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This study provides a promising strategy for designing separator modified materials to solve the shuttle effect of soluble LiPSs in Li-S batteries. [Display omitted] • A composite material consisting of the 3D connected carbon network and ultra-thin NiCo-LDH nanosheets was devised and manufactured. • The DFT calculations further provided a comprehensive demonstration of the synergy adsorption and catalytic conversion processes. • Li-S batteries that were assembled using modified separators demonstrated remarkable electrochemical performance. The shuttle effect of soluble lithium polysulfides (LiPSs) is primarily responsible for the unstable performance of lithium-sulfur (Li-S) batteries, which has severely impeded their continued development. In order to solve this problem, a special strategy is proposed. Specifically, ultra-thin NiCo based layered double hydroxides (named LDH or NiCo-LDH) nanosheets are implanted into a pre-designed 3D interconnected carbon networks (SPC) to obtain porous composite materials (named SPC-LDH). During the operation of the battery, the 3D interconnected porous carbon mesh was the first to rapidly adsorb LiPSs, and then the LDH on the surface of the carbon mesh was used to realize the catalytic conversion of LiPSs. This facilitates the electrochemical conversion reaction between S substances while addressing the "shuttle effect". As a result, the battery maintains a discharge capacity of 1401.9, 1114.3, 975.5, 880.7, 760.4 and 679.6 mAh g−1 at the current densities of 0.1, 0.2, 0.5, 1, 2 and 3C, respectively. After 200 cycles at 2C, the battery's capacity stays at 732.9 mAh g−1, meaning that the average rate of capacity decay is only 0.007 % per cycle. Moreover, in-situ XRD demonstrates the critical function of PP/SPC-LDH separators in inhibiting LiPSs and encouraging Li 2 S transformation. The strong affinity of SPC-LDH for Li 2 S 6 is also confirmed by density functional theory (DFT) calculation, offering more theoretical support for the synergistic adsorption process. This work offers a compelling method to develop modified separator materials that can counteract the "shuttle effect" in Li-S batteries. [ABSTRACT FROM AUTHOR]

Microplastics (MPs) usually appear in the aquatic environment as complex pollutants with other environmental pollutants, such as levofloxacin (LVFX). After 45-day exposure to LVFX and MPs with different particle sizes at environmental levels, we measured the weight, snout-to-vent length (SVL), and development stages of Rana nigromaculata. Furthermore, we analyzed proteins and genes related to immune system and thyroid axis regulation, intestinal histological, and bioaccumulation of LVFX and MPs in the intestine and brain to further explore the toxic mechanism of co-exposure. We found MPs exacerbated the effect of LVFX on growth and development, and the order of inhibitory effects is as follows: LVFX-MP3>LVFX-MP1>LVFX-MP2. 0.1 and 1 μm MP could penetrate the blood–brain barrier, interact with LVFX in the brain, and affect growth and development by regulating thyroid axis. Besides, LVFX with MPs caused severer interference on thyroid axis compared with LVFX alone. However, 10 μm MP was prone to accumulating in the intestine, causing severe histopathological changes, interfering with the intestinal immune system and influencing growth and development through immune enzyme activity. Thus, we concluded that MPs could regulate the thyroid axis by interfering with the intestinal immune system. [Display omitted] • MPs exacerbated effect of LVFX on growth and development. • MPs≤1 μm was more enriched in brain. • MPs≤1 μm could interact with LVFX in brain. • 10 μm MP was prone to accumulating in intestine. • 10 μm MP caused severer histopathological and immune response. [ABSTRACT FROM AUTHOR]

Microplastics (MPs) usually appear in the aquatic environment as complex pollutants in combination with other environmental pollutants, such as levofloxacin (LVFX). After a 45-day exposure to LVFX and MPs with different particle sizes at environmental levels, LVFX was neurotoxic to Rana nigromaculata tadpoles. The order of the effects of the exposure treatment on tadpole behavior was: LVFX-MP3>LVFX-MP1>LVFX-MP2 ≥ LVFX. Results of transcriptome analysis of tadpole brain tissue showed that LVFX in combination with 0.10 and 10.00 μm MP interferes with the nervous system through the cell adhesion molecules pathway. Interestingly, the order of effects of the co-exposure on oxidative stress in the intestine was inconsistent with that of tadpole behavior. We found that Paraacteroides might be a microplastic indicator species for the gut microbiota of aquatic organisms. The results of the targeted metabolism of neurotransmitters in the intestine suggest that in the LVFX-MP2 treatment, LVFX alleviated the intestinal microbiota disorder caused by 1.00 μm MP, by regulating intestinal microbiota participating in the TCA cycle VI and gluconeogenesis and tetrapyrrole biosynthesis I, while downregulating Met and Orn, and upregulating 5HIAA, thereby easing the neurotoxicity to tadpoles exposed to LVFX-MP2. This work is of great significance for the comprehensive assessment of the aquatic ecological risks of microplastics-antibiotic compound pollutants. [Display omitted] • LVFX was neurotoxic to tadpoles after co-exposure with microplastics. • The order of effects is LVFX-MP3>LVFX-MP1>LVFX-MP2 ≥ LVFX. • Paraacteroides might be a microplastic indicator species in gut. • LVFX alleviated the intestinal microbiota disorder caused by 1um MP. • LVFX regulated neurotransmitter metabolites by regulating intestinal microbiota. Synopsis ：Our research provided a new perspective for aquatic ecological risk assessment under co-exposure of antibiotics and microplastics. [ABSTRACT FROM AUTHOR]

Woody debris enter rivers during flood events, and the debris is captured and accumulates in the form of a debris jam in front of/around the pier. A woody debris jam can significantly increase the possibility of bridge failure, and it is hence necessary to investigate the mechanism and processes through which the debris is affecting the pier. In this study, physical modeling was conducted to investigate the temporal evolution of debris jam as well as the load and additional hydraulic head caused by the presence of the debris jam. Either dowels or seedling trees were used as debris. The experiment results showed that the horizontal debris jam plan area correlated with the frontal vertical area and this correlation resulted in the development of a method used to estimate the blockage ratio caused by the debris jam in the channel. The drag coefficient caused by the debris jam was also calculated using the measured load caused by the debris jam. In addition, the hydraulic head caused by debris jam was measured during the development of debris jam, and it was found that the hydraulic head was correlated with the blockage ratio and the Froude number. This study provided a spatio-temporal perspective into the development of debris jams. [ABSTRACT FROM AUTHOR]

Abstract Pesticides are proposed as one of the many causes for the global decline in reptile population. To understand the potential impact of alpha-cypermethrin (ACP) in reptiles, in the current study, we used a tri-trophic food web (plants - herbivores - natural enemies of predators) to examine the reproductive toxicity and biomarker changes. Based on the Maximum Residue Limit (MRL) of ACP in several agricultural products, we designed three concentrations 0, 2 (MRL), and 20 mg/kg wet weight as three treatment groups for this research. Male and female lizards were fed ACP contaminated or uncontaminated diets for eight weeks during the breeding phase. The number of deaths was different among the three groups, and a dose-dependent trend was found. Decreases in food consumption of 26.6% and 28.1% were observed in the low- and high-dose group, respectively. Dietary exposure significantly induced a dose-dependent decrease in body mass index in lizards. Significant variations in glutathione-S-transferaseb activities, catalase activities, and malondialdehyde levels in gonads, suggest that lizards were under oxidative stress. In addition, ACP exposure altered sexual hormone levels in males, reduced reproductive output of females, and induced histopathological changes in testes. These negative effects highlight that ACP dietary exposure is a potential threat to lizards' reproduction. Graphical abstract fx1 Highlights • The deaths of lizards in the high-dose group was significantly higher. • Lizards ate less ACP-contaminated mealworms. • Lizards were under oxidative stress after dietary exposure. • ACP dietary exposure could damage lizards' reproductive function. [ABSTRACT FROM AUTHOR]

Pesticides are one of major causes for amphibian population declines and the behavior of pesticide metabolite products to amphibians has become a rising concern. In this study, the acute toxicity and the chronic effects of triadimefon and triadimenol (the metabolite of triadimefon) on Rana. nigromaculata were investigated. In the acute assay, significant differences were observed in antioxidant enzyme activities and malondialdehyde levels between the triadimefon and triadimenol. The 96 h-acute toxicity of triadimefon (25.97 mg/L) and triadimenol (34.55 mg/L) to tadpoles was low. In 28d-chronic exposure, we studied the relative expression of tadpoles genes related to thyroid hormone-dependent metamorphic development, histological examination of liver and some biological index, including wet weight, snout-to-vent length (SVL) and development stages. The results revealed that the effects of triadimefon and triadimenol on tadpole development are driven by a disruption of the hormonal pathways involved in metamorphosis. Interestingly, triadimefon was more harmful on R. nigromaculata than triadimenol at high dose, whereas the reverse result was observed at low doses. According to the relative expression of thyroid hormone-dependent genes, we also found that the two compounds may have different mechanisms of toxic action on R. nigromaculata. Our study developed a pragmatic approach for use in the risk assessment of pesticide and its metabolite，and increased the information and understanding of the impacts of fungicides and other potential endocrine disrupting environmental contaminants on amphibians. [ABSTRACT FROM AUTHOR]

In recent years, serious environmental pollution has caused a decrease in the abundance of many species worldwide. Reptiles are the most diverse group of terrestrial vertebrates. There are large amounts of toxicological data available regarding myclobutanil, but the adverse effects of myclobutanil on lizards has not been widely reported. In this study, treatment groups were orally administered a single-dose of myclobutanil (20 mg/kg body weight (bw)). Subsequently, it was found that there were differences in myclobutanil levels between the different tissues and concentrations also changed with degradation time. The tissue concentrations of myclobutanil decreased in the order of: stomach > liver > lung > blood > testis > kidney > heart > brain. Based on our results, the liver and testis were considered to be the main target organs in lizards, indicating that the myclobutanil could induce potential hepatic and reproductive toxicity on lizards. Meanwhile, it was also demonstrated that the toxic effects of myclobutanil was different in different species, and the distribution of different pesticides in lizards were different. [ABSTRACT FROM AUTHOR]

Excessive antibiotics transferred into the aquatic environment may affect the development of amphibians. Previous studies on the aquatic ecological risk of ofloxacin generally ignored its enantiomers. The purpose of this study was to compare the effects and mechanisms of ofloxacin (OFL) and levofloxacin (LEV) on the early development of Rana nigromaculata. After 28-day exposure at environmental levels, we found that LEV exerted more severe inhibitory effects on the development of tadpoles than OFL. According to the enrichment results of differentially expressed genes in the LEV and OFL treatments, LEV and OFL had different effects on the thyroid development of tadpoles. dio2 and trh were affected by the regulation of dexofloxacin instead of LEV. At the protein level, LEV was the main component that affected thyroid development-related protein, while dexofloxacin in OFL had little effect on thyroid development. Furthermore, molecular docking results further confirmed that LEV was a major component affecting thyroid development-related proteins, including DIO and TSH. In summary, OFL and LEV regulated the thyroid axis by differential binding to DIO and TSH proteins, thereby exerting differential effects on the thyroid development of tadpoles. Our research is of great significance for comprehensive assessment of chiral antibiotics aquatic ecological risk. [Display omitted] • LEV exerted more severe effects on growth of tadpoles. • LEV and OFL had different effects on thyroid development. • LEV was the main component that affected thyroid development. • There was enantioselectivity on thyroid development-related gene and protein. • OFL and LEV differentially bound to thyroid development-related proteins. [ABSTRACT FROM AUTHOR]

We report a facile combustion method synthesis of reduced graphene oxide/CuI composites as a photocatalyst, in which CuI nanoparticles were homogeneously distributed on the surface of reduced graphene oxide (rGO), showing a good visible light response. The rGO-supported and unsupported CuI hybrids were tested over the photocatalytic reduction of CO 2 for methanol evolution in visible light. In the current study rGO-CuI composites have shown excellent yields (19.91 μmol g-cat −1 ). rGO provides a light-weight, charge complementary and two-dimensional material that interacts effectively with the CuI nanoparticles. [ABSTRACT FROM AUTHOR]

In this paper, we establish the quaternionic versions of several results in the complex pluripotential theory by using the quaternionic closed positive currents, which were introduced in [24] . We show that quasicontinuity, one of the most important properties of complex plurisubharmonic functions, holds also for quaternionic plurisubharmonic functions in H n . Moreover, we prove an equivalent characterization of the maximality, which is central to the pluripotential theory. A locally bounded plurisubharmonic function u is maximal if and only if it satisfies the homogeneous quaternionic Monge–Ampère equation ( Δ u ) n = 0 . [ABSTRACT FROM AUTHOR]

Abstract: Cancer diagnosis can be a complex process, which takes consideration of histopathological, clinical, immunophenotypic, and genetic features. Since non-random chromosomal translocations are specifically involved in the development of various cancers, the detection of these gene aberrations becomes increasingly important. In recent years, break-apart (or split-signal) fluorescence in situ hybridization (FISH) has emerged as an advantageous technique to detect gene translocations on tissue sections. However, FISH assays are technically challenging and require specialized fluorescence microscopes. Furthermore, the FISH signal is not stable for long term archiving due to photo bleaching. Our objective was to demonstrate the feasibility of brightfield break-apart in situ hybridization (ba-ISH) for anaplastic lymphoma kinase (ALK) and mucosa-associated lymphoid tissue translocation protein 1 (MALT1) genes as models. ALK or MALT1 break-apart probes were labeled with digoxigenin (DIG) or 2,4-dinitrophenyl (DNP) on both sides of a known gene breakpoint region and the hybridization sites were visualized with the combination of alkaline phosphatase (AP)-based blue and red detection. Therefore, normal genes are detected as purple dots by mixing blue and red colors while translocated genes are detected as isolated blue or red dots. Formalin-fixed, paraffin-embedded tonsil was used as control for the co-localized 5′ and 3′ probes. Gene translocations of ALK or MALT1 were detected as separate blue and red dots on ALCL and MALT lymphoma cases. Thus, ISH analyses of gene translocations can be conducted with a regular light microscope and the long term archiving of break-apart ISH slides can be achieved. [Copyright &y& Elsevier]

Abstract: The mechanisms by which mesenchymal stem cells (MSCs) may protect native tissue are incompletely understood. Understanding the mechanisms by which these cells release factors such as vascular endothelial growth factor (VEGF), may lead to enhanced protection. We hypothesized that stress, in the form of hypoxia or TNF, activates MSCs to release VEGF by STAT3 and p38 MAPK dependent mechanisms. Mouse MSCs from wild type (WT) and STAT3 knockout mice (STAT3KO) were harvested and purified by a single-step method using adhesion. The release of VEGF was analyzed by using MSC conditioned media under hypoxia or TNF stimulation with or without p38 MAPK inhibition. Activation of STAT3 and p38 MAPK was determined by analysis of cell lysates. MSCs released VEGF under normoxia, which was associated with constitutive STAT3 activity. STAT3 deficiency resulted in decreased MSC production of VEGF. In response to hypoxia or TNF, MSCs produced more VEGF, which was correlated with hypoxia or TNF activated p38 MAPK and STAT3. The p38 MAPK inhibitor significantly decreased hypoxia-induced or TNF-stimulated VEGF production in WT. Additionally, STAT3 ablation neutralized hypoxia-induced MSC release of VEGF. No effect of p38 MAPK inhibitor alone was observed on MSC release of VEGF in WT. However, inhibition of p38 MAPK blocked release of VEGF in STAT3KO MSCs. MSCs are a potent source of VEGF, the production of which is mediated by STAT3 under normoxia partly; however, following hypoxia or TNF exposure, MSC release of VEGF is mediated by both STAT3 and p38 MAPK. [Copyright &y& Elsevier]

Glucose oxidase was embedded in organic films through a layer-by-layer approach, where the enzyme demonstrated significantly enhanced electron-transfer reactivity and finely tuned enzymatic activity. An unmediated, reagentless glucose biosensor was accordingly prepared with two polyethylenimine/glucose oxidase bilayers-modified pyrolytic graphite electrode. A calibration linear range of glucose was 0.5–8.9 mM with a detection limit of 50 μM and sensitivity of 0.76 μA mM-1. [Copyright &y& Elsevier]

The vertebrate liver and heart arise from adjacent cell layers in the anterior lateral (AL) endoderm and mesoderm of late gastrula embryos, and the earliest stages of liver and heart development are interrelated through reciprocal tissue interactions. Although classical embryological studies performed several decades ago in chick and quail defined the timing of hepatogenic induction in birds and the important role for cardiogenic mesoderm in this process, almost nothing is known about the molecular aspects of avian liver development. Here we use in vivo and explantation assays to investigate tissue interactions and signaling pathways regulating Hex, a homeobox gene required for liver development, and the earliest stages of hepatogenesis in the chick embryo. We find that explants of late gastrula anterior lateral endoderm plus mesoderm, which have been used extensively for studies relating to heart development, also produce albumin-expressing hepatoblasts. Expression of Hex, the earliest known molecular marker for the hepatogenic endoderm, and albumin, indicative of early committed hepatoblasts, requires both autocrine Bmp signaling and a specific paracrine signal from the cardiogenic (anterior lateral) mesoderm. Endodermal expression of Fox2a, in contrast, requires the mesoderm but is independent of Bmp signaling. In vivo induction assays show that the ability of BMP2 to activate Hex expression in the endoderm is restricted to a region that is only slightly larger than the endogenous domain of Hex expression. Although Fgfs can substitute for the cardiogenic mesoderm to support the expression of Hex and albumin in the endoderm, several Fgf genes are expressed in the anterior lateral endoderm but an Fgf expressed predominantly in the mesoderm was not identified. Studies also showed that Fgf gene expression in the endoderm does not require a signal from the mesoderm. Mechanisms regulating endodermal signaling pathways activated by Fgfs may therefore be more complex than previously appreciated. [Copyright &y& Elsevier]

The rational use and the environmental safety of chiral pesticides have attracted significant research interest. Here, enantioselective toxic effects and the selective toxic mechanism of triticonazole (TRZ) against the aquatic microalgae Chlorella pyrenoidosa were studied. The 96h-EC 50 values of rac-, (R)-(−)-, and (S)-(+)-TRZ were 1.939, 0.853, and 22.002 mg/L, respectively. At a concentration of 1 mg/L, the contents of photosynthetic pigments of C. pyrenoidosa exposed to (R)-(−)-TRZ were lower than if exposed to S-(+)-form and racemate. Transmission electron microscopic images showed that the R-(−)-form compromised the integrity of cells and disrupted the chloroplast structure. R-(−)-TRZ stimulated vast reactive oxygen species (ROS) and significantly increased superoxide dismutase (SOD) and catalase (CAT) activities, as well as malondialdehyde (MDA) content. For lipid accumulation experiments, nicotinamide adenine dinucleotide (NADH) and triacylglycerol (TAG) accumulations in algal cells treated with R-(−)-TRZ were 171.50% and 280.76%, respectively, compared with the control group. This far exceeded levels of algal cells treated with S-(+)- and rac-TRZ. Based on these data, R-(−)-TRZ was concluded to selectively affect the photosynthetic system, antioxidant system, and lipid synthesis of algal cells, thus causing enantioselective toxic effects of TRZ against C. pyrenoidosa , which indicating that the use of racemate may cause unpredictable environmental harm. Therefore, to reduce the hidden dangers of chiral pesticides for the ecological environment, the environmental risk of TRZ should be evaluated at the stereoselective level. Image 1 • The 96 h-acute toxicity of triticonazole against C. pyrenoidosa was enantioselective. • Algal cells and chloroplasts were severly damaged after exposure to R-(−)-triticonazole. • The effect of triticonazole on the antioxidant system of chlorella was different. • There was enantioselective accumulation of NADH and TAG in the triticonazole treated algae. • Triticonazole should be evaluated at stereoselective level to reduce the dangers to environment. [ABSTRACT FROM AUTHOR]

Wild-type Proteinase K binds to two Ca2+ ions, which play an important role in regulating enzymaticactivity and maintaining protein stability. Therefore, a predetermined concentration of Ca2+ must be added during the use of Proteinase K, which increases its commercial cost. Herein, we addressed this challenge using a computational strategy to engineer a Proteinase K mutant that does not require Ca2+ and exhibits high enzymatic activity and protein stability. In the absence of Ca2+, the best mutant, MT24 (S17W–S176N-D260F), displayed an activity approximately 9.2-fold higher than that of wild-type Proteinase K. It also exhibited excellent protein stability, retaining 56.2 % of its enzymatic activity after storage at 4 °C for 5 days. The residual enzymatic activity was 65-fold higher than that of the wild-type Proteinase K under the same storage conditions. Structural analysis and molecular dynamics simulations suggest that the introduction of new hydrogen bond and π-π stacking at the Ca2+ binding sites due to the mutation may be the reasons for the increased enzymatic activity and stability of MT24. • In the absence of Ca2+, a mutant Proteinase K exhibited an activity approximately 9.2-fold higher than that of wild-type. • The mutant exhibited excellent protein stability, retaining 56.2 % of its enzymatic activity after storage at 4 °C for 5 days. • The introduction of hydrogen bond and π-π stacking at Ca2+ binding sites resulted in an increased in activity and stability. [ABSTRACT FROM AUTHOR]

More than 100 species of annual herb genus Suaeda widely distribute (Asia, North America, northern Africa and Europe), are rich in resources (about hundreds of millions of tons/Y) and have a long historical application. Most of them are mainly used for traditional food, feed and medicine. Recently, they have been employed to repair saline-alkali land and beautify the environment. So far, only 27 species have been reported on the bioactivity diversity, broad spectrum and effectiveness in clinical practice. Therefore, the in-depth and extensive research of Suaeda has become a research hotspot around the world. However, only one review summarized the nutritional, chemical and biological values of Suaeda. By searching the international authoritative databases (ACS Publications, ScienceDirect, PubMed, Springer, web of Science and Bing International etc.) and collecting 103 literatures closely related to Suaeda (1895–2021), herewith a comprehensive and systematic review was conducted on the phytology, chemistry, pharmacology and clinical application, enveloping the classification evolution between Amaranthaceae and Chenopodiaceae , distribution and common botanical characteristics; involving 9 chemical categories of 163 derivatives covering 14 new and 6 first-isolated ones, and appraising the content determination of 6 categories of components; mainly including the pharmacology of 13 species in vivo and vitro ; estimating the clinical application of 16 species cured the related diseases of eight human physiological system except for the motor system. It is expected that this paper will provide forward-looking scientific ideas and literature support for the further modern research, development and utilization of the genus. [Display omitted] [ABSTRACT FROM AUTHOR]

Durum wheat is an important food crop used primarily for pasta production. High-molecular-weight glutenin subunits (HMW-GS) encoded by the closely linked genes Glu-B1x and Glu-B1y are known for their combined effects on pasta quality, but their individual contributions and interactions remain poorly understood. In this study, we show that individual loss-of-function mutants of Glu-B1x (ΔBx6) and Glu-B1y (ΔBy8) were associated with significant reductions in gluten strength compared to the wildtype, with stronger effects in the ΔBxy double mutant. Reductions in gluten strength were reflected in reduced mixograph and alveograph parameters, gluten index, faster extrusion flow rates and increased cooking loss. Interestingly, the Glu-B1x mutation was also associated with significant increases in grain and semolina protein content, increased pasta firmness, reduced starch viscosity and increased amylose in ΔBx6 and ΔBxy. In general, the ΔBx6 mutation had stronger effects than the ΔBy8 mutation, and significant interactions between the two genes were frequent. In addition to the basic knowledge gained on the individual effects of the Bx6 and By8 subunits and their interactions, the genetic stocks developed in this study provide useful tools to study the effects of natural or synthetic HMW-GS on pasta quality parameters in a background lacking endogenous HMW-GS. Image 1 • Mutations for individual and combined high molecular weight glutenins reveal synergistic interactions on semolina and pasta quality. • Mutation in Glu-B1x showed generally stronger effects on pasta quality than mutations in the Glu-B1y. • The major effect of the mutations was a reduction on gluten strength. • A pasta wheat line with no high molecular weight glutenins is made publicly available. [ABSTRACT FROM AUTHOR]

Inspired by molybdoenzymes, herein, we successfully endow Mo single-atom catalyst with highly ORR catalytic activity though engineering the coordination environment. • A highly efficient Mo single-atom catalyst for ORR was designed and fabricated. • Tailoring the d-band center of Mo could optimize OOH*, O* and OH* adsorption. • This work provides valuable insight for designing efficient ORR catalysts and beyond. With a half filled d-electron shell, molybdenum (Mo) plays an important role as catalysts in the petrochemical industry. However, Mo is generally regarded as not catalytically active for oxygen reduction reaction (ORR) compared with other transition metals such as Fe and Co. Inspired by molybdoenzymes, herein, we successfully endow Mo single-atom catalyst with highly ORR catalytic activity though engineering the coordination environment. This unique Mo single-atom catalyst consists of oxygen and nitrogen dual-component coordinated central Mo atom anchored on porous carbon (Mo-O/N-C), showing prominent ORR catalytic performance compared to the state-of-the-art Pt/C under alkaline condition. The extraordinary performance of Mo-O/N-C electrocatalyst is also demonstrated in Zn-air batteries as an air cathode. Density functional theory (DFT) calculations reveal the oxygen and nitrogen dual-component coordination could tailor the d-band center of Mo, subsequently optimizing its binding capability with reaction intermediates (O*, OH* and OOH*), hence accelerating overall ORR process. This work not only provides an efficient and commercially competitive ORR catalyst, but advancing further development of other electrocatalysts through engineering the coordination environment. [ABSTRACT FROM AUTHOR]

Microglia are first responders to acute brain insults and initiate neuroinflammation to drive secondary tissue injury. Yet the key molecular switches in control of the inflammatory activity of microglia remain poorly understood. Intracerebral hemorrhage (ICH) is a devastating stroke subtype whereby a hematoma is formed within the brain parenchyma and associated with high mortality. Using a mouse model of ICH, we found upregulation of CD22 that predominantly occurred in microglia. Antibody blockade of CD22 led to a reduction in neurological deficits, brain lesion and hematoma volume. This was accompanied by reduced inflammatory activity, increased expression of alternative activation markers (CD206 and IL-10) and enhanced phagocytosis activity in microglia after ICH. CD22 blockade also led to an increase of phosphorylated SYK and AKT after ICH. Notably, the benefits of CD22 blockade were ablated in ICH mice subjected to microglial depletion with a colony-stimulating factor 1 receptor inhibitor PLX5622. Additionally, the protective effects of CD22 blockade was diminished in ICH mice receiving a SYK inhibitor R406. Together, our findings highlight CD22 as a key molecular switch to control the detrimental effects of microglia after acute brain injury, and provide a novel strategy to improve the outcome of ICH injury. [Display omitted] [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system, and its pathogenesis remains largely unclear. Much attention has been paid to the role of microRNAs (miRs) in regulation of autoimmune disease. Here, we found, for the first time, that miR-448 expression was significantly increased in periphery blood mononuclear cells (PBMC) and cerebrospinal fluid (CSF) of patients with MS, and its expression positively correlated with the disease severity. We further demonstrated that CD4 + T cells, especially the Th17 lineage, were the major source of miR-448 expression. Using gain- and loss-of-function approaches, we further verified that miR-448 could enhance Th17 differentiation, characterized by up-regulated expression levels of IL-17A and RORγt. Interleukin (IL)-1β as a potent driver of pathogenic Th17 cells was able to strongly induce miR-448 expression in CD4 + T cells through activating NF-κB pathway. Additionally, we identified that miR-448 directly targeted protein tyrosine phosphatase non-receptor type 2 (PTPN2), which has been known as an anti-inflammatory player with capacity to suppress Th17 differentiation. We also observed markedly decreased expression of PTPN2 in PBMC and CSF of MS patients. Our results suggest that miR-448 might promote Th17 differentiation in MS and thus aggravate the disease through inhibiting PTPN2. [ABSTRACT FROM AUTHOR]

Hyperthyroidism has been identified as a risk factor for cognitive disorders. The hippocampus is a key brain region associated with cognitive function, among which excitatory synapse transmission plays an important role in the process of learning and memory. However, the mechanism by which hyperthyroidism leads to cognitive dysfunction through a synaptic mechanism remains unknown. We investigated the synaptic mechanisms in the effects of hyperthyroidism in an animal model that involved repeated injection of triiodothyronine (T3). These mice displayed impaired learning and memory in the Novel object recognition test, Y-maze test, and Morris Water Maze test, as well as elevated anxiety in the elevated plus maze. Mature dendritic spines in the hippocampal CA1 region of hyperthyroid mice were significantly decreased, accompanied by decreased level of AMPA- and NMDA-type glutamate receptors in the hippocampus. In primary cultured hippocampal neurons, levels of AMPA- and NMDA-type glutamate receptors also decreased and whole-cell patch-clamp recording revealed that excitatory synaptic function was obviously attenuated after T3 treatment. Notably, pharmacological activation of AMPAR or NMDAR by intraperitoneal injection of CX546, an AMPAR agonist, or NMDA, an NMDAR agonist can restore excitatory synaptic function and corrected impaired learning and memory deficit in hyperthyroid mice. Together, our findings uncovered a previously unrecognized AMPAR and NMDAR-dependent mechanism involved in regulating hippocampal excitatory synaptic transmission and learning and memory disorders in hyperthyroidism. • Learning and memory ability was impaired in hyperthyroid mice. • The maturation of dendritic spines was inhibited in hyperthyroid mice. • T3 impaired the expression and function of excitatory postsynaptic receptors. • Learning and memory impairment caused by hyperthyroidism can be restored by increasing AMPAR or NMDAR function. [ABSTRACT FROM AUTHOR]

Background: Lower levels of myocardial Akt activity in males are associated with a higher incidence of heart failure and worsened cardiac function after ischemia/reperfusion (I/R). While Akt activation by estrogen provides cardioprotection in females, no information exists regarding the effect of testosterone on the myocardial Akt pathway following I/R. We hypothesized that following I/R: (1) endogenous testosterone will decrease myocardial Akt activation in male hearts; (2) endogenous testosterone will mediate downstream signals of Akt, including Bad, Bcl-2, and FOXO3a; (3) administration of exogenous testosterone will recapitulate negative effects on the Akt pathway in castrated male hearts. Methods and Results: Rat hearts from age-matched adult males, females, castrated males, males with androgen receptor blocker-flutamide, castrated males with chronic 5α-dihydrotestosterone (DHT) implantation, or acute testosterone infusion (ATI) (n = 9/group) were subjected to I/R (Langendorff). Castration or flutamide treatment significantly up-regulated myocardial Akt activation, increased downstream apoptosis-regulatory molecules p-Bad, Bcl-2, p-FOXO3a, but reduced Fas-L, consistent with decreased myocardial injury in male hearts following I/R. ATI administration, but not chronic DHT, reversed these effects on Akt signaling associated with further exacerbated cardiac dysfunction in castrated males. Notably, lower levels of MnSOD were observed in male hearts, and castration or flutamide treatment restored myocardial MnSOD expression to the levels of females in male hearts after I/R. Conclusion: Our study represents the initial evidence of testosterone-induced down-regulation of the Akt pathway in male hearts following I/R, thereby mediating cardiac injury through decreased p-Bad, reduced ratio of Bcl-2/Bax in the cytoplasm, and increased FOXO3a in the nucleus. [ABSTRACT FROM AUTHOR]

Abstract: With the advent of personalized medicine, anatomic pathology-based molecular assays, including in situ hybridization (ISH) and mRNA detection tests, are performed routinely in many laboratories and have increased in their clinical importance and complexity. These assays require appropriately fixed tissue samples that preserve both nucleic acid targets and histomorphology to ensure reliable test results for determining patient treatment options. However, all aspects of tissue processing, including time until tissue fixation, type of fixative, duration of fixation, post-fixation treatments, and sectioning of the sample, impact the staining results. ASCO/CAP has issued pre-analytical guidelines to standardize tissue processing for HER2 testing in breast carcinoma specimens: 10% neutral-buffered formalin (NBF) with a fixation time from at least 6 to 48h . Often, this recommendation is not followed to the detriment of staining results . In this paper, we used a human breast carcinoma cell line (MCF7) generated as xenograft tumors as a model system to analyze the effects of different pre-analytical conditions on ISH staining. We performed H&E, FISH and dual colorimetric HER2 ISH assays using specimens fixed across a range of times in six different commonly used fixatives. Additionally, we investigated the effects of varying tissue section thickness, which also impacted the quality of ISH staining. Finally, we evaluated the effects of three different decalcifying solutions on human breast specimens, typically a treatment that occurs post-fixation for evaluating metastases to bone. The results indicate that time and type of fixation treatment, as well as appropriate tissue thickness and post-fixation treatment, all contribute to the quality of ISH staining results. Our data support the ASCO/CAP recommendations for standardized tissue processing (at least 6h in formalin-based fixatives and 4μm section thickness) and indicate that certain fixatives and post-fixative treatments are detrimental to molecular staining results. [Copyright &y& Elsevier]

Abstract: Bispecific antibodies capable of redirecting the lytic potential of immune effector cells to kill tumor targets have long been recognized as a potentially potent biological therapeutic intervention. Unfortunately, efforts to produce such molecules have been limited owing to inefficient production and poor stability properties. Here, we describe a novel Fv-derived strategy based on a covalently linked bispecific diabody structure that we term dual-affinity re-targeting (DART). As a model system, we linked an Fv specific for human CD16 (FcγRIII) on effector cells to an Fv specific for mouse or human CD32B (FcγRIIB), a normal B-cell and tumor target antigen. DART proteins were produced at high levels in mammalian cells, retained the binding activity of the respective parental Fv domains as well as bispecific binding, and showed extended storage and serum stability. Functionally, the DART molecules demonstrated extremely potent, dose-dependent cytotoxicity in retargeting human PBMC against B-lymphoma cell lines as well as in mediating autologous B-cell depletion in culture. In vivo studies in mice demonstrated effective B-cell depletion that was dependent on the transgenic expression of both CD16A on the effector cells and CD32B on the B-cell targets. Furthermore, DART proteins showed potent in vivo protective activity in a human Burkitt''s lymphoma cell xenograft model. Thus, DART represents a biologically potent format that provides a versatile platform for generating bispecific antibody fragments for redirected killing and, with the selection of appropriate binding partners, applications outside of tumor cell cytotoxicity. [Copyright &y& Elsevier]

Abstract: The existing implementations of block-shift based filtering algorithms for deblocking are hard to achieve good smoothing performance and low computation complexity simultaneously due to their fixed block size and small shifting range. In this paper, we propose to integrate quadtree (QT) decomposition with the block-shift filtering for deblocking. By incorporating the QT decomposition, we can easily find the locations of uniform regions and determine the corresponding suitable block sizes. The variable block sizes generated by the QT decomposition facilitate the later block-shift filtering with low computational cost. In addition, large block based shift filtering can provide better deblocking results because the smoothing range of large blocks spans over the conventional 8×8 block size. Furthermore, we extend the proposed QT based block-shifting algorithm for deringing JPEG2000 coded images. Experimental results show the superior performance of our proposed algorithms. [Copyright &y& Elsevier]

Abstract: Stable transparent titania thin films were fabricated at room temperature by combining thenoyltrifluoroacetone (TTFA)-modified titanium precursors with amphiphilic triblock poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO, P123) copolymers. The obtained transparent titania thin films were systematically investigated by IR spectroscopy, PL emission and excitation spectroscopy and transmission electron microscopy. IR spectroscopy indicates that TTFA coordinates the titanium center during the process of hydrolysis and condensation. Luminescence spectroscopy confirms the in-situ formation of lanthanide complexes in the transparent titania thin film. TEM image shows that the in-situ formed lanthanide complexes were homogeneously distributed throughout the whole thin film. The quantum yield and the number of water coordinated to lanthanide metal center have been theoretically determined based on the luminescence data. [Copyright &y& Elsevier]

Effects of temperature on metabolism/biotransformation and toxicokinetics to lizards are significant, but frequently ignored in toxicology studies. Beta-cyfluthrin (BC) is a pyrethroid insecticide and has been widely used globally. The study aimed to understand the diverse adverse effects of BC to the lizard (Eremias argus) at different temperature regimes. We carried out a single oral BC treatment (20 mg/kg bw) for toxicokinetic study and a 7-day BC (10 mg/kg bw) gavage to look at toxicology by monitoring changes in the biomarkers HSP70, SOD, MDA, CarE, UDPGT, GST, cyp genes, and other metabolic responses. Results showed that BC was lethal to lizards, showing oxidative damages in the liver at ambient temperature (25 °C). Heat stress (35 °C) could exacerbate the oxidative damage (MDA increased) caused by BC, due to the disorder of the antioxidant defense system. The result of tissue distribution and toxicokinetic study also showed that temperature affected the BC biotransformation in lizards. The biotransformation of BC maybe relates to the activation of CarE and UDGPT by heat stress. However, the cyp system and GST didn't increase under BC or/and heat treatments. 1H-NMR metabolomics analysis showed that BC or/and heat stress interfered with energy and amino acid metabolism of the liver. Unlike acute lethal toxicity, the occurrence of the BC and heat stresses has detrimental effects on lizard individuals and populations on sub-lethal levels. Our results indicate that pollution and global warming (or some other extremely weather) may generate significant and harmful effects on lizards. Image 1 • Lethality was higher in beta-cyfluthrin(BC)-treated lizards at 25 °C. • Heat stress exacerbated the oxidative damage caused by BC in lizard liver. • Toxicokinetic characteristics of BC varied among tissues and temperature conditions. • Two detoxification enzymes, CarE and UDGPT, were activated under heat stress. • Thermal effects should be considered in ecotoxicology studies on lizards. [ABSTRACT FROM AUTHOR]