility of coronary heart disease (CHD).Methods: We conducted a case-control study with 499 CHD cases and 505 age- and sex- matched controls. Five single nucleotide polymorphisms (SNP) in NINJ2 (rs118050317, rs75750647, rs7307242, rs10849390 and rs11610368) were genotyped by Agena MassARRAY platform. Odd ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression to assess the association of NINJ2 polymorphism and CHD risk adjusting for age and gender..Results: NINJ2 rs118050317 significantly increased CHD risk among people older than 60 years old (allele: P = 0.010; heterozygote: P = 0.016; dominant: P = 0.015; additive: P = 0.021) and women (allele: P = 0.026; heterozygote: P = 0.015; dominant: P = 0.018; additive: P = 0.030). Rs118050317 and rs7307242 had strong relationship with hypertension risk in CHD patients. Additionally, rs75750647 significantly increased diabetes risk in multiple models among cases (allele: P = 0.014; homozygote: P = 0.037; heterozygote: P = 0.044; dominant: P = 0.019; additive: P = 0.013), whereas rs10849390 could protect CHD patients from diabetes in allele (P = 0.035), homozygote (P = 0.047) and additive (P = 0.037) models. We also observed two block (block 1: rs118050317 and rs75750647; block 2: rs7307242, rs10849390 and rs11610368) in NINJ2.Conclusion: Our results suggest that NINJ2 polymorphisms are associated with CHD risk.

Small cell lung cancer (SCLC) is highly aggressive and prone to hypervascular metastases. Recently, we found profilin 2 (PFN2) expression in SCLC but not in normal tissues. Furthermore, PFN2 expression had been shown to promote angiogenesis through exosomes. However, it remains unclear whether PFN2 contributes to the progression and metastasis of SCLC through angiogenesis. We report here that overexpression (OE) of PFN2 increased, whereas its knockdown (KD) decreased the proliferation, migration, and invasion of SCLC cell H446. The exosomes from OE-H446 (SCLC-OE-exo) exhibited similar effects on H446 properties. Culturing of endothelial cells (ECs) in SCLC-OE conditioned medium (CM) or SCLC-OE-exo increased the migration and tube formation ability of ECs, whereas SCLC-KD-CM and SCLC-KD-exo had inhibitory effects. Interestingly, both SCLC- and EC-derived exosomes were internalized in H446 more rapidly than in ECs. More importantly, OE-PFN2 dramatically elevated SCLC growth and vasculature formation as well as lung metastasis in tumor xenograft models. Finally, we found that PFN2 activated Smad2/3 in H446 and pERK in ECs, respectively. Taken together, our study revealed the role of PFN2 in SCLC development and metastasis, as well as tumor angiogenesis through exosomes, providing a new molecular target for SCLC treatment.

We investigate the photovoltaic characteristics of organic solar cells (OSCs) for two distinctly different nanostructures, by comparing the charge carrier dynamics for bilayer- and bulk-heterojunction OSCs. Most interestingly, both architectures exhibit fairly similar power conversion efficiencies (PCEs), reflecting a comparable critical domain size for charge generation and charge recombination. Although this is, at first hand, surprising, a detailed analysis points out the similarity between these two concepts. A bulk-heterojunction architecture arranges the charge generating domains in a 3D ensemble across the whole bulk, while bilayer architectures arrange the specific domains on top of each other, rather than sharp bilayers. Specifically, for the polymer PBDB-T-2F, we find that the enhanced charge generation in a bulk composite is partially compensated by reduced recombination in the bilayer architecture, when nonfullerene acceptors (NFAs) are used instead of a fullerene acceptor. Overall, we demonstrate that bilayer-heterojunction OSCs with NFAs can reach competitive PCEs compared to the corresponding bulk-heterojunction OSCs because of reduced nonradiative open-circuit voltage losses, and suppressed trap-assisted recombination, as a result of a vertically separated donor-to-acceptor nanostructure. In contrast, the bilayer-heterojunction OSCs with the fullerene acceptor exhibited poor photovoltaic characteristics compared to the corresponding bulk devices because of highly aggregated acceptor molecules on top of the polymer donor. Although free carrier generation is reduced in a in a bilayer-heterojunction, because of reduced donor/acceptor interfaces and a limited exciton diffusion length, more favorable transport pathways for unipolar charge collection can partially compensate the aforementioned disadvantages. We propose that the unique properties of NFAs may open a technical venue for the bilayer-heterojunction as a great and easy alternative to the bulk heterojunction.

Potentiostatic impedance spectroscopy (IS) is a well-established characterization technique for elucidating the electric resistivity and capacitive features of materials and devices. For solar cells, by applying a small voltage perturbation the current signal is recorded and the recombination processes and defect distributions can be accessed. In this work, a photo-impedance approach, named “light intensity modulated impedance spectroscopy” (LIMIS), is first time tested in all-solid-state photovoltaics by individually recording photocurrent (IMPS) and photovoltage (IMVS) responsivity signals due to a small light perturbation at open-circuit (OC), and combining them: LIMIS = IMVS/IMPS. The experimental LIMIS spectra from silicon, organic, and perovskite solar cells are presented and compared with IS. Our theoretical analyses, including equivalent circuit models, show a correction to the lifetimes values by obtaining the total differential resistances and capacitances combining IS and LIMIS. This correction addresses some discrepancies among different techniques, as also shown with photo-induced transient photovoltage. The experimental differences between IS and LIMIS proves the unsuitability of the superposition principle and suggest a bias-dependent photo-current correction to the empirical Shockley equation of the steady-state current at different illumination intensities around OC. In addition, new features are reported for the low-frequency capacitance of perovskite solar cells.

The performance of organic photovoltaics is largely dependent on the balance of short-circuit current density (JSC) and open-circuit voltage (VOC). For instance, the reduction of the active materials’ optical bandgap, which increases the JSC, would inevitably lead to a concomitant reduction in VOC. Here, we demonstrate that careful tuning of the chemical structure of photoactive materials can enhance both JSC and VOC simultaneously. Non-fullerene organic photovoltaics based on a well-matched materials combination exhibit a certified high power conversion efficiency of 12.25% on a device area of 1 cm2. By combining Fourier-transform photocurrent spectroscopy and electroluminescence, we show the existence of a low but non-negligible charge transfer state as the possible origin of VOC loss. This study highlights that the reduction of the bandgap to improve the efficiency requires a careful materials design to minimize non-radiative VOC losses. Materials design rules play a key role in enabling high performance in organic photovoltaics. Here the authors achieve 12.25% efficiency on 1 cm2 non-fullerene solar cells by tuning the side chains’ branching point and the fluorine substitutions in donor and acceptor materials.

Lead (Pb) poisoning in humans and fish represents a significant global problem. Bacillus subtilis (B. subtilis) is a widely used probiotic in aquaculture. Carassius auratus gibelio (C. gibelio) is one of the most important aquaculture species with great commercial value. The objective of this study was to evaluate the potential of B. subtilis in ameliorating lead-induced toxicity in C. gibelio. The fish were exposed for 60 days to waterborne Pb at 0, 0.05, 0.5 and 1 mg/L and/or dietary B. subtilis at 109 cfu/g. After 30 and 60 days, the fish were sampled and bioaccumulation, antioxidant activity and immune responses were assessed. The results revealed that B. subtilis confers significant protective effects against lead toxicity by preventing alterations in the levels of bioaccumulation, superoxide dismutase, catalase and glutathione. B. subtilis also assists in the recovery of blood δ-aminolevulinic acid dehydratase, lysozyme, and IgM levels while regulating the expression of immune-related genes including IL-10, lysozyme, TNF-α, IgM and Hsp70 after 60 days of lead exposure. Our results suggest that administration of B. subtilis (109 cfu/g) has the potential to combat lead toxicity in C. gibelio.

Heterogeneous multiprocessor platforms have been widely adopted as an efficient approach to providing high instruction throughput while keeping power and complexity under control. Although this approach can achieve improved performance for large-scale real-time systems, it results in a complex task scheduling problem. All tasks should be scheduled according to a proper strategy such that their deadlines will be met even in the worst case situations. In this work, we study the non-preemptive scheduling problem of periodic tasks with data dependency upon heterogeneous multiprocessor platforms. We first analyze the space, time and precedence constraints of tasks, and propose an exact formulation to determine the schedulability of tasks. Then, inspired from the Heterogeneous Earliest Finish Time (HEFT) algorithm, we present a list-based scheduling heuristic to schedule the jobs generated by the periodic tasks and minimize the jobs' finish time. The proposed approach is efficient and can help in guiding the design of heterogeneous multiprocessor systems.

We report two novel small-molecule non-fullerene acceptors, IF-TN and IDT-TN, with indenofluorene (IF) and indacenodithiophene (IDT) as their respective central electron-rich cores and naphthyl-fused indanone (N) as the electron-withdrawing end-groups. By pairing these non-fullerene acceptors with a widely used polymer PBDB-T, the fabricated polymer solar cells based on PBDB-T:IDT-TN obtain a power conversion efficiency up to 5.89%, associated with a relatively high open-circuit voltage of 0.97 V and a remarkably low non-radiative open-circuit voltage loss of 0.23 V. These findings provide an effective approach for the rational molecular design of small-molecule acceptors with low non-radiative open-circuit voltage loss.

Background In the previous study, we established an ischemia‐prone gerbil population (IG), which was selectively bred to increase the incidence of unilateral carotid arterial occlusion (UCO)‐induced ischemia in Mongolian gerbils. However, if the characteristics of ischemia model in IG are the same as those in general gerbils (GG), and if the neurological symptoms are associated with the neurological insults in IG is still unclear. Methods In the present study, we evaluated the UCO model in IG by analyzing neurological symptoms, neurological injury in the hippocampal CA1 region and compared with GG. Results The data showed that the ratios of neurological symptom scores ≥ 2 in the IG and GG groups were 65.0% vs 30.0%, respectively, and were significantly different (P

The aim of this study was to explore the effects of lead exposure on the antioxidant and immune responses of Crucian carp. Three hundred sixty healthy Crucian carp were randomly grouped into four groups and exposed to different doses of lead (0, 0.05, 0.5, and 1 mg/L). Fish were sampled at 30 and 60 days, respectively, and antioxidant capability, immune parameters, ALAD activity, and immune-related genes were assessed. The results showed that T-AOC and GSH activities of the liver were significantly increased in 60 days (P

The Mongolian gerbil has been a useful laboratory animal in many research fields, especially in ischemia studies. However, due to the variation of the circle of Willis (COW), the ischemic model is unstable and various. To solve this problem, we newly established an inbred strain of gerbils, restricting breeding and keeping to F23. The data on the breeding and growth of the animals are described in the present study. The genetic characteristics of F4 to F20 detected by microsatellite DNA and biochemical markers are also shown here. The results demonstrated that the frequency of ischemic model by unilateral carotid occlusion and the frequency of incomplete COW increased, increasing from 50% and 75% in F1 to 88.89% and 100% in F20, respectively. The ratios of consistent patterns of COW in parents were positively related with the number of inbred generations. A reproductive performance analysis indicated that the average size of litters in the inbred gerbils was less than that of outbred gerbils and that adult body weight was also lower in inbred gerbils; also, the pups in the 2nd litter were the best ones chosen to reproduce. The genetic detection results indicated that 26 out of 28 microsatellite loci and all 26 biochemical markers were homozygous in F20, showing comparably identical genetic composition in inbred gerbils. All the data demonstrated that an inbred strain of ischemia-prone gerbil has been established successfully. This strain can be used in stroke research and can largely reduce the number of animals needed in experiments.

Myeloid cells present in the tumor microenvironment can exist in immunosuppressive states that impede productive anti-tumor immunity. One strategy for targeting these immunosuppressive mechanisms is reprogramming of myeloid cells from immunosuppressive to immunostimulatory, resulting in the removal of the immune inhibition and unleashing of anti-tumor immunity. Triggering receptor expressed on myeloid cells-1 (TREM1) is an immunoglobulin superfamily cell surface receptor expressed primarily on neutrophils and subsets of monocytes and tissue macrophages. TREM1 signals through the association with DAP12 adaptor protein and mediates proinflammatory signaling, amplifies the host immune response to microbial pathogens, and has been implicated in the development of acute and chronic inflammatory diseases. TREM1 is also enriched in tumors, specifically on tumor-associated myeloid cells. To investigate the potential of TREM1 modulation as an anti-cancer therapeutic strategy, we developed PY159, an afucosylated humanized anti-TREM1 monoclonal antibody. We found that PY159 does not deplete TREM1-expressing cells, but rather acts as a TREM1 agonist. In vitro human blood assays showed that PY159 treatment upregulated activation markers on monocytes and stimulated neutrophil chemotaxis, as assayed by flow cytometry, transcriptional analysis, and in vitro migration assays. Furthermore, PY159 induced a selective set of proinflammatory cytokines and chemokines, which was dependent on PY159 afucosylation. We validated TREM1 expression in human tumors by single-cell RNAseq, immunohistochemistry, and flow cytometry, and found that it is expressed on myeloid populations, including tumor-associated neutrophils (TAN), tumor-associated macrophages (TAM), and monocytic myeloid-derived suppressive cells (mMDSC). We showed that PY159 can also induce proinflammatory cytokines and chemokines in dissociated human tumors in vitro, demonstrating that PY159 can reprogram tumor-associated myeloid cells. Finally, in vivo treatment of mice with a surrogate anti-mouse TREM1 antibody, PY159m, promoted anti-tumor efficacy in several syngeneic mouse tumor models, both as single-agent and in combination with checkpoint inhibitors, such as anti-PD-1 antibody. Together, these results demonstrate that therapeutic targeting of TREM1 with a TREM1 agonist antibody, PY159, promotes myeloid cell reprogramming and anti-tumor immunity. PY159 safety and tolerability have been demonstrated in non-human primates, and safety and efficacy of PY159 are currently being evaluated in first-in-human clinical trial (NCT04682431) including solid tumors that are resistant and refractory to standard of care therapies. Citation Format: Erin Mayes, Vladi Juric, Mikhail Binnewies, Pamela Canaday, Tian Lee, Subhadra Dash, Joshua L. Pollack, Joshua Rudolph, Vicky Huang, Xiaoyan Du, Nadine Jahchan, Asa J. Ramoth, Shilpa Mankikar, Manith Norng, Carlos Santamaria, Kevin P. Baker, Linda Liang. Therapeutic targeting of TREM1 with PY159 promotes myeloid cell reprogramming and unleashes anti-tumor immunity [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P104.

A standardization system is an organism, composed of a set of interacting elements in the process of standardization activity, to serve intended functions during a period of time in a country. After addressing the notion and connotations of standardization, this article proposes the elements and connotations of the Chinese standardization system and depicts the status quo of these elements. This system has introduced a new element, market-driven social organization standards, while preserving the legacy system of national, industry, provincial, and enterprise standards. This article describes its status quo too.

Simultaneously enhancing device performance and longevity, as well as balancing the requirements on cost, scalability, and simplification of processing, is the goal of interface engineering of organic solar cells (OSCs). In our work, we strategically introduce antimony (Sb3+) cations into an efficient and generic n-type SnO2 nanoparticles (NPs) host during the scalable flame spray pyrolysis synthesis. Accordingly, a significant switch of conduction property from an n-type character to a p-type character is observed, with a corresponding shift in the work function (WF) from 4.01 ± 0.02 eV for pristine SnO2 NPs to 5.28 ± 0.02 eV for SnO2 NPs with 20 mol. % Sb content (ATO). Both pristine SnO2 and ATO NPs with fine-tuned optoelectronic properties exhibit remarkable charge carrier extraction properties, excellent UV resistance and photo-stability being compatible with various state-of-the-art OSCs systems. The reliable and scalable pristine SnO2 and ATO NPs processed by doctor-blading in air demand no complex post-treatment. Our work offers a simple but unique approach to accelerate the development of advanced interfacial materials, which could circumvent the major existing interfacial problems in solution-processed OSCs.

The tumor microenvironment (TME) often contains high levels of suppressive myeloid cells that may contribute to innate checkpoint inhibitor (CPI) resistance. Pionyr's Myeloid Tuning approach involves altering the composition and/or the function of myeloid cells in the TME. To this end, therapeutic targeting of tumor-associated macrophages (TAMs) is a promising strategy to increase CPI response rates in solid tumor indications, as well as to overcome resistance to CPI therapies. Pionyr and others identified the transmembrane protein triggering receptor expressed on myeloid cells-2 (TREM2) as a highly enriched TAMs target. Furthermore, TREM2 mRNA expression negatively correlates with patient survival in a variety of tumor types, supporting the involvement of TAMs in tumor progression. Pionyr developed a lead anti-TREM2 monoclonal antibody (mAb), termed PY314, as well as a murinized version of PY314, termed PY314m. PY314m demonstrated significant anti-tumor activity either as single agent in CPI-sensitive syngeneic tumor models or in combination with anti-PD-1 in CPI-resistant syngeneic tumor models. Mechanistically, PY314m reduced the pro-tumorigenic MHC class II-low, M2-like TAMs, induced pro-inflammatory cytokine production, significant increased CD8+ T cell infiltration into the TME. These findings suggest that PY314 therapy could be used to overcome CPI resistance in humans. To select patients most likely to benefit from PY314 therapy, Pionyr developed a qualitative IHC assay that detects TREM2 expression levels in formalin-fixed, paraffin-embedded human tumor tissues. Screening for TREM2 expression in tumor tissues demonstrated that TREM2+ TAMs were present in multiple solid tumor indications and their number increased with disease grade in a selected set of indications. Ongoing efforts are aimed at better understanding localization of TREM2+ TAMs within the TME, and spatial relationship of the TREM2+ TAMs to other immune cells present in the TME. The TREM2 IHC assay will be used to test our hypothesis that patients with tumors with high level of TREM2+ TAMs are most likely to benefit from PY314 treatment. Citation Format: Nadine S. Jahchan, Mikhail Binnewies, Joshua L. Pollack, Ranna Mehta, Subhadra Dash, Christine Tun, Erick Lu, Xiaoyan Du, Kevin P. Baker, Len Reyno, Venkataraman Sriram. Tuning the tumor myeloid microenvironment (TME) by targeting TREM2+ tumor-associated macrophages to overcome resistance to immune checkpoint inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB071.

Embryo attachment, a precondition of ruminant pregnancy, has been recognized to be related to apoptosis in endometrial epithelial cells (EECs). In ruminants, interferon tau (IFNT) is secreted by trophoblast of conceptus and works in a concentration-dependent style. To verify the function of IFNT in caprine embryo attachment, caprine EECs were dealt with IFNT at 0, 1, 10 and 100 ng/ml. In this study, IFNT arrested caprine EEC cell cycle in G2 phase and induced cell apoptosis at 1 ng/ml and 10 ng/ml of IFNT. Interestingly, pro-apoptotic protein FAS and PRβ together with anti-apoptotic proteins SP1 and IGF1R were all up-regulated at 1 ng/ml of IFNT. It demonstrated that IFNT at 1 ng/ml might induce caprine EEC apoptosis and keep a balance between apoptosis and proliferation. Furthermore, regulation of HOXA10, COX-2, PRL, PTEN and STAT3 pathway in caprine EECs was likely to be contributed by IFNT at 1 ng/ml to improve the chances for embryo attachment.

Previous in vivo and in vitro studies have linked perfluorinated compound (PFC) exposure with metabolic interruption, but the inter-species difference and high treatment doses usually make the results difficult to be extrapolated to humans directly. The best strategy for identifying the metabolic interruption may be to establish the direct correlations between monitored PFCs data and metabolic data on human samples. In this study, serum metabolome data and PFC concentrations were acquired for a Chinese adult male cohort. The most abundant PFCs are PFOA and PFOS with concentration medians 7.56 and 12.78 nM, respectively; in together they count around 81.6% of the total PFCs. PFC concentration-related serum metabolic profile changes and the related metabolic biomarkers were explored by using partial least squares-discriminant analysis (PLS-DA). Respectively taking PFOS, PFOA and total PFC as the classifiers, serum metabolome can be differentiated between the lowest dose group (1st quartile PFCs) and the highest PFC dose group (4th quartile PFCs). Ten potential PFC biomarkers were identified, mainly involving in pollutant detoxification, antioxidation and nitric oxide (NO) signal pathways. These suggested that low-level environmental PFC exposure has significantly adverse impacts on glutathione (GSH) cycle, Krebs cycle, nitric oxide (NO) generation and purine oxidation in humans. To the best of our knowledge, this is the first report investigating the association of environmental PFC exposure with human serum metabolome alteration. Given the important biological functions of the identified biomarkers, we suggest that PFC could increase the metabolism syndromes risk including diabetes and cardiovascular diseases.

Organic solar cells based on multinary components are promising to further boost the device performance. The complex interplay of the morphology and functionality needs further investigations. Here, we report on a systematic study on the morphology evolution of prototype ternary systems upon adding sensitizers featuring similar chemical structures but dramatically different crystallinity, namely poly(3-hexylthiophene) (P3HT) and indene-C60-bis-adduct (ICBA) blends with poly[(4,4′-bis(2-ethylhexyl)dithieno[3,2-b:2′,3′-d]silole)-2,6-diyl-alt-(4,7-bis(2-thienyl)-2,1,3-benzothiadi-azole)-5,5′-diyl] (Si-PCPDTBT) and poly[2,6-(4,4-bis(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b′]-dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] (C-PCPDTBT), employing energy-filtered transmission electron microscopy (EFTEM) and resonant soft X-ray scattering (RSoXS). In addition, a combined density functional theory (DFT) and artificial neuronal network (ANN) computational approach has been utilized to calculate the solubility paramet...

Al-doped ZnO transparent films (AZO) with Ga partial substitution for Al were deposited on quartz at room temperature using radio frequency magnetron sputtering method. The film structure is characterized by ZnO hexagonal wurtzite phase with (002) preferred orientation, and the crystalline quality is improved with increasing Ga/Al ratio from 0 to 3.5. The Ga partial substitution leads to a great decrease in the room-temperature resistivity of AZO from 3.3 × 10−3 to 3.2 × 10−4 Ω cm, which is attributed to the increase of mobility from 2.1 to 8.8 cm2/V·s along with the large carrier concentrations in the magnitude of 1020∼1021cm−3. Combined with X-ray photoelectron spectroscopy analysis, it indicates that the addition of Ga is more effective as donors and causes less strain with respect to that of Al. Temperature dependent conductivity has been studied in the range of 80–320 K. The conductivity of the films with Ga/Al ≤ 2 demonstrates a linear relationship with temperature, which is rationalized by the weak localization mode arising from the constructive interference of scattering electrons. As the Ga/Al ratio increases to 3.5, the transport behavior turns to be metallic characterization at 255 K. This work demonstrates that the Ga partial substitution can be an effective way for obtaining AZO films having degenerate semiconducting behavior with a low resistivity in the magnitude of ∼10−4 Ω cm.

Radical resection is the first choice for hepatic alveolar echinococcosis (HAE). However, many patients with advanced HAE have no chance to be treated with curative resection owing to the long clinical latency. This study aimed to evaluate the necessity of aggressive operations, like palliative resection and orthotopic liver transplantation (OLT), in the management of advanced HAE. A retrospective study analyzed 42 patients with advanced HAE treated with palliative resection (N = 15), palliative nonresective procedures (N = 13), OLT (N = 3), or albendazole therapy alone (N = 11). The patients' condition before treatments was comparable among all the four groups. The overall 1-year, 3-year, and 5-year survival rates of the 42 cases were 81.0%, 45.2%, and 23.8%, respectively. No event occurred to end the follow-up during the 5-year observation period except death. The survival time (median ± standard error) of the palliative resection group (3.6 ± 1.4 years) was longer than that of the palliative nonresective procedures group (1.5 ± 0.2) and the albendazole therapy-alone group (1.0 ± 0.4). The 5-year survival rates after palliative resection and liver transplantation were 40.0% and 66.7%, compared with only 7.7% and 9.1% after palliative nonresective procedures or albendazole therapy alone. Therefore, we concluded that aggressive treatment with a multimodality strategy could contribute to prolonged survival in patients with advanced HAE. Moreover, the prognosis of the patients who received albendazole therapy alone or palliative nonresective procedures is poor.

Introduction: Treatment options continued to evolve in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), with many novel treatments available in recent years. The current study aimed to describe characteristics and treatment patterns of patients with R/R DLBCL who received ≥3 lines of therapy (LOT) using recent real-world data. Methods: This study used the PharMetrics Plus administrative claims database to identify adult patients who had ≥1 inpatient claim or ≥2 outpatient claims for DLBCL (ICD-10: C83.3) between 10/01/2015 and 09/30/2019. Patients were selected if they had ≥6-months of continuous eligibility before the first DLBCL diagnosis (index diagnosis). To capture newly diagnosed patients, the study excluded patients who had a claim for a possible DLBCL diagnosis and other hematologic malignancies (except hematologic conditions that may transform into DLBCL) before the index diagnosis and those who had stem cell transplantation (SCT) as the first treatment without prior chemotherapy (CT). An algorithm was developed to define LOT. In general, a new LOT was indicated by addition of a new drug or re-initiation of the previous LOT after a gap of ≥90 days. Pharmacologic therapies were categorized as CT or chemoimmunotherapy (CIT) or novel agent-based therapy (including brentuximab vedotin, ibrutinib, venetoclax, lenalidomide, obinutuzumab, nivolumab and pembrolizumab). SCT was counted as consolidation therapy instead of a separate line, while chimeric antigen receptor T cells (CAR-T) was counted as a separate line with preparation included (e.g., leukapheresis, bridging therapy, and lymphodepletion). Patients who received a third LOT (3L) comprised the study population, with the index date defined as the initiation date of 3L pharmacologic therapy or the infusion date of 3L SCT or CAR-T. 3L treatment distribution was described separately before and after the first CAR-T approval for DLBCL (10/18/2017). Treatment duration of 3L pharmacologic therapies was analyzed using Kaplan-Meier (KM) analysis. The proportion of patients initiating 4L during the observed follow-up period were described for all patients receiving a 3L. Due to the limited follow-up time and a high proportion of censoring, the current data was not mature to estimate rates of 4L initiation at different time points based on the KM analysis. All analyses were conducted for the overall study population and by treatment. Results: Among the 3,559 DLBCL patients receiving ≥1L treatment, 92.3% were treated with rituximab-containing regimens and 68.9% with R-CHOP or similar in 1L. There were 160 (4.5%) patients who received ≥3 LOT, with a mean age of 58.5 years and 64.4% male. Before CAR-T approval, 51 patients received 3L: 52.9% received CT/CIT, 33.3% received novel agent-based therapy, and 13.7% received SCT. After CAR-T approval, 109 patients received 3L: 45.9%, 30.3%, 7.3%, and 16.5% received CT/CIT, novel agent-based therapy, SCT and CAR-T, respectively. There were some differences in patient characteristics across treatment groups. Specifically, CAR-T patients had a relatively lower mean Charlson Comorbidity Index (CCI) score (2.9). The novel therapy group had a shorter median time from index diagnosis to index date (10.3 months). SCT patients were younger (mean 56.6 years) but with a relatively higher mean CCI score (4.2). The median follow-up time was 5.0 months and varied across treatments: from 3.9 months for CAR-T to 5.7 months for SCT. Among patients receiving pharmacologic treatments, the median treatment duration was 3.1 months and 2.8 months for the CT/CIT and novel agent-based therapy groups, respectively. During a median follow-up time of Conclusions: In patients with R/R DLBCL receiving 3L treatment post CAR-T approval, about 76% were treated with CT/CIT or novel agent-based therapies, though most of the novel agents are not indicated for DLBCL. CAR-T and SCT were used in 17% and 7% of patients, respectively. Treatment duration of 3L CT/CIT or novel agent-based therapies was short. A relatively high proportion of patients moved to the next LOT during a short follow-up period. These findings highlight the unmet need for more effective treatments among R/R DLBCL patients in 3L and later lines. Disclosures Xie: Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Wu:Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Liao:ADCT: Current Employment, Current equity holder in publicly-traded company. Du:Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Noman:Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Liang:Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Camardo:ADCT: Current Employment, Current equity holder in publicly-traded company. Chen:ADCT: Current Employment, Current equity holder in publicly-traded company.

Due to the ever-growing data and computing requirements of applications, it is very challenging for cloud scheduler to guarantee the optimal solution at a reasonable time. Although varieties of heuristics have been devised to solve the task scheduling problems in heterogeneous cloud systems, the results are still unsatisfactory, especially for large applications. Evolutionary algorithms outperform heuristics in terms of the quality of the solutions, however, they are often time-consuming and need lots of computing power. To address the above problems, this paper proposes an efficient differential evolution algorithm for task scheduling problems. This algorithm extends the canonical differential evolution in three aspects of hybrid initiation population, less greedy mutation and adaptive parameter adjustment. The results of the experiments indicate that our proposed algorithm consistently produces better solutions with smaller makespan and has the advantage of rapid convergence.

Avionics systems have to integrate and to manipulate numerous sensors, actuators and controllers while maintaining high quality of safety and reliability. Traditional chimney development method, which has shortages in the ability and efficiency, cannot be able to meet the increasing requirements of large scale avionics systems applications. In order to solve these problems, this paper proposes a FACE-based simulation and verification approach for avionics systems. First, by analysing the FACE standard, a FACE-based framework of avionics systems is designed to develop and deploy applications on different platforms. Then, based on the proposed framework, a simulation and verification approach for avionics systems designed by adopting the component packaging technology. Finally, the simulation and verification platform is established by integrating the component applications, exciter applications and display processing units in the avionics systems. Experimental results show that this approach not only guarantees the correctness and reliability of software applications, but also increases the flexibility, scalability and the cross-platform capability of avionics systems.

Background Any ailment in our organs can be visualized by using different modality signals and images. Hospitals are encountering a massive influx of large multimodality patient data to be analysed accurately and with context understanding. The deep learning techniques, like convolution neural networks (CNN), long short-term memory (LSTM), autoencoders, deep generative models and deep belief networks have already been applied to efficiently analyse possible large collections of data. Application of these methods to medical signals and images can aid the clinicians in clinical decision making. Purpose The aim of this study was to explore its potential application mechanism to the abalone basal ganglia neurons in rats based on deep learning. Patients and methods Firstly, in the GEO database, we obtained data on rat anesthesia, performing differential analysis, co-expression analysis, and enrichment analysis, and then we received the relevant module genes. Besides, the potential regulation of multi-factors on the module was calculated by hypergeometric test, and a series of ncRNA and TF were identified. Finally, we screened the target genes of anesthetized rats to gain insight into the potential role of anesthesia in rat basal lateral nucleus neurons. Results A total of 535 differentially expressed genes in rats were obtained, involving Mafb and Ryr2. These genes are clustered into 17 anesthesia-related expression disorder modules. At the same time, the biological processes favored by the module are regulation of neuron apoptotic process and transforming growth factor beta2 production. Pivot analysis found that 39 ncRNAs and 4 TFs drive anesthesia-related disorders. Finally, the mechanism of action was analyzed and predicted. The module was regulated by Acvr1. We believe that miR-384-5p in anesthetized rats can activate the TGF-beta signaling pathway. Further, it promotes anesthesia and causes exposure to the basal ganglia neuron damage of the amygdala. Conclusion In this study, the imbalance module was used to explore the multi-factor-mediated anesthesia application mechanism, which provided new methods and ideas for subsequent research. The results suggest that miR-384-5p can promote anesthesia damage to the abalone basal ganglia neurons in rats through a variety of biological processes and signaling pathways. This result lays a solid theoretical foundation for biologists to explore the application mechanism of anesthesiology further.

AimsThis study aimed to examine the association of different anatomical forms of obesity with adipose tissue insulin resistance and to assess the diagnostic value and contribution of obesity to adipose tissue insulin resistance.MethodsThis cross-sectional study included a total of 499 subjects aged 50 years or over. Multivariate regression analysis was conducted to clarify the association of different forms of obesity with adipose tissue insulin resistance (calculated as fasting insulin level×fasting free fatty acids level). Receiver operating characteristic cure analyses were used to assess the diagnostic value of each anthropometric indicator for adipose tissue insulin resistance. Attributable risk per cent and population attributable risk per cent were calculated to assess the contribution of obesity to adipose tissue insulin resistance.ResultsAfter adjustment for potential confounders, we showed that anthropometric indicators were all positively associated with adipose tissue insulin resistance. In males, waist circumference (WC) was the strongest associated factor (OR, 3.43 (95% CI 2.03 to 5.82)) and indicator (area under the curve (AUC): 0.79) of adipose tissue insulin resistance among those indicators. Here, abdominal obesity (WC≥90 cm) accounted for 64.9% of adipose tissue insulin resistance in the abdominal obese males. Accordingly, body mass index (BMI) was the strongest associated factor (OR,3.08 (95% CI 2.04 to 4.66)) and indicator (AUC: 0.78) of adipose tissue insulin resistance in females. Here, general obesity of BMI≥25 kg/m2 accounted for 66.2% of the adipose tissue insulin resistance in the general obese females. We further demonstrated that adipose tissue insulin resistance was associated or trended to be associated with the metabolic diseases of cardiovascular disease, type 2 diabetes and fatty liver in subjects with normal BMI and WC.ConclusionsMaintaining WC in males and BMI in females to a normal range could be an important strategy to significantly reduce the occurrence of adipose tissue insulin resistance and the subsequent metabolic diseases.