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Tumor-associated macrophages (TAM) play a crucial role in promoting cancer progression. Upon cytokine stimulation, TAM preferentially polarize to the anti-inflammatory and pro-tumor M2 subtype. The mechanism underlying such preferential polarization remains elusive. Here, we report that macrophage-specific deletion of the SUMO-specific protease Sentrin/SUMO-specific protease 3 promotes macrophage polarization towards M2 in bone marrow-derived macrophage (BMDM) induced by interleukin 4 (IL-4)/IL-13 and in an ex vivo model (murine Py8119 cell line), as well as in a mouse orthotopic tumor model. Notably, Sentrin/SUMO-specific protease 3 (SENP3) loss in macrophages accelerated breast cancer malignancy in ex vivo and in vivo models. Mechanistically, we identified Akt Serine/threonine kinase 1 (Akt1) as the substrate of SENP3 and found that the enhanced Akt1 SUMOylation upon SENP3 loss resulted in Akt1 hyper-phosphorylation and activation, which facilitates M2 polarization. Analysis of clinical data showed that a lower level of SENP3 in TAM has a strong negative correlation with the level of the M2 marker CD206, as well as with a worse clinical outcome. Thus, increased Akt1 SUMOylation as a result of SENP3 deficiency modulates polarization of macrophages to the M2 subtype within a breast cancer microenvironment, which in turn promotes tumor progression.

BACKGROUND: Vascular changes in liver fibrosis can result in increased intrahepatic vascular resistance and impaired blood circulation. This can hinder the recovery from fibrosis and may eventually lead to portal hypertension, a major cirrhosis complication. This report proposed a volume-averaged Murray’s deviation method to characterize intrahepatic circulation in the liver during fibrosis and its subsequent regression via X-ray phase-contrast computed tomography (PCCT). METHODS: Liver fibrosis was induced in 24 Sprague-Dawley rats by exposure to carbon tetrachloride (CCl(4)) for up to 10 weeks, after which, spontaneous regression commenced and continued until week 30. High-resolution three-dimensional (3D) imaging of the livers was performed with PCCT. The values of Murray’s deviation based on the volume-averaged and the conventional diameter-based methods were compared. After that, the intrahepatic circulation at different stages of fibrosis was evaluated using the volume-averaged method. The increase in collagen during liver fibrosis was assessed by pathological analyses. RESULTS: A comparison of the 2 methods showed that with an increase in the number of diameter measurements, the value of Murrary’s deviation obtained using the diameter-based method gradually approaches those of the volume-averaged method, with minimal variations. The value of Murray’s deviation increased with the development of fibrosis. After reversal, the value rapidly decreased and approached that of the normal state in both the main branches (1.05±0.17, 1.17±0.21, 1.34±0.18, and 1.17±0.19 in the normal, moderate, severe, and regressive groups, respectively; P

The development of hydrogen evolution activity (HER) electrocatalyst that can run durably and efficiently under the large current density is of special significance but still challengeable for the massive production of hydrogen. Herein, a CoP/Ni(OH)2 nanowire catalysts grown on Co foam (CF) with a three-dimensional heterojunction structure has been successfully prepared by electrodepositing nickel hydroxide on the surface of cobalt phosphide. The prepared CoP/Ni(OH)2–15 min sample reveals a superior HER activity and stability. It merely requires ultralow overpotentials of 108 and 175 mV to 100 and 500 mA cm−2, respectively. In addition, the long-term stability test shows that the catalyst (CoP/Ni(OH)2–15 min) can operate stably for at least 70 h at 400 mA cm−2. Utilizing NiFe-LDH/IF with high OER activity, the NiFe-LDH/IF || CoP/Ni(OH)2–15 min catalyst system possesses the same outstanding performance for overall water splitting (OWS), which can accomplish ≈ 500 mA cm−2 at 1.74 V in 1 M KOH electrolyte. Moreover, the NiFe-LDH/IF || CoP/Ni(OH)2–15 min couple can work for more than 80 h at 500 mA cm−2, indicating its a great prospect in the area of electrolysis water. Such excellent catalytic performance is mainly attributed to the armor effect of Ni(OH)2, which can not only promote the rapid decomposition of water molecules, but also prevent the loss of phosphorus and enhance the synergistic effect of CoP and Ni(OH)2. This work can offer a significant reference for the design with high-performance and durable transition metal phosphide electrocatalysts.

Nowadays, the harm of antibiotics residues in environments to human health and ecological safety has been causing more and more attention. In this paper, a biochar based iron material (MBC) was used to activate persulfate (PS) for the removal of sulfadiazine (SDZ) from aqueous solution. Experiment results indicate that the degradation and mineralization of SDZ by MBC/PS system reached 91.79 and 60 % within 60 min under the optimal reaction conditions, respectively. MBC/PS system exhibited a better performance on SDZ removal compared with MBC/H2O2 system. The addition of Cu2+ ion could enhance the degradation of SDZ by MBC/PS system. PO43-, Cl- and SO42- had a certain degree of inhibitory effect on the SDZ degradation. Both radicals and non-radical species such as SO4•-, •OH and 1O2 participated in the degradation reaction of SDZ by MBC/PS system, but •OH was the main radical species responsible for SDZ degradation. The liquid chromatograph-mass spectrometer (LC-MS) technique was used to identify the intermediate products of SDZ, and it was proposed that the degradation of SDZ might be achieved through hydrolyzation, hydroxylation, deamination and amino-oxidization processes. A possible reaction mechanism involving a synergistic effect between PS homogeneous and heterogeneous activation processes as well as both radicals and non-radicals reactions was finally proposed.

Supplemental Digital Content is available in the text., Objective: While the risk of acute coronary events has been associated with biological variability of circulating cholesterol, the association with variability of other atherogenic lipids remains less understood. We evaluated the longitudinal variability of 284 lipids and investigated their association with asymptomatic coronary atherosclerosis. Approach and Results: Circulating lipids were extracted from fasting blood samples of 83 community-sampled symptom-free participants (age 41–75 years), collected longitudinally over 6 months. Three types of coronary plaque volume (calcified, lipid-rich, and fibrotic) were quantified using computed tomography coronary angiogram. We first deconvoluted between-subject (CVg) and within-subject (CVw) lipid variabilities. We then tested whether the mean lipid abundance was different across groups categorized by Framingham risk score and plaques phenotypes (lipid-rich, fibrotic, and calcified). Finally, we investigated whether visit-to-visit variability of each lipid was associated with plaque burden. Most lipids (72.5%) exhibited higher CVg than CVw. Among the lipids (n=145) with 1.2-fold higher CVg than CVw, 26 species including glycerides and ceramides were significantly associated with Framingham risk score and the 3 plaque phenotypes (false discovery rate

To meet the current energy needs of society, the highly efficient and continuous production of clean energy is required. One of the key issues facing the green hydrogen evolution is the construction of efficient, low-cost electrocatalysts. Prussian blue (PB), Prussian blue analogs (PBAs), and their derivatives have tunable metal centers and have attracted significant interest as novel photo- and electrochemical catalysts. In this review, recent research progress into PB/PBA-based hollow structures, substrate-supported nanostructures, and their derivatives for green water splitting is discussed and summarized. First, several remarkable examples of nanostructured PB/PBAs supported on substrates (copper foil, carbon cloth, and nickel foam) and hollow structures (such as single-shelled hollow boxes, open hollow cages, and intricate hollow structures (multi–shell and yolk–shell)) are discussed in detail, including their synthesis and formation mechanisms. Subsequently, the applications of PB/PBA derivatives ((hydr)oxides, phosphides, chalcogenides, and carbides) for water splitting are discussed. Finally, the limitations in this research area and the most urgent challenges are summarized. We hope that this review will stimulate more researchers to develop technologies based on these intricate PB/PBA structures and their derivatives for highly efficient, green water splitting.

Over the past decades, there had been a growing concern for policy makers and scientists to implement the sustainable development (SD) agenda. To date, little efforts are made to instil early awareness and education for sustainable development (ESD) amongst the first-year undergraduates to become effective and responsible global citizens. As such, the learning of organic chemical-based socio-scientific issues (SSIs) within the scientific world is important to promote early awareness amongst chemistry undergraduates in SD. In this manuscript, for the first time comics drawing is being used as learning instruction to instil the ESD learning amongst first-year undergraduates at Universiti Malaysia Terengganu. In this activity, students made their own comics with regard to organic chemical-based SSIs they have read and shared their own comics, together with their reflective essays on the learning management system (LMS). Based on a survey result, students’ involvement in the current activity has resulted in their familiarity with the organic chemical-based SSIs. In addition, they have expressed a high degree of satisfaction toward the implemented activity and the chemistry content they learnt in this course based on the reflective essay received by the course instructor in the LMS.

A successive investigation of the endophytic fungus Stagonosporopsis oculihominis isolated from Dendrobium huoshanense led to the discovery of two undescribed secondary metabolites, (±)-stagonosporopsin A and stagonosporopsin B, and a new natural product, stagonosporopsin C. (±)-stagonosporopsin A is a pair of enantiomer. The structures of the isolated compounds, including their absolute configurations, were elucidated based on extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations and X-ray diffraction. Stagonosporopsin C exhibited moderate inhibitory activity against Staphylococcus aureus subsp. aureus ATCC29213 with an MIC50 value of 41.3 μM.

Exploration of the diastereodivergent synthesis of spirocyclic oxindoles has been challenging. Herein we report asymmetric [3 + 2] annulations of isatin-derived Morita-Baylis-Hillman (MBH) carbonates and 5-alkenylthiazol-4(5H)-ones. Interestingly, two different chiral catalysts, amide-phosphine and 4-dimethylaminopyridine (DMAP)-thiourea, could lead to two kinds of diastereomeric dispiro oxindoles with three contiguous stereogenic centers. The hexafluoroisopropanol (HFIP) additive plays a vital role in accelerating the reaction and tuning the diastereoselectivity. Moreover, both annulation adducts could be further converted to structurally diverse spirooxindoles.

Cardiovascular disease (CVD) is one of the leading causes of death worldwide. CVD includes coronary artery diseases such as angina, myocardial infarction, and stroke. "Lipid hypothesis" which is also known as the cholesterol hypothesis proposes the linkage of plasma cholesterol level with the risk of developing CVD. Conventional management involves the use of statins to reduce the serum cholesterol levels as means for CVD prevention or treatment. The regulation of serum cholesterol levels can potentially be regulated with biological interventions like monoclonal antibodies. Phage display is a powerful tool for the development of therapeutic antibodies with successes over the recent decade. Although mainly for oncology, the application of monoclonal antibodies as immunotherapeutic agents could potentially be expanded to CVD. This review focuses on the concept of phage display for antibody development and discusses the potential target antigens that could potentially be beneficial for serum cholesterol management.

A novel polyaniline (PAni) coated optical fiber sensor with Mach-Zehnder interferometers (MZI) configuration was developed to overcome the pitfalls of conventional sensing methods such as atomic absorption spectrometry (AAS), and anodic stripping voltammetry (ASV) in Pb detection. PAni with different Ani to AOT mixture ratios (5 : 3, 5 : 5, and 5 : 7) and different types of acid dopants (HCl, H2SO4 and H3PO4) were synthesized using chemical oxidation reaction. The emeraldine-salt form of PAnis was confirmed by FTIR and UV–Vis spectra. All the produced PAnis showed electrical conductivity from 4.5 × 10–3 to 4.2 × 10–1 S/cm. Among all PAnis, PAni-HCl possessed the highest electrical conductivity (4.2 × 10–1 S/cm) due to the low pH of HCl which provided more mobile carbocation. For sensor application, PAni-H2SO4 coated optical fiber sensor showed the best performance with the highest sensitivity of 0.0927 nm/ppm, fast response time of 11 s and limit of detection (LOD) of 30 ppm. The performance of this PAni-coated optical sensor is better than conventional methods with longer response time of 3 min and LOD of 5 ppm in Pb detection. This is due to the two steps dissociations of H2SO4 which can protonate larger amount of amine and imine groups along the PAni backbone to yield more active sites, which leads to the improvement in Pb detections. It is postulated that the mechanism of Pb detection is based on a bonding interaction that occurs between the Pb2+ cation and the double bond of N from the imine groups of PAni. Supporting data from FTIR, UV–Vis and electrical conductivity studies have confirmed the chemical interaction between PAni and Pb.

Cobalt-based oxides and hydroxides have always been one of the optimal catalysts for Oxygen Evolution Reaction (OER) in alkaline environment in recent years. However, it remains a challenge for simple cobalt oxides such as CoO, Co3O4 and CoOOH to provide high catalytic activity both with ideal conductivity and stability. Herein, we prepared a new type of sulfur-incorporated cobalt oxide nanocages as high efficiency OER catalyst using Co-MOF as precursor. With the help of sodium sulfide, one step water-warm immersion-alcohol refluxing method can achieve the cavitation of precursors and uniform incorporation of sulfur atoms meanwhile. The hollow cubic structure constructed by fluffy nanosheets is beneficial to the exposure of active sites, the regulation of electronic structure and improve the electron transfer speed. After electrochemical testing, the prepared CoS@CoO showed outstanding OER activity compared with other cobalt-based catalysts. More importantly, this material has also withstood the electrochemical test of long range due to the stable structural foundation provided by Co-MOF. This work comes up with a new idea for OER activity promotion of hollow doped cobalt-based catalysts through morphology control and electronic structure optimization.

Background/purpose Effective regulation of the inflammatory process is essential for pulp repair and regeneration. Meloxicam has anti-inflammatory activity in systemic administration. The purpose of this study is to observe effects of topically applied meloxicam on inflamed pulp and to explore its potential value in the treatment of pulpitis. Materials and methods The coronal pulp tissues of rat molars were stimulated with 10 mg/mL lipopolysaccharide (LPS group) and then treated with 500 μmol/L meloxicam (meloxicam group). The untreated pulp tissues were used as the control group. After 3 h of incubation in vitro, the gene expression of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in each group was detected by real-time RT-PCR. The pulp tissues of each group were randomly subcutaneously implanted into nude mice, and 500 μmol/L meloxicam was injected into the subcutaneous pocket of the meloxicam group. Haematoxylin eosin staining, Masson staining and immunohistochemical staining were performed on samples after 3 days and 4 weeks retrieval, respectively. Results Compared with the LPS group, the mRNA expression levels of TNF-α and IL-6 of the meloxicam group were significantly reduced in vitro. The inflammatory response and cyclooxygenase-2 expression of the meloxicam group were decreased, and osteodentin-like tissue was generated in the pulp cross section of the meloxicam group in vivo. Conclusion The topical application of meloxicam inhibits the inflammatory response of inflamed pulp and further promotes the formation of osteodentin-like tissues but fails to induce the formation of the pulp–dentin complex. Topically applied meloxicam has the potential to regulate pulp inflammation.

SUMOylation of proteins regulates cell behaviors and is reversibly removed by small ubiquitin-like modifier (SUMO)-specific proteases (SENPs). The SENP family member SENP3 is involved in SUMO2/3 deconjugation and has been reported to sense cell stress and accumulate in several human cancer cells and macrophages. We previously reported that Senp3-knockout heterozygous mice showed smaller liver, but the pertinent mechanisms of SENP3 and SUMOylated substrates remain unclear. Thus, in this study, we investigated the interacting proteins with SENP3 and the alteration in hepatocytes treated with the xenobiotic diethylnitrosamine (DEN), which is specifically transformed in the liver and induces DNA double-strand breaks. Our data revealed that a certain amount of SENP3 was present in normal, untreated hepatocytes; however, DEN treatment promoted rapid SENP3 accumulation. SENP3 was mainly localized in the nuclei, and its level was significantly increased in the cytoplasm after 2 h of DEN treatment. The application of the recent proximity-dependent biotinylation (BioID) method led to the identification of 310 SENP3-interacting proteins that were involved in not only gene transcription but also RNA splicing, protein folding, and metabolism. Furthermore, after DEN exposure for a short duration, ribosomal proteins as well as proteins associated with mitochondrial ATP synthesis, membrane transport, and bile acid synthesis, rather than DNA repair proteins, were identified. This study provides insights into the diverse regulatory roles of SENP3, and the BioID method seems to be efficient for identifying physiologically relevant insoluble proteins.

In mammals, oocytes are arrested at G2/prophase for a long time, which is called germinal vesicle (GV) arrest. After puberty, fully-grown oocytes are stimulated by a gonadotropin surge to resume meiosis as indicated by GV breakdown (GVBD). CCNB1 is accumulated to a threshold level to trigger the activation of maturation promoting factor (MPF), inducing the G2/M transition. It is generally recognized that the anaphase-promoting complex/cyclosome (APC/C) and its cofactor CDH1 (also known as FZR1) regulates the accumulation/degradation of CCNB1. Here, by using small interfering RNA (siRNA) and messenger RNA (mRNA) microinjection, immunofluorescence and confocal microscopy, immunoprecipitation, time-lapse live imaging, and immunoblotting analysis, we showed that Septin 4 regulates the G2/M transition by regulating the accumulation of CCNB1 via APC/CCDC20 . Depletion of Septin 4 caused GV arrest by reducing CCNB1 accumulation. Unexpectedly, the expression level of CDC20 was higher in Septin 4 siRNA-injected oocytes than in control oocytes, but there was no significant change in the expression level of CDH1. Importantly, the reduced GVBD after Septin 4 depletion could be rescued not only by over-expressing CCNB1 but also could be partially rescued by depleting CDC20. Taken together, our results demonstrate that Septin 4 may play a critical role in meiotic G2/M transition by indirect regulation of CCNB1 stabilization in mouse oocytes.

Background Brassinosteroid (BR) signaling regulates plant growth and development in concert with other signaling pathways. Although many genes have been identified that play a role in BR signaling, the biological and functional consequences of disrupting those key BR genes still require detailed investigation. Results Here we performed phenotypic and transcriptomic comparisons of A. thaliana lines carrying a loss-of-function mutation in BRI1 gene, bri1–5, that exhibits a dwarf phenotype and its three activation-tag suppressor lines that were able to partially revert the bri1–5 mutant phenotype to a WS2 phenotype, namely bri1–5/bri1–1D, bri1–5/brs1–1D, and bri1–5/bak1–1D. From the three investigated bri1–5 suppressors, bri1–5/bak1–1D was the most effective suppressor at the transcriptional level. All three bri1–5 suppressors showed altered expression of the genes in the abscisic acid (ABA signaling) pathway, indicating that ABA likely contributes to the partial recovery of the wild-type phenotype in these bri1–5 suppressors. Network analysis revealed crosstalk between BR and other phytohormone signaling pathways, suggesting that interference with one hormone signaling pathway affects other hormone signaling pathways. In addition, differential expression analysis suggested the existence of a strong negative feedback from BR signaling on BR biosynthesis and also predicted that BRS1, rather than being directly involved in signaling, might be responsible for providing an optimal environment for the interaction between BRI1 and its ligand. Conclusions Our study provides insights into the molecular mechanisms and functions of key brassinosteroid (BR) signaling genes, especially BRS1.

Rationally designing high-activity catalyst for oxygen evolution reaction (OER) is of primary importance due to its sluggish kinetic process in water splitting. Herein, we report a metallic (V) and nonmetallic (F) double doping in Co3O4 with nanoneedles structure, which is synthesized through facile oil bath and annealing. Electrochemical measurements show that the Co3O4 dopped with fluorine and vanadium (F0.2-V-Co3O4-350) only needs a low overpotential of 320 mV to afford a current density of 10 mA cm−2, which is superior to commercial RuO2. The excellent electrocatalytic performance can be attributed to double doping of vanadium and fluorine which have strong electron absorption effect to optimize the density of electrons in Co3O4. Besides, nanoneedles structure can enlarge exposure of active sites. And its great durability is evaluated through 2000 cycles CV test. Furthermore, the optimal ratio of fluorine to vanadium and different annealing temperatures of the target catalyst are explored reasonably.

As a variety of free radical scavenger, edaravone has shown its potential in producing antioxidant, anti‐inflammatory and neuroprotective effects in various disease models. However, the underlying mechanism behind the neuroprotective effects of edaravone remained unclear. This study is aimed at determining the effects of edaravone on neuroprotection and anti‐inflammatory through a propofol‐induced neural injury rat model. Firstly, an observation was made of apoptosis and neuroinflammation in the hippocampus of developing under the influence of propofol. It was found out that propofol could produce inflammatory effects in the hippocampus by enhancing the astrogliosis (GFAP) activation and elevating the level of neuronal nitric oxide synthase (nNOS), pro‐inflammatory cytokines interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α). Meanwhile, the increase of apoptosis cells and the decrease of neurons (NeuN) were speculated to aggravate neural injury. Furthermore, it was demonstrated that edaravone intervention can reverse the neural apoptosis and inflammation. Additionally, the intraperitoneal injection of edaravone, the intraperitoneal injection of the brain‐derived neurotrophic factor (BDNF)‐mimicking small compound (7,8 dihydroxyflavone) and the intracranial injection of the exogenous BDNF were all respectively effective in alleviating the propofol‐induced neural apoptosis and inflammation in the hippocampus. It was also found out that edaravone‐activated downstream signalling through tyrosine kinase receptor B (TrkB) receptors in astrocyte, microglia and neuron. However, the neural injury of propofol had no impact on long‐term learning and memory, except causing a short‐term neurotoxicity. In conclusion, edaravone could alleviate the propofol‐induced neural injury in developing rats through BDNF/TrkB pathway.

Background NOD-like receptors affect multiple stages of cancer progression in many malignancies. NACHT, LRR, and PYD domain-containing protein 7 (NLRP7) is a member of the NOD-like receptor family, although its role in tumorigenesis remains unclear. By analyzing clinical samples, we found that NLRP7 protein levels were upregulated in colorectal cancer (CRC). We proposed the hypothesis that a high level of NLRP7 in CRC may promote tumor progression. Here, we further investigated the role of NLRP7 in CRC and the underlying mechanism. Methods NLRP7 expression in human CRC and adjacent non-tumorous tissues was examined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. The effect of NLRP7 in CRC progression was investigated in vitro and in vivo. Proteins interacting with NLRP7 were identified by immunoprecipitation and mass spectrometry analysis while immunofluorescence staining revealed the cellular location of the proteins. Cellular ubiquitination and protein stability assays were applied to demonstrate the ubiquitination effect on NLRP7. Cloning and mutagenesis were used to identify a lysine acceptor site that mediates NLRP7 ubiquitination. Cytokines/chemokines affected by NLRP7 were identified by RNA sequencing, qRT-PCR, and enzyme-linked immunosorbent assay. Macrophage phenotypes were determined using qRT-PCR, flow cytometry, and immunohistochemistry. Results NLRP7 protein levels, but not mRNA levels, were upregulated in CRC, and increased NLRP7 protein expression was associated with poor survival. NLRP7 promoted tumor cell proliferation and metastasis in vivo and in vitro and interacted with ubiquitin-specific protease 10, which catalyzed its deubiquitination in CRC cells. NLRP7 stability and protein levels in CRC cells were modulated by ubiquitination and deubiquitination, and NLRP7 was involved in the ubiquitin-specific protease 10 promotion of tumor progression and metastasis in CRC. K379 was an important lysine acceptor site that mediates NLRP7 ubiquitination in CRC cells. In CRC, NLRP7 promoted the polarization of pro-tumor M2-like macrophages by inducing the secretion of C-C motif chemokine ligand 2. Furthermore, NLRP7 promoted NF-κB nuclear translocation and activation of C-C motif chemokine ligand 2 transcription. Conclusions We showed that NLRP7 promotes CRC progression and revealed an as-yet-unidentified mechanism by which NLRP7 induces the polarization of pro-tumor M2-like macrophages. These results suggest that NLRP7 could serve as a biomarker and novel therapeutic target for the treatment of CRC.

Mammalian sperm is highly susceptible to reactive oxygen species (ROS) during the cryopreservation process. Astaxanthin (AST), a red pigment of the carotenoid family, is recognized as having a variety of beneficial biological activities and effects, including antioxidant, anticancer, anti-diabetic, and anti-inflammatory. The present study aimed to investigate whether the presence of AST protected boar sperm from ROS stress during cryopreservation. Boar sperm was diluted with a freezing medium supplemented with different concentrations of AST (0, 0.5, 1, 2, or 5 μM). The addition of AST, especially at a concentration of 2 μM, exerted positive effects on post-thaw sperm motility parameters. Meanwhile, sperm plasma membrane integrity and acrosome integrity of post-thaw sperm were significantly increased, while lipid peroxidation was inhibited in response to 2 μM AST treatment. Interestingly, compared to the control, supplementation with 2 μM AST increased unsaturated fatty acids (UFAs) levels and decreased saturated fatty acids (SFAs) content in post-thaw sperm, leading to a decreased ratio of SFAs/UFAs in the AST group. In conclusion, the addition of AST to freezing extenders inhibited lipid peroxidation and regulated fatty acid composition of the sperm membrane, improved post-thaw sperm quality, and had no adverse effect on boar sperm in vitro fertilization (IVF) capacity and potential for embryonic development. Our data provide a novel insight into understanding the mechanisms of AST concerning protecting boar sperm quality against ROS damage during cryopreservation.

Excessive glutamate leading to excitotoxicity worsens brain damage after SAH and contributes to long-term neurological deficits. The drug ifenprodil is a non-competitive antagonist of GluN1-GluN2B N-methyl-d-aspartate (NMDA) receptor, which mediates excitotoxic damage in vitro and in vivo. Here, we show that cerebrospinal fluid (CSF) glutamate level within 48 h was significantly elevated in aSAH patients who later developed poor outcome. In rat SAH model, ifenprodil can improve long-term sensorimotor and spatial learning deficits. Ifenprodil attenuates experimental SAH-induced neuronal death of basal cortex and hippocampal CA1 area, cellular and mitochondrial Ca2+ overload of basal cortex, blood-brain barrier (BBB) damage, and cerebral edema of early brain injury. Using in vitro models, ifenprodil declines the high-concentration glutamate-mediated intracellular Ca2+ increase and cell apoptosis in primary cortical neurons, reduces the high-concentration glutamate-elevated endothelial permeability in human brain microvascular endothelial cell (HBMEC). Altogether, our results suggest ifenprodil improves long-term neurologic deficits through antagonizing glutamate-induced excitotoxicity.

Key points The aim was to determine whether detachment of the tectorial membrane (TM) from the organ of Corti in Tecta/Tectb-/- mice affects the biophysical properties of cochlear outer hair cells (OHCs). Tecta/Tectb-/- mice have highly elevated hearing thresholds, but OHCs mature normally. Mechanoelectrical transducer (MET) channel resting open probability (Po ) in mature OHC is ∼50% in endolymphatic [Ca2+ ], resulting in a large standing depolarizing MET current that would allow OHCs to act optimally as electromotile cochlear amplifiers. MET channel resting Po in vivo is also high in Tecta/Tectb-/- mice, indicating that the TM is unlikely to statically bias the hair bundles of OHCs. Distortion product otoacoustic emissions (DPOAEs), a readout of active, MET-dependent, non-linear cochlear amplification in OHCs, fail to exhibit long-lasting adaptation to repetitive stimulation in Tecta/Tectb-/- mice. We conclude that during prolonged, sound-induced stimulation of the cochlea the TM may determine the extracellular Ca2+ concentration near the OHC's MET channels. Abstract The tectorial membrane (TM) is an acellular structure of the cochlea that is attached to the stereociliary bundles of the outer hair cells (OHCs), electromotile cells that amplify motion of the cochlear partition and sharpen its frequency selectivity. Although the TM is essential for hearing, its role is still not fully understood. In Tecta/Tectb-/- double knockout mice, in which the TM is not coupled to the OHC stereocilia, hearing sensitivity is considerably reduced compared with that of wild-type animals. In vivo, the OHC receptor potentials, assessed using cochlear microphonics, are symmetrical in both wild-type and Tecta/Tectb-/- mice, indicating that the TM does not bias the hair bundle resting position. The functional maturation of hair cells is also unaffected in Tecta/Tectb-/- mice, and the resting open probability of the mechanoelectrical transducer (MET) channel reaches values of ∼50% when the hair bundles of mature OHCs are bathed in an endolymphatic-like Ca2+ concentration (40 μM) in vitro. The resultant large MET current depolarizes OHCs to near -40 mV, a value that would allow optimal activation of the motor protein prestin and normal cochlear amplification. Although the set point of the OHC receptor potential transfer function in vivo may therefore be determined primarily by endolymphatic Ca2+ concentration, repetitive acoustic stimulation fails to produce adaptation of MET-dependent otoacoustic emissions in vivo in the Tecta/Tectb-/- mice. Therefore, the TM is likely to contribute to the regulation of Ca2+ levels around the stereocilia, and thus adaptation of the OHC MET channel during prolonged sound stimulation.

Designing the specific crystal phase with better intrinsic activity and more active sites is a very promising strategy for earth-abundant electrocatalysts for oxygen evolution reaction (OER). Herein, a facile two-step method including the high-pressure microwave and the hydrothermal sulfurization is adopted to prepare the WSx/Ni9S8 hetero-catalyst on nickel foam (WSx/Ni9S8/NF). Firstly, WO3 polyhedrons homogeneously cover the surface of NF through the high-pressure microwave hydrothermal process. Secondly, WSx/Ni9S8 nanoparticles on the surface of NF can be synthesized after a hydrothermal sulfurization, which has been confirmed by scanning electron microscopy (SEM) elemental mapping and high-resolution transmission electron microscopy (HRTEM). The amorphous WSx and Ni9S8 phase may provide the dual active sites for OER. The electrochemical measurements show that WSx/Ni9S8/NF has superior OER activity with a low overpotential of 320 mV at the current density of 100 mA·cm−2, better than those of other samples. The enhanced OER performance may be due to the synergistic catalysis from Ni9S8 phase and high valence of W. Owing to the stable structure of Ni9S8, the long-term stability of WSx/Ni9S8/NF for at least 10 h can be obtained. This work may provide a new approach for the doped nickel sulfides crystal phase through high-pressure microwave hydrothermal assistance for OER.

Inflammation response is a regulated cellular process and excessive inflammation has been recognized in numerous diseases, such as cardiovascular disease, neurodegenerative disease, inflammatory bowel disease, and cancer. Tribulus terrestris L. (TT), also known as Bai Jili in Chinese, has been applied in traditional Chinese medicine for thousands of years while its anti-inflammatory activity and underlying mechanism are not fully elucidated. Here, we hypothesize Tribulus terrestris L. extract (BJL) which presents anti-inflammatory effect, and the action mechanism was also investigated. We employed the transgenic zebrafish line Tg(MPO:GFP), which expresses green fluorescence protein (GFP) in neutrophils, and mice macrophage RAW 264.7 cells as the in vivo and in vitro model to evaluate the anti-inflammatory effect of BJL, respectively. The production of nitric oxide (NO) was measured by Griess reagent. The mRNA expression levels of inflammatory cytokines and inducible nitric oxide synthase (iNOS) were measured by real-time PCR, and the intracellular total or phosphorylated protein levels of NF-κB, Akt, and MAPKs including MEK, ERK, p38, and JNK were detected by western blot. We found that BJL significantly inhibited fin transection or lipopolysaccharide- (LPS-) induced neutrophil migration and aggregation in zebrafish in vivo. In mice macrophage RAW 264.7 cells, BJL ameliorated LPS-triggered excessive release of NO and transcription of inflammatory cytokine genes including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β). BJL also reduced the LPS-induced elevations of intracellular iNOS and nuclear factor kappa B (NF-κB) which mediate the cellular NO and inflammatory cytokine productions, respectively. Moreover, LPS dramatically increased the phosphorylation of Akt and MAPKs including MEK, ERK, p38, and JNK in RAW 264.7 cells, while cotreatment BJL with LPS suppressed their phosphorylation. Taken together, our data suggested that BJL presented potent anti-inflammatory effect and the underlying mechanism was closely related to the inhibition of Akt/MAPKs and NF-κB/iNOS-NO signaling pathways.

It is still a challenge to develop the high-efficiency noble metal-based electrocatalyst with good dispersion and durability for hydrogen evolution reaction (HER) in wide pH range. Herein, we have successfully synthesized a nitrogen-doped carbon (NC) coated ultrafine ruthenium phosphides (RuP2) nanoparticles catalyst with a facile method. With the help of ethylene diamine tetraacetic acid (EDTA), the uniform RuP2 nanoparticles with ultrafine size of about 3 nm are well dispersed on the surface of the NC. The directed coordination between EDTA and Ru ion may be responsible for the excellent structure. Benefiting from the superior electrical conductivity of NC carrier and the reduced resistance of electrons to the active site, the prepared ultrafine RuP2@NC demonstrates the obviously enhanced electrocatalytic activity for HER, which results in higher current density and lower overpotentials (99, 98 and 196 mV to reach 10 mA cm−2 in 0.5 M H2SO4, 1 M KOH and 1 M PBS, respectively). The stability is also very good due to the close integration between ultrafine RuP2 and NC. This work provides a new view to rationally design and synthesize the highly effective, stable and great dispersion of phosphide-based electrocatalysts for HER.

In this study, three polymer precursor conformations, dilute, semi-dilute, and concentrated, were used to fabricate carbon molecular sieving (CMS) membranes via a fixed carbonization protocol. The effects of the precursor conformation on the microstructure of the resultant CMS membranes were characterized by Raman analysis. Their ability to separate light gases, such as H2/CH4 and H2/N2, was assessed with a single-gas system. Additionally, a novel method was proposed to detect the cutoff size of the CMS membranes created in this study. The method combined high-resolution transmission electron microscopy (HR-TEM) and a focused ion beam (FIB) system. Finally, due to the semi-dilute solution's denser polymer chains and lack of severe polymer entanglement, highly graphited CMS membranes with excellent gas separation performance were successfully synthesized using a semi-dilute polyetherimide dope solution. Interlayer distances in the carbon matrix were visualized and measured using our novel probing tool (HR-TEM and FIB) and software. The CMS membrane fabricated with a semi-dilute dope exhibited the best gas separation performance of the tested membranes. It had the most ordered carbon sheet orientation and exhibited a superior selectivity of H2/CH4 = 293 with a hydrogen permeability of 1138.7 Barrer, far surpassing the reported permselectivity of other membranes. We believe that the high H2/CH4 selectivity presented here is unprecedented for CMS membranes reported in the literature.

Arsenic (As)-contaminated paddy soil could result in elevated levels of As in rice plants and sequentially harm human health. The Fe3O4-modified biochar (NBC-Fe) prepared by the coprecipitation method was applied in a pot experiment to investigate its effect on mobility and bioavailability of As in soil and to reduce As accumulation in rice tissues (brown rice, husks, spikelets, leaves, stems, and roots). Compared with non-application (CK), application of NBC-Fe significantly increased the cation exchange capacity (CEC), decreased As availability, and raised the As concentration of crystalline hydrous oxide–bound fraction in the soil. The addition of 0.05–1.6% (w/w) NBC-Fe significantly reduced the As concentrations in brown rice by 9.4–47.3%, which was lower than the level set by the National Food Safety Standards of China (0.2 mg/kg). The NBC-Fe treatment decreased As concentrations in iron plaque (DCB-As), and the DCB-As had the very significant correlations (P

Co-regulation of the crystal plane and composition is a powerful strategy to effectively enhance the catalytic properties of nanomaterials. Herein, high-quality PtxRu nanocubes (PtxRu-NCs) with an adjustable composition and exposed (100) planes are synthesized by a simple hydrothermal method. For the ammonia electrooxidation reaction (AOR), Pt6Ru-NCs show obviously higher mass activity (192 mA mgPt−1) and specific activity (1.02 mA cm−2) than other PtxRu-NCs, Pt-NCs and commercial Pt nanocrystals. Density functional theory calculations demonstrate that the Pt6Ru (100) plane is more energetically favourable for the AOR than the Pt (100) plane due to the stronger binding of *NH2 and *NH. For the hydrogen evolution reaction (HER), the optimized Pt6Ru-NCs also deliver the smallest overpotential (37.6 mV) at 10 mA cm−2. The high activity of bifunctional Pt6Ru-NCs for both AOR and HER can be attributed to the crystal surface effect and Pt-Ru bimetallic interactions. A symmetric ammonia electrolyzer constructed here with Pt6Ru-NCs as the cathode and anode only requires 0.72 V electrolysis voltage for electrochemical hydrogen production.

Three new NiII/CoII-metal organic frameworks were self-assembled by the reaction of C3 symmetric 1,3,5-tribenzoic acid (H3BTC) and 2,4,6-tris(4-pyridyl)-1,3,5-triazine (4-TPT) ligands and NiII/CoII salts under solvothermal conditions. Isomorphous MOF1 and MOF2 exhibit a 3D pillar-layer framework based on binuclear M2(OH)(COO)2 units connected by tritopic BTC3- and 4-TPT ligands with a novel (3,5)-connected topology net. MOF3 displays a 3-fold interpenetrated 3D network exhibiting a (3,4)-connected topology net. The porous MOF3 can reversibly take up I2. The activated MOFs contain both Lewis acid (NiII center) and basic (uncoordinated pyridyl or carboxylic groups) sites, and act as bifunctional acid-base catalysts. The catalytic measurements demonstrate that the activated MOF3 exhibits good activities for benzyl alcohol oxidation and the Knoevenagel reaction and can be recycled and reused for at least four cycles without losing its structural integrity and high catalytic activity. Thus, the catalytic properties for the oxidation-Knoevenagel cascade reaction have also been studied.

Pyronin-9-thione (PY-S) is a key synthetic intermediate to develop various fluorescent probes for biological labeling and imaging. We developed a facile synthesis of PY-S from pyronin with a high yield up to 90%. The investigation of the reaction mechanism disclosed that the trisulfur radical anion (S3˙−) played a key role in the formation of the CS bond. The new established methodology was proved to have a short reaction time, operation easiness, and low toxicity and is suitable for the gram-scale synthesis of PY-S.

The title reaction has been established under the cooperative bimetallic catalysis of iridium and copper catalysts, which afforded indole C3-allylation products with branched selectivity in moderate yields (up to 78%) and good enantioselectivities (up to 97 : 3 er). This reaction not only represents the first catalytic asymmetric ring-opening reaction of vinylcyclopropanes with C3-unsubstituted indoles, but also has provided an atom-economic and straightforward method for the synthesis of C3-allylic indoles with high regio- and enantioselectivity.

Objective: This study aimed to elucidate the pharmacological effects of sesamin (Ses) and its mechanism of action towards PM2.5-induced cardiovascular injuries. Method: Forty Sprague Dawley (SD) rats were randomly divided into five groups: a saline control group; a PM2.5 exposure group; and low-, middle-, and high-dose Ses pretreatment groups. The SD rats were pretreated with different concentrations of Ses for 21 days. Afterward, the rats were exposed to ambient PM2.5 by intratracheal instillation every other day for a total of three times. The levels of inflammatory markers, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-6 (IL-6), and indicators related to oxidative responses, such as total superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA), were measured in the blood and heart. The expression of ferroptosis-related proteins in heart tissues was determined via western blot and immunohistochemistry. Results: Ses pretreatment substantially ameliorated cardiovascular injuries in rats as evidenced by the decrease in the pathological score and collagen area. The decreased levels of SOD, GSH, and GSH-Px in the heart and serum were inhibited by Ses. In addition, Ses not only notably increased the activity of antioxidant enzymes but also reduced the levels of MDA, CK, LDH, CK-MB, IL-6, TNF-α, IL-1β, and IL-6. Furthermore, Ses pretreatment upregulated the expression levels of GPX4, SLC7A11, TFRC, and FPN1 and inhibited the expression levels of FTH1 and FTL. Conclusion: Ses pretreatment could ameliorate PM2.5-induced cardiovascular injuries perhaps by inhibiting ferroptosis. Therefore, Ses pretreatment may be a novel strategy for the prevention and treatment of PM2.5-induced cardiovascular injury.

This study reports Ca-Fe isotope compositions of mineral separates in a set of peridotite xenoliths including ten lherzolites, one harzburgite, and one wehrlite from Hainan Island, south China. Iron isotope compositions show a small variation ( 2‰) in previous studies should be dominated by disequilibrium sub-solidus Ca redistribution between cpx and opx, which is driven by the changes of mantle temperature and chemical composition in pyroxene. The wehrlite, which was formed by reaction of peridotite with an evolved, silica-undersaturated melt, has δ44/40Ca of 3.22‰ and δ56/54Fe of 0.22‰, significantly heavier than the value of fertile mantle. Such heavy isotope signatures in the wehrlite are best explained by diffusion during the metasomatic melt percolating the refractory mantle. In summary, this study reveals that significant kinetic Ca isotope fractionations could occur in the mantle by inter-mineral Ca diffusion during re-equilibration upon cooling and Ca diffusion from melt into peridotite during melt percolation.