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Antihypertensive, lipid‐lowering, and blood glucose‐lowering drugs have slowed down the aging process in animal models. In humans, studies are limited, have short follow‐up times, and show mixed results. Therefore, this study aimed to estimate the effects of commonly used medications on functional aging, cognitive function, and frailty. We included information on individuals from three Swedish longitudinal population‐based studies collected between 1986 and 2014. Our exposures were the 21 most used groups of medications among individuals aged 65 years and older in the Swedish population in 2022. Functional aging index (n = 1191), cognitive function (n = 1094), and frailty index (n = 1361) were the outcomes of interest. To estimate the medication effects, we used a self‐controlled analysis, where each individual is his/her own control, thereby adjusting for all time‐stable confounders. The analysis was additionally adjusted for time‐varying confounders (chronological age, Charlson Comorbidity Index, smoking, body mass index, and the number of drugs). The participants were 65.5–82.8 years at the first in‐person assessment. Adrenergics/inhalants (effect size = 0.089) and lipid‐modifying agents/plain (effect size = 0.082) were associated with higher values of cognitive function (improvement), and selective calcium channel blockers with mainly vascular effects (effect size = −0.129) were associated with lower values of the functional aging index (improvement). No beneficial effects were found on the frailty index. Adrenergics/inhalants, lipid‐modifying agents/plain, and selective calcium channel blockers with mainly vascular effects may benefit functional biomarkers of aging. More research is needed to investigate their clinical value in preventing adverse aging outcomes. [ABSTRACT FROM AUTHOR]

Chemical structure segmentation constitutes a pivotal task in cheminformatics, involving the extraction and abstraction of structural information of chemical compounds from text-based sources, including patents and scientific articles. This study introduces a deep learning approach to chemical structure segmentation, employing a Vision Transformer (ViT) to discern the structural patterns of chemical compounds from their graphical representations. The Chemistry-Segment Anything Model (ChemSAM) achieves state-of-the-art results on publicly available benchmark datasets and real-world tasks, underscoring its effectiveness in accurately segmenting chemical structures from text-based sources. Moreover, this deep learning-based approach obviates the need for handcrafted features and demonstrates robustness against variations in image quality and style. During the detection phase, a ViT-based encoder-decoder model is used to identify and locate chemical structure depictions on the input page. This model generates masks to ascertain whether each pixel belongs to a chemical structure, thereby offering a pixel-level classification and indicating the presence or absence of chemical structures at each position. Subsequently, the generated masks are clustered based on their connectivity, and each mask cluster is updated to encapsulate a single structure in the post-processing workflow. This two-step process facilitates the effective automatic extraction of chemical structure depictions from documents. By utilizing the deep learning approach described herein, it is demonstrated that effective performance on low-resolution and densely arranged molecular structural layouts in journal articles and patents is achievable. [ABSTRACT FROM AUTHOR]

A 2–26.5GHz broadband amplifier monolithic microwave integrated circuit (MMIC) based on the 0.15 μm GaN high electron mobility transistor process has been developed. The broadband amplifier adopts a two‐stage distributed amplifier cascade structure, which improves the gain of the broadband amplifier. Further, the capacitive coupling is used to improve the gain bandwidth product of the power amplifier. To improve the output return loss of the wideband amplifier, a tuning stub is introduced at the output of the circuit. The on‐wafer measurement results show that the amplifier has a gain greater than 18 dB, gain flatness less than ±1.4 dB, and saturated output power >35 dBm with a >13% power added efficiency in the whole band. [ABSTRACT FROM AUTHOR]

Major advances in scientific discovery and insights that stem from the development and use of new techniques and models can bring remarkable progress to conventional toxicology. Although animal testing is still considered as the "gold standard" in traditional toxicity testing, there is a necessity for shift from animal testing to alternative methods regarding the drug safety testing owing to the emerging state-of-art techniques and the proposal of 3Rs (replace, reduce, and refine) towards animal welfare. This review describes some recent research methods in drug discovery toxicology, including in vitro cell and organ-on-a-chip, imaging systems, model organisms (C. elegans, Danio rerio, and Drosophila melanogaster), and toxicogenomics in modern toxicology testing. [ABSTRACT FROM AUTHOR]

• The paper reports results of first experiment on three tandem cylinders with helical strakes. • Three vibration modes are proposed through analysis of amplitude and frequency. • Helical strakes can reduce multi frequency instability phenomenon. • The best WIG suppression occurs in "S" helical strakes, and the vibration suppression efficiency of up to 665 %. • Further explanation of WIG suppression mechanism through vortex dynamics. Helical strakes as a classic passive control method for vortex-induced vibration (VIV), have been extensively studied, but wake-induced galloping (WIG) control of three tandem cylinders has received no previous attention. The current wind tunnel experimental study tries to fill this gap in the context of mechanical science. WIG of three tandem cylinders considering different structures of helical strakes is modeled and investigated. Helical strakes with varying heights G , pitches P , and cross-sectional shapes (square "S", involute "I", and D-shaped "D") are first designed. Wind tunnel tests are conducted to experimentally study the dynamics responses of tandem cylinders (m*ξ = 0.09) at different spacings, and three vibration modes are obtained. This study delves into the characterization and quantification of the impact of various parameters of helical strakes on WIG of three tandem cylinders. These aspects, scarcely addressed in existing research, are thoroughly explored through statistical analysis, focusing on vibration amplitude, vibration frequency, and wavelet analysis. It is found that helical strakes can effectively suppress the multi-frequency vibration instability of bare cylinders. For wind speeds below 6 m/s, the "S" helical strakes achieves a vibration suppression efficiency of up to 665 %; Three-dimensional computational fluid dynamics (3D-CFD) demonstrate the coupling effect in the flow field, revealing that the "S" helical strakes has a greater impact on boundary layer formation than the "D" helical strakes; Reducing the pitch of the helical strakes can enhance the disturbance ability of the spanwise position, thereby increasing its suppression effect. This work improves vibration reduction and sheds light on how the helical strakes' cross-section controls vibrations in the tandem cylinders. [Display omitted] [ABSTRACT FROM AUTHOR]

The drug repurposing of known approved drugs (e.g., lopinavir/ritonavir) has failed to treat SARS-CoV-2-infected patients. Therefore, it is important to generate new chemical entities against this virus. As a critical enzyme in the lifecycle of the coronavirus, the 3C-like main protease (3CLpro or Mpro) is the most attractive target for antiviral drug design. Based on a recently solved structure (PDB ID: 6LU7), we developed a novel advanced deep Q-learning network with a fragment-based drug design (ADQN–FBDD) for generating potential lead compounds targeting SARS-CoV-2 3CLpro. We obtained a series of derivatives from the lead compounds based on our structure-based optimization policy (SBOP). All of the 47 lead compounds obtained directly with our AI model and related derivatives based on the SBOP are accessible in our molecular library. These compounds can be used as potential candidates by researchers to develop drugs against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Abstract: To understand a putative causal link for depression and pain, we retrieved summary statistics from genome-wide association studies conducted for pain at 7 different body sites (N = 151,922-226,683) and major depression disorder (MDD, Ncase/control = 246,363/561,190). We conducted a bidirectional Mendelian randomization analysis using distinct genome-wide association studies-identified single nucleotide polymorphisms for each trait as instrumental variables and performed several sensitivity analyses to verify Mendelian randomization assumptions. We also conducted functional annotation analysis using 396 tissue-specific annotations from the roadmap project. Across 7 different body sites, genetic predisposition to depression was associated with pain at the neck/shoulder (odds ratio [OR] = 1.08 per one log-unit increase in depression risk, 95% confidence interval [CI]: 1.06-1.10), back (OR = 1.05, 95% CI: 1.04-1.07), abdominal/stomach (OR = 1.03, 95% CI: 1.02-1.04), as well as headache (OR = 1.10, 95% CI: 1.07-1.12), but not with pain on the face, hip, and knee. In the reverse direction, genetically instrumented multisite chronic pain (OR = 1.78 per one increment in the number of pain site, 95% CI: 1.51-2.11) and headache (OR = 1.55 per one log-unit increase in headache risk, 95% CI = 1.13-2.10) were associated with MDD. Functional annotation analysis showed differential clustering patterns where depression clustered closely with headache and neck/shoulder pain, exhibiting substantial brain tissue enrichment. Our study indicates that depression is a causal risk factor for headache and pain localized at neck/shoulder, back, and abdominal/stomach, rather than pain at face, hip, and knee, and suggests common neurological pathologies underlying the development of depression, headache, and neck/shoulder pain. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between obesity‐related traits and risk of rheumatoid arthritis (RA). Methods: We conducted genetic correlation analysis and a 2‐sample Mendelian randomization (MR) study, using genome‐wide genetic data based on >850,000 individuals of European ancestry. Summary statistics were collected from the largest genome‐wide association study conducted to date for body mass index (BMI; n = 806,810), waist‐to‐hip ratio (WHR; n = 697,734), WHR adjusted for BMI (WHRadjBMI; n = 694,649), and RA (ncase = 14,361, ncontrol = 43,923). We conducted cross‐trait linkage disequilibrium score regression and ρ‐HESS analyses to quantify genetic correlation between pairs of traits (causal overlap). For each obesity‐related exposure, we utilized independent, genome‐wide significant single‐nucleotide polymorphisms (P < 5 × 10−9) as instruments to perform MR analysis (causal relationship). We interrogated the causal relationship both in the general population and in a sex‐specific manner and calculated odds ratios (ORs) and 95% confidence intervals (95% CIs). Sensitivity analyses were performed to validate MR model assumptions. Results: Despite a negligible overall genetic correlation between the 3 obesity‐related traits and RA, we found significant local genetic correlations at several regions on chromosome 6 (positions 28–29M, 30–35M, and 50–52M), highlighting a shared genetic basis. We further observed an increased risk of RA per SD increment (4.8 kg/m2) in genetically predicted BMI (OR 1.22 [95% CI 1.09–1.37]). The effect was consistent across sensitivity analyses and comparable between sexes (OR 1.22 [95% CI 1.04–1.44] in male subjects and 1.19 [95% CI 1.04–1.36] in female subjects). However, we did not find evidence supporting a causal role of either WHR (OR 0.98 [95% CI 0.84–1.14]) or WHRadjBMI (OR 0.90 [95% CI 0.79–1.04]) in RA. Conclusion: Genetically predicted BMI significantly increases RA risk. Future studies are needed to understand the biologic mechanisms underlying this link. [ABSTRACT FROM AUTHOR]

The insect olfactory recognition system plays a crucial role in the feeding and reproductive behaviors of insects. The odorant receptor co-receptor (Orco), as an obligatory chaperone, is critical for odorant recognition by way of forming heteromeric complexes with conventional odorant receptors (ORs). To investigate the biological functions of Orco in perceiving host plant volatiles and sex pheromone, the Orco gene was identified from the chive maggot Bradysia odoriphaga transcriptome data. Multiple sequence alignment reveals that BodoOrco exhibits an extremely high sequence identity with Orcos from other dipteran insects. The expression of BodoOrco is significantly higher in adults than in larvae and pupae, and the BodoOrco gene is primarily expressed in the antennae of both sexes. Furthermore, the Y-tube assay indicated that knockdown of BodoOrco leads to significant reductions in B. odoriphaga adults' response to all tested host plant volatiles. The dsOrco -treated unmated male adults show less attraction to unmated females and responded slowly compared with dsGFP control group. These results indicated that BodoOrco is involved in recognition of sex pheromone and host plant volatiles in B. odoriphaga and has the potential to be used as a target for the design of novel active compounds for developing ecofriendly pest control strategies. [Display omitted] • BodoOrco gene is primarily expressed in the antennae of both sexes. • The knockdown of BodoOrco leads to significant reductions in B. odoriphaga adults' response to all testedplant volatiles. • The dsOrco -treated unmated male adults show less attraction to unmated females. [ABSTRACT FROM AUTHOR]

[Display omitted] • Carbonated recycled aggregate pervious concrete's purification abilities were analysed. • The adsorption capacity and microorganism degradation were quantitative assessed. • The water purification mechanism of pervious concrete was investigated. • A water purification model of pervious concrete was proposed. By carbonation treatment, the disadvantages of recycled aggregates (RAs), such as a high porosity, high crushing index and weak interface transition zone, can be improved to some extent. However, the purification performance of carbonated recycled aggregate pervious concrete (CRAPC) remains unknown. In this study, the purification performance of three types of pervious concrete prepared from natural aggregates (NAs), RAs and carbonated recycled aggregates (CRAs) was investigated. High-throughput sequencing of microorganisms was carried out as well. The results reveal that pervious concrete has a significant purification capacity, and the pervious concrete prepared by RAs and CRAs can further improve the ability to remove pollutants. Compared with natural aggregate pervious concrete (NAPC), recycled aggregate pervious concrete (RAPC) and CRAPC were more favourable for pollutant adsorption and microorganism growth due to their special pore structure. Furthermore, although the purification capacity of CRAPC was slightly inferior to that of RAPC, its mechanical properties and alkalinity were improved. In addition, the purification mechanism of pervious concrete mainly includes adsorption and microorganism degradation. The total COD removal amounts of NAPC, CRAPC and RAPC were 87.00 mg/L, 104.00 mg/L and 108.00 mg/L, respectively. The adsorption amounts were 10.00, 12.50, and 16.75 mg/L, and the microorganism degradation amounts were 77.00, 91.50 and 91.25 mg/L, respectively. Compared with adsorption, microorganism degradation plays a major role in total pollutant removal. Furthermore, a water purification model for pervious concrete is proposed. [ABSTRACT FROM AUTHOR]

Objective: We conducted a Mendelian randomization (MR) study to disentangle the comparative effects of lipids and apolipoproteins on ischemic stroke. Methods: Single‐nucleotide polymorphisms associated with low‐ and high‐density lipoprotein (LDL and HDL) cholesterol, triglycerides, and apolipoprotein A‐I and B (apoA‐I and apoB) at the level of genomewide significance (p < 5 × 10−8) in the UK Biobank were used as instrumental variables. Summary‐level data for ischemic stroke and its subtypes were obtained from the MEGASTROKE consortium with 514,791 individuals (60,341 ischemic stroke cases, and 454,450 non‐cases). Results: Increased levels of apoB, LDL cholesterol, and triglycerides were associated with higher risk of any ischemic stroke, large artery stroke, and small vessel stroke in the main and sensitivity univariable MR analyses. In multivariable MR analysis including apoB, LDL cholesterol, and triglycerides in the same model, apoB retained a robust effect (p < 0.05), whereas the estimate for LDL cholesterol was reversed, and that for triglycerides largely attenuated. Decreased levels of apoA‐I and HDL cholesterol were robustly associated with increased risk of any ischemic stroke, large artery stroke, and small vessel stroke in all univariable MR analyses, but the association for apoA‐I was attenuated to the null after mutual adjustment. Interpretation: The present MR study reveals that apoB is the predominant trait that accounts for the etiological basis of apoB, LDL cholesterol, and triglycerides in relation to ischemic stroke, in particular large artery and small vessel stroke. Whether HDL cholesterol exerts a protective effect on ischemic stroke independent of apoA‐I needs further investigation. ANN NEUROL 2020;88:1229–1236 [ABSTRACT FROM AUTHOR]

Efficient and accurate prediction of molecular properties, such as lipophilicity and solubility, is highly desirable for rational compound design in chemical and pharmaceutical industries. To this end, we build and apply a graph-neural-network framework called self-attention-based message-passing neural network (SAMPN) to study the relationship between chemical properties and structures in an interpretable way. The main advantages of SAMPN are that it directly uses chemical graphs and breaks the black-box mold of many machine/deep learning methods. Specifically, its attention mechanism indicates the degree to which each atom of the molecule contributes to the property of interest, and these results are easily visualized. Further, SAMPN outperforms random forests and the deep learning framework MPN from Deepchem. In addition, another formulation of SAMPN (Multi-SAMPN) can simultaneously predict multiple chemical properties with higher accuracy and efficiency than other models that predict one specific chemical property. Moreover, SAMPN can generate chemically visible and interpretable results, which can help researchers discover new pharmaceuticals and materials. The source code of the SAMPN prediction pipeline is freely available at Github (https://github.com/tbwxmu/SAMPN). [ABSTRACT FROM AUTHOR]

Heavy metals, a class of persistent environmental toxicants, are harmful to human health. Cd and Pb are two of the most common toxic heavy metals that have been linked with cancers and malfunction of the nervous system. Notably, contamination of Mn usually coexisted with Cd and Pb in environmental and occupational settings. Studies regularly examined the toxic effects on individual metals; however, potential health and toxic effects of mixtures containing two or more heavy metals are unknown. Here, we investigated toxic effects of Cd, Pb, Mn, and their binary and ternary mixtures in the nematode Caenorhabdities elegans. The toxic outcomes, including effects on growth, reproduction, and feeding, were measured via high-throughput platform analysis. The transgenic strain BY250 with GFP in dopaminergic neurons was used to explore the neurodegenerative effects induced by single metals or their mixtures. The combination index(CI) for mixtures effect was calculated using isobolograms methods. Following the exposure, we found significant toxic effects in C. elegans. For single metals, the toxicity order for growth, reproduction, and feeding were Pb > Cd > Mn. For mixtures, the mixture of Cd + Mn induced a less than addictive effect in C. elegans , whereas the mixtures of Cd + Pb, Pb + Mn, and Cd + Pb + Mn induced greater-than-additive effects. Both single metals and their mixtures induced abnormality in dopaminergic neurons. These results showed combinative toxic and neurodegenerative effects of heavy metal mixtures, and future studies will focus on characterization of concentration-response patterns and identification of potential molecular mechanisms in C. elegans model. • The toxic effects of heavy metal mixtures were assessed using high-throughput screening assay in C. elegans. • The mixture of Cd + Mn induced antagonistic effect in C. elegans , whereas the mixtures of Cd + Pb, Pb + Mn, and Cd + Pb + Mn induced greater-than-additive (synergistic) effects. • Both single metals and their mixtures induced abnormality in dopaminergic neurons in transgenic strain BY250. [ABSTRACT FROM AUTHOR]

Aflatoxins are a group of potent fungal metabolites produced by Aspergillus and commonly contaminate groundnuts and cereal grains. Aflatoxin B 1 (AFB 1), the most potent mycotoxin, has been classified as Group 1 human carcinogen because it can be metabolically activated by the cytochrome P450 (CYP450) in the liver to form AFB 1 -DNA adducts and induce gene mutations. Increasing evidence has shown the gut microbiota as a key mediator of AFB 1 toxicity through multiple interactive host-microbiota activities. To identify specific bacterial activity that modulates AFB 1 toxicity in Caenorhabditis (C.) elegans , we established a 3-way (microbe-worm-chemical) high-throughput screening system using C. elegans fed E. coli Keio collection on an integrated robotic platform, COPAS Biosort. We performed 2-step screenings using 3985 Keio mutants and identified 73 E. coli mutants that modulated C. elegans growth phenotype. Four genes (aceA, aceB, lpd , and pflB) involved in the pyruvate pathway were identified from the screening and confirmed to increase the sensitivity of all animals to AFB 1. Taking together, our results indicated that disturbances in bacterial pyruvate metabolism might have a significant impact on AFB 1 toxicity in the host. [Display omitted] • Bacterial diets have large impacts on worm growth in response to AFB 1. • 3-way (Microbe-host-chemical) high-throughput screening platform identified up to 73 E. coli mutants modulating host growth. • Four genes (aceA, aceB, lpd , and pflB) were identified modulating AFB 1 toxicity in C. elegans. • Our data showed that bacterial pyruvate pathway may be critical in meditating AFB 1 toxicity in C. elegans. [ABSTRACT FROM AUTHOR]

[Display omitted] • Aggregate carbonation and concrete carbonation treatments with recycled aggregate pervious concrete were compared. • The mechanisms of aggregate carbonation and concrete carbonation were investigated. • The environmental benefits of aggregate carbonation and concrete carbonation were analysed. • The concrete carbonation method is recommended for recycled aggregate pervious concrete. Using recycled aggregates (RAs) to manufacture pervious concrete is one of the resource utilization methods of construction and demolition waste (C&DW). However, because of the poor quality of RAs, the mechanical strength of recycled aggregate pervious concrete (RAPC) is comparatively low, which limits its application to a certain extent. In this study, two types of carbonated recycled aggregate pervious concrete (CRAPC-I and CRAPC-II) were prepared by aggregate carbonation and concrete carbonation, respectively. First, the physical properties, such as the permeability, hardened density, porosity, and compressive strength, of CRAPC-I, CRAPC-II and recycled aggregate pervious concrete (RAPC) were measured. Second, the microstructure and mineralogical composition were investigated by scanning electron microscopy (SEM), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). Besides, the strengthening mechanisms and environmental benefits of the CRAPC were analysed. The obtained results show that both aggregate carbonation and concrete carbonation can improve the compressive strength while ensuring acceptable permeability of pervious concrete, and concrete carbonation is more effective. Under the same carbonation conditions, concrete carbonation sequesters more CO 2 than aggregate carbonation, which is more beneficial to the environment. This study may have the potential for the promotion and application of CRAPC. [ABSTRACT FROM AUTHOR]

• The effects of meta-surface structure on energy harvesting under elastic interference are considered. • By analyzing the frequency, the 'coupled vortex-induced vibration' is proposed. • The performance of the 0.6H cylinder is better，116.3% higher than taht of the 1.0H cylinder. • "V" meta-surface has the best performance, and its output power is 66.04% higher than that of 0.6H cylinder. Energy harvesting by means of flow-induced vibrations (FIVs) enables continuous supply of power to micro electromechanical systems. Furthermore, FIV is one of the most popular means of energy harvesting. Inspired by wake-induced galloping and aerodynamic changes to a meta-surface structure, a wind-energy harvester (WEH) with a simple structure and high energy density is designed based on FIV (FIV-WEH). Furthermore, the effect of the meta-surface structure on FIV enhancement under elastic interference is discussed. Four experimental models with different heights under an elastic interference are designed: 0.8H cylinder (0.20 m), 0.6H cylinder (0.15 m), 0.4H cylinder (0.10 m), and 0.2H cylinder (0.05 m). The results show that the performance of the 0.6H cylinder is the strongest. It is 116.3% stronger than that of an ordinary cylinder. Based on the experimental models, a series of grooves with different angles is designed, abbreviated as 'Vα', where 'V' indicates that the repeating units are V-shaped and α indicates the centre angle corresponding to the chord length between adjacent repeating units. The addition of a meta-surface structure significantly changes the vibration behaviour of FIV-WEHs. Moreover, the larger the meta-surface structure size, the earlier the coupling vibration region appears. Therefore, the coupling vibration region first appeared on the 'V12' meta-surface, then on the 'V7.2' meta-surface, and finally, on the 'V3.6' meta-surface. A 'peak' phenomenon is observed, and its reason is explained by analysing the frequency. This study also identified a 'coupled vortex-induced vibration' region. Three different shapes of meta-surface structures are designed: 'V', 'T', and 'D' meta-surfaces. The results show that the performance of the 'V' and 'D' meta-surfaces is significantly improved compared to that of a bare cylinder. The 'V' meta-surface can increase the effective wind-speed bandwidth for energy utilization and exhibits the best performance, which is 66.04% higher than that of the 0.6H cylinder. Furthermore, the reason for the enhanced energy-harvesting performance of the 'V' meta-surface is explained through numerical simulations. : [Display omitted] [ABSTRACT FROM AUTHOR]

Battery Electric Vehicles (BEVs) are considered to have higher energy efficiency and advantages to better control CO2 emissions compared to Internal Combustion Engine Vehicles (ICEVs). However, in the context that a large amount of thermal power is still used in developing countries, the CO2 emission reduction effectiveness of BEVs can be weakened or even counterproductive. To reveal the impact of the electricity generation mix on carbon emissions from vehicles, this paper compares the life cycle carbon emissions of BEVs with ICEVs considering the regional disparity of electricity generation mix in China. According to Life Cycle Assessment (LCA) analysis and regional electricity carbon intensity, this study demonstrates that BEVs in the region with high penetration of thermal power produce more CO2 emissions, while BEVs in the region with higher penetration of renewable energy have better environmental performance in carbon emission reduction. For instance, in the region with over 50% penetration of renewable energy, a BEV can reduce more CO2 (18.32 t) compared to an ICEV. Therefore, the regions with high carbon emissions from vehicles need to increase the proportion of renewable generation as a priority rather than promoting BEVs. [ABSTRACT FROM AUTHOR]

Simple Summary: It is well known that animal morphological traits are influenced by both genetic and environmental factors, but further research is needed to investigate the extent to which the environment influences morphological traits under the same genetic background. As one of the most widely distributed freshwater shrimp species in the world, the crayfish has a strong territorial and combative habit, so the influence of the aquaculture environment on its morphological development is more obvious. Meanwhile, under the same environment, different sexes of crayfish also showed corresponding morphological differences due to their reproductive functions. In this study, juvenile crayfish hatched from the same population were cultured in different growing environments, and the effects of environment and sex on their morphological characteristics were evaluated by mathematical models such as correlation analysis, pathway analysis, and gray correlation, so as to provide a basis for the artificial selection of crayfish in the later stage of development. In this study, juvenile crayfish hatched from the same population were cultured in different growing environments: pond (D1), paddy field (D2), and aquaculture barrel (D3), and fed for 60 days. Crayfishes were selected randomly, females and males, 50 tails each from six groups (D1-♀, D1-♂, D2-♀, D2-♂, D3-♀, D3-♂) to measure the following morphological traits: full length (X1), body length (X2), chelicerae length (X3), chelicerae weight (X4), cephalothorax length (X5), cephalothorax width (X6), cephalothorax height (X7), eye spacing (X8), caudal peduncle length (X9), and caudal peduncle weight (X10). We found that the coefficient of variation (CV) of X4 was the largest in each culture mode, and males (28.58%~38.67%) were larger than females (37.76%~66.74%). The CV of X4 of crayfish cultured in D1 and D2 was larger than that of D3. All traits except X8 were positively correlated with body weight (p < 0.05). After pathway analysis, we found that X4, X5, X7, and X10 were significantly correlated with the body weight of D1-♀; the equation was YD1-♀ = −29.803 + 1.249X4 + 0.505X5 + 0.701X7 + 1.483X10 (R2 = 0.947). However, X2, X4, and X6 were significantly correlated with the body weight of D1-♂; the equation was YD1-♂ = −40.881 + 0.39X2 + 0.845X4 + 1.142X6 (R2 = 0.927). In D2-♀, X1, X4, X5, and X10 were significantly correlated with body weight; the equation was YD2-♀ = −12.248 + 0.088X1 + 1.098X4 + 0.275X5 + 0.904X10 (R2 = 0.977). X4 and X5 played a major role in the body weight of D2-♂ with the equation: YD2-♂ = −24.871 + 1.177X4 + 0.902X5 (R2 = 0.973). X3 and X10 mainly contributed to the body weight of D3-♀ with the equation: YD3-♀ = −22.476 + 0.432X3 + 3.153X10 (R2 = 0.976). X1 and X4 mainly contributed to the body weight of D3-♂ with the equation: YD3-♂ = −34.434 + 0.363X1 + 0.669X4 (R2 = 0.918). Comparing the pathway analysis with the gray relation analysis, we could conclude that the traits most correlated with body weight in D1-♀ were X10 and X7; in D1-♂, X6; in D2-♀, X10, X1, and X5; in D2-♂, X5; in D3-♀, X10; and in D3-♂, X4 and X1. [ABSTRACT FROM AUTHOR]

Nickel is the most prevailing metal allergen with the highest sensitization rate among the "TOP 25" contact allergens and can affect about 15% of the human population. It is an essential trace metal in plants, animals, and humans. However, the environmental levels of nickel are considerably higher than what is needed for human life. Exposure to high levels of nickel can lead to skin allergies, lung fibrosis, and carcinogenesis. Few existing studies have closely examined the toxicity of nickel, let alone investigated the effective detoxification pathways. Here, we developed a high-throughput screening platform to comprehensively evaluate the nickel toxicity in wild-type C. elegans and explore the underlying detoxification mechanisms in transgenic nematodes. We demonstrated that nickel exerted multiple toxic effects on growth, brood size, feeding, and locomotion in C. elegans. Of which, brood size is the most sensitive endpoint. Nickel was found to first bind to phytochelatin (PC) after entering the worms' body and this PC-Ni complex was further transported by the ABC transporter, CeHMT-1, into the coelomocytes for further detoxification. Our study also demonstrated that the high-throughput screening platform is a promising system for evaluation and investigation of the ecological risks of heavy metals. • NiSO4 effected growth, brood size, feeding, and locomotion in N2 C. elegans. • Of the 4 tested endpoints, brood size is the most sensitive endpoint. • Nickel absorbed by the worm and forms the PC-Ni complex with phytochelatin. • The PC-Ni complex were transported by HMT-1 into coelomocytes for detoxification. [ABSTRACT FROM AUTHOR]

Background Objective Materials and methods Results Discussion and conclusion Apoptosis is an important pathologic mechanism of erectile dysfunction after radical prostatectomy. Studies have shown that programmed cell death factor 4 is connected to the modulation of apoptosis in many cells. However, the programmed cell death factor 4 function in the cavernous nerve injury erectile dysfunction is unclear.This investigation aimed to explore the programmed cell death factor 4 function in erectile dysfunction in rats with bilateral cavernous nerve crush.The experiment used 30 male Sprague Dawley rats (18 months old) that were screened for normal erectile function by the apomorphine test. Ten rats were randomized into Sham and bilateral cavernous nerve crush groups to detect changes in programmed cell death factor 4 expression. The remaining 20 rats were distributed at random to four groups: the Sham group treated by sham surgery, the phosphate‐buffered saline group, the lentivirus containing negative control short hairpin RNA group, and the lentivirus containing short hairpin RNA targeting programmed cell death factor 4 group underwent bilateral cavernous nerve crush and were afterward administered intracavernous injections of phosphate‐buffered saline, lentivirus containing negative control short hairpin RNA, or lentivirus containing short hairpin RNA targeting programmed cell death factor 4. Electrical stimulation of the cavernous nerve was conducted 2 weeks later for penile erectile function assessment. The cavernous tissue was collected for histological analysis and western blotting.The apoptosis level in rat corpus cavernosum was elevated, and programmed cell death factor 4 expression was increased after bilateral cavernous nerve crush. Knockdown of programmed cell death factor 4 significantly improved erectile function in bilateral cavernous nerve crush rats. Furthermore, lentivirus containing short hairpin RNA targeting programmed cell death factor 4 treatment raised smooth muscle content and attenuated cavernous fibrosis and apoptotic levels. Additionally, programmed cell death factor 4 was found to mediate the PI3K/AKT pathway.Elevated programmed cell death factor 4 expression may be an important pathogenetic mechanism for erectile dysfunction after bilateral cavernous nerve crush, and the knockdown of programmed cell death factor 4 enhanced erectile function in 18‐month‐old rats after cavernous nerve damage. The potential mechanism may be the stimulation of the PI3K/AKT pathway to attenuate the cavernous apoptosis level. [ABSTRACT FROM AUTHOR]

Age is a dominant risk factor for some of the most common neurological diseases. Biological ageing encompasses interindividual variation in the rate of ageing and can be calculated from clinical biomarkers or DNA methylation data amongst other approaches. Here, we tested the hypothesis that a biological age greater than one's chronological age affects the risk of future neurological diagnosis and the development of abnormal signs on clinical examination. We analysed data from the Swedish Adoption/Twin Study of Aging (SATSA): a cohort with 3175 assessments of 802 individuals followed-up over several decades. Six measures of biological ageing were generated: two physiological ages (created from bedside clinical measurements and standard blood tests) and four blood methylation age measures. Their effects on future stroke, dementia or Parkinson's disease diagnosis, or development of abnormal clinical signs, were determined using survival analysis, with and without stratification by twin pairs. Older physiological ages were associated with ischaemic stroke risk; for example one standard deviation advancement in baseline PhenoAgePhys or KDMAgePhys residual increased future ischaemic stroke risk by 29.2% [hazard ratio (HR): 1.29, 95% confidence interval (CI) 1.06–1.58, P = 0.012] and 42.9% (HR 1.43, CI 1.18–1.73, P = 3.1 × 10−4), respectively. In contrast, older methylation ages were more predictive of future dementia risk, which was increased by 29.7% (HR 1.30, CI 1.07–1.57, P = 0.007) per standard deviation advancement in HorvathAgeMeth. Older physiological ages were also positively associated with future development of abnormal patellar or pupillary reflexes, and the loss of normal gait. Measures of biological ageing can predict clinically relevant pathology of the nervous system independent of chronological age. This may help to explain variability in disease risk between individuals of the same age and strengthens the case for trials of geroprotective interventions for people with neurological disorders. [ABSTRACT FROM AUTHOR]

Identifying metabolic biomarkers of frailty, an age‐related state of physiological decline, is important for understanding its metabolic underpinnings and developing preventive strategies. Here, we systematically examined 168 nuclear magnetic resonance‐based metabolomic biomarkers and 32 clinical biomarkers for their associations with frailty. In up to 90,573 UK Biobank participants, we identified 59 biomarkers robustly and independently associated with the frailty index (FI). Of these, 34 associations were replicated in the Swedish TwinGene study (n = 11,025) and the Finnish Health 2000 Survey (n = 6073). Using two‐sample Mendelian randomization, we showed that the genetically predicted level of glycoprotein acetyls, an inflammatory marker, was statistically significantly associated with an increased FI (β per SD increase = 0.37%, 95% confidence interval: 0.12–0.61). Creatinine and several lipoprotein lipids were also associated with increased FI, yet their effects were mostly driven by kidney and cardiometabolic diseases, respectively. Our findings provide new insights into the causal effects of metabolites on frailty and highlight the role of chronic inflammation underlying frailty development. [ABSTRACT FROM AUTHOR]

The decomposition characteristics of SF6 gas-insulated equipment remarkably vary under different working pressures (0.3?0.7 MPa). Thus, the influence of pressure should be considered when adopting decomposed components for spark discharge fault diagnosis. A series of experiments on SF6 spark discharge decomposition under various pressures were performed on the spark discharge simulation experimental platform. The influence of pressure on SF6 spark discharge decomposed components were analyzed quantitatively combined with molecule chemical decomposition mechanisms. Results show that the species of spark decomposed components do not vary under different pressures. However, pressure directly affects the accumulated energy of the electrons in the spark channel, leading to diverse dissociation intensities of electrons on SF6. This phenomenon further affects the rate of neutral-neutral molecule and ion-molecule reactions responsible for the decomposed components. Finally, the yields and effective generation rates of decomposed components CF4, SOF4, SO2F2, SOF2, and SO2 decline with varying degrees under increasing pressure. Moreover, mathematic regression equations were derived for the effective generation rates of the components influenced by pressure. [ABSTRACT FROM AUTHOR]

Searching for reliable indicators for evaluating prognosis diagnosed with clear cell renal cell carcinoma (ccRCC) is crucial for improving clinical therapies. However, current researches have looked mainly at the prognostic value of a single intratumoral indicator, neglecting tumor‐infiltrating immune cells (TIICs) in the microenvironment. This study examined whether the integration of Ring finger protein 43 (RNF43) expression and CD163+ tumor‐associated macrophage (TAM) infiltration in combination with clinical indexes forecast ccRCC patient outcome with relatively high accuracy. Firstly, the expression of RNF43 and CD163 were detected with immunohistochemistry. Totally, 346 ccRCC patients were random separated evenly into training and validation datasets to make further analyses. We found that RNF43 expression was negatively correlated with infiltration level of CD163+ TAM in ccRCC, which was closely associated with the TNM stage and outcome of these patients. The multiple regression analysis demonstrated that RNF43, CD163, and TNM stage could function as independent risk factors in overall survival (OS) and progression‐free survival (PFS) prediction of ccRCC. Furthermore, a better postoperative prognosis index for ccRCC patients was obtained by combining RNF43 and CD163+ TAMs, which assessed with time‐dependent C‐index analyses and a nomogram. Consequently, combining RNF43 and CD163+ TAMs along with TNM stage acquired robust accuracy in forecasting outcome of patients with ccRCC. In conclusion, combining intratumoral RNF43 expression, CD163+ TAM infiltration, and TNM stage could significantly enhance the veracity in forecasting postoperative outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Statins are lipid-lowering drugs and starting treatment has been associated with DNA methylation changes at genes related to lipid metabolism. However, the longitudinal pattern of how statins affect DNA methylation in relation to lipid levels has not been well investigated. Methods: We conducted an epigenetic association study in a longitudinal Swedish twin sample in previously reported lipid-related CpGs (cg10177197, cg17901584 and cg27243685). First, we applied a mixed-effect model to assess the association between blood lipids (total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), total triglyceride (TG)) and DNA methylation. Then, we performed a piecewise latent linear–linear growth curve model (LGCM) to explore the long-term changing pattern of lipids and methylation in response to statin treatment. Finally, we used a bivariate autoregressive latent trajectory model with structured residuals (ALT-SR) to analyze the cross-lagged effects in different lipid-CpG pairs in statin users and non-users. Results: We replicated the associations between TC, LDL, HDL and DNA methylation level in cg17901584 and cg27243685 (P values ranged from 4.70E−12 to 1.84E−04). From the piecewise LGCM, we showed that TC and LDL significantly decreased in statin users before treatment started and then remained stable. For non-statin users, we only found a slightly significant decreasing trend for TC and TG. We observed a similar dynamic pattern for methylation levels at cg27243685 and cg17901584. Before statin initiation, cg27243685 showed a significantly increasing trend and cg17901584 a decreasing trend, but post-treatment, there were no additional changes. From the ALT-SR model, we found TG levels to be significantly associated with the DNA methylation level of cg27243685 at the next measurement in statin users (estimate = 0.383, 95% CI: 0.173, 0.594, P value < 0.001). Conclusions: Longitudinal blood lipid and DNA methylation levels change after statin treatment initiation, where the latter is mostly a response to alterations in lipid levels and not vice versa. [ABSTRACT FROM AUTHOR]

The latest biological findings observe that the motionless "lock‐and‐key" theory is not generally applicable and that changes in atomic sites and binding pose can provide important information for understanding drug binding. However, the computational expenditure limits the growth of protein trajectory‐related studies, thus hindering the possibility of supervised learning. A spatial‐temporal pre‐training method based on the modified equivariant graph matching networks, dubbed ProtMD which has two specially designed self‐supervised learning tasks: atom‐level prompt‐based denoising generative task and conformation‐level snapshot ordering task to seize the flexibility information inside molecular dynamics (MD) trajectories with very fine temporal resolutions is presented. The ProtMD can grant the encoder network the capacity to capture the time‐dependent geometric mobility of conformations along MD trajectories. Two downstream tasks are chosen to verify the effectiveness of ProtMD through linear detection and task‐specific fine‐tuning. A huge improvement from current state‐of‐the‐art methods, with a decrease of 4.3% in root mean square error for the binding affinity problem and an average increase of 13.8% in the area under receiver operating characteristic curve and the area under the precision‐recall curve for the ligand efficacy problem is observed. The results demonstrate a strong correlation between the magnitude of conformation's motion in the 3D space and the strength with which the ligand binds with its receptor. [ABSTRACT FROM AUTHOR]

Mycotoxins seriously threaten the quality of maize seriously around the world. A total of 426 samples of maize kernel from northeast and northwest China were analyzed in this study. Ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) was performed to analyze the mycotoxin contamination of maize samples. The results showed that it was contaminated by mycotoxins in maize. The average contamination levels of fumonisins, deoxynivalenol, aflatoxins, zearalenone, ochratoxin A, T-2 and HT-2 were 937, 431, 22, 27, 2 and 12 μg/kg, respectively. Concentration of mycotoxins in some samples exceeded their limit, but most were still at safe levels. The contamination level of FBs and DON were most significative. The proportion of mycotoxins exceeding the maximum limit standard was in the following order: 8.0%, 8.0%, 7.0%, 1.6%, 1.4% and 0.0%. The contamination of mycotoxins in maize varies from region to region. [ABSTRACT FROM AUTHOR]

Self-recovery ability after over thermal fault decomposition is a fundamental factor determining the stability of environmentally friendly insulation medium C5F10O in engineering applications. This article proposes 42 possible reaction pathways for the decomposition products of C5F10O to reform C5F10O after overheating fault based on its thermal decomposition and industrial synthesis pathways. Dominant reaction paths and reactants in the recovery process at temperature of 298–1000 K are theoretically analyzed according to the chemical equilibrium constant and rate constant, which were calculated based on the density functional theory using the thermodynamics properties of the reactions such as activation energy and enthalpy. According to the results, at low temperatures, 26 of the 42 proposed reactions have the equilibrium constants greater than 1, and the rate constants of them are much higher than that of the decomposition reactions, proving that decomposed C5F10O can be partly recovered after the overheating fault is removed. Among the recovery pathways, reactions with primary or secondary decomposition products of C5F10O as the reactants hold higher equilibrium constants and are the dominant reactions for the recovery process. R11, R8, and R5 hold the largest rate constants in similar reactions and contribute the most to the restoration of C5F10O, that is, (CF3)2CFCO $\cdot $ , (CF3)2CFCOF $\cdot $ , and CF3OCCF(CF3)2 are the dominant reactants for the formation of C5F10O. And the synthesis reactions R22, R17, R7, and R15 of these reactants are also necessary for the self-recovery process of C5F10O. [ABSTRACT FROM AUTHOR]

[Display omitted] • Effect of Fe- or Ni-based catalyst on the pathway of hydrogen transfer is examined. • Fe-based catalyst minimize H-shuttle effect of solvent, while Ni catalyst enhances it. • DHA exhibits lower capacity of hydrogen donor than THN as liquefied solvent. • THN more effectively transfers gaseous H 2 to radicals from coal pyrolysis than DHA. The H-donating solvent plays a crucial role in both oil yield and products distribution during direct coal liquefaction. Meanwhile, liquefaction catalyst significantly influences the H-donating behavior of the solvent and the pathways of hydrogen transfer. In view of insufficient understanding on the impact of catalysts on H-donating behavior of solvent and hydrogen transfer pathways in direct liquefaction, in this study, non-H-donating solvents including naphthalene, 1-methylnaphthalene and pyrene (Py) and H-donating solvents including tetralin (THN) and 9,10-dihydroanthracene (DHA) were chosen as the solvents. The Shenhua nano-sized Fe-based and the prepared Ni/Al 2 O 3 catalysts were used to investigate their effect on H-donating behavior of the solvent and H-shuttling mechanism. Results show that liquefaction solvent obviously affects coal conversion and products distribution no matter Fe-based or Ni-based catalyst was used. When non-H-donating solvent is used as liquefaction solvent, coal conversion is lower than that with THN or DHA as solvent. The addition of Py to THN as solvent improves the utilization of effective hydrogen in non-catalytic liquefaction, which is ascribed to hydrogen transfer effect of Py; however, hydrogen transfer mainly occurs through direct combination of gaseous H 2 with radicals generated from coal pyrolysis in presence of Fe-based catalyst, with minimal shuttle action of solvent hydrogen. On the contrary, the Ni-based catalyst aids in enhancing the hydrogen shuttle effect of the solvent, and the hydrogen transfer path primarily involves H 2 to solvent and then to coal, which is ascribed to good hydrogenation ability of Ni-based catalyst. Under the action of Fe-based catalyst, DHA as liquefaction solvent exhibits lower H-donating capability compared to THN, and approximately 65% of total hydrogen consumption is effectively utilized for coal liquefaction, along with about 35% of total hydrogen consumption for the hydrogenation, ring opening, and side-chain scission reactions of DHA. However, about 96% of total hydrogen consumption is effectively utilized for coal liquefaction when THN used as solvent, indicating that THN as liquefication solvent is more conducive to the transfer of gaseous hydrogen to free radical fragments from coal pyrolysis compared to DHA. [ABSTRACT FROM AUTHOR]

[Display omitted] • 1b and 1f showed 2.9 ∼ 4.5-fold more potent TRPV4 inhibition activity than RN9893. • The IC 50 s of 1b and 1f against TRPV4 are 0.71 ± 0.21 and 0.46 ± 0.08 μM, respectively. • 1b and 1f significantly alleviated acute lung injury symptoms in mice. • RN9893 analogues are potent TRPV4 inhibitors. RN-9893, a TRPV4 antagonist identified by Renovis Inc., showcased notable inhibition of TRPV4 channels. This research involved synthesizing and evaluating three series of RN-9893 analogues for their TRPV4 inhibitory efficacy. Notably, compounds 1b and 1f displayed a 2.9 to 4.5-fold increase in inhibitory potency against TRPV4 (IC 50 = 0.71 ± 0.21 μM and 0.46 ± 0.08 μM, respectively) in vitro , in comparison to RN-9893 (IC 50 = 2.07 ± 0.90 μM). Both compounds also significantly outperformed RN-9893 in TRPV4 current inhibition rates (87.6 % and 83.2 % at 10 μM, against RN-9893′s 49.4 %). For the first time, these RN-9893 analogues were profiled in an in vivo mouse model, where intraperitoneal injections of 1b or 1f at 10 mg/kg notably mitigated symptoms of acute lung injury induced by lipopolysaccharide (LPS). These outcomes indicate that compounds 1b and 1f are promising candidates for acute lung injury treatment. [ABSTRACT FROM AUTHOR]

In the multimedia era, exploding image and video data highlight the importance of video compression for storage and transmission. The All-Intra structure is a coding mode in HEVC and VVC, in which each frame is encoded using intra coding, and in this paper learned All-Intra coding is explored on the basis of the research of the learned image compression. A channel-wise contextual module based on channel segmentation is introduced to fully exploit non-local information. Then, two distinct attention mechanisms are designed for different feature layers to enhance the effectiveness of the transform network. Additionally, a post-processing module is employed to enhance the quality of decoded frames. Experimental results on the Kodak and Tecnick datasets demonstrate that the proposed method performs better than the majority of the recent learning-based methods and traditional image codecs (BPG, JPEG2000 and JPEG), and also perform better than traditional video codecs in terms of PSNR. • A novel video compression framework specially designed for I frame is introduced. • A channel-wise contextual module enhances context-based entropy modeling. • A post-processing module aims to enhance the quality of the reconstructed frames. • Two distinct attention mechanisms are designed for different feature layers. [ABSTRACT FROM AUTHOR]

Background. Genetic polymorphisms in mammalian target of rapamycin (mTOR) signaling axis can influence the susceptibility of cancer. The relationship between mTOR gene variants rs2295080 T/G and rs1883965 G/A and the risk of cancer remains inconsistent. The present study is aimed at comprehensively investigating the association between mTOR polymorphisms and susceptibility to cancer. Methods. We conducted a comprehensive assessment using odds ratios (ORs), corresponding 95% confidence intervals (CIs), and in silico tools to evaluate the effect of mTOR variations. Immunohistochemical staining (IHS) and GSEA analysis were used to investigate the expression of mTOR in urinary system cancer. Results. The pooled analysis involved 22 case-control studies including 14,747 cancer patients and 16,399 controls. The rs2295080 T/G polymorphism was associated with the risk of cancer (G-allele versus T-allele, OR = 0.89 , 95 % CI = 0.80 –0.98, P = 0.023 ; GT versus TT, OR = 0.88 , 95 % CI = 0.81 –0.96, P = 0.004 ; GG+GT versus TT, OR = 0.87 , 95 % CI = 0.78 –0.96, P = 0.008), especially for cancers of the urinary system, breast, and blood. Variation rs1883965 G/A was associated with cancer susceptibility, especially for digestive cancer. IHS analysis showed that mTOR was upregulated in prostate and bladder cancer. GSEA revealed that the insulin signaling pathway, lysine degradation pathway, and mTOR signaling pathway were enriched in the high mTOR expression group. Conclusions. The mTOR rs2295080 T/G polymorphism may be associated with susceptibility of urinary cancer. The expression of mTOR is positively correlated with tumor malignancy in prostate cancer. [ABSTRACT FROM AUTHOR]

Non‐obstructive azoospermia (NOA) is the most severe form of male infertility, and it is primarily associated with genetic defects. We performed whole‐exome sequencing of 236 patients with NOA and identified a homozygous pathogenic variant of autophagy‐related 4D cysteine peptidase (ATG4D) in two siblings from a consanguineous family and compound heterozygous pathogenic variants of ATG4D in two sporadic cases. The expression of LC3B, a regulator of autophagic activity, was significantly decreased, and the apoptosis rate of spermatogenic cells in testicular tissues was increased. Transfection of GC‐2spd cells with a ATG4D mutant plasmid (Flag‐Atg4dmut) significantly decreased the expression level of Lc3b and increased the rate of apoptosis. Moreover, a pathogenic variant in X‐linked ATG4A and compound heterozygous pathogenic variants of ATG4B were identified in one patient each. All novel variants were segregated by disease phenotype and were predicted to be pathogenic. Our findings revealed that autophagy‐related cysteine peptidase family genes may play crucial roles in human spermatogenesis and identified ATG4D as a novel candidate gene for male infertility due to NOA. [ABSTRACT FROM AUTHOR]

The loss of shale gas from conventional wells during coring directly affects the accuracy of measurement of shale gas content and the efficient development and utilization of shale gas. The existing methods to determine shale gas loss are not sufficiently accurate. This study used the forward modeling approach with consideration of the main influencing factors [FM (a, b)] to accurately calculate the volume of shale gas loss. Simulations of shale gas loss were run in an independently developed indoor experimental platform. A comparative analysis with established fitting methods showed that shale gas mainly exists in either a free state or an adsorbed state, and a pressure differential between the interior and exterior of the core is the primary cause of shale gas loss during coring. The FM (a, b) model simulations of shale gas loss showed reductions in average error of 16.77% and 4.6% compared to that of the improved US Bureau of Mines Method (USBM) and the curve fitting method, respectively. This study established a novel, highly accurate and widely applicable method of calculating the volume of lost shale gas. [ABSTRACT FROM AUTHOR]

Abnormal alterations in the expression and biological function of retinoid X receptor alpha (RXRα) have a key role in the development of cancer. Potential modulators of RXRα as anticancer agents are explored in growing numbers of studies. A series of (4/3-(pyrimidin-2-ylamino)benzoyl)hydrazine-1-carboxamide/carbothioamide derivatives are synthesised and evaluated for anticancer activity as RXRα antagonists in this study. Among all synthesised compounds, 6A shows strong antagonist activity (half maximal effective concentration (EC50) = 1.68 ± 0.22 µM), potent anti-proliferative activity against human cancer cell lines HepG2 and A549 cells (50% inhibition of cell viability (IC50) values < 10 µM), and low cytotoxic property in normal cells such as LO2 and MRC-5 cells (IC50 values > 100 µM). Further bioassays indicate that 6A inhibits 9-cis-RA-induced activity in a dose-dependent manner, and selectively binds to RXRα-=LΒD with submicromolar affinity (Kd = 1.20 × 10−7 M). 6A induces time-and dose-dependent cleavage of poly ADP-ribose polymerase, and significantly stimulates caspase-3 activity, leading to RXRα-dependent apoptosis. Finally, molecular docking studies predict the binding modes for RXRα-LBD and 6A. Compound 6A with low cytotoxic property in normal cells acts as a selective RXR alpha ligand to promote TNF alpha-mediated apoptosis of cancer cells. [ABSTRACT FROM AUTHOR]

Highlights • A novel dynamic scenarios method considering power time correlation is designed. • A modified multi-objective algorithm is proposed to solve stochastic optimization. • The dynamic scenarios have smallest Brier Score for each event. • The modified multi-objective algorithm has stronger global search capability. • Voltage unbalance caused by single-phase photovoltaics has a significant decrease. Abstract With the increasing number of single-phase photovoltaics integrated into three-phase distribution network, voltage unbalance problem is becoming serious, which leads to the abnormal operation of distribution network. Therefore, in distribution network, not only energy efficiency needs to be enhanced, but also voltage unbalance needs to be decreased to ensure the security of system. This paper establishes a stochastic multi-objective optimization model for three-phase distribution network to minimize active power losses and voltage unbalance simultaneously, where the discrete decision variables are coordinated with continuous regulation of solar reactive outputs. For the purpose, the stochastic processes of solar active power are modelled in a scenarios-based framework. A novel dynamic scenarios method is designed to describe the uncertainty of solar power as well as power time correlation based on the time covariance obtained by the forgetting factor identification, which not only reflects forecast errors, but also power fluctuation. Hence, the stochastic processes are converted into a series of equivalent deterministic scenarios. In order to better solve the multi-objective problem, a modified non-dominated sorting genetic algorithm-II is proposed, in which crossover rate and mutation rate are dynamically revised by a fuzzy logic controller. Besides, a two-stage constraint handling strategy is constructed to ensure the solutions with smaller constraints deviation and better fitness have higher priority to be reserved. Finally, simulation is conducted on the modified IEEE 123 node distribution network with lots of single-phase photovoltaics. The results show that with more accurate scenarios and stronger algorithm global search capability, the multi-objective optimization gains significant decrease of active power losses and voltage unbalance. [ABSTRACT FROM AUTHOR]

Uncertainty of the wind power output is the main influence factor for wind power utilization in the bulk power system. Because of the large capacity and the load characteristic, energy-intensive load holds great potentials to share the burden of wind power fluctuation smoothing. In this paper, a direct control scheme of the energy-intensive load power is proposed to smooth the wind power fluctuation. Based on the characteristic of the energy-intensive load production technology, the feasibility of energy-intensive load control and its influence on the production are discussed. A feedback control is designed to regulate the saturable reactor and transformer tap changer when the power support from the bulk power system is limited. Regulation capacity is analyzed quantitatively based on the energy-intensive load equivalent circuit model. A grid-connected energy-intensive enterprise driven by self-generation wind power plants and thermal power plants is studied as an example case. By the proposed energy-intensive load control scheme, power fluctuation of the wind farms can be smoothed with the minimum control cost. Besides, the regulation requirement of the bulk power system is eased correspondingly so that the utilization capacity of the power system can be improved significantly. Simulation is done on the real-time digital simulator to verify the effectiveness of the proposed control method. [ABSTRACT FROM AUTHOR]

Sparse-spike deconvolution is widely applied for improving the resolution of stacked seismogram. However, the method frequently suffers from instability and low accuracy owing to the nonuniqueness of the inverse problem. A traditional alternative is linear deconvolution, but its processing result is band limited to the effective band of raw data. We developed a band-controlled sparse deconvolution (BCSD) algorithm that inverts for seismic data with suitable bandwidth to guarantee resolution and accuracy simultaneously. Besides, BCSD is able to rebuild reflectivity and in this case it turns into sparse-spike inversion. The new algorithm was implemented through minimizing a cost function including three terms: a data misfit term that is applicable for reconstructing high-resolution seismic data, a sparse constraint term bringing in high-frequency constituents, and a high-pass-filtered term controlling the retrieved bandwidth. A 1D synthetic series example illustrated the potential benefits of retrieving band-controlled seismic response, and the inability of the existing approach in recovering such a seismic data. Two 2D model and a field data examples demonstrate that BCSD can provide a better seismogram than linear deconvolution in term of broadening the frequency band of data and meanwhile guaranteeing the stability and reliability. [ABSTRACT FROM AUTHOR]

Optimisation of reserve purchased in advance becomes increasingly essential to hedge against the growing level of power unbalance brought by the integration of large‐scale wind power. Moreover, due to the centralised integration mode of wind farms, cross‐region reserve sharing strategy becomes quite imperative. Therefore, this study presents a dynamic reserve demand estimation (DRDE) model, which synthetically considers N − 1 contingency along with load and wind forecast error. In the proposed approach, historical data is rearranged by a two‐dimensional binning technique and fitted by the versatile probability distribution model, which assisting the model reacts to different prediction level in each dispatch period dynamically. Furthermore, a cost‐effectivity oriented reserve allocation strategy for the multi‐area system is developed based on the DRDE model. The efficiency of the proposed method is tested in both 6‐bus test system and IEEE 118‐bus test system. The results show that, whether in the scenario of self‐sufficient reserve supplying or cross‐region reserve sharing strategy, the proposed estimation model effectively reduces the expectation of both load shedding and wind curtailment. Moreover, the proposed strategy improves the economy of system operation on the premise of ensuring system reliability. [ABSTRACT FROM AUTHOR]

Aimed to clarify the correlation characteristics between the internal partial discharge (PD) in the negative direct current (DC) gas‐insulated system (GIS) and gas pressure, and to establish an insulation fault diagnosis method based on decomposition component analysis, this study on PD decomposition of sulphur hexafluoride (SF6) was conducted under different pressures on the basis of constructing a SF6 decomposition experimental platform under DC PD. A stainless steel needle‐plate electrode was used to simulate the insulation defects of metal protrusions in GIS. SOF2, SO2 F2, CO2, SO2, and CF4 data generated from SF6 decomposition were obtained under different pressures. The variation law of component concentration and effective characteristic ratio with pressure were analysed in detail. In addition, a mathematical formula for pressure and decomposition components was deduced according to gas micro‐ionisation theory. The effective content and formation rate were defined to validate the relationship. Results show that the concentration of SF6 decomposition components decreased gradually with increasing pressure with a strong regularity. Furthermore, the relationship between pressure and component concentration derived from the theory can explain the relationship between the effective content of SF6 decomposition components and the effective formation rate and pressure variations. [ABSTRACT FROM AUTHOR]

As the installed capacity of wind power is growing, the stochastic variability of wind power leads to the mismatch of demand and generated power. Employing the regulating capability of demand to improve the utilization of wind power has become a new research direction. Meanwhile, the micro combined heat and power (micro-CHP) allows residential consumers to choose whether generating electricity by themselves or purchasing from the utility company, which forms a residential hybrid energy system. However, the impact of the demand response with hybrid energy system contained micro-CHP on the large-scale wind power utilization has not been analyzed quantitatively. This paper proposes an operation optimization model of the residential hybrid energy system based on price response, integrating micro-CHP and smart appliances intelligently. Moreover, a novel load aggregation method is adopted to centralize scattered response capability of residential load. At the power grid level, a day-ahead stochastic economic dispatch model considering demand response and wind power is constructed. Furthermore, simulation is conducted respectively on the modified 6-bus system and IEEE 118-bus system. The results show that with the method proposed, the wind power curtailment of the system decreases by 78% in 6-bus system. In the meantime, the energy costs of residential consumers and the operating costs of the power system reduced by 10.7% and 11.7% in 118-bus system, respectively. [ABSTRACT FROM AUTHOR]

In this study, the stereoselectivity of flufiprole enantiomers in regards to their bioactivity, acute toxicity and environmental fate is reported for the first time. Four types of representative insects ( Plutella xylostella , Nilaparvata lugens , Mythimna separata and Acyrthosiphon pisum ) were used to investigate enantioselective bioactivity. Acute toxicities of flufiprole enantiomers toward two non-target organisms were also evaluated. Moreover, stereoselective degradation in four vegetables under field conditions was studied in response to food safety concerns. The bioactivity of ( R )-flufiprole was 1.9–5.1 times higher than that of ( S )-flufiprole. ( R )-flufiprole also showed 3.7–5.7 times higher acute toxicity to Scenedesmus obliquus and Trichogramma japonicum Ashmead than ( S )-flufiprole. Opposite stereoselective degradation of the two enantiomers was observed in pak choi, spinach cucumber, and tomato. ( S )-flufiprole degraded faster in pak choi and spinach, resulting in an enrichment of ( R )-isomer. By contrast, ( R )-isomer was preferentially degraded in cucumber and tomato. Molecular simulation technology was used to illuminate the mechanism of enantioselective bioactivity. The Glide Score (−5.82 kcal/mol) for ( R )-isomer was better than that (−5.11 kcal/mol) of ( S )-isomer and this calculation showed ( R )-flufiprole was more effective in pest control. Consequently, significant stereoselectivity of flufiprole enantiomers should be taken into account when assessing the environmental health risk of the pesticide. [ABSTRACT FROM AUTHOR]

A highly selective and sensitive method for simultaneous quantitation of osthole, bergapten and isopimpinellin in rat plasma and tissues was developed by liquid chromatography–tandem quadrupole mass spectrometry (LC–MS/MS). After liquid–liquid extraction of samples with methyl tert-butyl ether, the analytes and dextrorphan (internal standard, IS) were separated by a Hypersil GOLD AQ C18 column with gradient elution of acetonitrile and water containing 0.5‰ formic acid. Three determinands were detected using an electrospray ionization (ESI) tandem mass spectrometry in the multiple reaction monitoring (MRM) modes with positive electrospray ionization. Calibration curves were recovered over the concentration ranges of 1–200 ng/ml, 1–500 ng/ml, 0.25–200 ng/ml for osthole, bergapten and isopimpinellin in plasma; 1–100 ng/ml, 1–500 ng/ml, 0.5–100 ng/ml for osthole, bergapten and isopimpinellin in tissues, respectively. The intra-day precision (R.S.D.) was within 13.90% and the intra-day accuracy (R.E.) was within −6.27 to 6.84% in all biological matrixes. The inter-day precision (R.S.D.) was less than 13.66% and the inter-day accuracy (R.E.) was within −10.64 to 13.04%. Then the method was successfully applied to investigate plasma pharmacokinetic study and tissue distribution of osthole, bergapten and isopimpinellin in rats after oral administration of Fructus Cnidii extraction, especially for testis/uterus tissue distribution. The results demonstrated that osthole, bergapten and isopimpinellin were absorbed and eliminated rapidly with wide distributions in rats. Distribution data of these three bioactive components in testis/uterus tissues could offer useful information for the further preclinical and clinical studies of Fructus Cnidii in the treatment of genital system disease. [ABSTRACT FROM AUTHOR]

Juniperus formosana Hayata (J. formosana) is a commom needlebush cultivar growing in China. Six new compounds (1–6), including four cadinene sesquiterpenoids (1 – 4), one abietane diterpenoid (5), and one β-naphthol derivative (6), along with 18 known compounds (7 – 24) were isolated and identified through phytochemical investigation on the heartwood of J. formosana. The structures of these compounds were fully elucidated by their 1D and 2D NMR, HR-ESI-MS, UV, and IR spectral data analyses. The absolute configurations of compounds 1 , 3 , and 5 were confirmed by experimental and calculated electronic circular dichroism (ECD) data. Moreover, X-ray crystallographic analysis was carried out to characterize the structure of compound 4. The inhibitory effects on the nitric oxide (NO) production of all the isolated compounds were initially examined in RAW264.7 macrophages induced by lipopolysaccharide (LPS). The results showed that compounds 3 and 12 possessed significant inhibitory potency on NO generation with IC 50 values of 3.41 μM and 6.15 μM among the new and known compounds, respectively. The expressions of IL-1β, IL-6, and TNF-α were measured in LPS-stimulated RAW264.7 cells to evaluate the anti-inflammatory effects of compounds 1 – 24. Compounds 1–6 and 9–12 exhibited potent anti-inflammatory effects. Additionally, the expressions of p38, Erk, and IκBα proteins were further determined to explore the anti-inflammatory mechanism of the most potent compounds 3 and 12. Overall, our findings indicate the potential of J. formosana for developing medicine candidates as the treatments of inflammation. [Display omitted] • Chemical investigation of J. formosana yielded six new compounds. • The absolute configuration of compounds has been established by ECD data. • The isolated compounds showed moderate to potent anti-inflammatory activity. • The anti-inflammatory mechanisms of 3 and 12 were discussed. [ABSTRACT FROM AUTHOR]

The d -pantolactone derivative, (R)-4-methoxy-benzoic acid 4,4-dimethyl-2-oxo-tetrahydro-furan-3-yl ester (3m), exhibited fatty acid synthase inhibitory activity with IC 50 value of 13.68 ± 2.79 μM. Like reference compound C75 , compound 3m also showed similar inhibition of lipid accumulation on the proliferation of HepG2 cells. Molecular docking was further used to predict the interaction model of 3m and KR domain of human fatty acid synthase. A novel series of fatty acid synthase (FAS) inhibitors with D-(−)-pantolactone moiety and potential utility for the treatment of obesity were designed, synthesized and characterized, in which the structure of compound 3k was further confirmed by single X-ray diffraction. The mouse FAS inhibitory activity of synthesized compounds was evaluated. Major synthesized compounds (except 3g , 3i , 3k , 3l, and 3n) exhibited moderate FAS inhibitory properties with IC 50 values in the range of 13.68 ± 1.52–33.19 ± 1.39 μM, reference inhibitor C75 has IC 50 value of 13.86 ± 2.79 μM. Eight compounds (3c , 3d , 3e , 3f , 3j , 3m , 3q and 3r) also displayed inhibitory effect on lipid accumulation in human HepG2 cells. Additionally, the molecular docking study revealed that compound 3m having good inhibition activity against FAS and lipid accumulation also showed promising binding affinities with hFAS, while its binding model with hFAS (PDB ID: 4PIV) was different from that of reference compound C75. [ABSTRACT FROM AUTHOR]