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Local heat and active site coordination of the catalyst to improve electrocatalytic water splitting performance. [Display omitted] • An electrolyzer required only a 1.5 V battery or a 1.53 V solar panel to drive overall water splitting. • The presence of NIR irradiation leads to a 24.6 % and 15.8 % increase in catalytic efficiency for HER and OER. • The combination of a generic heterostructure based on Co 9 S 8 with other electrocatalysts also contributes to the enhancement of the photothermal effect. • The heterostructure exhibited strong bifunctional activities and stabilities in both the OER and HER. The increase of reaction temperature of electrocatalysts and the construction of heterogeneous structures is regarded as an efficient method to improve the electrocatalytic water splitting activity. Here, we report an approach to enhance the local heat and active sites of the catalyst by building a heterostructure with Co 9 S 8 to significantly improve its electrocatalytic performance. The as-fabricated Co 9 S 8 @Ce-NiCo LDH/NF electrode possesses a notable photothermal ability, as it effectively converts near-infrared (NIR) light into the local heat, owing to its significant optical absorption. Leveraging these favorable qualities, the prepared Co 9 S 8 @Ce-NiCo LDH/NF electrode showed impressive performance in both hydrogen evolution reaction (HER) (η 100 = 144 mV) and oxygen evolution reaction (OER) (η 100 = 229 mV) under NIR light. Compared to the absence of the NIR light, the presence of NIR irradiation leads to a 24.6 % increase in catalytic efficiency for HER and a 15.8 % increase for OER. Additionally, other dual-functional electrocatalysts like NiCo-P, NiFeMo, and NiFe(OH) x also demonstrated significantly enhanced photothermal effects and improved catalytic performance owing to the augmented photothermal conversion when combined with Co 9 S 8. This work offers novel pathways for the development of photothermal-electrocatalytic systems that facilitate economically efficient and energy-conserving overall water splitting processes. [ABSTRACT FROM AUTHOR]

The Co-WS 2 heterostructure, loaded on nanofibers with faster electron transport rates, was designed and developed using a top-down approach to achieve high HER performance in alkaline electrolytes. Driven by the inherent electric field induced by the work function difference between Co and WS 2 , efficient electron transfer at the interface optimizes the adsorption energy of reaction intermediates and boosts catalytic activity. [Display omitted] Designing and developing cost-effective, high-performance catalysts for hydrogen evolution reaction (HER) is crucial for advancing hydrogen production technology. Tungsten-based sulfides (WS x) exhibit great potential as efficient HER catalysts, however, the activity is limited by the larger energy required for water dissociation under alkaline conditions. Herein, we adopt a top-down strategy to construct heterostructure Co-WS 2 nanofiber catalysts. The experimental results and theoretical simulations unveil that the work functions-induced built-in electric field at the interface of Co-WS 2 catalysts facilitates the electron transfer from Co to WS 2 , significantly reducing water dissociation energy and optimizing the Gibbs free energy of the entire reaction step for HER. Besides, the self-supported catalysts of Co-WS 2 nanoparticles confining 1D nanofibers exhibit an increased number of active sites. As expected, the heterostructure Co-WS 2 catalysts exhibit remarkable HER activity with an overpotential of 113 mV to reach 10 mA cm−2 and stability with 30 h catalyzing at 23 mA cm−2. This work can provide an avenue for designing highly efficient catalysts applicable to the field of energy storage and conversion. [ABSTRACT FROM AUTHOR]

[Display omitted] Cobalt-based catalysts are one of the preferred materials for effective activation of hydrogen peroxide, and metal element doping and active site dispersion are effective methods to enhance their catalytic activity. In this work, manganese-doped cobalt silicate@diatomite composites with enhanced photo-Fenton-like oxidation performance were prepared and used for degradation of methyl orange (MO) dyes. Experiments showed that manganese doping increased the specific surface area of the samples and decreased the band gap energy of the materials. Moreover, the samples doped with manganese elements had better photo-Fenton-like properties. The degradation of methyl orange by Co0.25MnSi@DE/H 2 O 2 -UV reached more than 95%. In addition, density-functional theory (DFT) calculations showed that the Mn-doped samples were more prone to activate H 2 O 2 than non-manganese-doped samples, and the synergistic effect from using a bimetallic catalyst increased the photo-Fenton oxidation activity in the system. ESR spectroscopy and bursting tests indicated that the possible degradation mechanism consisted of hydroxyl radicals and superoxide radicals generated by the synergistic effect of cobalt ions and manganese under UV radiation. This study thus presents a feasible idea for the preparation of cobalt-based photo-Fenton catalysts that also provides a basis for understanding the catalytic mechanism analysis of other types of bimetallic catalysts. [ABSTRACT FROM AUTHOR]

[Display omitted] Two-dimensional (2D) beta indium sulfide (β -In 2 S 3) shows great potential in photocatalytic hydrogen production due to its broad-spectrum response, relatively negative conduction band edge, high carrier mobility and low toxicity. However, the high charge recombination rate limits the application of In 2 S 3. Here, we in-situ grew 2D cadmium sulfide (CdS) on the surface of In 2 S 3 doped with copper ions (Cu2+) to construct a heterojunction photocatalyst that suppresses charge recombination. The in-situ grown method and shared sulfur composition were conducive to forming the efficient interface contact between In 2 S 3 and CdS, promoting charge transfer and showing the high spatial charge separation rate, resulting in a hydrogen production rate of 868 µmol g-1h−1. The induced Cu2+ extended the light absorption range and stabilized the photocatalyst. By creating stable 2D/2D heterojunction photocatalysts with high charge separation efficiency, this work opens new possibilities for applying In 2 S 3 materials in photocatalytic hydrogen production. [ABSTRACT FROM AUTHOR]

[Display omitted] Pathogenic biofilm induced oral diseases have posed a significant treat to human health, such as periodontitis resulting from the formation of bacterial biofilm on teeth and gums. The traditional treatment methods such as mechanical debridement and antibiotic therapy encounter the poor therapeutic effect. Recently, numerous nanozymes with excellent antibacterial effect have been widely used in the treatment of oral diseases. In this study, a novel iron-based nanozyme (FeSN) generated by histidine-doped FeS 2 with high peroxidase-like (POD-like) activity was designed for the oral biofilm removal and treatment of periodontitis. FeSN exhibited an extremely high POD-like activity, and enzymatic reaction kinetics and theoretical calculations had demonstrated its catalytic efficiency to be approximately 30 times than that of FeS 2. The antibacterial experiments showed that FeSN had robust antibacterial activity against Fusobacterium nucleatum in the presence of H 2 O 2 , causing a reduction in the levels of glutathione reductase and ATP in bacterial cells, while increasing the level of oxidase coenzyme. The ultrahigh POD-like activity of FeSN allowed for easy detection of pathogenic biofilms and promoted the breakdown of biofilm structure. Furthermore, FeSN demonstrated excellent biocompatibility and low cytotoxicity to human fibroblast cells. In a rat model of periodontitis, FeSN exhibited significant therapeutic effects by reducing the extent of biofilm formation, inflammation, and alveolar bone loss. Taken together, our results suggested that FeSN, generated by self-assembly of two amino acids, represented a promising approach for biofilm removal and periodontitis treatment. This method has the potential to overcome the limitations of current treatments and provide an effective alternative for periodontitis treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] Construction of Z-scheme heterojunction photocatalysts with efficient electron-hole pairs separation and robust oxidation abilities is a promising strategy to decompose volatile organic compounds (VOCs). Herein, UV-light-driven BiOCl and visible-light-driven Bi 2 WO 6 were successfully combined via a one-pot hydrothermal method and compact Z-scheme heterojunction photocatalyst BiOCl/Bi 2 WO 6 was obtained. Owing to the similar precursors and synthesis conditions, the integrated BiOCl/Bi 2 WO 6 heterojunction was intimate and homogenous, which resulted in the efficient separation of photogenerated carriers, and generated abundant holes (h+), hydroxyl radicals (·OH) and superoxide radicals (·O 2 –). The optimal BiOCl/Bi 2 WO 6 photocatalyst (BWOCl-2), achieved by tailoring the amount of hydrochloric acid, exhibited almost 100 % of toluene degradation and excellent durability. Electron spin resonance (ESR) results revealed that h+, ·O 2 – and ·OH were dominant active species in the BiOCl/Bi 2 WO 6 photocatalytic system. The degradation intermediate products were monitored by in situ Diffuse Reflection Infrared Fourier Transform spectroscopy (DRIFTS) and the possible photocatalytic mechanism was also revealed according to the band structure of BiOCl/Bi 2 WO 6 heterojunction. This work provided a novel avenue to design an efficient homogenous heterojunction photocatalyst for the efficient degradation of VOCs under sunlight. [ABSTRACT FROM AUTHOR]

[Display omitted] The introduction of oxygen vacancies (Ov) into photoanodes has been considered an effective method to enhance the photoelectrochemical (PEC) water splitting performance. The efficiency of water splitting is related to light absorption, charge separation to the electrode surface, and charge injection into the electrolyte. However, introducing Ov from a single level cannot meet the above objectives. In this work, we present the fabrication of BiVO 4 (BVO) photoanodes with bulk and surface Ov, and their respective roles in the PEC performance have been studied. The bulk O V of the photoanode could increase the carrier density and improve the separation efficiency of photogenerated electrons and holes. The surface Ov provide abundant surface active sites, and enhance the charge injection efficiency. Charge separation efficiency of the nitrogen-treated BVO (N:BVO) (69.1 % at 0.75 V vs RHE and 85.1 % at 1.23 V vs RHE) has a noticeable increase compared with that of BVO (51.2 % at 0.75 V vs RHE and 64.6 % at 1.23 V vs RHE), nevertheless, only a minor enhancement of charge injection efficiency (from 49.1 % to 56.5 % at 1.23 V vs RHE). After the deposition of NiFeOOH, the photoanodes present superior charges injection efficiency in the whole range of applied potential. The as-synthesized N:BVO/U-NiFeOOH photoanode exhibits a photocurrent density of 5.52 mA·cm−2 at 1.23 V vs RHE with a 97 % Faradaic efficiency for O 2 /H 2 evolution. Thus, there is a synergistic effect between the bulk O V and surface O V on the BVO photoanode, exhibiting highly promoted PEC water splitting activity relative to the individual O V decorated BVO for oxygen evolution reaction, which provides a promising strategy for fabricating efficient solar water splitting systems. [ABSTRACT FROM AUTHOR]

• EDDI supports on-demand inference acceleration over Edge-Cloud Collaboration. • Two novel components are introduced in EDDI, namely Evaluator and Optimizer. • Evaluator derives an approximate solution to construct a DNN into an DAG. • Optimizer enables a collaborative optimization of the early-exit and the partition. • EDDI can achieve better performance in model accuracy, latency, and throughput. As the development of deep neural network (DNN) tasks that feature a directed acyclic graph (DAG) surges in modern industries, simultaneously meeting the latency and accuracy requirements of these key DNN tasks has remained elusive. The general feasible solution is to find an optimal DNN partition that combines cloud with edge computing to implement edge–cloud collaboration for DNN inference. Nevertheless, the dynamicity of network conditions and the uncertain availability of cloud computing resources pose formidable obstacles to this collaborative inference. In this study, we formulate the optimization of DNN partition as a minimum cut problem in DAG derived from DNN and then propose an early-exit DAG-DNN inference (EDDI) framework that supports synergistically on-demand inference acceleration for DAG DNN. This framework introduces two novel components: (1) Evaluator that derives an approximately optimal solution for constructing DNN into appropriate DAG, assisting in solving the optimization problem; and (2) Optimizer that enables collaborative optimization of the early exit and DNN partition strategy at run time to improve performance while meeting user-defined latency requirements. Quantitative evaluations show that EDDI outperforms state-of-the-art schemes by 10.6%, 3.3%, and 3%, on average, in terms of model accuracy, inference latency, and throughput under diverse latency constraints, respectively. Meanwhile, latency speedup ratio increases by an average of 8% and 4% under varying network conditions and cloud server capacities, respectively. [ABSTRACT FROM AUTHOR]

The use of plant polysaccharides in aquaculture is recognized as a healthy strategy to enhance disease resistance and reduce medication use. Salvia miltiorrhiza polysaccharide (SMP) can regulate the immune function of higher vertebrates. However, the effects of SMP on fish have not been fully investigated. In this study, the ability of SMP to activate the macrophages of Siberian sturgeon (Acipenser bareii) was analyzed in vitro. The effects of SMP on immune cell activity of hybrid sturgeon (A. baerii ♀ × Acipenser schrenckii ♂) and resistance to Aeromonas hydrophila were further detected in vivo. The in vitro results showed that SMP up-regulated phagocytosis, respiratory burst, inducible nitric oxide synthase activity, nitric oxide (NO) concentration, and cytokine mRNA expression of macrophages. The in vivo results showed that dietary supplementation with SMP enhanced the respiratory burst of macrophages and proliferative activity of lymphocytes. Dietary supplementation with SMP increased serum concentrations of lysozyme and NO, and improved the survival rate of hybrid sturgeon challenged with A. hydrophila. Collectively, these results suggest that SMP can improve the immune function and disease resistance of sturgeon. This study provides a theoretical basis for the application of SMP for healthy farming of sturgeon. • Salvia miltiorrhiza polysaccharide (SMP) activated macrophages of sturgeon i n vitro. • SMP improved the immune cell activity of sturgeon in vivo. • SMP enhanced the disease resistance against Aeromonas hydrophila in sturgeon. • SMP alleviated pathological damage to the spleen, liver, and valvular intestine of sturgeon post-challenge with A. hydrophila. [ABSTRACT FROM AUTHOR]

The nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor crucial in cellular defense against oxidative and electrophilic stresses. Recent research has highlighted the significance of NRF2 in normal erythropoiesis and anemia. NRF2 regulates genes involved in vital aspects of erythroid development, including hemoglobin catabolism, inflammation, and iron homeostasis in erythrocytes. Disrupted NRF2 activity has been implicated in various pathologies involving abnormal erythropoiesis. In this review, we summarize the progress made in understanding the mechanisms of NRF2 activation in erythropoiesis and explore the roles of NRF2 in various types of anemia. This review also discusses the potential of targeting NRF2 as a new therapeutic approach to treat anemia. [Display omitted] • NRF2 is essential for erythroid homeostasis. • NRF2 protein stability is regulated by interactions with KEAP1 and other factors. • The expression of NRF2 during erythroid development is dynamic. • Targeting NRF2 offers potential therapeutic benefits for anemia treatment. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a fatal and intractable disease accompanied by the comorbidity of chronic neuropathic pain. Here, we purposed to explore the therapeutic effect and the underlying mechanism of Resolvin D2 (RvD2) on neuropathic pain after SCI. The in vivo model of traumatic SCI rats was established. Primary microglia isolated from neonatal rats were induced by TNF-α in vitro. The locomotor ability was assessed by the Basso-Beattie-Besnahan score. Hargreaves methods and Von Frey fibrofilaments were used to evaluate the symptoms of neuropathic pain including allodynia and hyperalgesia in rats. The cytotoxicity of RvD2 was evaluated by MTT assay. ELISA kit was applied to access the levels of inflammatory factors. And the expression levels of related mRNA and proteins were determined by qRT-PCR, western blotting and immunofluorescence staining. The targeting relationship between miR-155 and PTEN was verified by dual-luciferase reporter (DLR) assay. We found that RvD2 mitigated locomotor dysfunction, allodynia and hyperalgesia of SCI rats. In addition, RvD2 treatment suppressed pro-inflammatory phenotype but promoted anti-inflammatory differentiation in microglia. Furthermore, RvD2 treatment inhibited the upregulated expression level of miR-155 which was caused by NF-κB activation and then recovered the autophagy flux via targeting PTEN, thereby relieving the inflammatory response in the TNF-α-induced primary microglia. In summary, RvD2 treatment could recover the autophagy flux via suppressing NF-κB-modulated miR-155 expression to activate anti-inflammatory microglia and then inhibit the inflammatory response and even mitigate neuropathic pain following SCI. • RvD2 could alleviate neuropathic pain evoked by spinal cord injury in rats. • RvD2 inhibited microglia M1 polarization-mediated neuroinflammation. • RvD2 restored the impaired autophagic flux via modulating miR-155/PTEN axis. • RvD2 may promote autophagy through AKT/mTOR pathway. [ABSTRACT FROM AUTHOR]

Prostate cancer is one of the leading causes of death in men worldwide, revealing a substantial heterogeneity in terms of molecular and clinical behaviors. Tumor infiltrating immune cell is associated with prognosis and response to immunotherapy in several cancer types. However, until now, the immune infiltrate profile of distinct subtypes for prostate cancer remains poorly characterized. In this study, using immune infiltration profiles as well as transcriptomic datasets, we characterized this subtype of prostate tumors. We observed that the FLI1 subtype of prostate tumors was highly enriched in immune system processes, immune related KEGG pathways and biological processes. We also expanded this approach to explore the immune infiltration profile of the high FLI1 expression subtype for skin cutaneous melanoma, similar results were found. Investigation of the association of immune infiltration features with the FLI1 expression demonstrated that many important features were associated with the FLI1 expression. • FLI1 subtype of prostate cancer was significantly enriched with many important immune cell types. • The FLI1 expression level was significantly correlated with prolonged survival time and many immune related features. • Similar results were observed in the high FLI1 expression subtype of skin cutaneous melanoma. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is the most common primary malignant bone tumor diagnosed in children and adolescents. Unfortunately, OS patients with metastatic or recurrent disease are highly resistant to front line chemotherapy that significantly limits the long-term survival rate. Since majority of chemotherapeutic agents used in OS work by generating DNA damages, enhanced DNA repair pathways are generally associated with chemoresistance in OS treatment. However, the exact mechanisms of chemoresistance in OS are not fully understood. Our study found that paralogue of XRCC4 and XLF (PAXX), which was identified recently as a novel factor of non-homologous end joining (NHEJ), is upregulated in chemoresistant OS cells. Importantly, PAXX deficiency re-sensitizes chemoresistant OS cells to doxorubicin and cisplatin. Mechanistically, chemoresistance to doxorubicin or cisplatin results in enhanced PAXX-Ku70 interaction and elevated NHEJ efficiency. We also identified a small molecule M11 that interrupts PAXX-Ku70 interaction and re-sensitizes chemoresistant OS cells to doxorubicin and cisplatin. Thus, our data provide evidence that PAXX could serve as a novel target to overcome chemoresistance in OS treatment. • PAXX is up-regulated in doxorubicin and cisplatin resistant OS cells. • NHEJ is positively correlated with resistance to doxorubicin and cisplatin. • PAXX deficiency generates excellent synergy with doxorubicin and cisplatin. [ABSTRACT FROM AUTHOR]

Iron homeostasis is vital to organismal health; it is maintained by the iron regulatory protein (IRP)–iron-responsive element (IRE) signaling pathway. In the Chinese mitten crab Eriocheir sinensis , Es Fer-1 and Es Fer-2 reportedly have a putative IRE, but an IRP has not yet been identified. In this study, we successfully amplified the full-length cDNA of Es IRP using gene cloning and rapid amplification of cDNA ends techniques. The length of this cDNA was 4474 bp, and it included a 2682-bp open reading frame encoding 893 amino acids. Using quantitative real-time PCR, mRNA transcripts of Es IRP were detected in various tissues. The highest and lowest expression level was detected in the muscle and gills, respectively. In response to Staphylococcus aureus and Vibrio parahaemolyticus challenge, the transcription level of Es IRP was downregulated and that of Es Fer-1 and Es Fer-2 was upregulated in hemocytes. Es IRP knockdown resulted in increased expression of both Es Fer-1 and Es Fer-2. After Es Fer-1 and Es Fer-2 knockdown, the bacterial clearance ability of E. sinensis against S. aureus and V. parahaemolyticus was impaired. In conclusion, our results suggest that the IRP–IRE signaling pathway plays an important role in the innate immune system response in E. sinensis. • IRP–IRE signaling pathway has a key role in innate immunity in Eriocheir sinensis. • Es IRP knockdown increases the expression of ferritins (Es Fer-1 and Es Fer-2). • Es Fer-1 and Es Fer-2 knockdown impairs bacterial clearance ability of E. sinensis. [ABSTRACT FROM AUTHOR]

Abstract Extracellular pH strongly affects cellular metabolism and function. An acidic environment induced under pathological conditions leads to cardiomyocyte injury and dysfunction, but the underlying mechanisms are still poorly understood. Autophagy has been reported as a cytoprotective mechanism that maintains cellular metabolism and viability by removing misfolded proteins and damaged organelles. In our research, we found that acidic environments inhibit autophagosome formation in cardiomyocytes. Up-regulation of autophagic activity, however, ameliorates the cell injury induced by acidic treatments.We also found that acidic treatments reduce the level of α-tubulin acetylation, as detected by Western blot and immunofluorescence staining, and that the number of autophagosomes increase after up-regulating α-tubulin acetylation by Taxol, suggesting that α-tubulin acetylation may play an important role in acidic pH-induced changes in autophagy. Furthermore, an HDAC6 activity assay showed an increase in HDAC6 activity after acidic treatment and that inhibiting HDAC6 activity by tubastatin A or specific siRNA up-regulates α-tubulin acetylation and autophagosome formation. These data confirm that autophagy plays a protective role against acidic pH-induced cell injury and indicate that HDAC6-mediated α-tubulin acetylation is an important mechanism of acidic pH-dependent autophagy in cardiomyocytes. Highlights • Acidic environments reduce a-tubulin acetylation in cardiomyocytes. • The level of α-tubulin acetylation regulates autophagic activity in cardiomyocytes under acidic conditions. • Cardiomyocytes cultured in acidic environments express more greater activity of HDAC6. • Inhibitting HDAC6 activity up-regulates α-tubulin acetylation and autophagic activity. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • The Ni particle size of Ni/AlSBA-15 can be tuned by adjusting the Al content. • Semihydrogenation of phenylacetylene (PA) over Ni/AlSBA-15 is structure-sensitive. • NiZn and NiGa alloys were formed on AlSBA-15 supported bimetallic catalysts. • NiZn 3 /AlSBA-15 showed 90.3% selectivity to styrene at nearly 100% conversion of PA. • NiZn 3 /AlSBA-15 displayed stable activity and selectivity over 100 h on-stream. Abstract A series of nonprecious monometallic Ni/AlSBA-15 and bimetallic Ni M (M = Zn, Ga, Cu, or Fe)/AlSBA-15 catalysts were prepared using a urea precipitation method and applied to the semihydrogenation of phenylacetylene. The catalysts were characterized by various techniques, showing that the Ni particle size of catalyst can be tuned by adjusting the Al content, and NiZn and NiGa supported catalysts exhibited geometric and electronic effects that originated from the bimetallic alloy. Among all the catalysts studied, NiZn 3 /AlSBA-15, with a turnover frequency of 10.89 s−1 comparable to that of precious Pd-based catalysts, presented the highest selectivity to styrene (90.3%) at nearly 100% conversion of phenylacetylene in semibatch operation. This catalyst was further evaluated in a continuous fixed-bed reactor for semihydrogenation of a model C 8 aromatic fraction of pyrolysis gasoline (a mixture of phenylacetylene, styrene, ethylbenzene and xylene), which aimed at assessing its practical application of recovering styrene from pyrolysis gasoline. The results showed that at complete conversion of phenylacetylene, the styrene concentration in the product was always kept at a stable level and higher than its initial concentration over 100 h of time on stream, demonstrating high selectivity and good stability of NiZn 3 /AlSBA-15. Finally, the application of NiZn 3 /AlSBA-15 was extended to other phenylacetylene derivatives. [ABSTRACT FROM AUTHOR]

Abstract Mulberry crinkle leaf virus (MCLV) is a novel geminivirus recently identified from the woody plant mulberry (Morus alba L.). Little is known about the functions of the proteins encoded by the MCLV genome. Here, all the MCLV-encoded proteins were examined for the ability to suppress gene silencing by an agroinfiltration assay in combination with northern blot analysis of green fluorescent protein (GFP) mRNA and western blot analysis. Of the six proteins, only one protein, V3, which has been predicted to play a role in viral movement, was found to suppress the gene silencing induced by a sense GFP gene in Nicotiana benthamiana 16c. The minimal amino acid sequence of V3 that maintains suppressor activity was also determined by constructing truncated mutants lacking different lengths of the amino acid sequences at the N- or C-terminus of the V3 protein. The results showed that the 94 N-terminal amino acid residues of V3 are sufficient to maintain V3 suppressor activity. In addition, the subcellular location of the V3 protein was investigated by confocal laser scanning microscopy after the expression of a V3-RFP fused protein in leaf epidermal cells of N. benthamiana. The results indicated that the V3 protein localized not only to the cytoplasm but also to the nucleus of N. benthamiana , implying that V3 can shuttle between the nucleus and the cytoplasm. Deletion mutant analysis indicated that a putative nuclear localization signal (NLS) between aa 118–134 might be responsible for the nuclear distribution of the V3 protein. Given the importance of RNA silencing in plant-virus interactions, the identification of a silencing suppressor of MCLV should be valuable in understanding the pathogenicity and molecular biology of this virus. [ABSTRACT FROM AUTHOR]

Abstract The ubiquitin-proteasome system is involved in numerous cellular processes, such as signal transduction, autophagy, cell cycle control, embryogenesis, and regulation of immune response. Neural precursor cell expressed developmentally downregulated 8 (NEDD8) is a ubiquitin-like protein that activates Cullin-RING ligases and modifies substrates via neddylation. However, there is limited information on how neddylation regulates innate immunity in crustaceans. In the present study, we identified the evolutionarily conserved NEDD8 with the ubiquitin homologue domain in the Chinese mitten crab (Eriocheir sinensis), named it Es NEDD8. Then, we analyzed the expression patterns and cellular location of its substrate, Es Cullin4. qRT-PCR showed that both Es NEDD8 and Es Cullin4 were widely expressed in all the selected tissues, and Es Cullin4 was significantly upregulated in hemocytes after bacterial stimulation. Moreover, silencing of Es Cullin4 significantly suppressed the expression of antimicrobial peptides (AMPs) in the hemocytes after bacterial stimulation, and inhibition of Es Cullin4 neddylation by treatment with the NEDD8-activating enzyme inhibitor MLN4924 significantly inhibited the expression of the AMPs. Thus, the results show that Es NEDD8-modified Es Cullin4 could control antimicrobial activities via regulation of AMPs expression in the Chinese mitten crab. Highlights • We identified a ubiquitin-like protein in Eriocheir sinensis and named it Es NEDD8. • Es Cullin4 and Es NEDD8 were ubiquitously expressed in all the tested tissues. • Es Cullin4 could be induced by both Gram-positive and Gram-negative bacteria. • Es Cullin4 was upregulated significantly in the hemocytes after bacterial stimulation. • Es Cullin4 regulated AMPs expression and neddylation by Es NEDD8 was essential. [ABSTRACT FROM AUTHOR]

Abstract Background Information Divalent metal transporter 1 (DMT1) and transferrin receptor (TfR1) are vital proteins for cellular iron uptake. These proteins have hypoxia-responsive elements (HREs) in their 5'-regulatory region, and they are regulated by hypoxia-inducible factor 1α (HIF-1α) transcriptionally under hypoxic condition. Besides, iron regulatory protein 1 (IRP1) regulates DMT1 and TfR1 by binding to iron-responsive elements (IREs) present in their mRNAs to control cellular iron homeostasis. Results Here, we explored the effect of acute hypoxia on iron uptake. Ferrous iron uptake was elevated by DMT1(+IRE) and TfR1 under acute hypoxia. The luciferase activity analysis revealed that the functional HREs of DMT1 and TfR1 were increased. However, their IREs-dependent luciferase activities were reduced simultaneously. The mRNA stability of TfR1 and DMT1(+IRE) was suppressed under acute hypoxia. The mRNA levels of TfR1 and DMT1(+IRE) were restrain by silencing IRP1. In sharp contrast, HIF-1α overexpression enhanced the mRNA levels of TfR1 and DMT1(+IRE), which reversed the inhibition of IRP1 on both. HIF-1α konckdown suppressed the hypoxia-induced increase expression of TfR1 and DMT1(+IRE), whereas both proteins had little change when further decreased the IRP1 expression under hypoxia. Hypoxia upregulated the protein expression of Ferrtin-L in a time-dependent manner, yet there was no different when IRP1 silencing or overexperssion under hypoxia. The lactate dehydrogenase (LDH) release induced by hypoxia was increased by TfR1 siRNA silence. Conclusions We propose that HIF-1/HRE system might play a principal part in hypoxia induced iron uptake. [ABSTRACT FROM AUTHOR]

Abstract The cryopreservation of cumulus oocyte complexes (COCs) is an important process in reproductive medicine. However, this process slows both embryo and offspring development. In this study, the effects of maturation medium supplementation with lycium barbarum polysaccharide (LBP) on the developmental competence of vitrified-warmed mouse COCs and the possible mechanisms facilitating this process were investigated. The addition of LBP to the maturation medium improved the maturation rate and enhanced the developmental competence of vitrified-warmed mouse COCs. This may reduce endoplasmic reticulum stress (ERS), preventing cell death and activating both PI3K/AKT and MAPK3/1. In conclusion, cryopreservation lowers the maturation rate and developmental competence of COCs, which can be ameliorated by the application of LBP after warming during maturation. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. LncRNA has been confirmed to participate in a variety of cancers. The purpose of this study was to explore the effect of FOXP4-AS1 on the development of osteosarcoma (OS) and its underlying mechanism. FOXP4-AS1 expressions in 60 OS tissues and paracancerous tissues were detected by qRT-PCR (quantitative real-time polymerase chain reaction). We confirmed that FOXP4-AS1 was overexpressed in OS tissues than that of paracancerous tissues. The disease-free survival and overall survival of OS patients were not correlated with age, gender and tumor location, but remarkably correlated with FOXP4-AS1 expression, tumor size and lung metastasis. For in vitro experiments, MG63 cells expressed a higher expression of FOXP4-AS1, whereas U2OS cells expressed a lower expression, which were selected for the following studies. Overexpressed FOXP4-AS1 led to enhanced proliferation, migration and invasion, shortened G0/G1 phase, as well as inhibited cell cycle. Knockdown of FOXP4-AS1 in MG63 cells obtained the opposite results. Furthermore, RIP assay indicated that FOXP4-AS1 could inhibit LATS1 expression by binding to LSD1 and EZH2, so as to participate in OS development. In conclusion, these results revealed that FOXP4-AS1 is overexpressed in OS, and is the independent risk factor in OS prognosis. Upregulated FOXP4-AS1 promotes the proliferation, migration and cell cycle, but inhibits apoptosis of OS cells. Furthermore, FOXP4-AS1 participates in the development and progression of OS by downregulating LATS1 via binding to LSD1 and EZH2. [ABSTRACT FROM AUTHOR]

Scavenger receptors (SRs) are important pattern recognition receptors (PRRs), which play significant roles in host defense against pathogens by identifying pathogen-associated molecular patterns (PAMPs). In this study, we report the cloning and characterization of a SR from Eriocheir sinensis ( Es SR-B1) which is a 500 amino acid protein encoded by a gene comprised of 2726 nucleotides with a 1503 bp open reading frame. The domains of Es SR-B1 were found to be evolutionarily conserved. Es SR-B1 was widely detected in different tissues of E. sinensis and significantly up-regulated in hemocytes after stimulation by Staphyloccocus aureus or Vibrio parahaemolyticus . Recombinant Es SR-B1 protein could bind to bacteria and promote phagocytosis upon bacterial stimulation. Moreover, antimicrobial peptide expression was reduced in Es SR-B1-silenced hemocytes after challenge by S. aureus or V. parahaemolyticus . Thus, Es SR-B1 has a critical role in the binding of bacteria and subsequent promotion of hemocyte phagocytosis. [ABSTRACT FROM AUTHOR]

[Display omitted] Constructing carbon electrodes with abundant heteroatoms and appropriate graphitic interlayer spacing remains a major challenge for achieving high gravimetric and volumetric potassium storage capacities with fast kinetics. Herein, we constructed 3D graphene-like N, F dual-doped carbon sheets induced by Ni template (N, F-CNS-Ni) with dense structure and rich active sites, providing a promising approach to address the facing obstacles. Highly reversible K-ion insertion/extraction is realized in the graphitic carbon structure, and K-adsorption capability is enhanced by introducing N/F heteroatoms. As a result, the N, F-CNS-Ni electrode exhibits ultrahigh gravimetric and volumetric capacities of 404.5 mA h g−1 and 281.3 mA h cm−3 at 0.05 A/g, respectively, and a superb capacity of 259.3 mA h g−1 with a capacity retention ratio of 90 % even after 600 cycles at 5 A/g. This work presents a simple Ni-based template method to prepare graphene-like carbon nanosheets with high packing density and rich heteroatoms, and offers mechanism insight for achieving superior K-ion storage. [ABSTRACT FROM AUTHOR]

In most asthma patients, symptoms are controlled by treatment with glucocorticoid, but long-term or high-dose use can produce adverse effects. Therefore, it is crucial to find new therapeutic strategies. β-sitosterol could suppress type Ⅱ inflammation in ovalbumin (OVA)-induced mice, but its mechanisms have remained unclear. A binding activity of β-sitosterol with glucocorticoid receptor (GR) was analyzed by molecular docking. Human bronchial epithelial cells (BEAS-2B) and human bronchial smooth muscle cells (HBSMC) were treated with different concentrations (0, 1, 5, 10, 20, and 50 μg/mL) of β-sitosterol for suitable concentration selection. In transforming growth factor (TGF)-β1 treated BEAS-2B and HBSMC, cells were treated with 20 μg/mL β-sitosterol or dexamethasone (Dex) to analyze its possible mechanism. In OVA-induced mice, 2.5 mg/kg β-sitosterol or Dex administration was performed to analyze the therapeutic mechanism of β-sitosterol. A GR antagonist RU486 was used to confirm the mechanism of β-sitosterol in the treatment of asthma. A good binding of β-sitosterol to GR (score = −8.2 kcal/mol) was found, and the GR expression was upregulated with β-sitosterol dose increase in BEAS-2B and HBSMC. Interleukin (IL)-25 and IL-33 secretion was significantly decreased by β-sitosterol in the TGF-β1-induced BEAS-2B, and the levels of collagen 1A and α-smooth muscle actin (SMA) were reduced in the TGF-β1-induced HBSMC. In the OVA-challenged mice, β-sitosterol treatment improved airway inflammation and remodeling through suppressing type Ⅱ immune response and collagen deposition. The therapeutic effects of β-sitosterol were similar to Dex treatment in vitro and in vivo. RU486 treatment clearly hampered the therapeutic effects of β-sitosterol in the TGF-β1-induced cells and OVA-induced mice. This study identified that β-sitosterol binds GR to perform its functions in asthma treatment. β-sitosterol represent a potential therapeutic drug for allergic asthma. • A good binding of β-sitosterol to glucocorticoid receptor (GR). • β-sitosterol might be an alternative to dexamethasone (Dex) in the treatment of asthma. • β-sitosterol targets GR to reduce airway inflammation and remodeling. [ABSTRACT FROM AUTHOR]

Curcumin is a natural antioxidant that is isolated from turmeric ( Curcuma longa ) and exhibits strong free radical scavenging activity, thus functional for anti-aging. However, poor stability and low solubility of curcumin in aqueous conditions limit its biomedical applications. Previous studies have shown that the anti-oxidation activity of curcumin embedded in silk fibroin films could be well preserved, resulting in the promoted adipogenesis from human mesenchymal stem cells (hMSCs) cultured on the surface of the films. In the present study, curcumin was encapsulated in both silk fibroin films (silk/cur films) and nanoparticles (silk/cur NPs), and their anti-aging effects were compared with free curcumin in solution, with an aim to elucidate the mechanism of anti-aging of silk-associated curcumin and to better serve biomedical applications in the future. The morphology and structure of silk/cur film and silk/cur NP were characterized using SEM, FTIR and DSC, indicating characteristic stable beta-sheet structure formation in the materials. Strong binding of curcumin molecules to the beta-sheet domains of silk fibroin resulted in the slow release of curcumin with well-preserved activity from the materials. For cell aging studies, rat bone marrow mesenchymal stem cells (rBMSCs) were cultured in the presence of free curcumin (FC), silk/cur film and silk/cur NP, and cell proliferation and markers of aging (P53, P16, HSP70 gene expression and β-Galactosidase activity) were examined. The results indicated that cell aging was retarded in all FC, silk/cur NP and silk/cur film samples, with the silk-associated curcumin superior to the FC. [ABSTRACT FROM AUTHOR]

Five new α-aminophosphonates are synthesized and characterized by EA, FT-IR, 1 H NMR, 13 C NMR, 31 P NMR, ESI-MS and X-ray crystallography. The X-ray analyses reveal that the crystal structures of 1–5 are monoclinic or triclinic system with the space group P 21/c, P − 1, P − 1, P 2(1)/c and P − 1, respectively. All P atoms of 1–5 have tetrahedral geometries involving two O-ethyl groups, one C α atom, and a double bond O atom. The binding interaction of five new α-aminophosphonate N-derivatives ( 1–5 ) with calf thymus(CT)-DNA have been investigated by UV–visible and fluorescence emission spectrometry. The apparent binding constant (Kapp) values follows the order: 1 (3.38 × 10 5 M −1 ) > 2 (3.04 × 10 5 M −1 ) > 4 (2.52 × 10 5 M −1 ) > 5 (2.32 × 10 5 M −1 ) > 3 (2.10 × 10 5 M −1 ), suggesting moderate intercalative binding mode between the compounds and DNA. In addition, fluorescence spectrometry of bovine serum albumin (BSA) with the compounds 1–5 showed that the quenching mechanism might be a static quenching procedure. For the compounds 1–5 , the number of binding sites were about one for BSA and the binding constants follow the order: 1 (2.72 × 10 4 M −1 ) > 2 (2.27 × 10 4 M −1 ) > 4 (2.08 × 10 4 M −1 ) > 5 (1.79 × 10 4 M −1 ) > 3 (1.17 × 10 4 M −1 ). Moreover, the DNA cleavage abilities of 1 exhibit remarkable changes and the in vitro cytotoxicity of 1 on tumor cells lines (MCF-7, HepG2 and HT29) have been examined by MTT and shown antitumor effect on the tested cells. [ABSTRACT FROM AUTHOR]

High-order staggered-grid finite-difference (SFD) schemes have been universally used to improve the accuracy of wave equation modeling. However, the high-order SFD coefficients on spatial derivatives are usually determined by the Taylor-series expansion (TE) method, which just leads to great accuracy at small wavenumbers for wave equation modeling. Some conventional optimization methods can achieve high accuracy at large wavenumbers, but they hardly guarantee the small numerical dispersion error at small wavenumbers. In this paper, we develop new optimal explicit SFD (ESFD) and implicit SFD (ISFD) schemes for wave equation modeling. We first derive the optimal ESFD and ISFD coefficients for the first-order spatial derivatives by applying the combination of the TE and the sampling approximation to the dispersion relation, and then analyze their numerical accuracy. Finally, we perform elastic wave modeling with the ESFD and ISFD schemes based on the TE method and the optimal method, respectively. When the appropriate number and interval for the sampling points are chosen, these optimal schemes have extremely high accuracy at small wavenumbers, and can also guarantee small numerical dispersion error at large wavenumbers. Numerical accuracy analyses and modeling results demonstrate the optimal ESFD and ISFD schemes can efficiently suppress the numerical dispersion and significantly improve the modeling accuracy compared to the TE-based ESFD and ISFD schemes. [ABSTRACT FROM AUTHOR]

Protein–protein interaction (PPI) networks are emerging as valuable prototypes to study important problems in molecular cellular biology and systems biomedicine. An analysis of the topological properties of a PPI network is very helpful for understanding the function and structure of networks. In this study, we analyzed the topological patterns in the BioPlex network containing interactions among 10,961 proteins; most interactions were previously undocumented. The BioPlex network is a comprehensive map of human protein interactions and represents the first phase of a long-term effort to profile the entire human ORFEOME collection. Similar to other biological networks, we observed that the BioPlex network has several topological properties. We also quantified correlations profiles for the BioPlex network and compared them to randomized versions of the same network. We found that for the BioPlex network, edges between proteins with intermediate degrees were strongly suppressed, whereas edges between low-connected proteins were favored. Finally, the degrees of essential genes were compared with the degrees of non-essential genes and randomly selected proteins. There were no significant differences between the groups. [ABSTRACT FROM AUTHOR]

Background Mounting studies have illustrated an important role of HOTAIR in cancer progress, but few studies have reported its function in brain disease, including nerve cell-associated ischemic infarct. This study aimed to investigate the function of HOTAIR in ischemic infarct, involving its association with the level of NOX2 during hypoxia-induced ischemic infarct. Methods Ischemic infarct mice model was established by hypoxia induction, and cerebral dysfunction was evaluated with the surface cerebral blood flow in the ipsilateral hemisphere. HOTAIR expression in isolated infarction lesion and NOX2 protein level in the circulation were detected. HT22 cells were subjected to hypoxia treatment in vitro for functional studies, including TUNEL-positive cells detection for apoptosis analysis. Results HOTAIR expression was significantly up-regulated in infarction lesion from ischemic infarct mice, in line with increased NOX2 production, while similar results were also observed in hypoxia treated HT22 cells, which was then reversed by HOTAIR interference. Functional studies demonstrated that HOTAIR showed positive regulation on TUNEL-positive cells and apoptosis. Further in vitro study confirmed that HOTAIR silencing could improve cerebral function of ischemic infarct mice, and markedly decreased NOX2 production in the circulation. Conclusion High expression of HOTAIR promoted the onset of ischemic infarct induced by hypoxia. Moreover, the finding showed that HOTAIR promoted ischemic infarct induced by hypoxia through regulating NOX2 expression, which could add our understanding of the molecular mechanisms in ischemic infarct. [ABSTRACT FROM AUTHOR]

Essential genes are those that are indispensable for the survival and propagation of an organism. TATA-containing genes are associated with responses to various stresses and are highly regulated. Although both essential genes and TATA genes are very important in the function of biological systems, their relationship remains unclear because they have typically been researched independently. In this study, to investigate the relationship between essential genes and TATA genes, S. cerevisiae genes were classified as: essential TATA-containing, non-essential TATA-containing, essential non-TATA, and non-essential non-TATA genes. Network-based methods were applied to analyze these four gene categories in the S. cerevisiae perturbation sensitivity (PS) network, which was created from the transcriptional profiling of hundreds of different gene disruptions. All of the topological properties were found to be statistically discriminative among the four gene categories, and the non-essential TATA-containing genes had the most important roles in the yeast PS network. [ABSTRACT FROM AUTHOR]

• IFNAR1 expression in CD4+ and CD8+ T cells is higher in CRC. • Peripheral blood CD4+ T IFNAR1 levels positively associate with TME CD8+ T cell infiltration. • CD8+ T IFNAR1 expressions were negative associated with plasma IL-2, IFN-γ, and TNFα. • IFNAR1 levels in peripheral blood CD8+ T negatively associate with chemosensitivity. IFN-α receptor (IFNAR) is critical for maintaining the crosstalk between cancer cells and lymphocytes. We investigated IFNAR1 expression in peripheral blood CD4+ and CD8+ T cells and explored their relationships with plasma cytokines, chemosensitivity and infiltrated T cells in the tumor microenvironment (TME) of colorectal cancer (CRC). The levels of IFNAR1, IFN-γ, and PD1 in peripheral T cells were tested using flow cytometry. Immunohistochemical staining of IFNAR1 in CRC tissues was performed. A cytometric bead array was used to determine the plasma concentrations of cytokines. In CRC patients, IFNAR1 levels were significantly increased in peripheral blood T cells, and plasma IL-6 levels were also significantly increased. Pearson correlation analysis revealed that IFNAR1 expression in CD8+ T cells was negatively associated with plasma IL-2, IFN-γ, and TNFα. IFNAR1 expression in CD4+ T cells was positively associated with TME infiltrated levels of CD8+ T cells. The levels of CD8+ T cells with IFNAR1 and plasma IFN-γ were associated with chemosensitivity. Collectively, IFNAR1 levels in CD4+ and CD8+ T cells were significantly upregulated in CRC patients and positively associated with T-cell infiltration. IFNAR1 may be a chemotherapy biomarker for predicting response. [ABSTRACT FROM AUTHOR]

ɛ-Poly- l -lysine (EPL) is a food-grade cationic antimicrobial compound with a wide antimicrobial spectrum against bacteria, yeasts, and molds. However, EPL can be subject to rapid depletion after initial application and lose activity quickly. To address this problem, this study used Escherichia coli O157:H7 and tryptic soy agar (TSA) deep-well depletion model to evaluate the prolonged antibacterial efficacy of EPL stabilized with emulsions formed by three types of emulsifier: (1) phytoglycogen octenyl succinate (PG-OS), an amphiphilic carbohydrate particulate; (2) waxy corn starch octenyl succinate (WCS-OS), an amphiphilic hyperbranched polysaccharide; and (3) Tween 20, a neutral small-molecule surfactant. During 20 days of storage at 4 °C, the residual antibacterial efficacy of EPL in PG-OS emulsion was the greatest. In contrast, Tween-20 and WCS-OS emulsions were not as effective as PG-OS emulsion to retain antibacterial activity. Meanwhile, equilibrium dialysis showed the greatest EPL retention with PG-OS emulsion, suggesting the impact of electrostatic and structural properties of emulsifiers at the oil-water interface on prolonged EPL efficacy against E. coli O157:H7. [ABSTRACT FROM AUTHOR]

Cryopreservation of cumulus oocyte complexes (COCs) is important for reproductive medicine. However, the vitrified-warmed COCs have lower maturation rate and subsequent developmental competence compared with fresh COCs. The present study was aimed to evaluate the effects of supplementation of the maturation medium with C-type natriuretic peptide (CNP) on the developmental competence of vitrified-warmed mouse COCs. Addition of CNP to the maturation medium improved the maturation rate and enhanced the developmental competence of vitrified-warmed mouse COCs. The reason may be that vitrified COCs led to a decline in cyclic guanosine monophosphate (cGMP) levels. Furthermore, addition of CNP to the maturation medium elevated cGMP levels of the vitrified-warmed COCs. In conclusion, cryopreservation-associated lower maturation rate and developmental competence of COCs may be ameliorated by CNP during maturation culture after warming. [ABSTRACT FROM AUTHOR]

Gene therapy has held great promise for treating specific acquired and inherited diseases. However, the lack of safe and efficient gene delivery systems remains as the major challenge. Poly(β-amino ester)s (PBAEs) have attracted much attention due to their outstanding properties in biosafety, DNA delivery efficiency and convenience in synthesis. In this paper, we reported the further enhancement of the PBAE functions by increasing its positive charge through conjugating with low molecular weight polyethylenimine (LPEI). The resulted LPEI–PBAE polymer was able to condense minicircle DNA (mcDNA) forming nanoparticles with a diameter of 50–200 nm. Furthermore, as compared to parental PBAE and a commercial transfection reagent very common in laboratory application, the LPEI–PBAE demonstrated significantly higher transfection efficiency with little cytotoxicity. These results suggested LPEI–PBAEs are worthy of further optimization for gene therapy applications. [ABSTRACT FROM AUTHOR]

SKF-96365 is a TRPC channel antagonist commonly used to characterize the potential functions of TRPC channels in different systems, which was recently reported to induce QTc prolongation on ECG by inhibiting TRPC channels. The present study investigates whether the blockade of cardiac repolarization currents would be involved in the increase of QTc interval. Cardiac repolarization currents were recorded in HEK 293 cells stably expressing human ether-à-go-go-related gene potassium (hERG or hKv11.1) channels, hKCNQ1/hKCNE1 channels ( I Ks ) or hKir2.1 channels and cardiac action potentials were recorded in guinea pig ventricular myocytes using a whole-cell patch technique. The potential effect of SKF-96365 on QT interval was evaluated in ex vivo guinea pig hearts. It was found that SKF-96365 inhibited hERG current in a concentration-dependent manner (IC 50 , 3.4 μM). The hERG mutants S631A in the pore helix and F656 V of the S6 region reduced the inhibitory sensitivity with IC 50 s of 27.4 μM and 11.0 μM, suggesting a channel pore blocker. In addition, this compound inhibited I Ks and hKir2.1currents with IC 50 s of 10.8 and 8.7 μM. SKF-96365 (10 μM) significantly prolonged ventricular APD 90 in guinea pig ventricular myocytes and QTc interval in ex vivo guinea pig hearts. These results indicate that the TRPC channel antagonist SKF-96365 exerts blocking effects on hERG, I Ks , and hKir2.1 channels. Prolongation of ventricular APD and QT interval is related to the inhibition of multiple repolarization potassium currents, especially hERG channels. [ABSTRACT FROM AUTHOR]

Highly transparent Dy 3+ -doped terbium gallium garnet (TGG) single crystal was grown by Czochralski (Cz) method. Phase composition of the crystal was tested by XRD measurements. The distribution coefficient of Dy 3+ in the crystal was obtained. The optical and magneto-optical properties were analyzed in detail, and magnetic properties of the Dy 3+ -TGG crystal were studied. The paramagnetic behavior is observed down to 10 K. The as-grown crystal exhibited high optical transmittance, particularly in the visible region. The Faraday rotation was investigated over visible and near-infrared regions (VIS–NIR) at room temperature. The Verdet constants increase at measured wavelengths and high thermal stability was found in Dy 3+ -doped TGG, as compared to the properties of pure TGG, indicating that Dy 3+ -doped crystals are preferable for magneto-active materials used in Faraday devices at VIS–NIR wavelengths. [ABSTRACT FROM AUTHOR]

The kinetics of the hydrodesulfurization (HDS) of dibenzothiophene (DBT), 4,6-dimethyldibenzothiophene (4,6-DMDBT), and their hydrogenated intermediates over bulk tungsten phosphide (WP) was studied. WP possessed high hydrogenation/dehydrogenation activity but was highly sensitive to piperidine inhibition. 4,6-DMDBT reacted faster than DBT, and both DBT and 4,6-DMDBT reacted mainly through the hydrogenation pathway. The methyl groups suppressed the direct desulfurization of 4,6-DMDBT but significantly promoted the hydrogenation of 4,6-DMDBT and the dehydrogenation of 1,2,3,4-tetrahydro-4,6-dimethyldibenzothiophene (TH-4,6-DMDBT) and 1,2,3,4,4a,9b-hexahydro-4,6-dimethyldibenzothiophene, but decreased the rate of hydrogenation of TH-4,6-DMDBT. Piperidine inhibited the HDS of 4,6-DMDBT much more strongly than that of DBT. Substantial dehydrogenation of TH-4,6-DMDBT to 4,6-DMDBT and two of its isomers occurred. The formation of these 4,6-DMDBT isomers in the dehydrogenation of TH-4,6-DMDBT and the hydrocracking of 1-methyl-4-(3-methylcyclohexyl)-benzene, as well as the formation of cyclopentylphenylmethane and (cyclopentylmethyl)cyclohexane, is ascribed to the metallic character of WP. [ABSTRACT FROM AUTHOR]

The variable lymphocyte receptors (VLRs) are found in jawless vertebrates (agnathans), and specifically recognize bacteria and viruses via their leucine-rich repeats (LRRs). VLRs are believed to be adaptive immune response molecules. Echinoderms do not have adaptive immune systems; however, in the present study, a VLR cDNA named Aj-VLRA was cloned and characterized from sea cucumber, Apostichopus japonicus . The complete cDNA of Aj-VLRA was 3072 bp, including a 1995 bp open reading frame encoding 664 amino acids comprising LRR domains, a predicted transmembrane helix and an N-terminal signal peptide. As determined by quantitative real-time reverse transcription polymerase chain reaction, Aj-VLRA transcripts are ubiquitously expressed in the body wall, longitudinal muscles, intestine and respiratory tree of A. japonicus . The expression level of Aj-VLRA was upregulated after challenge with four common marine bacteria. In situ hybridization showed that the expression of Aj-VLRA was widely distributed in the four tissues, particularly in the cytoplasm of epidermal cells. Recombinantly expressed Aj-VLRA (including the LRR domains) could bind to bacteria including Micrococcus lysodeikticus (Gram+) and Vibrio anguillarum (Gram−). Collectively, the results suggested that Aj-VLRA is related to an innate immune response of A. japonicus . [ABSTRACT FROM AUTHOR]

Background and objectives. The creation of cardiomyocytes derived from human induced pluripotent stem cells (hiPS-CMs) has spawned broad excitement borne out of the prospects to diagnose and treat cardiovascular diseases based on personalized medicine. A common feature of hiPS-CMs is their spontaneous contractions but the mechanism(s) remain uncertain. Methods. Intrinsic activity was investigated by the voltage-clamp technique, optical mapping of action potentials (APs) and intracellular Ca 2+ (Ca i ) transients (Ca i T) at subcellular-resolution and pharmacological interventions. Results. The frequency of spontaneous Ca i T (sCa i T) in monolayers of hiPS-CMs was not altered by ivabradine, an inhibitor of the pacemaker current, I f despite high levels of HCN transcripts (1–4). HiPS-CMs had negligible I f and I K1 (inwardly-rectifying K + -current) and a minimum diastolic potential of − 59.1 ± 3.3 mV (n = 18). APs upstrokes were preceded by a depolarizing-foot coincident with a rise of Ca i . Subcellular Ca i wavelets varied in amplitude, propagated and died-off; larger Ca i -waves triggered cellular sCaTs and APs. SCa i Ts increased in frequency with [Ca 2+ ] out (0.05-to-1.8 mM), isoproterenol (1 μM) or caffeine (100 μM) (n ≥ 5, p < 0.05). HiPS-CMs became quiescent with ryanodine receptor stabilizers (K201 = 2 μM); tetracaine; Na–Ca exchange (NCX) inhibition (SEA0400 = 2 μM); higher [K + ] out (5 → 8 mM), and thiol-reducing agents but could still be electrically stimulated to elicit Ca i Ts. Cell–cell coupling of hiPS-CM in monolayers was evident from connexin-43 expression and Ca i T propagation. SCa i Ts from an ensemble of dispersed hiPS-CMs were out-of-phase but became synchronous through the outgrowth of inter-connecting microtubules. Conclusions. Automaticity in hiPS-CMs originates from a Ca 2+ -clock mechanism involving Ca 2+ cycling across the sarcoplasmic reticulum linked to NCX to trigger APs. [ABSTRACT FROM AUTHOR]

Cyprininae is the largest subfamily (>1300 species) of the family Cyprinidae and contains more polyploid species (∼400) than any other group of fishes. We examined the phylogenetic relationships of the Cyprininae based on extensive taxon, geographical, and genomic sampling of the taxa, using both mitochondrial and nuclear genes to address the phylogenetic challenges posed by polyploidy. Four datasets were analyzed in this study: two mitochondrial gene datasets (465 and 791 taxa, 5604 bp), a mitogenome dataset (85 taxa, 14,771 bp), and a cloned nuclear RAG1 dataset (97 taxa, 1497 bp). Based on resulting trees, the subfamily Cyprininae was subdivided into 11 tribes: Probarbini (new; Probarbus + Catlocarpio ), Labeonini Bleeker, 1859 ( Labeo & allies), Torini Karaman, 1971 ( Tor , Labeobarbus & allies), Smiliogastrini Bleeker, 1863 ( Puntius , Enteromius & allies), Poropuntiini ( Poropuntius & allies), Cyprinini Rafinesque, 1815 ( Cyprinus & allies), Acrossocheilini (new; Acrossocheilus & allies), Spinibarbini (new; Spinibarbus ), Schizothoracini McClelland, 1842 ( Schizothorax & allies), Schizopygopsini Mirza, 1991 ( Schizopygopsis & allies), and Barbini Bleeker, 1859 ( Barbus & allies). Phylogenetic relationships within each tribe were discussed. Two or three distinct RAG1 lineages were identified for each of the following tribes Torini, Cyprinini, Spinibarbini, and Barbini, indicating their hybrid origin. The hexaploid African Labeobarbus & allies and Western Asian Capoeta are likely derived from two independent hybridization events between their respective maternal tetraploid ancestors and Cyprinion . [ABSTRACT FROM AUTHOR]

Osteoblasts regulate bone formation and remodeling, and are main target cells of oxidative stress in the progression of osteonecrosis. The stem cell factor (SCF)-c-Kit pathway plays important roles in the proliferation, differentiation and survival in a range of cell types, but little is known about its functions in osteoblasts. In this study, we found that c-Kit is functionally expressed in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. Its ligand SCF exerted significant cyto-protective effects against hydrogen peroxide (H 2 O 2 ). SCF activated its receptor c-Kit in osteoblasts, which was required for its cyto-protective effects against H 2 O 2 . Pharmacological inhibition (by Imatinib and Dasatinib) or shRNA-mediated knockdown of c-Kit thus inhibited SCF-mediated osteoblast protection. Further investigations showed that protection by SCF against H 2 O 2 was mediated via activation of c-Kit-dependent Akt pathway. Inhibition of Akt activation, through pharmacological or genetic means, suppressed SCF-mediated anti-H 2 O 2 activity in osteoblasts. In summary, we have identified a new SCF-c-Kit-Akt physiologic pathway that protects osteoblasts from H 2 O 2 -induced damages, and might minimize the risk of osteonecrosis caused by oxidative stress. [ABSTRACT FROM AUTHOR]

The TATA box is the core sequence of the promoter and the binding site of many transcription factors. Based on the presence or absence of TATA box, genes can be defined as TATA-containing or TATA-less genes. Many important stress-response functions and highly variable expression patterns are found to be correlated with the TATA box. However, until now, the relationships and differences between TATA-containing and TATA-less genes remain unclear. In this study, based on the transcriptional profiling of the Saccharomyces cerevisiae genome, the perturbation sensitivity (PS) network is constructed. The topological and biological properties are used to investigate differences between TATA-containing and TATA-less genes. Significant differences are found in all topological properties and most of the biological properties. Notably, the TF number, determined mathematically by the number of transcription factors regulating a gene, demonstrates the highest discrimination between TATA-containing and TATA-less genes when all properties are estimated by the F-score. [ABSTRACT FROM AUTHOR]

Proteins are responsible for performing the vast majority of cellular functions which are critical to a cell's survival. The knowledge of the subcellular localization of proteins can provide valuable information about their molecular functions. Therefore, one of the fundamental goals in cell biology and proteomics is to analyze the subcellular localizations and functions of these proteins. Recent large-scale human genomics and proteomics studies have made it possible to characterize human proteins at a subcellular localization level. In this study, according to the annotation in Swiss-Prot, 8842 human proteins were classified into seven subcellular localizations. Human proteins in the seven subcellular localizations were compared by using topological properties, biological properties, codon usage indices, mRNA expression levels, protein complexity and physicochemical properties. All these properties were found to be significantly different in the seven categories. In addition, based on these properties and pseudo-amino acid compositions, a machine learning classifier was built for the prediction of protein subcellular localization. The study presented here was an attempt to address the aforementioned properties for comparing human proteins of different subcellular localizations. We hope our findings presented in this study may provide important help for the prediction of protein subcellular localization and for understanding the general function of human proteins in cells. [ABSTRACT FROM AUTHOR]

[Display omitted] • Carbon fibers modified with ionic liquid was prepared as SPME fiber. • Simultaneous determination method of phytohormones by LC–MS/MS was developed. • Phytohormones were determined during different development stages in strawberries. • Level Changes and roles of phytohormones in strawberries were studied. In the present document, we report a novel miniaturized dispersive solid-phase extraction based on carbon fibers functionalized with ionic liquid for the determination of multiple-phytohormones and investigation on temporal distribution of phytohormones during the development in strawberry. 1-(3-Aminopropyl)-3-methylimidazolium bromide was modified on the carbon fibers by using covalent functionalization to prepare ionic liquid-carbon fibers (IL-CFs). It contains the structural feature suitable for the simultaneous extraction of a variety of phytohormones. The main experimental parameters were optimized, and the method was used to determine phytohormones during fruit development in strawberries. The limits of detection and quantification of the proposed method were found to be in the range of 0.00330−0.283 ng mL−1 and 0.0110−0.944 ng mL−1, respectively. All the relative recoveries were in the range of 81.7–121.4% with RSD ≤ 10.0 % (n = 3). This report highlighted the level changes of multiple-phytohormones during different developmental stages in strawberries. The level of cytokinins and ABA increased as strawberry fruits ripened, while IAA content steadily decreased. Meanwhile GA 7 level was relatively stable in all stages, and SA level exhibited fluctuations. [ABSTRACT FROM AUTHOR]

Highlights: [•] The perturbation sensitivity (PS) network of S. cerevisiae is constructed from transcriptional profiling. [•] The essential and non-essential genes are analyzed by 12 topological properties in the PS network. [•] The essentiality of each property is estimated by the F-score. [Copyright &y& Elsevier]

Abstract: Proteins do not exert their function in isolation of one another, but interact together in protein–protein interaction (PPI) networks. Analysis of topological properties of proteins in the PPI network is very helpful to understand the function of proteins. However, until recently, no one has ever undertaken to investigate toxin targets by topological properties. In this study, for the first time, 12 topological properties are used to investigate the characteristics of toxin targets in the PPI network. Most of the topological properties are found to be statistically discriminative between toxin targets and other proteins, and toxin targets tend to play more important roles in the PPI network. In addition, based on the topological properties and the sequence information, support vector machine (SVM) is used to predict toxin targets. The results obtained by the jackknife test and 10-fold cross validation are encouraging, indicating that SVM is a useful tool for predicting toxin targets, or at least can play complementary roles in relevant areas. [Copyright &y& Elsevier]

Abstract: Cancer cells adapt to chronic stress in the tumor microenvironment by inducing the expression of glucose-regulated protein 78 (GRP78), a major endoplasmic reticulum chaperone with Ca2+-binding and antiapoptotic properties. The effect in and potential role of its expression in progression of and prognosis for gastric cancer (GC) are unclear. In the present study, we investigated the clinical value of GRP78 expression in judgment of the severity of and prognosis for GC in a retrospective cohort study of 160 patients who underwent D2 radical gastrectomy and adjuvant chemotherapy. GRP78 expression was detected using immunohistochemistry. The relationships of GRP78 expression with age, sex, differentiation, invasion depth, disease stage, lymph node metastasis, and time to recurrence (TTR) were analyzed. The GRP78 expression was higher in tumors from patients with deep tumor infiltration, with poor differentiation, at late disease stages, and with lymph node metastasis than that in tumors from patients without. Also, GRP78 positivity was associated with short TTR (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.07–4.85; P =0.041). Subgroup analysis revealed that the HR in the GRP78-high group increased significantly in patients who did not receive taxane-containing regimens (HR, 2.21; 95% CI, 1.23–7.36; P =0.038). In contrast, in the patients who received taxane-based chemotherapy, the association between GRP78 positivity and increased risk of recurrence was not statistically significant (HR, 1.16; 95% CI, 0.81–2.98; P =0.111). In the patients with GRP78 expression, those who underwent taxane-containing chemotherapy had longer median TTRs than did those who did not undergo this treatment (P =0.017). Downregulation of GRP78 expression markedly inhibited proliferation of the GC cells at the G1 phase, whereas GRP78 overexpression promoted cell-cycle progression. These findings suggest that GRP78 overexpression promotes GC cells proliferation and is an independent indicator of poor prognosis for GC. [Copyright &y& Elsevier]

[Display omitted] • Cloned three nuclear loci to study the evolution of polyploidy in the Cyprininae. • At least 13 independent polyploidization events are hypothesized. • Offered hypotheses on the origin of each polyploid group. • Provided rough timeframes for the polyploidization events. • Divided the evolutionary history of Cyprinine into three stages. Despite the rarity of polyploidy in animals, some groups with polyploid species exhibit complicated and interesting patterns of reticulate evolution. Here we focus on fishes in the subfamily Cyprininae, the largest polyploid group of vertebrates. The large number of polyploid taxa poses significant challenges for phylogenetic and evolutionary studies on this subfamily. In this study, we cloned and sequenced three single-copy nuclear loci to investigate the evolution of polyploidy in the Cyprininae. Topologies of nuclear gene trees were compared with a newly reconstructed mitochondrial tree. The data provided herein corroborate the hybrid origins of the tribes Torini, Cyprinini, Spinibarbini, Barbini, and also Probarbini. Based on results from this study and previous studies, we hypothesize that at least 13 independent polyploidization events have occurred during the evolution of the Cyprininae. We offer hypotheses on the origin of each polyploid group and show that a diploid group or the diploid ancestor of a polyploid group might have served as progenitor of one or two other polyploid groups. The evolutionary history of Cyprinine (since its first divergence) can be divided into three stages: the "Diploid stage" (69.2–43.4 Ma or million years ago), the "Tetraploidization stage" (43.4–18.9 Ma), and the "Hexaploidization stage" (18.9 Ma to present). The second stage is when all tetraploidization events happened, while the last stage is when all hexaploidization events and most genus- or species-specific polyploidization events occurred. The post-polyploidization dynamics of polyploid groups are complicated and warrant more genomic level studies. We showed that the subfamily Cyprininae may represent a more complicated polyploid system than most, if not all, other vertebrates and some plants, if one or more of the following factors are considered: number of polyploid species, number of different ploidy levels, and number and type of independent polyploidization events. [ABSTRACT FROM AUTHOR]

Abstract: Neointimal hyperplasia is the primary lesion underlying atherosclerosis and restenosis after percutaneous coronary intervention. Calcitonin gene-related peptide (CGRP) is produced by alternative splicing of the primary transcript of the calcitonin/CGRP gene. Originally identified as a strongly vasodilatory neuropeptide, CGRP is now known to be a pleiotropic peptide widely distributed in various organs and tissues. Our aim was to investigate the possibility that CGRP acts as an endogenous vasoprotective molecule. We compared the effect of CGRP deficiency on neointimal formation after wire-induced vascular injury in wild-type and CGRP knockout (CGRP−/−) mice. We found that neointimal formation after vascular injury was markedly enhanced in CGRP−/− mice, which also showed a higher degree of oxidative stress, as indicated by reduced expression of nitric oxide synthase, increased expression of p47phox, and elevated levels of 4HNE, as well as greater infiltration of macrophages. In addition, CGRP-deficiency led to increased vascular smooth muscle cell (VSMC) proliferation within the neointima. By contrast, bone marrow-derived cells had little or no effect on neointimal formation in CGRP−/−mice. In vitro analysis showed that CGRP-treatment suppressed VSMC proliferation, migration, and ERK1/2 activity. These results clearly demonstrate that endogenous CGRP suppresses the oxidative stress and VSMC proliferation induced by vascular injury. As a vasoprotective molecule, CGRP could be an important therapeutic target in cardiovascular disease. [Copyright &y& Elsevier]

Abstract: The cyprinid tribe Labeonini (sensuRainboth, 1991) is a large group of freshwater fishes containing around 40 genera and 400 species. They are characterized by an amazing diversity of modifications to their lips and associated structures. In this study, a total of 34 genera and 142 species of putative members of this tribe, which represent most of the generic diversity and more than one third of the species diversity of the group, were sampled and sequenced for four nuclear genes and five mitochondrial genes (totaling 9465bp). Phylogenetic relationships and subdivision of this tribe were investigated and the placement and status of most genera are discussed. Partitioned maximum likelihood analyses were performed based on the nuclear dataset, mitochondrial dataset, combined dataset, and the dataset for each nuclear gene. Inclusion of the genera Paracrossochilus, Barbichthys, Thynnichthys, and Linichthys in the Labeonini was either confirmed or proposed for the first time. None of the genera Labeo, Garra, Bangana, Cirrhinus, and Crossocheilus are monophyletic. Taxonomic revisions of some genera were made: the generic names Gymnostomus Heckel, 1843, Ageneiogarra Garman, 1912 and Gonorhynchus McClelland, 1839 were revalidated; Akrokolioplax Zhang and Kottelat, 2006 becomes a junior synonym of Gonorhynchus; the species Osteochilus nashii was found to be a member of the barbin genus Osteochilichthys. Five historical hypotheses on the classification of the Labeonini were tested and rejected. We proposed to subdivide the tribe, which is strongly supported as monophyletic, into four subtribes: Labeoina, Garraina, Osteochilina, and Semilabeoina. The taxa included in each subtribe were listed and those taxa that need taxonomic revision were discussed. [Copyright &y& Elsevier]