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The Cu collector is modified with Ag and Sn coatings through a simple and efficient substitution reaction. Ag demonstrates higher lithiophilicity compared to Sn, and the gradient modification of the Cu foam enables control over the deposition site of Li metal. This leads to improved space utilization and enhanced C-rate performance of the 3D scaffold. [Display omitted] Metallic lithium (Li) is highly desirable for Li battery anodes due to its unique advantages. However, the growth of Li dendrites poses challenges for commercialization. To address this issue, researchers have proposed various three-dimensional (3D) current collectors. In this study, the selective modification of a 3D Cu foam scaffold with lithiophilic elements was explored to induce controlled Li deposition. The Cu foam was selectively modified with Ag and Sn to create uniform Cu foam (U-Cu) and gradient lithiophilic Cu foam (G-Cu) structures. Density Functional Theory (DFT) calculations revealed that Ag exhibited a stronger binding energy with Li compared to Sn, indicating superior Li induction capabilities. Electrochemical testing demonstrated that the half cell with the G-Cu@Ag electrode exhibited excellent cycling stability, maintaining 550 cycles with an average Coulombic efficiency (CE) of 97.35%. This performance surpassed that of both Cu foam and G-Cu@Sn. The gradient modification of the current collectors improved the utilization of the 3D scaffold and prevented Li accumulation at the top of the scaffold. Overall, the selective modification of the 3D Cu foam scaffold with lithiophilic elements, particularly Ag, offers promising prospects for mitigating Li dendrite growth and enhancing the performance of Li batteries. [ABSTRACT FROM AUTHOR]

The virulence of SARS-CoV-2 decreases with increasing infectivity, the primary approaches for antiviral treatments will be preventing or minimizing the complications resulting from virus infection. ADAM metallopeptidase domain 17 (ADAM17) activation by SARS-CoV-2 infection has a dual effect on the development of the disease: increased release of inflammatory cytokines and dysregulation of Angiotensin converting enzyme II (ACE2) on cell surfaces, inflammatory cytokine infiltration and loss of ACE2 protective function lead to a significant increase in the incidence of related complications. Importantly, pathologically activated ADAM17 showed superior features than S protein in regulating ACE2 expression and participating in the intra cellular replication of SARS-CoV-2. In short, SARS-CoV-2 elicits only a limited immune response when it promotes its own replication and pathogenicity through ADAM17. Therefore, the pathological activation of ADAM17 may also represent a diminished innate antiviral defense and an altered strategy of SARS-CoV-2 infection. In this review, we summarized recent advances in our understanding of the pathophysiology of ADAM17, with a focus on the new findings that SARS-CoV-2 affects ADAM17 expression through Furin protein converting enzyme and Mitogen-activated protein kinase (MAPK) pathway, and raises the hypothesis that SARS-CoV-2 may mediates the pathological activation of ADAM17 by hijacking the actin regulatory pathway, and discussed the underlying biological principles. • The complications induced by SARS-CoV-2 infection are related to pathological activation of ADAM17 • The mechanism of pathological activation of ADAM17 by SARS-CoV-2 remains unclear • The role of actin cytoskeleton in SARS-CoV-2 infection was hypothesized [ABSTRACT FROM AUTHOR]

This paper examines the stationary distribution of the stochastic Lotka-Volterra model with infinite delay. Since the solutions of stochastic functional or delay differential equations depend on their history, they are non-Markov, which implies that traditional techniques based on the Markov property, cannot be applicable. This paper uses the variable substituting technique to obtain a higher-dimensional stochastic differential equation without delay. In this paper it is shown that the new equation satisfies the strong Feller property and strong Markov property, by which the invariant measure follows from the Krylov-Bogoliubov Theorem. Since distribution of the original model is actually the marginal distribution of the new equation, these results also show that there exists the stationary distribution for the original equation. Moreover, when the noise intensity is strongly dependent on the population size, by Hörmander's theorem, this paper also shows that the stationary distribution of this stochastic Lotka-Volterra system with infinite delay holds a C ∞ -smooth density. [ABSTRACT FROM AUTHOR]

Deficiency of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase (HL) is an autosomal recessive inborn error of acyl-CoA metabolism affecting the last step of leucine degradation. Patients with HL deficiency (HLD) can develop a potentially fatal cardiomyopathy. We created mice with cardiomyocyte-specific HLD (HLHKO mice), inducing Cre recombinase-mediated deletion of exon 2 at two months of age. HLHKO mice survive, but develop left ventricular hypertrophy by 9 months. Also, within minutes after intraperitoneal injection of the leucine metabolite 2-ketoisocaproate (KIC), they show transient left ventricular hypocontractility and dilation. Leucine-related acyl-CoAs were elevated in HLHKO heart (e.g., HMG-CoA, 34.0 ± 4.4 nmol/g versus 0.211 ± 0.041 in controls, p < 0.001; 3-methylcrotonyl-CoA, 5.84 ± 0.69 nmol/g versus 0.282 ± 0.043, p < 0.001; isovaleryl-CoA, 1.86 ± 0.30 nmol/g versus 0.024 ± 0.014, p < 0.01), a similar pattern to that in liver of mice with hepatic HL deficiency. After KIC loading, HMG-CoA levels in HLHKO heart were higher than under basal conditions, as were the ratios of HMG-CoA/acetyl-CoA and of HMG-CoA/succinyl-CoA. In contrast to the high levels of multiple leucine-related acyl-CoAs, biomarkers in urine and plasma of HLHKO mice show isolated hyper-3-methylglutaconic aciduria (700.8 ± 48.4 mmol/mol creatinine versus 37.6 ± 2.4 in controls, p < 0.001), and elevated C5-hydroxyacylcarnitine in plasma (0.248 ± 0.014 μmol/L versus 0.048 ± 0.005 in controls, p < 0.001). Mice with liver-specific HLD were compared, and showed normal echocardiographic findings and normal acyl-CoA profiles in heart. This study of nonhepatic tissue-specific HLD outside of liver reveals organ-specific origins of diagnostic biomarkers for HLD in blood and urine and shows that mouse cardiac HL is essential for myocardial function in a cell-autonomous, organ-autonomous fashion. [ABSTRACT FROM AUTHOR]

Poor sensitivity to sorafenib has been an important constraint on the efficacy of targeted therapy in advanced hepatocellular carcinoma (HCC). Therefore, it is particularly important to explore effective therapeutic targets to improve the sensitivity of HCC cells to sorafenib. Upregulation of IGF2BP3 is strongly associated with tumor invasion, early recurrence and poor prognosis in various human cancers, including HCC, but its roles in the sorafenib treatment of HCC remain unclear. In our study, IGF2BP3 knock-down significantly promoted ferroptosis in HCC cells through the evaluation of the Reactive Oxygen Species (ROS), Fe2+ and malondialdehyde (MDA) levels after sorafenib administration. In addition, NRF2 mRNA was identified as an important target of IGF2BP3 by bioinformatics analysis, RNA binding protein immunoprecipitation (RIP) and RNA pulldown experiments. More importantly, IGF2BP3, as an m6A (N6-Methyladenosine) reader, was shown to promote the stability of NRF2 mRNA by reading its m6A modification. Similar results were obtained from in vivo experiments. In summary, our study uncovered the role of IGF2BP3- NRF2 axis on ferroptosis in HCC, providing significant evidence for new anti-cancer strategies aimed at improving the efficacy of sorafenib. • IGF2BP3 negatively regulates sorafenib-induced ferroptosis in HCC cells. • IGF2BP3 can bind to the mRNA of NRF2. • IGF2BP3 inhibits ferroptosis by stabilizing NRF2 mRNA in an m6A-dependent manner. • IGF2BP3 knock-down improves the efficacy of sorafenib in nude mice. [ABSTRACT FROM AUTHOR]

The heat treatment has significant effect on the sensory and flavor quality of Boletus edulis product. We evaluated the sensory properties and volatile flavor compounds (VFCs) of six dried Boletus edulis products subjected to different heat treatment temperatures, as well as the correlation of VFCs with Maillard reaction products. The color of the dried samples turned brown as the drying temperature increased, and the content of seventeen free amino acids (FAAs) and five monosaccharides decreased simultaneously. When compared to vacuum drying methods, the content of Arg and Glu reduced significantly, reaching its lowest point at 100 °C. Sixty VFCs were identified by HS-SPME/GC-MS, and the contents of aldehydes, ketones, sulfur-containing compounds, nitrogen-containing compounds increased with heat treatments. Furthermore, the content changes of 17 FAAs, 5 monosaccharides and VFCs related to Maillard reaction were further analyzed, which allowed us to speculate on the formation mechanism of VFCs through the Maillard reaction at high drying temperatures. These findings not only provide valuable insights into understanding the sensory and flavor characteristics of Boletus edulis products, but also offer theoretical support for the dehydration of Boletus edulis and other similar heat sensitive edible mushroom products. [Display omitted] • The higher the drying temperature, the darker the color of Boletus edulis. • Maillard reactions products in Boletus edulis at different dryness were different. • Arginine was the main amino acid involved in Maillard reaction of Boletus adults. • The flavor of Boletus edulis was enhanced by Maillard reaction. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction is a central contributor to the development of most cardiovascular diseases and is characterised by the reduced synthesis or bioavailability of the vasodilator nitric oxide together with other abnormalities such as inflammation, senescence, and oxidative stress. The use of patient-specific and genome-edited human pluripotent stem cell-derived endothelial cells (hPSC-ECs) has shed novel insights into the role of endothelial dysfunction in cardiovascular diseases with strong genetic components such as genetic cardiomyopathies and pulmonary arterial hypertension. However, their utility in studying complex multifactorial diseases such as atherosclerosis, metabolic syndrome and heart failure poses notable challenges. In this review, we provide an overview of the different methods used to generate and characterise hPSC-ECs before comprehensively assessing their effectiveness in cardiovascular disease modelling and high-throughput drug screening. Furthermore, we explore current obstacles that will need to be overcome to unleash the full potential of hPSC-ECs in facilitating patient-specific precision medicine. Addressing these challenges holds great promise in advancing our understanding of intricate cardiovascular diseases and in tailoring personalised therapeutic strategies. [Display omitted] [ABSTRACT FROM AUTHOR]

Modern insecticide substitutes using acetylcholine receptors (nAChR) as biochemical targets, such as neonicotinoid insecticides (NNIs), have been extensively researched. Only 12 compounds have been experimentally realized since the initial discovery of imidacloprid. Increasingly, the bottleneck in this field is to rapidly determine the synthesizability of NNI substitutes. Here, we designed a coupled evaluation system for synthesis prediction and validation, including the synthesis probability, reaction path difficulty, and electron transfer characteristics of NNIs and their substitutes. Firstly, a total of 1475 eigenvalues were generated and 52 critical eigenvalues were screened out through the Pearson's correlation coefficient. The positive and unlabeled (PU) machine learning was constructed using the critical eigenvalues NNIs, including 12 experimentally synthesized NNIs (positive samples) and 73 unsynthesized NNI substitutes (unlabeled samples). Results identified 3 NNI substitutes that were highly promising candidates for synthesis (synthesis probability > 0.5). The results of density functional theory demonstrated the ranking of their reaction ease was UN-1 (31.4 kcal/mol) > UN-2 (81.6 kcal/mol) > UN-3 (3.35 ×103 kcal/mol). Time-dependent density functional theory revealed that changes in the electron distribution and electron excitation type were critical factors affecting their synthesizability, and the local excitation type was more favorable for the synthesizability of NNI substituents. The findings provide significant guidance for NNIs synthesis, reducing the possible space of unlabeled samples to 95.89% of their original size, while also minimizing the cost of research on subsequent NNI substitutes. [Display omitted] • Synthesis prediction model were developed by machine learning techniques. • PU learning was the first time to predict the synthesis probability of NNI substitutes. • Three NNI substitutes that were highly promising candidates for synthesis were identified. • The local excitation type was more favorable for the NNI synthesizability. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have undergone a comprehensive study for their involvements in tumor treatments. The purpose of our study was to explore the biological effects and regulatory mechanisms of lncRNA LINC01194 (LINC01194) in laryngeal squamous cell carcinoma (LSCC). The levels of LINC01194 in 105 LSCC patients were detected by RT-qPCR. The diagnostic and prognostic value of LINC01194 in LSCC patients were statistically analyzed. The potential functions of LINC01194 in proliferation, apoptosis, and metastasis of LSCC cells were evaluated. The interaction among LINC01194, miR-655 and SOX18 was explored by bioinformatics analysis, luciferase reporter assays and biotinylated RNA pull-down. We found that the expression levels of LINC01194 were highly expressed in LSCC, which was negatively correlated with the clinical outcome of LSCC patients. The area under the ROC curve for LINC01194 was up to 0.8388. Functional assays indicated that LINC01194 knockdown distinctly inhibited LSCC cells proliferation, induced apoptosis, and also attenuated LSCC cells migration and invasion in vitro. Furthermore, we elucidated that LINC01194 promoted SOX18 expression in LSCC cells via functioning as a molecular sponge for miR-655. Overall, based on our findings, LINC01194 served as a tumor promoter and potentially represents a novel prognostic indicator and therapeutic target in LSCC. • : LncRNA LINC01194 was a novel LSCC-related lncRNA. • : Overexpression of LINC01194 promoted the proliferation and metastasis of LSCC cells. • : LncRNA LINC01194 sponged miR-655 to increase SOX18 expression. [ABSTRACT FROM AUTHOR]

The last decade saw major advances in understanding the metabolism of Coenzyme A (CoA) thioesters (acyl-CoAs) and related inborn errors (CoA metabolic diseases, CAMDs). For diagnosis, acylcarnitines and organic acids, both derived from acyl-CoAs, are excellent markers of most CAMDs. Clinically, each CAMD is unique but strikingly, three main patterns emerge: first, systemic decompensations with combinations of acidosis, ketosis, hypoglycemia, hyperammonemia and fatty liver; second, neurological episodes, particularly acute "stroke-like" episodes, often involving the basal ganglia but sometimes cerebral cortex, brainstem or optic nerves and third, especially in CAMDs of long chain fatty acyl-CoA metabolism, lipid myopathy, cardiomyopathy and arrhythmia. Some patients develop signs from more than one category. The pathophysiology of CAMDs is not precisely understood. Available data suggest that signs may result from C o A s equestration, to xicity and r edistribution (CASTOR) in the mitochondrial matrix has been suggested to play a role. This predicts that most CAMDs cause deficiency of CoA, limiting mitochondrial energy production, and that toxic effects from the abnormal accumulation of acyl-CoAs and from extramitochondrial functions of acetyl-CoA may also contribute. Recent progress includes the following. (1) Direct measurements of tissue acyl-CoAs in mammalian models of CAMDs have been related to clinical features. (2) Inborn errors of CoA biosynthesis were shown to cause clinical changes similar to those of inborn errors of acyl-CoA degradation. (3) CoA levels in cells can be influenced pharmacologically. (4) Roles for acetyl-CoA are increasingly identified in all cell compartments. (5) Nonenzymatic acyl-CoA-mediated acylation of intracellular proteins occurs in mammalian tissues and is increased in CAMDs. [ABSTRACT FROM AUTHOR]

[Display omitted] • This is the first report of the isolation of acyl-quinic acids from the root bark of Acanthopanax gracilistylus W. W. Smith (Acanthopanacis Cortex). • Acyl-quinic acids (1a – 27) possessed significant inhibitory activities on COX-2 (in vitro). • Acyl-quinic acids (1a – 6) were determined as novel oxyneolignan-(−)-quinic acids heterodimers, representing a new class of natural products. Eleven new acyl-quinic acids (AQAs) 1a – 9 , and 18 known AQAs 10 – 27 were isolated from the root bark of Acanthopanax gracilistylus W. W. Smith (Acanthopanacis Cortex). The planar structures of 1a – 9 were determined based on their HR-ESIMS, IR, and NMR data. The absolute configurations of 1a – 6 were identified by comparing the experimental and the calculated electronic circular dichroism (ECD) spectra. This is the first report of the isolation of AQAs from Acanthopanacis Cortex. Notably, 1a – 6 were determined as unusual oxyneolignan-(−)-quinic acids heterodimers, representing a new class of natural products. The inhibitory activities of 1a – 27 on neutrophil elastase (NE) and cyclooxygenase-2 (COX-2) were studied in vitro , and the results indicated they possessed significant inhibitory activities on COX-2. Among them, the IC 50 values of 1a – 9 were 0.63±0.014, 0.75±0.028, 0.15±0.023, 0.63±0.016, 0.30±0.013, 35.63±4.600, 8.70±1.241, 16.51±0.480, 0.69±0.049, 0.39±0.017, and 0.26±0.080 μ M, respectively. This study represents the inaugural disclosure of the anti-COX-2 constituents found in Acanthopanacis Cortex , thereby furnishing valuable insights into the exploration of novel COX-2 inhibitors derived from natural reservoirs. [ABSTRACT FROM AUTHOR]

The biodegradation treatment of dioxins has long been of interest due to its good ecological and economic effects. In this study, the biodegradability of polychlorinated dibenzo-p-dioxins (PCDDs) were investigated by constructing machine learning and multiple linear regression models. The maximum chlorine atomic charge (q Hirshfeld Cl+), which characterizes the biodegradation ability of PCDDs, was used as the response value. The random forest model was used to rank the importance on the 1471 descriptors of PCDDs, and the BCUTp-1 h, Q XZ , JGI4, ATSC8c, VE3_Dt, topoShape, and maxwHBa were screened as the important descriptors by Pearson's correlation coefficient method. A quantitative structure-activity relationship (QSAR) model was constructed to predict the biodegradability of PCDDs. In addition, the extreme gradient boosting (XGBoost) and random forest model were also constructed and proved the good predictability of QSAR model. The biodegradability of polychlorinated dibenzofurans (PCDFs) can also be predicted by the constructed three models from a certain level after adjusting some model parameters, which further proved the versatility of the models. Besides, the sensitivity analysis of the QSAR model and a 3D-QSAR model was developed to investigate the biodegradability mechanisms of PCDDs. Results showed that the descriptors BCUTp-1 h, JGI4, and maxwHBa were the key descriptors in the biodegradability effect by the sensitivity analysis of the QSAR model. Coupled with the results of PCDDs biodegradability 3D-QSAR model, BCUTp-1 h, JGI4, and maxwHBa were confirmed as the main descriptors that affect the biodegradability of dioxins. This study provides a novel theoretical perspective for the research of the biodegradation of both PCDDs and PCDFs dioxins. [Display omitted] • PCDDs biodegradability models were developed by machine learning techniques. • The biodegradability model of PCDDs was compatible for the degradation of PCDFs. • BCUTp-1 h, JGI4, and maxwHBa were the key descriptors affect the biodegradability. [ABSTRACT FROM AUTHOR]

Layered LiNi 0.8 Co 0.15 Al 0.05 O 2 (NCA) is a potential cathode material for the next generation of lithium-ion batteries due to its high energy density. However, the rapid attenuation of capacity caused by harmful phase change (H 2 -H 3) and the side reaction between the active material and the electrolyte during the cycle have hindered its further development. In order to solve these problems, the side reaction can be alleviated by fast lithium-ion conductor Li 1.5 Al 0.5 Zr 1.5 (PO 4) 3 (LAZP) coating on the surface of NCA. At the same time, the doping of Zr4+ also inhibits the generation of harmful phase transition, which improves the cycle life and rate performance of NCA. After 300 cycles at 1C, the capacity loss rate of 1.0 wt% LAZP-NCA is 13.4%, and even at 5C, the capacity loss rate is only 16.3% after 200 cycles. In addition, the full cell composed of 1.0 wt% LAZP-NCA and graphite still has 72.1% capacity retention after 300 cycles at 1C. Therefore, this work provides a new idea for turning NCA into a commercial cathode material for lithium-ion batteries. (a) Structural schematic diagram of LAZP coated modified NCA. (b) Cyclic performance diagram of NCA and 1.0 wt% LAZP-NCA at 1C and 5C. (c) Cyclic performance diagrams of NCA and 1.0 wt% LAZP-NCA assembled with graphite as full batteries. [Display omitted] • Fast lithium-ion conductor LAZP coated NCA was prepared via a wet chemical method. • LAZP coating inhabits side reactions between the electrolyte and active material. • Zr4+ doping alleviates harmful H 2 -H 3 phase transition of the NCA. • Co-modification improves electrochemical performances compared to pure NCA. [ABSTRACT FROM AUTHOR]

Recently, sulfur dioxide (SO 2) has been considered to be a beneficial bio-regulator in animals. However, the positive roles of SO 2 in plant adaptation to drought stress are still unclear. In this study, we investigated the physiological and molecular changes that are induced by SO 2 fumigation to improve the drought tolerance of foxtail millet seedlings. The relative water content in the leaves of drought-stressed seedlings was significantly improved by pre-exposure to 30 mg/m3 SO 2. These responses might be related to decreased stomatal apertures and a reduced leaf transpiration rate, which were induced by SO 2 under drought conditions. In addition, the SO 2 pretreatment markedly enhanced proline accumulation in the leaves of drought-stressed seedlings, which was supported by increased Δ1-pyrroline-5-carboxylate synthetase (P5CS) activity, decreased proline dehydrogenase (ProDH) activity, and the corresponding transcripts. Moreover, the SO 2 application upregulated the enzyme activity of catalase (CAT) and peroxidase (POD) in the leaves of drought-stressed plants, as well as their transcripts, which contributed to the scavenging of hydrogen peroxide (H 2 O 2) and alleviated drought-induced oxidative damage, as indicated by the decreased malondialdehyde (MDA) level in SO 2 -pretreated plants. Together, these results indicate that the application of SO 2 might enhance drought tolerance by reducing stomatal apertures, increasing proline accumulation, and promoting antioxidant defence in foxtail millet seedlings. This study presents new insight into the beneficial roles of SO 2 in plant responses to drought stress. Image 1 • SO 2 fumigation enhanced drought tolerance of foxtail millet seedlings. • SO 2 induced stomatal closure in the leaves of foxtail millet seedlings. • SO 2 enhanced proline accumulation in the leaves of drought-stressed seedlings. • SO 2 alleviated drought-induced oxidative damage in the leaves of foxtail millet seedlings. [ABSTRACT FROM AUTHOR]

Abstract The extensive occurrence of antibiotics (such as ciprofloxacin) in aqueous environment had raised severe concerns due to their impacts on humans and the ecosystem. In this study, a novel nickel alginate particles adsorbent had been successfully developed by combining an alginate matrix with nickel ion through immobilization and crosslinking technology and then was applied for the batch adsorption study of ciprofloxacin to evaluate its potential performance. The as-prepared adsorbent exhibited excellent adsorption performance at the condition of the pH 7 and 328.15 K, and the results indicated that the maximum adsorption capacity was 135.18 mg g−1. The isotherm and kinetic studies were well fitted to the Langmuir and pseudo-second-order models, respectively. A thermodynamics analysis displayed that the ciprofloxacin adsorption process was endothermic, feasible and spontaneous. The as-prepared adsorbent before and after adsorption was characterized through SEM, EDX and XPS analyses, and the particle size of the as-prepared adsorbent was roughly 914 µm. Hydrogen bond, the cation bonding bridge and n-π electron-donor-acceptor interaction might be the driving force of the ciprofloxacin adsorption process. This study demonstrated that this as-prepared adsorbent was a promising and efficient material for the ciprofloxacin adsorption from the aqueous solution. Graphical abstract A novel nickel alginate particles (NAPs) adsorbent was successfully synthesized for effective CIP removal. The maximum adsorption capacity (135.18 mg g−1) was captured at pH 7, 318.15 K, and the initial CIP concentration of 120 mg L−1. The relevant studies demonstrated that the CIP adsorption onto the NAPs adsorbent might be administrated by the n-π electron-donor-acceptor interaction (n-π EDA interaction), hydrogen bond and the cation bonding bridge. The NAPs adsorbent was of great significance for the treatment of low concentration CIP-contaminated wastewater. fx1 Highlights • Novel nickel alginate particles (NAPs) adsorbent were successfully prepared for effective CIP removal. • The NAPs adsorbent exhibited excellent adsorption capacity (135.18 mg·g−1) for CIP. • Kinetics, isotherm and thermodynamic studies of CIP adsorption were performed. • The possible adsorption mechanisms of CIP relied on n-π EDA interaction, hydrogen bond and cation bonding bridge. • The NAPs adsorbent provided a new point for the CIP removal from the contaminated water environment. [ABSTRACT FROM AUTHOR]

[Display omitted] Vacuum assistance is used for filtering solid substances onto porous substrates to create composite membranes typically. However, the potential of this approach has rarely been assessed in facilitating the distribution of liquids within those porous substrates to fabricate composite membranes in typical interfacial polymerization. In this work, we demonstrate the advantages of vacuum-assisted interfacial polymerization (VAIP) in terms of substrate universality, monomer concentration range, and performance reproducibility in the fabrication of polyimide nanofiltration membranes. Aqueous solutions of PIP can be homogeneously distributed by vacuum filtration on diverse microfiltration substrates of polyether sulfone (PES), Nylon-66, polyvinylidene fluoride (PVDF), cellulose acetate (CA), and mixed cellulose esters (MCE), respectively. Interfacial polymerization is then performed on these substrates using different concentrations of piperazine (PIP, 0.0075–0.1000 wt%) and trimoyl chloride (TMC, 0.0112–0.1500 wt%). Remarkably, a uniform and ultra-thin polyamide layer with a thickness of 15 nm can be achieved at an exceptionally low PIP concentration of 0.0250 wt%, exhibits a rejection rate of over 98.8 % for Na 2 SO 4 and a water permeance of 25.8 L·m−2·h−1·bar−1. The membranes with a diameter of 30 cm demonstrate reproducibility in nanofiltration performance and satisfactory long-term stability. This method offers a simple yet effective strategy for regulating the liquid distribution and optimizing interfacial polymerization in fabricating polyamide composite membranes. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancers, is an incurable and lethal disease. Although great progresses have been made in understanding the mechanism of ccRCC, metabolic reprogramming in ccRCC remains largely unclear. Here, we showed that lipid desatutation might be a metabolic hallmark of ccRCC. We demonstrated sterol regulatory element-binding protein 1 (SREBP1) is overexpressed in ccRCC cell lines and positively correlated with NF-κB activation. Further, SREBP1 is required for lipid desaturation and cell growth in ccRCC. Mechanistically, we demonstrated that SREBP1-driven lipid desaturation promotes NF-κB activation. Our finding reveals a crucial roles for SREBP1 in lipid desaturation of ccRCC through regulation of NF-κB signaling, which provides not only new insights in regulatory mode of NF-κB signaling but also a novel target for potential metabolic therapies. [ABSTRACT FROM AUTHOR]

The novel Ni/CdS composite photocatalyst was successfully synthesized by an efficient and simple photo-deposition method. Importantly, the morphology and structural characterization showed that the CdS prepared by solvothermal method was nanorod-like and no impurities. The deposited Ni nanoparticles are uniformly dispersed on the surface of the CdS nanorods. The optical properties results showed that it more conducive to absorption of light after introduction of Ni nanoparticles, which is beneficial to photocatalytic spite water to hydrogen evolution. The kinetic study indicants that the hydrogen production activity of the composite catalyst Ni/CdS (471.2 μmol) is about 70 times higher than that of the pure CdS (6.7 μmol) under the same conditions. In addition, the time of photo-deposition and the pH of the hydrogen production system have a great effect on the activity of the composite catalyst. The roles of Ni nanoparticles over CdS nanorods for improved photocatalytic stability and activity were systematically studied by means of SEM, TEM, XRD, XPS, UV–Vis absorption spectra and fluorescence spectra etc. The introduction of Ni nanoparticles has significantly enhanced the stability and activity of CdS nanorods. Ni nanoparticles act as electron outlet, it may combine with protons in the solution to form hydrogen molecules and can avoid the recombination of photogenerated electron hole pairs. [ABSTRACT FROM AUTHOR]

Understanding dose-responses is crucial for determining the utility of biomarkers in ecotoxicity assessment. Nitrofurazone is a broad-spectrum antibiotic that is widely used in the aquaculture industry in China despite its detrimental effects on ecosystems. Potential dose-response models were examined for the effect of nitrofurazone on two antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPx), in the ciliated protozoan Euplotes vannus . This was achieved by measuring enzyme activity and gene expression profiling of SOD and GPx in ciliate cells exposed to nitrofurazone at doses ranging from 0 to 180 mg l −1 for 6 h, 12 h, 18 h and 24 h. Dose-response dynamics were characterized by mathematical models. Results showed that: 1) dose-response patterns differed significantly among the tested endpoints, nitrofurazone concentrations and durations of exposure; 2) GPx activity was the best candidate biomarker because of its linear dose-response relationship; 3) SOD activity and mRNA relative expression levels of GPx and SOD are also candidate biomarkers but their dose-responses were non-linear and therefore more difficult to interpret; 4) partitioning the dose-response dynamic model by piecewise function can help to clarify the relationships between biological endpoints. This study demonstrates the utility of dynamic model analysis and the potential of antioxidant enzymes, in particular GPx activity, as a candidate biomarkers for environmental monitoring and risk assessment of nitrofurazone in the aquaculture industry. [ABSTRACT FROM AUTHOR]

Simulating the dynamics of a nonequilibrium quantum many-body system by computing the two-time Green's function associated with such a system is computationally challenging. However, we are often interested in the time-diagonal of such a Green's function or time-dependent physical observables that are functions of one time. In this paper, we discuss the possibility of using dynamic mode decomposition (DMD), a data-driven model order reduction technique, to characterize one-time observables associated with the nonequilibrium dynamics using snapshots computed within a small time window. The DMD method allows us to efficiently predict long time dynamics from a limited number of trajectory samples. We demonstrate the effectiveness of DMD on a model two-band system. We show that, in the equilibrium limit, the DMD analysis yields results that are consistent with those produced from a linear response analysis. In the nonequilibrium case, the extrapolated dynamics produced by DMD is more accurate than a special Fourier extrapolation scheme presented in this paper. We point out a potential pitfall of the standard DMD method caused by insufficient spatial/momentum resolution of the discretization scheme. We show how this problem can be overcome by using a variant of the DMD method known as higher order DMD. • Perform accurate and efficient simulation of nonequilibrium many-body dynamics. • Use Dynamic mode decomposition (DMD) to approximate two-time Green's function. • Improve the accuracy of DMD by higher order DMD (HODMD). • Demonstrate the efficiency and accuracy of DMD and HODMD on a model two-band system. [ABSTRACT FROM AUTHOR]

Neutrophil (polymorphonuclear leukocyte, PMN) recruitment in the liver sinusoid takes place in almost all liver diseases and contributes to pathogen clearance or tissue damage. While PMN rolling unlikely appears in liver sinusoids and Mac-1 or CD44 is assumed to play respective roles during in vivo local or systematic inflammatory stimulation, the regulating mechanisms of PMN adhesion and crawling dynamics are still unclear from those in vivo studies. Here we developed a two-dimensional in vitro sinusoidal model with primary liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs) to investigate TNF-α-induced PMN recruitment under shear flow. Our data demonstrated that LFA-1 dominates the static or shear resistant adhesion of PMNs while Mac-1 decelerates PMN crawling on LSEC monolayer. Any one of LFA-1, Mac-1, and CD44 molecules is not able to work effectively for mediating PMN transmigration across LSEC monolayer. The presence of KCs only affects the randomness of PMN crawling. These findings further the understandings of PMN recruitment under shear flow in liver sinusoids. [ABSTRACT FROM AUTHOR]

Recently, we reported that Ilexgenin A exhibits anti-cancer activities and induces cell arrest. Here, we investigated the effect of Ilexgenin A on the inflammation, angiogenesis and tumor growth of hepatocellular carcinoma (HCC). Our current study revealed that Ilexgenin A significantly inhibited the inflammatory cytokines TNF-α and IL-6 levels and downregulated pro-angiogenic factor VEGF production and transcription in HepG2 cells. The underlying mechanism for Ilexgenin A effects appears to be through inhibiting STAT3 and PI3K pathways. Furthermore, we found that not only Ilexgenin A inhibited STAT3 and PI3K pathways in HepG2 cells but also blocked these signaling pathways in HUVECs. Most importantly, by employing two HCC xenografts models - HepG2 and H22, we showed that Ilexgenin A reduced tumor growth and exhibited synergy effect with Sorafenib. ELISA assay, histological analysis and immunohistochemistry examination revealed that the expression of VEGF and MVD was significantly decreased after the treatment with Ilexgenin A and the combination. Moreover, Ilexgenin A could enhance caspase-3/7 activity in vitro and transmission electron microscope indicated that the combination induced evident apoptosis of tumor cells and caused the structural changes of mitochondria in vivo. Although no apparent adverse effects occurred during the treatment period, Sorafenib monotherapy elicited hepatotoxicity for specific expression in the increased level of AST and the ratio of AST/ALT. However, the combination could remedy this adverse effect. In conclusion, the results described in the present study identifies Ilexgenin A as a promising therapeutic candidate that modulates inflammation, angiogenesis, and HCC growth. [ABSTRACT FROM AUTHOR]

Acetyl-coenzyme A (Ac-CoA) is a core metabolite with essential roles throughout cell physiology. These functions can be classified into energetics, biosynthesis, regulation and acetylation of large and small molecules. Ac-CoA is essential for oxidative metabolism of glucose, fatty acids, most amino acids, ethanol, and of free acetate generated by endogenous metabolism or by gut bacteria. Ac-CoA cannot cross lipid bilayers, but acetyl groups from Ac-CoA can shuttle across membranes as part of carrier molecules like citrate or acetylcarnitine, or as free acetate or ketone bodies. Ac-CoA is the basic unit of lipid biosynthesis, providing essentially all of the carbon for the synthesis of fatty acids and of isoprenoid-derived compounds including cholesterol, coenzyme Q and dolichols. High levels of Ac-CoA in hepatocytes stimulate lipid biosynthesis, ketone body production and the diversion of pyruvate metabolism towards gluconeogenesis and away from oxidation; low levels exert opposite effects. Acetylation changes the properties of molecules. Acetylation is necessary for the synthesis of acetylcholine, acetylglutamate, acetylaspartate and N -acetyl amino sugars, and to metabolize/eliminate some xenobiotics. Acetylation is a major post-translational modification of proteins. Different types of protein acetylation occur. The most-studied form occurs at the epsilon nitrogen of lysine residues. In histones, lysine acetylation can alter gene transcription. Acetylation of other proteins has diverse, often incompletely-documented effects. Inborn errors related to Ac-CoA feature a broad spectrum of metabolic, neurological and other features. To date, a small number of studies of animals with inborn errors of CoA thioesters has included direct measurement of acyl-CoAs. These studies have shown that low levels of tissue Ac-CoA correlate with the development of clinical signs, hinting that shortage of Ac-CoA may be a recurrent theme in these conditions. Low levels of Ac-CoA could potentially disrupt any of its roles. [ABSTRACT FROM AUTHOR]

Ectopic expression of lineage-specific transcription factors facilitates the conversion of mammalian somatic cells into dopaminergic (DA) neurons, which is a promising strategy for cell therapy of Parkinson's disease (PD). However, this approach still has some drawbacks limiting its clinical application due to the potential risks of integrating vectors into the host genome. Therefore, it is critical to seek a more desired approach to generate DA neurons derived from mammalian somatic cells. Here, we report that mouse embryonic fibroblasts (MEFs) can be efficiently converted into DA neurons by using small molecules along with specific growth factors. These neuron-like cells generate DA neuronal morphology, and acquire immunocytochemical and calcium imaging special for neuronal electrophysiological profile. More importantly, these converted cells can secrete dopamine, indicating that they are functionally similar to DA neurons. Taken together, our study might provide a promising cell source for treating PD by using chemical approach without introduction of exogenous transcription factors. [ABSTRACT FROM AUTHOR]

Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP), widely applied as flame retardant into a variety of products, can be physically leached out to the aquatic environment. Measurable values of TDCIPP have been found in the environment and within biota. Many toxicological assessments have shown that TDCIPP could cause developmental toxicity and oxidative stress in fish. In this study, we focused on the effects of TDCIPP on the growth and oxidative stress of an important commercial fish species in China, silver carp (Hypophthalmichthys molitrix). Fish larvae was exposed to environmentally relevant concentrations (0.05, 0.5, 5 and 50 μg/L) of TDCIPP for 7, 14 and 28 days. Simultaneously, the transcription levels of genes associated with the growth hormone/insulin-like growth factor (GH/IGF) axis and the antioxidative enzymes were examined. The body length and body mass of silver carp larvae decreased significantly only under exposure to 5 and 50 μg/L of TDCIPP at 14 days compared with the control group, while differences on those paraments were observed at 0.05, 0.5, 5 and 50 μg/L when larvae were exposed for 28 days. The observation evidenced the time- and dose- dependent growth inhibitions caused by TDCIPP on silver carp larvae. Exposure to TDCIPP also decreased the contents of GH and IGF1 in fish attended by significant down-regulation of gh and igf1. Moreover, TDCIPP up-regulated the expression of cat , sod1 and gstt followed by an increase of the activities of catalase (CAT) and superoxide dismutase (SOD) and the levels of malondialdehyde (MDA) and glutathione (GSH), but the activities of glutathione peroxidase (GPX) were decreased. These results suggested that growth inhibition and oxidative stress co-occurred in silver carp larvae after exposure to environmentally relevant concentrations of TDCIPP accompanied by the abnormal expression of genes which associated with the GH/IGF axis and antioxidative enzymes. • TDCIPP exposure decreased body length and body mass in silver carp larvae. • TDCIPP exposure down-regulated expression of genes involved in the GH/IGF axis. • TDCIPP exposure induced oxidative stress in silver carp larvae. • TDCIPP exposure up-regulated expression of antioxidative enzyme genes. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of 11-aminoalkoxy benzophenanthridine derivatives were synthesized. • 14 shows the most TDP1 inhibition. • 14 induces the cellular TDP1cc formation in MCF-7 cells. • 14 shows synergistic effect with topotecan in MCF-7, A549, H460 and HepG2 cells. • Benzophenanthridine scaffold is a chemotype for the discovery of TDP1 inhibitors. Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an enzyme that repairs DNA lesions caused by the trapping of DNA topoisomerase IB (TOP1)-DNA break-associated crosslinks. TDP1 inhibitors have synergistic effect with TOP1 inhibitors in cancer cells and can overcome cancer cell resistance to TOP1 inhibitors. Here, we report the synthesis of 11-aminoalkoxy substituted benzophenanthridine derivatives as selective TDP1 inhibitors and show that six compounds 14 , 16, 18 , 20 , 25 and 27 exhibit high TDP1 inhibition potency. The most potent TDP1 inhibitor 14 (IC 50 = 1.7 ± 0.24 μM) induces cellular TDP1cc formation and shows synergistic effect with topotecan in four human cancer cell lines MCF-7, A549, H460 and HepG2. [ABSTRACT FROM AUTHOR]

Genes and the environment both influence the metabolic processes that determine fitness. To illustrate the importance of metabolism for human brain evolution and health, we use the example of lipid energy metabolism, i.e. the use of fat (lipid) to produce energy and the advantages that this metabolic pathway provides for the brain during environmental energy shortage. We briefly describe some features of metabolism in ancestral organisms, which provided a molecular toolkit for later development. In modern humans, lipid energy metabolism is a regulated multi-organ pathway that links triglycerides in fat tissue to the mitochondria of many tissues including the brain. Three important control points are each suppressed by insulin. (1) Lipid reserves in adipose tissue are released by lipolysis during fasting and stress, producing fatty acids (FAs) which circulate in the blood and are taken up by cells. (2) FA oxidation. Mitochondrial entry is controlled by carnitine palmitoyl transferase 1 (CPT1). Inside the mitochondria, FAs undergo beta oxidation and energy production in the Krebs cycle and respiratory chain. (3) In liver mitochondria, the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) pathway produces ketone bodies for the brain and other organs. Unlike most tissues, the brain does not capture and metabolize circulating FAs for energy production. However, the brain can use ketone bodies for energy. We discuss two examples of genetic metabolic traits that may be advantageous under most conditions but deleterious in others. (1) A CPT1A variant prevalent in Inuit people may allow increased FA oxidation under nonfasting conditions but also predispose to hypoglycemic episodes. (2) The thrifty genotype theory, which holds that energy expenditure is efficient so as to maximize energy stores, predicts that these adaptations may enhance survival in periods of famine but predispose to obesity in modern dietary environments. [ABSTRACT FROM AUTHOR]

Mercury (Hg) is a global environmental contaminant, and excessive mercury levels in water can adversely affect the growth of fish. Silver carp (Hypophthalmichthys molitrix) is one of the important freshwater aquaculture fish in China, and its natural resources have been critically declining. However, the effects of Hg2+ exposure on the growth hormone/insulin-like growth factor (GH/IGF) axis and its toxic mechanism are still unclear. In this study, we systematically evaluated the bioaccumulation, histomorphology, antioxidant status, hormone levels, and GH/IGF axis toxicity of juvenile silver carp after exposure to environmental-related concentrations of Hg2+ (0, 0.05, 0.5, 5, and 50 µg/L) for 28 days. Results showed that the Hg2+ bioaccumulation in the liver increased with a rise in Hg2+ concentration and time of exposure. The body length (BL), body weight (BW), weight growth rate (WGR) and specific growth rate (SGR) all decreased after Hg2+ exposure. The serum levels of growth hormones (GH and IGF) and thyroid hormones (T3 and T4) were significantly decreased, and the expressions of GH/IGF axis-related genes were significantly downregulated after 7, 14, and 28 days of Hg2+ exposure. Correlations between the growth parameters and growth hormones or expression of genes in GH/IGF axis further suggested that environmentally relevant concentrations of Hg2+ could have adverse effects on growth. In addition, with increasing Hg2+ exposure, superoxide activities of dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST)and levels of reduced glutathione (GSH) and malondialdehyde (MDA) were significantly increased, whereas the activity of glutathione peroxidase (GPx) significantly decreased and oxidative stress-related gene significantly changed. Liver lesions were mainly characterized by inflammatory cell infiltration, hepatocyte necrosis and fat vacuolation after exposure to Hg2+. Taken together, the results indicate that Hg2+ exposure leads to growth inhibition and oxidative stress in juvenile silver. • Mercury exposure caused histological alterations of liver • Mercury exposure induced the antioxidant defense of liver. • Mercury exposure alters GH/IGF axis-related genes expression of juvenile silver carp. • Growth of juvenile silver carp was inhibited by environmentally relevant levels of mercury. [ABSTRACT FROM AUTHOR]

Soil alkalization severely limits plant growth and development, however, the mechanisms of alkaline response in plants remain largely unknown. In this study, we performed physiological and transcriptomic analyses using two alfalfa cultivars (Medicago sativa L.) with different sensitivities to alkaline conditions. The chlorophyll content and shoot fresh mass drastically declined in the alkaline-sensitive cultivar Algonquin (AG) following alkaline treatment (0–25 mM Na 2 CO 3 solution), while the alkaline-tolerant cultivar Gongnong NO.1 (GN) maintained relatively stable growth and chlorophyll content. Compared with AG, GN had higher contents of Ca2+ and Mg2+; the ratios of Ca2+ and Mg2+ to Na+, proline and soluble sugar, as well as higher enzyme activities of peroxidase (POD) and catalase (CAT) under the alkaline conditions. Furthermore, transcriptomic analysis identified three categories of alkaline-responsive differentially expressed genes (DEGs) between the two cultivars: 48 genes commonly induced in both the cultivars (CAR), 574 genes from the tolerant cultivar (TAR), and 493 genes from the sensitive cultivar (SAR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that CAR genes were mostly involved in phenylpropanoid biosynthesis, lipid metabolism, and DNA replication and repair; TAR genes were significantly enriched in metabolic pathways, such as biosynthesis of amino acids and secondary metabolites including flavonoids, and the MAPK signaling pathway; SAR genes were specifically enriched in vitamin B6 metabolism. Taken together, the results identified candidate pathways associated with genetic variation in response to alkaline stress, providing novel insights into the mechanisms underlying alkaline tolerance in alfalfa. • Alkaline stress (25 mM Na 2 CO 3) reduced chlorophyll and growth of alfalfa seedlings. • Alkaline-tolerant cultivar showed a better ion balance and ROS homeostasis. • MAPK signaling and secondary metabolisms are involved in the alkaline tolerance. [ABSTRACT FROM AUTHOR]

PbO 2 , PbO 2 /Pb 3 O 4 composite, and Pb 3 O 4 were synthesized respectively via the simple hydrothermal method under different reaction durations (3–48 ​h). All the prepared samples were used as anode materials to decontaminate methyl orange (MO) to explore the corresponding electrochemical advanced oxidation performance. The detailed experimental designs suggested that the combination of PbO 2 and Pb 3 O 4 offered enhanced electrochemical advanced oxidation performance, which was due to possible synergistic effects. XPS results suggest that the content of adsorbed oxygen species (O ads) is obviously higher in PbO 2 /Pb 3 O 4 composite. It is very likely due to more oxygen vacancies in the crystal structure of PbO 2 /Pb 3 O 4 composite, which will adsorb more oxygen species, promote charge transfer and provide more electrochemical active surface area to generate oxidizing agents. Besides, the presence of Pb 3 O 4 can suppress the oxygen evolution and improve the accelerated life. Meanwhile, the effects of current density, catalyst loading amount and initial MO concentration on electro-catalysis degradation of MO were explored. Experimental results suggested that MO removal efficiency was 94.3%, the reaction kinetic constant could reach 2.08 ⅹ 10-2 min-1, and COD removal efficiency was 34.2% after 150 ​min of reaction under optimized conditions: current density was 5 ​mA ​cm-2, catalyst loading amount was 1 ​mg ​cm-2 and initial MO concentration was 50 ​mg ​L-1. Furthermore, possible degradation mechanisms of MO was proposed according to the analyzed results obtained from UV–Vis and HPLC-MS. Relative ratio of PbO 2 and Pb 3 O 4 can be altered by changing the hydrothermal reactions durations, and PbO 2 /Pb 3 O 4 composite exhibited enhanced electrochemical advanced oxidation performance. [Display omitted] • Ratio of PbO 2 and Pb 3 O 4 can be adjusted by hydrothermal reaction durations. • PbO 2 /Pb 3 O 4 composite displayed enhanced electro-catalytic performance. • Role of different operating conditions was investigated. • Degradation byproducts of MO were identified and the possible pathways were proposed. [ABSTRACT FROM AUTHOR]

Abstract: Since antibiotics with a broad spectrum of activity would select for resistance among the normal flora, colicins having a narrow spectrum of activity can potentially be developed as novel antibiotics. Colicin-based bactericidal proteins with modified spectra of activity might also be developed by further gene fusion or gene modification. To achieve these goals, it is necessary to first build an efficient system to produce large amounts of colicin. In the presence of an immunity gene, we successfully constructed an expression vector pQE30-cfa-cfi producing high levels of His-tagged colicin 5 (60–80mg/L). We found that the purified His-tagged colicin 5 possesses narrow-spectrum bactericidal activity against nonimmune Escherichia coli cells. It is highly toxic to sensitive E. coli cells at a low concentration of 0.01μg/ml, while it is nontoxic to other tested gram-negative bacteria, gram-positive bacteria and yeast at a high concentration of 1000μg/ml. His-tagged colicin 5 kills sensitive cells by permeabilizing their cell membranes. It is not hemolytic to rabbit erythrocytes and has no obvious cytotoxicity to other nucleated mammalian cells at a high concentration of 500μg/ml. The His-tagged colicin 5 is similar to wild-type colicin 5 in spectrum and bactericidal activity against E. coli. It is a potential novel antibiotic particularly for treating human and animal infections caused by pathogenic E. coli. Besides producing high level of colicin 5, the highly efficient expression vector constructed here might also be a useful tool to develop colicin-based artificial bactericidal proteins. [Copyright &y& Elsevier]

Abstract: We report a novel protein family consisting of three members, each of which contains RUN and TBC motifs and appears to be associated with small G protein-mediated signal transduction pathway. We named these proteins as small G protein signaling modulators (SGSM1/2/3). Northern blot analysis revealed that human SGSM2/3 are expressed ubiquitously in various tissues, whereas SGSM1 is expressed mainly in brain, heart, and testis. Mouse possessed the same protein family genes, and the in situ hybridization and immunohistochemical staining of tissue sections revealed that mouse Sgsm1/2/3 are expressed in the neurons of central nervous system, indicating the strong association of Sgsm family with neuronal function. Furthermore, endogenous Sgsm1 protein was localized in the trans-Golgi network of mouse Neuro2a cells by immunofluorescence microscopy. Expression of various cDNA constructs followed by immunoprecipitation assay revealed that human SGSM1/2/3 proteins are coprecipitated with RAP and RAB subfamily members of the small G protein superfamily. Based on these results, we postulated that the SGSM family members function as modulators of the small G protein RAP and RAB-mediated neuronal signal transduction and vesicular transportation pathways. [Copyright &y& Elsevier]

[Display omitted] • A series of furoquinolinedione analogues was synthesized. • A series of isoxazoloquinolinedione analogues was synthesized. • Isoxazoloquinolinediones are TDP2 inhibitors with IC 50 at sub-micromolar range. • The SAR was analyzed. Based on our previous study on the development of the furoquinolinedione and isoxazoloquinolinedione TDP2 inhibitors, the further structure–activity relationship (SAR) was studied in this work. A series of furoquinolinedione and isoxazoloquinolinedione derivatives were synthesized and tested for enzyme inhibitions. Enzyme-based assays indicated that isoxazoloquinolinedione derivatives selectively showed high TDP2 inhibitory activity at sub-micromolar range, as well as furoquinolinedione derivatives at low micromolar range. The most potent 3-(3,4-dimethoxyphenyl)isoxazolo[4,5- g ]quinoline-4,9-dione (70) showed TDP2 inhibitory activity with IC 50 of 0.46 ± 0.15 μM. This work will facilitate future efforts for the discovery of isoxazoloquinolinedione TDP2 selective inhibitors. [ABSTRACT FROM AUTHOR]

Emulsion gels with potato starch in the continuous phase and octenyl succinic anhydride (OSA) starch at the interface were developed, and they were used to modulate salt release. OSA starch (70–110 mg/g) stabilized emulsions had droplet size in the range of 377–574 nm, and they presented good creaming stability (integral transmission<20%) during a centrifugation test. Different volume (100–300 mg/g) of the emulsion was added into potato starch dispersion, and gels were formed after heating and shearing. Microstructural observation revealed that oil droplets aggregated in the gels with higher concentration of emulsions (250 and 300 mg/g), but these gels had more uniform gel networks with evenly distributed pores. The increase in emulsion volume contributed to gels with higher storage modulus and stiffness. The swelling ratios of all the emulsion gels were relatively low (<15%), which were negatively correlated with emulsion content. Salt (NaCl) release from emulsion gels in water and α-amylase solution was monitored, and it was faster and higher in the gels with lower emulsion content. When α-amylase was included in the dispersing media, significantly faster salt release was observed. Image 1 • Higher emulsion content contributed to gels with higher mechanical properties. • The gels containing higher volume of emulsion had more compact microstructures. • Salt was released at lower rates in the gels with higher volume of emulsions. [ABSTRACT FROM AUTHOR]

Metal-organic frameworks (MOFs) have become a versatile platform for gas capture/separation and luminescent sensing of toxic pollutants, and the combination of both of these properties depends on the robust framework and pre-designed pore functionality which is critical to achieve the targeted applications. In this work, a novel Cd(II)-MOF {(NH 2 Me 2)[Cd 3 (μ 3 -OH) (tpt) (TZB) 3 (H 2 O) 2 (1,4-dioxane) 5 } n (1 , H 2 TZB ​= ​4-(1H-tetrazol-5-yl)benzoic acid, tpt ​= ​2,4,6-tri (pyridin-4-yl)-1,3,5-triazine) comprising of a {Cd 3 (OH)}5+ cluster-based unit (SBU) has been solvothermally formed from nitrogen-rich and highly fluorescent organic ligands. The porous structure 1 is composed of cages and segments which are affixed by high density of free nitrogen atoms. The activated Cd(II)-MOF (1a) exhibits a relative high C 2 H 2 sorption capacity than that of CO 2 which endows it with a C 2 H 2 /CO 2 sorption selectivity of 7.26 ​at room temperature. Furthermore, complex 1 could behave as a luminescent sensor for highly discriminative detection of explosive 2,4,6-trinitrophenol (TNP) via remarkable fluorescence quenching (K sv ​= ​6.16✕104 ​M−1). A novel porous Cd(II)-MOF has been prepared from nitrogen-rich and highly fluorescent organic ligands. The porous structure 1 is composed of cages and segments which are affixed by high density of free nitrogen atoms. The activated Cd(II)-MOF exhibits a relative high C 2 H 2 sorption capacity than that of CO 2 which endows it with a C 2 H 2 /CO 2 sorption selectivity of 7.6 at room temperature. Furthermore, complex 1 could behave as a luminescent sensor for highly discriminative detection of explosive 2,4,6-trinitrophenol (TNP) via remarkable fluorescence quenching (K sv ​= ​6.16✕104). Image 1 • A new Cd(II)-MOF having the pacs-type network was prepared. • The MOF is composed of cages and segments with excellent water stability. • The MOF shows high C 2 H 2 uptake capacity and moderate high C 2 H 2 /CO 2 selectivity • The MOF could be used as a luminescent sensor for highly discriminative detection of TNP [ABSTRACT FROM AUTHOR]

Different regions and states of the human colon are likely to have a distinct influence on immune cell functions. Here we studied the immunometabolic mechanisms for spatial immune specialization and dysregulated immune response during ulcerative colitis at single-cell resolution. We revealed that the macrophages and CD8+ T cells in the lamina propria of the human colon possessed an effector phenotype and were more activated, while their lipid metabolism was suppressed compared with those in the epithelial. Also, IgA+ plasma cells accumulated in lamina propria of the sigmoid colon were identified to be more metabolically activated versus those in the cecum and transverse colon, and the improved metabolic activity was correlated with the expression of CD27. In addition to the immunometabolic reprogramming caused by spatial localization colon, we found dysregulated cellular metabolism was related to the impaired immune functions of macrophages and dendritic cells in patients with ulcerative colitis. The cluster of OSM+ inflammatory monocytes was also identified to play its role in resistance to anti -TNF treatment, and we explored targeted metabolic reactions that could reprogram them to a normal state. Altogether, this study revealed a landscape of metabolic reprogramming of human colonic immune cells in different locations and disease states, and offered new insights into treating ulcerative colitis by immunometabolic modulation. • We depicted a metabolic landscape of human colonic immune cells in different locations and states at single-cell resolution. • Immune cells in lamina propria possessed an effector phenotype but suppressed lipid metabolism versus those in epithelial. • Dysregulated cellular metabolism was related to the impaired immune functions in patients with ulcerative colitis. • We explored pathways related to anti-TNF resistance showing the potential immunometabolic modulation to ulcerative colitis. [ABSTRACT FROM AUTHOR]

[Display omitted] Photoelectrochemical (PEC) water splitting on semiconductor electrodes is considered to be one of the important ways to produce clean and sustainable hydrogen fuel, which is a great help in solving energy and environmental problems. Bismuth vanadate (BiVO 4) as a promising photoanode for photoelectrochemical water splitting still suffers from poor charge separation efficiency and photo-induced self-corrosion. Herein, we develop heterojunction-rich photoanodes composed of BiVO 4 and iron vanadate (FeVO 4), coated with nickel iron oxide (NiFeO x /FeVO 4 /BiVO 4). The formation of the interface between BiVO 4 and FeVO 4 (Bi-VO 4 -Fe bridges) enhances the interfacial interaction, resulting in improved performance. Meanwhile, high-conductivity FeVO 4 and NiFeO x oxygen evolution co-catalysts effectively enhance bulk electron/hole separation, interface water's kinetics and photostability. Concurrently, the optimized NiFeO x /FeVO 4 /BiVO 4 possesses a remarkable photocurrent density of 5.59 mA/cm2 at 1.23 V versus reversible hydrogen electrode (vs RHE) under AM 1.5G (Air Mass 1.5 Global) simulated sunlight, accompanied by superior stability without any decreased of its photocurrent density after 14 h. This work not only reveals the crucial role of built-in electric field in BiVO 4 -based photoanode during PEC water splitting, but also provides a new guide to the design of efficient photoanode for PEC. [ABSTRACT FROM AUTHOR]

Tibial Dyschondroplasia (TD), a metabolic disease of fast growing poultry birds that effects the growth of bone and cartilage, is characterized by anorexia, mental depression and lameness. Wnt/β-catenin pathway can mediate the occurrence of TD, and previous study showed the therapeutic effect of TanshinoneⅡA to TD Broilers. However there is no report about the effect of TanshinoneⅡA treating TD broiler chicken through wnt/β-catenin pathway. The objective of this study was to explore the potential mechanism of how Tanshinone II A treats TD. Hematoxylin and eosin staining was used to study histologic pathology of growth plates. Key gene expressions were tested by western blot and reverse transcription quantitative real-time PCR. Results compared with control groups, showed the TD broilers' growth plate performed significantly better by treating with TanshinoneⅡA. After chickens treated by TanshinoneⅡA, the gene and protein expression of WNT5α and BMP-2 were increased (P < 0.05), but the β-catenin were decreased (P < 0.05), which are all key genes expressed in wnt/β-catenin pathway. Therefore, TanshinoneⅡA can potentially treat TD by affecting the expression of genes in wnt/β-catenin pathway and it has availability to use as treatment for TD broilers. • Tanshinone II A, a Chinese herb extract, ability to cure Tibial Dyschondroplasia (TD) of broiler chickens. • Health conditions, pathology changes, key gene expressions in wnt/β-catenin pathway were tested. • Tanshinone II A is able to improve thiram-induced TD broilers performance through wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]

Propionic acidemia (PA) is a severe autosomal recessive metabolic disease caused by deficiency of propionyl-CoA carboxylase (PCC). We studied PA transgenic (Pat) mice that lack endogenous PCC but express a hypoactive human PCCA cDNA, permitting their survival. Pat cohorts followed from 3 to 20 weeks of age showed growth failure and lethal crises of lethargy and hyperammonemia, commoner in males (27/50, 54%) than in females (11/52, 21%) and occurring mainly in Pat mice with the most severe growth deficiency. Groups of Pat mice were studied under basal conditions (P-Ba mice) and during acute crises (P-Ac). Plasma acylcarnitines in P-Ba mice, compared to controls, showed markedly elevated C3- and low C2-carnitine, with a further decrease in C2-carnitine in P-Ac mice. These clinical and biochemical findings resemble those of human PA patients. Liver acyl-CoA measurements showed that propionyl-CoA was a minor species in controls (propionyl-CoA/acetyl-CoA ratio, 0.09). In contrast, in P-Ba liver the ratio was 1.4 and in P-Ac liver, 13, with concurrent reductions of the levels of acetyl-CoA and other acyl-CoAs. Plasma ammonia levels in control, P-Ba and P-Ac mice were 109 ± 10, 311 ± 48 and 551 ± 61 μmol/L respectively. Four-week administration to Pat mice, of carglumate (N-carbamyl-L-glutamic acid), an analogue of N-carbamylglutamate, the product of the only acyl-CoA-requiring reaction directly related to the urea cycle, was associated with increased food consumption, improved growth and absence of fatal crises. Pat mice showed many similarities to human PA patients and provide a useful model for studying tissue pathophysiology and treatment outcomes. [ABSTRACT FROM AUTHOR]

[Display omitted] Thermal runaway is a hazardous risk, occurring more readily in high-energy–density lithium-ion batteries (LIBs), which leads to a rapid temperature rise and even combustion or explosion when using flammable electrolyte systems. Flame retardants (FRs), such as trimethyl phosphate (TMPa) and triethyl phosphate (TEP), are commonly utilized due to their effective flame suppression, low toxicity, and excellent thermal stability. However, the lack of in-depth understanding of the flame retardancy mechanism and solid electrolyte interphase (SEI) formation process has made the development of functional electrolytes difficult at present. In this study, we clarified the flame retardancy and interfacial reaction mechanisms of low-flammable TMPa localized high-concentration electrolytes (LHCE) using hybrid ab initio and reactive force field (HAIR) schemes. Long-term HAIR simulation reveals that phosphorous radicals produced by the decomposition of TMPa capture carbon radicals, encouraging their polymerization into low-flammable oligomers, while fluorine-containing solvents in the electrolyte capture hydrogen radicals and produce nonflammable hydrofluoric acid (HF). This synergistic flame retardancy mechanism provides essential atomic-level insights for the rational design of high-safety electrolytes in the future. [ABSTRACT FROM AUTHOR]

[Display omitted] Valence modulation of transition metal oxides represents a highly effective approach in designing high-performance catalysts, particularly for pivotal applications such as the hydrogen evolution reaction (HER) in solar/electric water splitting and the hydrogen economy. Recently, there has been a growing interest in high-valence transition metal-based electrocatalysts (HVTMs) due to their demonstrated superiority in HER performance, attributed to the fundamental dynamics of charge transfer and the evolution of intermediates. Nevertheless, the synthesis of HVTMs encounters considerable thermodynamic barriers, which presents challenges in their preparation. Moreover, the underlying mechanism responsible for the enhancement in HVTMs still needs to be discovered. Hence, the universal synthesis strategies of the HVTMs are discussed, and direct Raman spectroscopic evidence for intermediates regulation is revealed to guide the further design of the HVTM electrocatalysts. This work offers new insights for facile designing of HVTMs electrocatalysts for energy conversion and storage through adjusting the reaction pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] The pressing need to address the global water crisis has spurred research efforts toward exploring alternative sources and technologies, and harvesting atmospheric water from the humid air emerges as a promising solution. Liquid desiccants, known for their high absorption capacity, have been widely utilized for moisture capture, but their water yield is mainly restricted by sluggish adsorption and desorption dynamics. To address this limitation, we present a facile strategy to promote the absorption/desorption dynamics of moisture by virtue of capillary transport and enlarged interfaces in a photothermal wood enhancer. These enhancers are fabricated via partial delignification of natural balsa woods followed by low-temperature carbonization to endow them with photothermal properties. The moisture absorption rate shows a notable increase of 103% and 84% under the relative humidity (RH) of 60% and 90%, respectively, within the initial two hours by applying the three enhancers. On the other hand, the desorption efficiency is doubled, reaching 80% in two hours under 60 °C with the enhancers. Moreover, the desorption can be driven by solar energy with an evaporation rate of 1.217 kg·m−2·h−1. This work provides a design strategy combining capillary and interfacial effects to enhance moisture harvesting without altering hygroscopic materials. [ABSTRACT FROM AUTHOR]

[Display omitted] Directional sweat-wicking by Janus fabrics has gained substantial attention in promoting personal wet-thermal management for optimal human comfort. During intense physical exercise, excessive sweating can cause the flooding of fabrics and weaken their wicking capabilities once the inner capillary channels are saturated. To address this issue, we develop a photothermal Janus fabric through a facile polydopamine (PDA) deposition followed by single-sided spray-coating of hydrophobic polydimethylsiloxane (PDMS). Such innovative fabrics enable directional sweat-wicking through a Janus structure and persistent removal of excessive sweat by solar-powered evaporation. Under sunlight, our photothermal Janus fabrics exhibit an enhanced evaporation rate, approximately twice compared with that of conventional Janus fabrics (∼1.143 ± 0.027 kg m-2h−1), making them suitable for high sweating rates during vigorous exercise. Furthermore, these fabrics help to maintain the skin temperature within the normal range, preventing hypothermia caused by profuse sweating. In addition, our photothermal Janus fabrics exhibit excellent washing durability even after multiple washing cycles, ensuring prolonged performance and safety. [ABSTRACT FROM AUTHOR]

[Display omitted] Dual–carbon engineering combines the advantages of graphite and hard carbon, thereby optimizing the potassium storage performance of carbon materials. However, dual–carbon engineering faces challenges balancing specific capacity, capability, and stability. In this study, we present a coordination engineering of Zn–N 4 moieties on dual–carbon through additional P doping, which effectively modulates the symmetric charge distribution around the Zn center. Experimental results and theoretical calculations unveil that additional P doping induces an optimized electronic structure of the Zn–N 4 moieties, thus enhancing K+ adsorption. A single–atom Zn metal coordinated with nitrogen and phosphorus reduces the K+ diffusion barrier and improves fast K+ migration kinetics. Consequently, Zn–NPC@rGO exhibits high reversible specific capacities, excellent rate capability, and impressive cycling stability, and remarkable power and energy densities for potassium–ion capacitors (PICs). This study provides insights into crucial factors for enhancing potassium storage performance. [ABSTRACT FROM AUTHOR]

Highlights • The R-D relationship of the screen content video is related to video contents. On the basis of this fact, CTUs in screen content videos are classified into three types: T-CTUs, SI-CTUs and NI-CTUs according to their pixel activity and DCT coefficient distribution. • Disparate CTUs present vastly different R-D relationships. For this reason, instead of the unitive parameter update method in the R- λ model, the parameters used to code specific kind of CTU are updated according to the information of the last same kind of coded CTU rather than the last CTU. • Before assigning bits to each CTU, the bits allocated to text region, screen image region and nature image region are determined. When a scene change occurs, the bit allocation method which relied on the distortion and CTU number changes into the one only related to the number of CTUs. Abstract The popularity of 3D screen content videos like 3D animations calls for better coding performance of screen content videos. The exiting R- λ rate control model is designed to enable the coding performance of conventional nature videos, which can not accurately describe the Rate-Distortion (R-D) relationships of the screen content videos, especially for videos containing limited colors and sharper edges. This paper proposes a new rate control (RC) scheme which takes the divergent characteristics of text contents, screen images and nature images in screen content videos into consideration. In particular, the content-based rate control algorithm is developed at Coding Tree Unit (CTU) level, where CTUs are divided into three categories including Text-CTUs (T-CTUs), Screen Image-CTUs (SI-CTUs) and Nature Image-CTUs (NI-CTUs). Three R- λ models reflecting different R-D relationships of different CTUs are established, and the model parameters are updated on the basis of their own models. Furthermore, in view of the fact that continuity and mutability simultaneously exist in screen content videos, two bit allocation schemes for regions containing only one content are determined in this paper. Experimental results show that the proposed RC scheme achieves 0.749 dB BDPSNR increase under the Low Delay configuration and 0.637 dB BDPSNR increase under the Random Access configuration on average, compared to the default R- λ model in HEVC Screen Content Coding extension (HEVC-SCC) reference software. [ABSTRACT FROM AUTHOR]

Underwater bionic robotics and vehicles that use flexible structures as power sources have attracted considerable attention. Thus, the underwater dynamic behaviors of the flexible structure of a variable cross-section actuated by smart actuators must be further investigated. In this study, underwater dynamic hysteresis modeling and feedforward compensation of a flexible caudal fin driven by macro fiber composites (MFC) at different frequencies were investigated. The MFC-actuated flexible caudal fin is considered a Euler–Bernoulli beam. A revised hydrodynamic function governed by the thickness of the viscous layer and the gap-to-width ratio of the cross-section was developed. Then, a characteristic-frequency-dependent extended transform function model is proposed for the hydrodynamic response of a non-uniform beam. An asymmetric hysteresis model is presented to characterize the rate-independent hysteresis behavior of the MFC actuators. Further, the underwater dynamic equation of the MFC-actuated caudal fin with hysteresis is obtained by connecting the two established models in series. Experiments demonstrate the dynamic behavior between the underwater responses of the caudal fin and the input voltages have an ellipse-like shape and vary in shape and size with oscillating frequency. The ellipse-like dynamic hysteresis loop first grows, reaching its maximum at the resonant frequency, and then decreases, because of the frequency-dependent dynamic behavior. Meanwhile, a phase shift of approximately 90°between the input voltage and underwater dynamic response was observed at the resonant state. Furthermore, the experimental results demonstrate that the proposed model can describe the nonlinear underwater dynamic hysteresis behavior of the proposed caudal fin at different frequencies. The trajectory tracking performances are remarkably improved over a broad frequency range with the proposed compensator. Consequently, the effectiveness of the proposed dynamic model and compensation method was demonstrated. These results are helpful for robotic fish or autonomous underwater vehicles propelled by oscillating foils actuated by smart actuators, including MFC. • A characteristic-frequency-dependent extended transform function model is proposed. • An asymmetric hysteresis model is presented to characterize the rate-independent hysteresis. • The nonlinear underwater dynamic hysteresis behavior of the MFC-actuated caudal fin is well described. • Tracking performances of the MFC-actuated caudal fin are remarkably improved with the compensator. [ABSTRACT FROM AUTHOR]

The disadvantages of the current chemical and instrumental analysis methods for soil heavy metal pollution are that they have a high detection cost, long cycle times, and may cause secondary pollution. The aims of this study were to improve the rapid detection of soil heavy metal pollution over large areas. This study combined aircraft technology, embedded development, computer software, electronic information, and other technical methods to create a novel solution to the problem, i.e., an integrated unmanned aerial vehicle (UAV) based soil heavy metal pollution rapid detection system (UAV-SHMPRDS) was built. The key technologies required for a rapid detection system were developed, including the development of a hardware system based on a UAV and an X-ray fluorescence spectrum (XRF) analyzer, the design and implementation of a control system software system, and the implementation of a data inversion processing algorithm. Finally, a prototype UAV-SHMPRDS was constructed. Testing showed that the system improved regionalized soil heavy metal pollution detection efficiency. This study provides new solutions for the current problems encountered in the actual rapid detection of soil heavy metal pollution. • A developed system combining XRF and UAV is beneficial to rapid regional detection. • Combined interdisciplinary and multiple technologies to build a novel prototype. • The key technologies required for a rapid detection system were developed. • Tests showed that the system improved regionalized heavy metal pollution detection efficiency. • Provides new solutions for problems encountered in the actual rapid detection. Heavy metal pollution detection is of great significance to environmental protection. XRF can easily detect the content of heavy metals, but the efficiency is low. The development of an instrument system combining XRF and UAV will be beneficial to the rapid detection of regional heavy metals detection. [ABSTRACT FROM AUTHOR]

[Display omitted] Visible light-driven photo-Fenton-like technology is a promising advanced oxidation process for water remediation, while the construction of effective synergetic system remains a great challenge. Herein, iron hydroxide oxide (α-FeOOH) with controllable oxygen vacancy defects were engineered on reduced graphene oxide (rGO) nanosheets (named as OVs -FeOOH/rGO) through an in-situ redox method for boosting visible light-driven photo-Fenton-like oxidation. By adjusting the pH environment to modulate the redox reaction kinetics between graphene oxide (GO) and ferrous salt precursors, the oxygen vacancy concentration in α-FeOOH could be precisely controlled. With optimized oxygen vacancy defects obtained at pH 5, the OVs -FeOOH/rGO displayed superior photo-Fenton-like performance for Rhodamine B degradation (99% within 40 mins, rate constant of 0.2278 mg−1 L min−1) with low H 2 O 2 dosage (5 mM), standing out among the reported photo-Fenton-like catalysts. The catalyst also showed excellent reusability, general applicability, and tolerance ability of realistic environmental conditions, which demonstrates great potential for practical applications. The results reveal that moderate oxygen vacancy defects can not only strengthen absorption of visible light and organic pollutants, but also promote the charge transfer to simultaneously accelerate the photogenerated electron-hole separation and Fe(III)/Fe(II) Fenton cycle, leading to the remarkable photo-Fenton-like oxidation performance. This work sheds light on the controllable synthesis and mechanism of oxygen vacancy defects to develop efficient photo-Fenton-like catalysts for wastewater treatment. [ABSTRACT FROM AUTHOR]

The CD40-mediated immune response contributes to a wide variety of chronic inflammatory diseases. CD40 antagonists have potential as novel therapies for immune disorders. However, the CD40 pathway has not been well characterized in the rhesus monkey Macaca mulatta , which is a valuable animal model for human immune disease. An 834 bp transcript was cloned from peripheral blood mononuclear cells (PBMCs) of rhesus monkey using specific primers designed according to the predicted sequence of M. mulatta CD40 (mmCD40) in GenBank. Sequence analysis demonstrated that mmCD40 is highly homologous to human CD40 (hCD40), with an amino acid sequence identity of 94%. Genes encoding the extracellular domain of mmCD40 and the Fc fragment of the hIgG1 were inserted into a pPIC9K plasmid to produce mmCD40Ig by Pichia pastoris . Approximately 15–20 mg of the mmCD40Ig protein with ∼90% purity could be recovered from 1 L of culture. The purified mmCD40Ig protein can form dimers and can specifically bind CD40L-positive cells. Additionally, the mmCD40Ig protein can bind hCD40L protein in phosphate buffered saline and form a stable combination in a size-exclusion chromatography assay using a Superdex 200 column. Moreover, mmCD40Ig is as efficient as M. mulatta CTLA4Ig (mmCTLA4Ig) to suppress Con A-stimulated lymphocyte proliferation. Additionally, mmCD40Ig only showed mild immunosuppressive activity in a one-way mixed lymphocyte reaction (MLR) system. These results suggest that mmCD40Ig secreted by P. pastoris was productive and functional, and it could be used as a tool for pathogenesis and therapies for chronic inflammatory diseases in a M. mulatta model. [ABSTRACT FROM AUTHOR]