Search

The redox-based protein S -nitrosylation is a conserved mechanism modulating nitric oxide (NO) signaling and has been considered mainly as a non-enzymatic reaction. S -nitrosylation is regulated by the intracellular NO level that is tightly controlled by S -nitrosoglutathione reductase (GSNOR). However, the molecular mechanisms regulating S -nitrosylation selectivity remain elusive. Here, we characterize an Arabidopsis " repressor of " gsnor1 (rog1) mutation that specifically suppresses the gsnor1 mutant phenotype. ROG1, identical to the non-canonical catalase, CAT3, is a transnitrosylase that specifically modifies GSNOR1 at Cys-10. The transnitrosylase activity of ROG1 is regulated by a unique and highly conserved Cys-343 residue. A ROG1C343T mutant displays increased catalase but decreased transnitrosylase activities. Consistent with these results, the rog1 mutation compromises responses to NO under both normal and stress conditions. We propose that ROG1 functions as a transnitrosylase to regulate the NO-based redox signaling in plants. • ROG1 or CAT3 acts as a transnitrosylase to regulate NO signaling in plants • Cysteine-343 is vital for ROG1 activity • ROG1 transnitrosylates GSNOR1 to regulate its stability • rog1 mutants have reduced sensitivity to NO under normal and stress conditions Chen et al. identify and characterize the non-canonical catalase ROG1/CAT3 as a transnitrosylase in Arabidopsis. ROG1 contains a highly conserved cysteine-343, which is crucial for its activity, and ROG1 transnitrosylates GSNOR1 to regulate its stability. ROG1 regulates NO signaling under both normal and stress conditions. [ABSTRACT FROM AUTHOR]

The n -dimensional torus T ( k 1 , k 2 , … , k n ) (including the k -ary n -cube Q n k ) is one of the most popular interconnection networks. A paired k -disjoint path cover (paired k -DPC for short) of a graph is a set of k disjoint paths joining k distinct source-sink pairs that cover all vertices of the graph. In this paper, we consider the paired 2-DPC problem of n -dimensional torus. Assuming k i ≥ 3 for i = 1 , 2 , … , n , with at most one k i being even, then T ( k 1 , k 2 , … , k n ) with at most 2 n − 3 faulty edges always has a paired 2-DPC. And the upper bound 2 n − 3 of edge faults tolerated is optimal. The result is a supplement of the results of Chen [3] and [4] . [ABSTRACT FROM AUTHOR]

As a special energy rock containing methane, coal mining often entails the fatal risk of gas outbursts due to the differential enrichment of methane. However, the current key preventative techniques such as mining a protective layer and pre-drainage of gas are not applicable to conventional soft coal seams. Based on a field study of the Xinyuan Coal Mine in the Qinshui Basin, a new technique for controlling gas outbursts through surface hydraulic fracturing of underground coal rock is proposed. The specific implementation includes drilling, perforation, fluid injection, pumping unit installation, and coal mining operation. The key parameters are the displacement (12 m3/min), fluid volume (2000 m3), and anionic surfactant fracturing fluid. Comparative analysis shows that such a high displacement can increase the net pressure, form a fracture network, and adjust the formation pressure. The massive amount of fracturing fluid expands the effective depth. The anionic surfactant sodium dodecyl benzene sulfonate (SDBS) contributes to the migration of the fracturing fluid and the inhibition of gas desorption. The field results reveal that the hydraulic fracture propagation distance reached 330 m. After fracturing, the maximum water content was 3.35 greater than the original content. The gas concentration, pure gas quantity, and average gas drainage volume of the boreholes reached 1.58, 1.96, and 2.98 times those of the unfractured roadway, respectively. Furthermore, although the measured gas content was 5.97–12.69 m3/t, no dynamic coal and gas phenomenon was detected. This technique is characterized by the fact that the fracturing fluid can drive away the free methane, inhibit the adsorbed methane, and slow down the gas emission rate, which eliminates the occurrence of gas outbursts from the soft coal seam. [ABSTRACT FROM AUTHOR]

Summary Nitric oxide (NO) regulates diverse cellular signaling through S -nitrosylation of specific Cys residues of target proteins. The intracellular level of S -nitrosoglutathione (GSNO), a major bioactive NO species, is regulated by GSNO reductase (GSNOR), a highly conserved master regulator of NO signaling. However, little is known about how the activity of GSNOR is regulated. Here, we show that S -nitrosylation induces selective autophagy of Arabidopsis GSNOR1 during hypoxia responses. S -nitrosylation of GSNOR1 at Cys-10 induces conformational changes, exposing its AUTOPHAGY-RELATED8 (ATG8)-interacting motif (AIM) accessible by autophagy machinery. Upon binding by ATG8, GSNOR1 is recruited into the autophagosome and degraded in an AIM-dependent manner. Physiologically, the S -nitrosylation-induced selective autophagy of GSNOR1 is relevant to hypoxia responses. Our discovery reveals a unique mechanism by which S -nitrosylation mediates selective autophagy of GSNOR1, thereby establishing a molecular link between NO signaling and autophagy. [ABSTRACT FROM AUTHOR]

The toxic effects of neonicotinoid pesticides on honeybees is a global concern, whereas little is known about the effect of stereoisomeric pesticides among honeybee social behavior. In this study, we investigated the effects of stereoisomeric dinotefuran on honeybee social behavior. We found that honeybees exhibit a preference for consuming food containing S-dinotefuran, actively engage in trophallaxis with S-dinotefuran–consuming peers, and consequently acquire higher levels of S-dinotefuran compared with R-dinotefuran. In comparison to R-dinotefuran, S-dinotefuran stimulates honeybees to elevate their body temperature, thereby attracting more peers for trophallaxis. Transcriptome analysis revealed a significant enrichment of thermogenesis pathways due to S-dinotefuran exposure. Additionally, metabolome data indicated that S-dinotefuran may enhance body temperature by promoting lipid synthesis in the lysine degradation pathway. Consequently, body temperature emerges as a key factor influencing honeybee social behavior. Our study is the first to highlight the propensity of S-dinotefuran to raise honeybee body temperature, which prompts honeybee to preferentially engage in trophallaxis with peers exhibiting higher body temperatures. This preference may lead honeybees to collect more dinotefuran-contaminated food in the wild, significantly accelerating dinotefuran transmission within a population. Proactive trophallaxis further amplifies the risk of neonicotinoid pesticide transmission within a population, making honeybees that have consumed S-dinotefuran particularly favored within their colonies. These findings may contribute to our understanding of the higher risk associated with neonicotinoid use compared with other pesticides. [Display omitted] • Honeybees favor S-dinotefuran–infused food. • Honeybees prefer trophallaxis with peers that have fed on S-dinotefuran. • Proactive trophallaxis speeds dinotefuran diffusion. • S-dinotefuran stimulates higher honeybee body temperature compared with R-dinotefuran. [ABSTRACT FROM AUTHOR]

How reciprocal regulation of carbon and nitrogen metabolism works is a long-standing question. In plants, glucose and nitrate are proposed to act as signaling molecules, regulating carbon and nitrogen metabolism via largely unknown mechanisms. Here, we show that the MYB-related transcription factor ARE4 coordinates glucose signaling and nitrogen utilization in rice. ARE4 is retained in the cytosol in complexing with the glucose sensor OsHXK7. Upon sensing a glucose signal, ARE4 is released, is translocated into the nucleus, and activates the expression of a subset of high-affinity nitrate transporter genes, thereby boosting nitrate uptake and accumulation. This regulatory scheme displays a diurnal pattern in response to circadian changes of soluble sugars. The are4 mutations compromise in nitrate utilization and plant growth, whereas overexpression of ARE4 increases grain size. We propose that the OsHXK7-ARE4 complex links glucose to the transcriptional regulation of nitrogen utilization, thereby coordinating carbon and nitrogen metabolism. [Display omitted] • Rice glucose sensor OsHXK7 and transcription factor ARE4 form a complex in cytosol • Glucose induces ARE4 release from the complex and subsequent nuclear translocation • ARE4 transactivates expression of nitrate transporter genes OsNRT2s • ARE4 positively regulates nitrogen utilization Coordination of carbon-nitrogen metabolism is vital for crop productivity. Ma, Nian, Yu, et al. show that rice transcription factor ARE4 and glucose sensor OsHXK7 form a complex that is retained in cytosol. Glucose induces dissociation of the complex and nuclear localization of ARE4, thereby activating expression of nitrate transporter genes to promote nitrogen utilization. [ABSTRACT FROM AUTHOR]

Post-stroke depression (PSD) occurs about 40% among all stroke survivors, but the effective pharmacotherapy is inadequately understood. The present study investigated the effects of a natural polyphenol trans -resveratrol (RES) on behavioral changes after middle cerebral artery occlusion (MCAO) and examined what its molecular targets may be. RES was shown to decrease the infarct size and neurological scores after MCAO, suggesting the amelioration of brain damage and motor activity. RES also reversed the depressive-like behaviors 13 days after MCAO, both in the forced swimming and sucrose consumption tests. Moreover, MCAO-induced series abnormalities related to depressive-like behaviors, such as an abnormal adrenal gland weight to body weight ratio, an increased expression of the corticotropin-releasing factor (CRF) in the frontal cortex, hippocampus and hypothalamus, the differential expression of glucocorticoid receptor (GR) in these three brain regions, and a decreased brain-derived neurotrophic factor (BDNF) level, were ameliorated after treatment with increasing doses of RES at 10, 20 and 40 mg/kg via gavage. These findings provide compelling evidence that RES protects the brain against focal cerebral ischemia-induced injury, but most of all is its antidepressant-like effect on PSD, which might at least in part be mediated by regulation of hypothalamus–pituitary–adrenal axis function. [ABSTRACT FROM AUTHOR]

Dinotefuran is known to negatively affect honeybee (Apis mellifera) behavior, but the underlying mechanism remains unclear. The magnetoreceptor (MagR, which responds to magnetic fields) and cryptochrome (Cry2, which is sensitive to light) genes are considered to play important roles in honey bees' homing and localization behaviors. Our study found that dinotefuran, even without direct contact, can act like a magnet, significantly altering MagR expression in honeybees. This non-contact exposure reduced the bees' homing rate. In further experiments, we exposed foragers to light and magnetic fields, the MagR gene responded to magnetic fields only in the presence of light, with Cry2 playing a key switching role in the magnetic field receptor mechanism (MagR-Cry2). Yeast two-hybrid and BiFc assays confirmed an interaction of these two genes. Moreover, the bees' homing rate was significantly reduced when the expression of these genes was decreased using RNAi. These findings suggest that changes in MagR and Cry2 expression are critical to the reduction in homing ability caused by non-contact dinotefuran exposure. This study reveals the potential navigation mechanisms of honey bees during homing and foraging and shows that the impact of dinotefuran on honey bee populations is more extensive than previously understood., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Reactive oxygen species (ROS) and nitric oxide (NO) are two critical classes of signaling molecules that regulate plant development and stress responses. The intracellular level of S-nitrosoglutathione (GSNO), a major bioactive NO species, is regulated by the highly conserved GSNO reductase (GSNOR). However, the molecular mechanisms underlying ROS-mediated regulation of GSNOR remain largely unclear. Here, we show that H 2 O 2 negatively regulates the activity of GSNOR1 during ovule development in Arabidopsis. S-sulfenylation of GSNOR1 at Cys-284 inhibits its enzymatic activity. A GSNOR1 C284S mutation causes a reduction of the total SNO level in pistils, thereby disrupting NO homeostasis and eventually leading to defective ovule development. These findings illustrate a unique mechanism by which ROS regulates ovule development through S-sulfenylation-mediated inhibition of the GSNOR activity, thereby establishing a molecular link between ROS and NO signaling pathways in reproductive development., Competing Interests: Conflict of interest All authors declare no conflict of interests., (Copyright © 2025 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.)

Boron neutron capture therapy (BNCT) is based on nuclear reactions between thermal neutron and boron-10 preferentially distributed in the cancer cells. 10 B-boronophenylalanine (BPA) is the approved drug for treatment of oral cancers for BNCT. However, the predictive biomarkers to evaluate therapeutic efficacy and side-effects have not been clarified yet. Here we performed comprehensive analysis of mRNA expression using human oral squamous carcinoma SAS cells after BPA-BNCT. The expression of particular mRNAs including inflammatory and immune-related responses and transcription factors, namely CSF2, ATF3, MAFB, PTGS2 and TNFAIP3 was increased 24 h after neutron irradiation of therapeutic dose of BPA-BNCT. NF-κB pathway genes were also activated after BNCT. The early increase of the gene product of CSF2 gene, granulocyte-macrophage colony stimulating factor (GM-CSF), in culture supernatant of SAS cells was observed by ELISA analysis after BPA-BNCT at a setting dose of 24 Gy-eq. The GM-CSF level was also increased after equivalent dose of gamma-ray and carbon beam irradiation. GM-CSF may be involved in local and systemic early responses of BNCT for particular types of cancer., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MItsuko Masutani reports financial support was provided by Cancer Intelligence Care Systems, Inc. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Transforming growth factor-beta (TGF-β), an immunosuppressive cytokine, is often elevated in various tumors and inhibits the immune system's ability to combat tumor cells. Despite promising results from TGF-β inhibitor therapies, their clinical efficacy remains limited., Purpose: This study aimed to enhance the antitumor capabilities of natural killer (NK) cells in the presence of TGF-β by exploring the potential of asiaticoside, a natural compound with established clinical safety., Study Design: The effects of asiaticoside on NK cells were investigated to determine its potential to counteract TGF-β-induced immunosuppression and elucidate the underlying mechanisms., Methods: Natural compounds were screened using a Luminex assay to identify those promoting Interferon-γ (IFN-γ) secretion from NK cells. Asiaticoside-pretreated NK cells' cytotoxicity was assessed against K562, OVCAR8, and A2780 cells using organoids from ascites-derived ovarian cancer (OC) cells. In vivo efficacy was evaluated with B16 melanoma lung metastasis and subcutaneous tumor models in C57BL/6 mice, using asiaticoside as a 50 mg/kg injection. The compound's ability to enhance NK cell-driven anti-neoplastic responses was further assessed in an OC murine model. Effects on TGF-β/SMAD pathways and mitochondrial functions were examined through various microscopy and metabolomic techniques. The involvement of the mTOR/DRP1 axis in asiaticoside-mediated restoration of mitochondrial oxidation in NK cells after TGF-β suppression was determined using the mTOR inhibitor rapamycin and the DRP1 inhibitor Mdivi-1., Results: Asiaticoside-treated NK cells retained their ability to suppress tumor growth and metastasis despite TGF-β presence. Asiaticoside downregulated TGF-β receptors 1 (TGFBR1) expression, impaired the protein stability of TGFBR1 and TGF-β receptors 2 (TGFBR2), and reduced SMAD2 phosphorylation, preventing SMAD2 translocation from the mitochondria. This preserved mitochondrial respiration and maintained NK cell antitumor activity., Conclusion: The study concludes that asiaticoside has significant potential as a strategy for "priming" NK cells in cellular immunotherapy. By demonstrating that asiaticoside degrades the TGF-β receptor, leading to reduced phosphorylation of SMAD2 and preventing its mitochondrial translocation, thereby maintaining mitochondrial integrity. Meantime, asiaticoside counteracts TGF-β-induced suppression of mitochondrial oxidative and aerobic respiration through the mTOR/DRP1 pathways. The research uncovers a previously unreported pathway for preserving mitochondrial respiration and NK cell functionality. A detailed mechanistic insight into how asiaticoside functions at the molecular level was explored. Its ability to counteract the immunosuppressive effects of TGF-β makes it a valuable candidate for enhancing the effectiveness of immunotherapies in treating a variety of tumors with elevated TGF-β levels., Competing Interests: Declaration of competing interest We are submitting our manuscript titled " Asiaticoside modulates human NK cell functional fate by mediating metabolic flexibility in the tumor microenvironment" for publication consideration in the esteemed "Phytomedicine". The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Ocean alkalinity enhancement is considered as an effective atmospheric CO 2 removal approach, but currently, little is known about the carbon sequestration potential of implementing olivine addition in offshore waters. We investigated the effect of olivine addition on the seawater carbonate system by carrying out a deck incubation experiment in the Northern Yellow Sea; the dissolution rate of olivine was calculated based on the increase in seawater alkalinity (TA), and the CO 2 sequestration potential was evaluated. The results showed that the dissolution of olivine increased seawater TA and decreased partial pressure of CO 2 , resulting in oceanic CO 2 uptake from the atmosphere through sea-air exchange; it also increased seawater pH and mitigated ocean acidification to a certain extent. The addition of 1 ‰ olivine had a more significant effect on the seawater carbonate system than 0.5 ‰ olivine addition. The average dissolution rate constant of olivine was 1.44 ± 0.15 μmol m -2  d -1 . Assuming that olivine settles completely on the seabed due to gravity, the theoretically maximum amount of CO 2 removed by applying 1 tonne of olivine per square meter area in the Northern Yellow Sea is only 2.0 × 10 -4  t/m 2 . Therefore, when olivine addition is implemented in the offshore waters, it is necessary to consider reducing the olivine size, prolonging the settling time of olivine in the water column; and spreading olivine in well-mixed waters to prolong the residence time through repeated resuspension, thus increasing its potential in carbon sequestration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

During the development of deep coalbed methane (CBM), the production of coal fines is common and suppresses the yield of CBM. This work takes the deep CBM wells in the Qinshui Basin as a case study, and the output, composition, morphology, and sources of coal fines were investigated through scanning electron microscopy, X-ray diffraction, proximate analysis, and particle size measurement including image analysis, laser diffraction, and dynamic light scattering. The results indicate that, in comparison with shallow CBM wells, deep wells produce a greater quantity of coal fines which are darker in color and have smaller particle sizes, with the majority being less than 10 μm. The coal fines exist predominantly as aggregates that contained the iron-bearing and clay minerals. Based on the Liddinger particle settling model, the water production volume required for the coal fines to return to the surface in the Wuxiang block was calculated to be 8.55 m 3 /d. This work can provide a scientific basis for the prevention and control of coal fines in deep CBM wells., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Most cases of hepatocellular carcinoma (HCC) are able to be diagnosed through regular surveillance in an identifiable patient population with chronic hepatitis B or cirrhosis. Nevertheless, 50% of global cases might present incidentally owing to symptomatic advanced-stage HCC after worsening of liver dysfunction. A systematic search based on PUBMED was performed to identify relevant outcomes, covering newer surveillance modalities including secretory proteins, DNA methylation, miRNAs, and genome sequencing analysis which proposed molecular expression signatures as ideal tools in the early-stage HCC detection. In the face of low accuracy without harmonization on the analytical approaches and data interpretation for liquid biopsy, a more accurate incidence of HCC will be unveiled by using deep machine learning system and multiplex immunohistochemistry analysis. A combination of molecular-secretory biomarkers, high-definition imaging and bedside clinical indexes in a surveillance setting offers a comprehensive range of HCC potential indicators. In addition, the sequential use of numerous lines of systemic anti-HCC therapies will simultaneously benefit more patients in survival. This review provides an overview on the most recent developments in HCC theranostic platform., Competing Interests: Declaration of interests None., (Copyright © 2023 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Boron neutron capture therapy (BNCT) is a selective radiotherapy based on nuclear reaction that occurs when 10 B atoms accumulated in cancer cells are irradiated by thermal neutrons, triggering a nuclear fission response leading to cell death. Despite its growing importance in cancer treatment, molecular characterization of its effects is still lacking. In this context, proteomics investigation can be useful to study BNCT effect and identify potential biomarkers. Hence, we performed proteomic analysis with nanoLC-MS/MS (liquid chromatography coupled to tandem mass spectrometry) on extracellular vesicles (EVs) isolated from SAS cultures treated or not with 10 B-boronophenylalanine (BPA) and different doses of neutron irradiation, to study the cellular response related to both boron administration and neutrons action. Despite the interference of fetal bovine serum in the medium, we were able to stratify BPA- and BPA+ conditions and to identify EVs-derived proteins characterizing pathways potentially related to a BNCT effect such as apoptosis, DNA repair and inflammatory response. In particular, KLF11, SERPINA1 and SERPINF2 were up-regulated in BPA+, while POLE and SERPINC1 were up-regulated in BPA-. These results provide the first proteomic investigation of EVs treated with BNCT in different conditions and highlight the potentiality of proteomics for improving biomarkers identification and mechanisms understanding of BNCT.

Hyperbaric oxygen (HBO) therapy is an effective treatment for patients with disorders of consciousness (DOC). In this study, real-time electroencephalogram (EEG) recordings were obtained from patients with DOC during HBO therapy. EEG microstate indicators including mean microstate duration (MMD), ratio of total time covered (RTT), global explained variance (GEV), transition probability, mean occurrence, and mean global field power (GFP) were compared before and during HBO therapy. The results showed that the duration of microstate C in all patients with DOC increased after 20 min of HBO therapy ( p  < 0.05). Further statistical analysis found that the duration of microstate C was longer in the higher CRS-R group (≥8, 17 cases) than in the lower group (<8, 24 cases) during HBO treatment. In the higher CRS-R group, the transition probabilities from microstate A to microstate C and from microstate C to microstate A also increased significantly compared with the probability before treatment ( p  < 0.05). Microstate C is generally considered to be related to a salience network; an increase in the transition probability between microstate A and microstate C indicates increased information exchange between the auditory network and the salience network. The results of this study show that HBO therapy has a specific activating effect on attention and cognitive control in patients and causes increased activity in the primary sensory cortex (temporal lobe and occipital lobe). This study demonstrates that real-time EEG detection and analysis during HBO is a clinically feasible method for assessing brain function in patients with DOC. During HBO therapy, some EEG microstate indicators show significant changes related to the state of consciousness in patients with chronic DOC. This will be complementary to important electrophysiological indicators for assessing consciousness and may also provide an objective foundation for the precise treatment of patients with DOC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Xu, Ge, Xue, Liu, Wang, Wu, Liu, Chen, Zhuang, Geng, Chen, Wang, Yu, He and Zhao.)

Studying the bioaccumulation behavior and toxicity of triazole fungicides is a crucial part of comprehensively evaluating the environmental fate and aquatic toxicity.The current research aimed to reveal the toxic effects of propiconazole and difenoconazole on fish through acute toxicity test, bioaccumulation test and oxidase system activity determination. Here, the propiconazole and difenoconazole concentrations were 11.3 mg/L and 31.2 mg/L for LC 50 -96 h, both having low toxicity. LC-MS/MS was used to determine the propiconazole and difenoconazole concentrations in five organs (muscle, gill, liver, intestine, and kidney) of Procypris meru. The findings indicate that the bioconcentration coefficients of propiconazole and difenoconazole in grass flower carp were 0.66-27.08 and 2.43-22.72, which belonged to medium enrichment pesticides. The bioconcentration coefficients decreased with the increase of exposure concentration. The two fungicides could induce oxidative stress in fish liver, and the activities of three antioxidant enzymes were inhibited in varying degrees (p < 0.05). The results showed that the content of T3 increased, and T4 decreased when exposed to one-tenth LC 50 for 7 days. This study shows that triazole pesticides have bioaccumulation risks on aquatic organisms and clear environmental hormonal effects., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Poly-amino acid (PAA) is a promising biomaterial in biomedical engineering due to its similar amide bond structure to collagen and excellent biocompatibility, but the lack of osteogenic activity and inferior mechanical strength limit its long-term application in orthopedics. In this study, a poly-amino acid/poly (p-benzamide) (PAA-PBA) copolymer with high mechanical strength was designed and fabricated by the method of solution polymerization. The chain structures, thermal properties and mechanical properties of these polymers were evaluated and results showed that PBA greatly promoted the mechanical properties of PAA, and the copolymer performed the maximum mechanical strengths with compressive strength, bending strength and tensile strength of 123 MPa, 107 MPa and, 95 MPa, respectively. To increase the bioactivity of surface, a bioactive coating that consists of poly-(dopamine) (PDA) nanolayers and tripeptide Arginine-Glycine-Aspartic acid (RGD) on sulfonated PAA-PBA copolymer was created. A porous structure appeared on the surface after modification, the surface roughness and hydrophilicity of copolymer has been improved obviously after introducing PDA and RGD peptide coating. The in vitro bioactivity evaluation demonstrated that the RGD-functionalized sample showed a significantly improved ability to promote bone apatite mineralization, cell adhesion, proliferation and osteogenic differentiation. In a word, such a strategy of material synthesis and surface modification method shows a great potential for broadening the use of PAA in the application of load-bearing bone substitute biomaterials., Competing Interests: Declaration of Competing Interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Thiamethoxam, an insecticide with high usage and large amounts of environmental residues, has been reported to affect the pupation and survival of honey bee larvae at sublethal concentrations. The molecular mechanisms are not fully understood. In this study, we measured the response of juvenile hormone (JH) to environmental concentrations of thiamethoxam using liquid chromatography-tandem mass spectrometry (LC-MS/MS), monitored the dynamic changes in the transcription of genes encoding major JH metabolic enzymes (CYP15A1, FAMET, JHAMT and JHE) using RT-qPCR, and analysed the transcriptome changes in worker larvae under thiamethoxam stress using RNA-seq. Thiamethoxam significantly increased the levels of JH3 in honey bee larvae, but no significant changes in the transcript levels of the four major metabolic enzymes were observed. Thiamethoxam exposure resulted in 140 differentially expressed genes (DEGs). P450 CYP6AS5 was upregulated, and some ion-related, odourant-related and gustatory receptors for sugar taste genes were altered significantly. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that amino acid metabolism and protein digestion and absorption were influenced by thiamethoxam. These changes may do harm to honey bee caste differentiation, foraging behaviour related to sensory perception and nutrient levels of bee colonies. These results represent the first assessment of the effects of thiamethoxam on JH in honey bee larvae and provides a new perspective and molecular basis for the study of JH regulation and thiamethoxam toxicity to honey bees., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Poly(ADP-ribose) glycohydrolase (Parg) is a central enzyme for poly(ADP-ribose) degradation. We established a Parg +/- mice strain by deletion of a part of exon 1 and around 0.4-kb upstream of sequences of the Parg gene. Parg -/- embryos obtained by intercrossing the Parg +/- mice died in utero between 4.5 and 9.5 days postcoitum. We examined whether poly(ADP-ribose) polymerase-1 (Parp-1) deficiency could rescue embryonic lethality of Parg -/- mice. Parg -/- Parp-1 -/- mice were born viable at a reduced frequency from the expected mendelian ratio in the intercross progeny of Parg +/- Parp-1 -/- mice. The results suggest a possibility that the presence of Parp-1 is responsible for the lethality of Parg -/- embryos, and Parg molecules or Parg activity degrading poly(ADP-ribose) might be important for embryogenesis. In Parg -/- Parp-1 -/- mice, Parg protein was not detected in various tissues, and the protein level of Timm23, a 5'-upstream gene of Parg, was reduced compared with that in Parg +/+ Parp-1 -/- mice. Parg -/- Parp-1 -/- mice showed retarded growth compared with Parg +/+ Parp-1 -/- mice, and died within 3 months of age accompanied with severe renal failure. Glomerular sclerosis, tubular dilatation, and hyaline casts in the kidney were observed in Parg -/- Parp-1 -/- mice. An increase in blood urea nitrogen (p < 0.05), a marked increase of albumin level in urine (p < 0.01) and its concomitant decrease in serum (p < 0.05) were also detected in Parg -/- Parp-1 -/- mice compared with the Parg +/+ Parp-1 -/- counterpart. The results imply that the combined Parg and Parp-1 loss with a hypomorphic state of Timm23 leads to the development of severe renal failure., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Despite significant recent progress, machine vision systems lag considerably behind their biological counterparts in performance, scalability, and robustness. A distinctive hallmark of the brain is its ability to automatically discover and model objects, at multiscale resolutions, from repeated exposures to unlabeled contextual data and then to be able to robustly detect the learned objects under various nonideal circumstances, such as partial occlusion and different view angles. Replication of such capabilities in a machine would require three key ingredients: ( i ) access to large-scale perceptual data of the kind that humans experience, ( ii ) flexible representations of objects, and ( iii ) an efficient unsupervised learning algorithm. The Internet fortunately provides unprecedented access to vast amounts of visual data. This paper leverages the availability of such data to develop a scalable framework for unsupervised learning of object prototypes-brain-inspired flexible, scale, and shift invariant representations of deformable objects (e.g., humans, motorcycles, cars, airplanes) comprised of parts, their different configurations and views, and their spatial relationships. Computationally, the object prototypes are represented as geometric associative networks using probabilistic constructs such as Markov random fields. We apply our framework to various datasets and show that our approach is computationally scalable and can construct accurate and operational part-aware object models much more efficiently than in much of the recent computer vision literature. We also present efficient algorithms for detection and localization in new scenes of objects and their partial views., Competing Interests: The authors declare no conflict of interest.

Interleukin 15 (IL-15) is one of the most important cytokines that regulate the biology of natural killer (NK) cells 1 . Here we identified a signaling pathway-involving the serine-threonine kinase AKT and the transcription factor XBP1s, which regulates unfolded protein response genes 2,3 -that was activated in response to IL-15 in human NK cells. IL-15 induced the phosphorylation of AKT, which led to the deubiquitination, increased stability and nuclear accumulation of XBP1s protein. XBP1s bound to and recruited the transcription factor T-BET to the gene encoding granzyme B, leading to increased transcription. XBP1s positively regulated the cytolytic activity of NK cells against leukemia cells and was also required for IL-15-mediated NK cell survival through an anti-apoptotic mechanism. Thus, the newly identified IL-15-AKT-XBP1s signaling pathway contributes to enhanced effector functions and survival of human NK cells.

Resveratrol has been widely investigated for its potential health properties, although little is known about its mechanism in vivo. Previous studies have indicated that resveratrol produces antinociceptive effects in mice. Calcium channels and calcium/caffeine-sensitive pools are reported to be associated with analgesic effect. The present study was to explore the involvement of Ca2+ channel and calcium/caffeine-sensitive pools in the antinociceptive response of resveratrol. Tail-flick test was used to assess antinociception in mice treated with resveratrol or the combinations of resveratrol with MK 801, nimodipine, CaCl2, ryanodine and ethylene glycol tetraacetic acid (EGTA), respectively. The Ca2+/calmodulin-dependent protein kinase II (CaMKII) and brain-derived neurotrophic factor (BDNF) levels in the spinal cord were also investigated when treated with the above drugs. The results showed that resveratrol increased the tail flick latency in the tail-flick test, in dose-dependent manner. N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK 801 potentiated the antinociceptive effects of sub-threshold dose of resveratrol at 10 mg/kg. Ca2+ channel blocker, however, abolished the antinociceptive effects of resveratrol. In contrast to these results, EGTA or ryanodine treatment (i.c.v.) potentiated resveratrol-induced antinociception. There was a significant decrease in p-CaMKII and an increase in BDNF expression in the spinal cord when combined with MK 801, nimodipine, ryanodine and EGTA. While an increase in p-CaMKII level and a decrease in BDNF expression were observed when high dose of resveratrol combined with CaCl2. These findings suggest that resveratrol exhibits the antinociceptive effects by inhibition of calcium channels and calcium/caffeine-sensitive pools.

Nitric oxide (NO) regulates multiple developmental events and stress responses in plants. A major biologically active species of NO is S-nitrosoglutathione (GSNO), which is irreversibly degraded by GSNO reductase (GSNOR). The major physiological effect of NO is protein S-nitrosylation, a redox-based posttranslational modification mechanism by covalently linking an NO molecule to a cysteine thiol. However, little is known about the mechanisms of S-nitrosylation-regulated signaling, partly due to limited S-nitrosylated proteins being identified. In this study, we identified 1,195 endogenously S-nitrosylated peptides in 926 proteins from the Arabidopsis (Arabidopsis thaliana) by a site-specific nitrosoproteomic approach, which, to date, is the largest data set of S-nitrosylated proteins among all organisms. Consensus sequence analysis of these peptides identified several motifs that contain acidic, but not basic, amino acid residues flanking the S-nitrosylated cysteine residues. These S-nitrosylated proteins are involved in a wide range of biological processes and are significantly enriched in chlorophyll metabolism, photosynthesis, carbohydrate metabolism, and stress responses. Consistently, the gsnor1-3 mutant shows the decreased chlorophyll content and altered photosynthetic properties, suggesting that S-nitrosylation is an important regulatory mechanism in these processes. These results have provided valuable resources and new clues to the studies on S-nitrosylation-regulated signaling in plants., (© 2015 American Society of Plant Biologists. All Rights Reserved.)

Nitric oxide (NO) and reactive oxygen species (ROS) are two classes of key signaling molecules involved in various developmental processes and stress responses in plants. The burst of NO and ROS triggered by various stimuli activates downstream signaling pathways to cope with abiotic and biotic stresses. Emerging evidence suggests that the interplay of NO and ROS plays a critical role in regulating stress responses. However, the underpinning molecular mechanism remains poorly understood. Here, we show that NO positively regulates the activity of the Arabidopsis (Arabidopsis thaliana) cytosolic ascorbate peroxidase1 (APX1). We found that S-nitrosylation of APX1 at cysteine (Cys)-32 enhances its enzymatic activity of scavenging hydrogen peroxide, leading to the increased resistance to oxidative stress, whereas a substitution mutation at Cys-32 causes the reduction of ascorbate peroxidase activity and abolishes its responsiveness to the NO-enhanced enzymatic activity. Moreover, S-nitrosylation of APX1 at Cys-32 also plays an important role in regulating immune responses. These findings illustrate a unique mechanism by which NO regulates hydrogen peroxide homeostasis in plants, thereby establishing a molecular link between NO and ROS signaling pathways., (© 2015 American Society of Plant Biologists. All Rights Reserved.)

Cortical gamma band oscillations (GBO, 30-80 Hz, typically ∼40 Hz) are involved in higher cognitive functions such as feature binding, attention, and working memory. GBO abnormalities are a feature of several neuropsychiatric disorders associated with dysfunction of cortical fast-spiking interneurons containing the calcium-binding protein parvalbumin (PV). GBO vary according to the state of arousal, are modulated by attention, and are correlated with conscious awareness. However, the subcortical cell types underlying the state-dependent control of GBO are not well understood. Here we tested the role of one cell type in the wakefulness-promoting basal forebrain (BF) region, cortically projecting GABAergic neurons containing PV, whose virally transduced fibers we found apposed cortical PV interneurons involved in generating GBO. Optogenetic stimulation of BF PV neurons in mice preferentially increased cortical GBO power by entraining a cortical oscillator with a resonant frequency of ∼40 Hz, as revealed by analysis of both rhythmic and nonrhythmic BF PV stimulation. Selective saporin lesions of BF cholinergic neurons did not alter the enhancement of cortical GBO power induced by BF PV stimulation. Importantly, bilateral optogenetic inhibition of BF PV neurons decreased the power of the 40-Hz auditory steady-state response, a read-out of the ability of the cortex to generate GBO used in clinical studies. Our results are surprising and novel in indicating that this presumptively inhibitory BF PV input controls cortical GBO, likely by synchronizing the activity of cortical PV interneurons. BF PV neurons may represent a previously unidentified therapeutic target to treat disorders involving abnormal GBO, such as schizophrenia.