NCPbook: a comprehensive database of non-canonical peptides.

Non-canonical peptides (NCPs) are a class of peptides generated from regions previously thought of as non-coding, such as introns, 5' untranslated regions (UTRs), 3' UTRs, and intergenic regions. In recent years, the significance and diverse functions of NCPs have come to light, yet a systematic and comprehensive NCP database remains absent. Here, we developed NCPbook (https://ncp.wiki/ncpbook/), a database of evidence-supported NCPs, which aims to provide a resource for efficient exploration, analysis, and manipulation of NCPs. NCPbook incorporates data from diverse public databases and scientific literature. The current version of NCPbook includes 180,676 NCPs across 29 different species, evidenced by mass spectrometry (MS), ribosome profiling (Ribo-seq), or molecular experiments (ME). These NCPs are distributed across kingdoms, comprising 123,408 from 14 plant species, 56,999 from seven animal species, and 269 from eight microbial species. Furthermore, NCPbook encompasses 9,166 functionally characterized NCPs playing important roles in immunity, stress resistance, growth, and development. Equipped with a user-friendly interface, NCPbook allows users to search, browse, visualize, and retrieve data, making it an indispensable platform for researching NCPs in various plant, animal, and microbial species.

In Situ Fe-Substituted Hexacyanoferrate for High-Performance Aqueous Potassium Ion Batteries.

The eco-friendliness, safety, and affordability of aqueous potassium batteries (AKIBs) have made them popular for large-scale energy storage devices. However, the cycling and rate performance of research materials, particularly cobalt hexacyanoferrate, have yet to meet satisfactory standards. Herein, a room-temperature drafted K1.66 Fe0.25 Co0.75 [Fe(CN)6 ]·0.83H2 O (KFCHCF) sample is reported using an in situ substitution strategy. A higher concentration of ferrocyanide ions decreases the water content and increases the potassium content, while citric acid works as a chelating agent and is responsible for Fe-substitution in the KFCHCF sample. The resultant KFCHCF sample exhibits good rate performance, and about 97% and 90.6% of discharge capacity are conserved after 400 and 1000 cycles at 100 and 200 mA g-1 , respectively. The full cell using the KFCHCF cathode and 1,4,5,8-naphthalenetetracarboxylic dianhydride-derived polyimide (PNTCDA) anode maintains ≈74.93% and 74.35% of discharge capacity at 200 mA g-1 and 1000 mA g-1 for 1000 and >10,000 cycles, respectively. Furthermore, ex situ characterizations demonstrate the high reversibility of K-ions and structural stability during the charge-discharge process. Such high performance is attributed to the fast K-ion migration and crystal structure stabilization caused by in situ Fe-substitution in the KFCHCF sample. Other hexacyanoferrates can be synthesized using this method and used in grid-scale storage systems.

Nonspecific phospholipase C4 hydrolyzes phosphosphingolipids and sustains plant root growth during phosphate deficiency.

Phosphate is a vital macronutrient for plant growth, and its availability in soil is critical for agricultural sustainability and productivity. A substantial amount of cellular phosphate is used to synthesize phospholipids for cell membranes. Here, we identify a key enzyme, nonspecific phospholipase C4 (NPC4) that is involved in phosphosphingolipid hydrolysis and remodeling in Arabidopsis during phosphate starvation. The level of glycosylinositolphosphorylceramide (GIPC), the most abundant sphingolipid in Arabidopsis thaliana, decreased upon phosphate starvation. NPC4 was highly induced by phosphate deficiency, and NPC4 knockouts in Arabidopsis decreased the loss of GIPC and impeded root growth during phosphate starvation. Enzymatic analysis showed that NPC4 hydrolyzed GIPC and displayed a higher activity toward GIPC as a substrate than toward the common glycerophospholipid phosphatidylcholine. NPC4 was associated with the plasma membrane lipid rafts in which GIPC is highly enriched. These results indicate that NPC4 uses GIPC as a substrate in planta and the NPC4-mediated sphingolipid remodeling plays a positive role in root growth in Arabidopsis response to phosphate deficiency.

Examining treatment targets and equity in bone-active medication use within secondary fracture prevention: a systematic review and meta-analysis.

PURPOSE: This systematic review seeks to evaluate the proportion of fragility fracture patients screened in secondary fracture prevention programs who were indicated for pharmacological treatment, received prescriptions for bone-active medications, and initiated the prescribed medication. Additionally, the study aims to analyze equity in pharmacological treatment by examining equity-related variables including age, sex, gender, race, education, income, and geographic location. METHODS: We conducted a systematic review to ascertain the proportion of fragility fracture patients indicated for treatment who received prescriptions and/or initiated bone-active medication through secondary fracture prevention programs. We also examined treatment indications reported in studies and eligibility criteria to confirm patients who were eligible for treatment. To compute the pooled proportions for medication prescription and initiation, we carried out a single group proportional meta-analysis. We also extracted the proportions of patients who received a prescription and/or began treatment based on age, sex, race, education, socioeconomic status, location, and chronic conditions. RESULTS: This review included 122 studies covering 114 programs. The pooled prescription rate was 77%, and the estimated medication initiation rate was 71%. Subgroup analysis revealed no significant difference in treatment initiation between the Fracture Liaison Service and other programs. Across all studies, age, sex, and socioeconomic status were the only equity variables reported in relation to treatment outcomes. CONCLUSION: Our systematic review emphasizes the need for standardized reporting guidelines in post-fracture interventions. Moreover, considering equity stratifiers in the analysis of health outcomes will help address inequities and improve the overall quality and reach of secondary fracture prevention programs.

In silico homology modeling of dengue virus non-structural 4B (NS4B) protein and its molecular docking studies using triterpenoids.

BACKGROUND: Dengue fever has become a significant worldwide health concern, because of its high morbidity rate and the potential for an increase in mortality rates due to lack of adequate treatment. There is an immediate need for the development of effective medication for dengue fever. METHODS: Homology modeling of dengue virus (DENV) non-structural 4B (NS4B) protein was performed by SWISS-MODEL to predict the 3D structure of the protein. Structure validation was conducted using PROSA, PROCHECK, Ramachandran plot, and VERIFY-3D. MOE software was used to find out the in-Silico inhibitory potential of the five triterpenoids against the DENV-NS4B protein. RESULTS: The SWISS-MODEL was employed to predict the three-dimensional protein structure of the NS4B protein. Through molecular docking, it was found that the chosen triterpenoid NS4B protein had a high binding affinity interaction. It was observed that the NS4B protein binding energy for 15-oxoursolic acid, betulinic acid, ursolic acid, lupeol, and 3-o-acetylursolic acid were - 7.18, - 7.02, - 5.71, - 6.67 and - 8.00 kcal/mol, respectively. CONCLUSIONS: NS4B protein could be a promising target which showed good interaction with tested triterpenoids which can be developed as a potential antiviral drug for controlling dengue virus pathogenesis by inhibiting viral replication. However, further investigations are necessary to validate and confirm their efficacy.

Reporting Practices of Serum Protein Electrophoresis in Pakistan - a Multicenter Survey.

BACKGROUND: Serum Protein Electrophoresis (SPE) is crucial for the diagnosis and follow-up of monoclonal gammopathy (MG), as it helps to separate and identify these paraproteins. Currently, Pakistan lacks standardized guidelines for SPE reporting and analytical performance. This survey aims to analyze reporting variations from Consultant Chemical Pathologists in Pakistani laboratories. METHODS: This cross-sectional survey was conducted by the section of Chemical Pathology, Department of Pathology and Laboratory Medicine, at Aga Khan University Hospital, Karachi. A previously validated and published tool was used with some modifications to assess analytical techniques, reporting patterns, and interpretations provided with SPE by different laboratories. Frequency and percentages were calculated for each response and descriptive results were also evaluated. Differences between laboratories were also assessed qualitatively. RESULTS: Out of the eight laboratories contacted, seven participated in the survey, yielding a response rate of 87.5%. Immunofixation Electrophoresis (IFE) was used by all labs for serum immunotyping. All labs reported a new small abnormal band in patients with no known monoclonal gammopathy or with a known M-protein. Variations were found in terminologies used to label paraprotein, terminologies used to report normal and pathological SPE patterns, electrophoretic technique, methods for quantifying paraprotein in the gamma region on SPE and for albumin quantification. Similarly, the number of decimal places reported, reporting of multiple monoclonal proteins and small paraprotein in the beta region or monoclonal proteins less than 1 g/L, approach for screening, number of fractions reported in gamma region and reporting of interferences were also not standardized and var-iations were noticed. CONCLUSIONS: Our survey highlighted variations in practices of SPE reporting. These differences in laboratory practices could result in inconsistent test results, which could adversely affect patient care.

Reproducibility and stability of the immature platelet fraction using Sysmex XN-10.

BACKGROUND: The Immature Platelet Fraction (IPF) is an indicator of thrombopoiesis which is a useful parameter in thrombocytopenia. It demonstrates compensatory mechanisms in production of platelets, but currently not implemented in routine clinical practice. The aim of this study was to establish the reproducibility and stability of IPF, for both percentage (%-IPF) and absolute (A-IPF) measurements.Material/methods: A total of 71 samples, of which 45 for reproducibility and 26 for stability analysis, were assayed for full blood count using the Sysmex XN-10 analyser at room temperature (RT:19-25 °C). For reproducibility analysis, IPF measurements were analysed 11 times by different appraisers using the same sample, while for stability analysis, IPF was measured over fourteen hourly-intervals up to 24 h (n = 21) and then separately extended beyond the point of stability to 72 h (n = 5). RESULTS: Reproducibility analysis of %-IPF and A-IPF (n = 45) showed very reliable results, with the range of mean CV% values between 1.25-8.90% and 1.70-9.96%, respectively. On the other hand, overall, stability analysis of %-IPF and A-IPF (n = 21) at RT over 24 h showed reliable results, with pooled mean CV% values of 1.32% and 1.43%, respectively, with no significant difference between %-IPF and A-IPF (p = 0.767 and p = 0.821). All %-IPF and A-IPF values had exceeded the set acceptance criterion of stability (CV% ≥ 10.0%) before 72 h. CONCLUSIONS: Overall, %-IPF and A-IPF reproducibility and storage at RT for 24 h predominantly demonstrates the suitability of their usage for testing on the Sysmex XN-series analysers.

Metformin Alleviates Pain States by Regulating the Balance of Spinal Synaptic Transmission.

BACKGROUND: Metformin has been shown to have potent analgesic effects; however, the underlying mechanism of synaptic plasticity mediating analgesia remained ambiguous. METHODS: In this study, animal behavioral tests, whole-cell patch­clamp recording, immunofluorescence staining, and network pharmacology techniques were applied to elucidate the mechanisms and potential targets of metformin-induced analgesia. RESULTS: Single or consecutive injections of metformin significantly inhibited spinal nerve ligation (SNL)-induced neuropathic pain, and formalin-induced acute inflammatory pain. Network pharmacology analysis of metformin action targets in pain database-related targets revealed 25 targets, including five hub targets (nitric oxide synthase 1 (NOS1), NOS2, NOS3, epidermal growth factor receptor (EGFR), and plasminogen (PLG)). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that metformin-induced analgesia was markedly correlated with calcium signaling and synaptic transmission. Intrathecal injection of metformin significantly reversed nerve injury-induced c-Fos (neural activity biomarker) mRNA and protein expression in neuropathic rats by regulating NOS2 expression. In addition, whole-cell recordings of isolated spinal neurons demonstrated that metformin dose-dependently inhibited the enhanced frequency and amplitude of miniature excitatory synaptic currents (mEPSCs) but did not affect those of miniature inhibitory synaptic currents (mIPSCs) in neuropathic pain. CONCLUSIONS: This study further demonstrated that metformin might inhibit spinal glutamatergic transmission and abnormal nociceptive circuit transduction by monitoring synaptic transmission in pain. Results of this work provide an in-depth understanding of metformin analgesia via synaptic plasticity.

Estimation of Prediction Intervals for Performance Assessment of Building Using Machine Learning.

This study utilizes artificial neural networks (ANN) to estimate prediction intervals (PI) for seismic performance assessment of buildings subjected to long-term ground motion. To address the uncertainty quantification in structural health monitoring (SHM), the quality-driven lower upper bound estimation (QD-LUBE) has been opted for global probabilistic assessment of damage at local and global levels, unlike traditional methods. A distribution-free machine learning model has been adopted for enhanced reliability in quantifying uncertainty and ensuring robustness in post-earthquake probabilistic assessments and early warning systems. The distribution-free machine learning model is capable of quantifying uncertainty with high accuracy as compared to previous methods such as the bootstrap method, etc. This research demonstrates the efficacy of the QD-LUBE method in complex seismic risk assessment scenarios, thereby contributing significant enhancement in building resilience and disaster management strategies. This study also validates the findings through fragility curve analysis, offering comprehensive insights into structural damage assessment and mitigation strategies.

Ion Pre-Embedding Engineering of δ-MnO2 for Chemically Self-Charging Aqueous Zinc Ions Batteries.

Aqueous zinc ion batteries (ZIBs), especially those with self-charging properties, have been promisingly developed in recent years. Yet, most inorganic materials feature high redox potential, which limit their development in the self-charging field. To achieve this target, by pre-embedding potassium ions into δ-MnO2 to reduce the energy barrier in oxygen adsorption, the first application of MnO2 in self-charging ZIBs is realized. The design features a facile two-electrode configuration with no excessively complex component to allow for energy storage and conversion. Due to the voltage difference between the oxygen in the air and the discharge products, a redox reaction can be carried out spontaneously to realize the self-charging process. After the chemical self-charging process, the Zn-K0.37 MnO2 ·0.54H2 O/C cell achieves an open circuit voltage of around 1.42 V and a discharge capacity of 201 mAh g-1 , reflecting the promising self-charging capability. Besides, the chemically self-charging ZIBs operate well in multiple modes of constant current charge/discharge/chemical charging. And decent cycling capability can also be achieved at extreme temperatures and high mass loading. This work promotes the development of ZIBs and further broadens the application of inorganic metal oxides in the self-charging systems.

Motile microorganisms hybrid nanoliquid flow with the influence of activation energy and heat source over a rotating disc.

The present article examines the consequences of a magnetic field, Hall current, and thermal radiation on the spinning flow of hybrid nanofluid (HNF) across a revolving disc. The core objective of the study is to improve the energy transference rate through hybrid nano liquid for industrial and engineering operations. The HNFs have advanced thermophysical characteristics. Therefore, in the current study, a superior class of nanomaterials (carbon nanotubes (CNTs) and Al2O3) are added to the base fluid. The modeled equations are demoted to a dimensionless set of Ordinary differential equations (ODEs) through similarity conversion and are analytically solved by engaging the homotopy analysis method. The physical constraints' effect on energy, velocity, motile microorganism, and mass profiles have been drawn and discussed. For accuracy, the results are compared to the published studies, which ensures the accuracy and reliability of the technique and results. It is observed that the energy communication rate lessens with the flourishing values of thermal radiation and for Hall current. Furthermore, it is noted that due to its carbon-carbon bonding in CNTs, it has a greater tendency for energy propagation than Al2O3nanoparticles.

Thoracoscopic vs open repair of congenital diaphragmatic hernia after extracorporeal membrane oxygenation: a comparison of intra-operative data.

PURPOSE: ECMO is an escalation treatment for hypoxic respiratory failure in patients with CDH. Open repair has been advocated after ECMO indicating that physiological changes associated to thoracoscopic repair were not well tolerated. METHODS: We have performed a retrospective review of all patients who underwent ECMO prior CDH repair over a 7 year period (2015-2021). Outcome measures were intra-operative Ph, PCO2, PO2 and FiO2 at 30 min, 1 h 30 min, and 2 h 30 min of surgery, operative time and recurrence rate. Data are shown in median (range). RESULTS: Eleven patients required ECMO prior CDH repair. Six of eleven (55%) were done thoracoscopically (Group A) and five of eleven (45%) via laparotomy (Group B). Two of six (33%) patients (Group A) were converted to a laparotomy, one of six (16%) patient developed a recurrence, and there was no recurrence in Group B. Two of five (40%) patients died within the first 60 days of life, whilst there was no death in Group A. Intra-operative values are shown below. CONCLUSION: Whilst this is a preliminary report of a limited number of patients, there is no obvious difference of intra-operative blood gas parameters during surgical repair in patients after ECMO. Thoracoscopic CDH repair may be considered in patients after ECMO.

Fatty acid exporter 1 enhances seed oil content in Brassica napus.

Fatty acid exporter 1 (FAX1) is an initial transporter for fatty acid (FA), in charge of transporting FA from the inside of the plastid to the outside. Brassica napus (B. napus) has nineteen members in the FAX family, of which there are six FAX1 homologous genes. Here, we generated the BnaFAX1 CRISPR mutants (BnaA09.FAX1 and BnaC08.FAX1 were both edited) and overexpression (OE) plants of BnaA09.FAX1 in B. napus. The results showed that the FA content was increased by 0.6-0.9% in OE plant leaves, and the seed oil content was increased by 1.4-1.7% in OE lines, compared to WT. Meanwhile, the content of triacylglycerol, diacylglycerol, and phosphatidylcholine was significantly increased in OE seeds. Moreover, seedling biomass and plant height of OE plants were increased compared to WT plants. However, the traits above had no significant difference between the mutants and WT. These results suggest that BnaA09.FAX1 plays a role in improving seed oil accumulation and plant growth, while the function of BnaFAX1 may be compensated by other homologous genes of BnaFAX1 and other BnaFAX genes in the mutants. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01346-0.

Genomic characterization of high-risk Escherichia coli and Enterobacter hormaechei clones recovered from a single tertiary-care hospital in Pakistan.

AIMS: Spread of carbapenem-resistant Enterobacterales have become a global problem. We characterized extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales from urinary tract infections cases from Allied Hospital Faisalabad, Pakistan. METHODS AND RESULTS: Eleven (22%, 11/50) ESBL-producing Enterobacterales (Escherichia coli; n = 10 and Enterobacter hormaechei; n = 1) were recovered and processed through VITEK-2, PCR, rep-PCR followed by whole-genome sequencing (WGS) of ESBL-producing Ent. hormaechei and carbapenem-resistant E. coli isolates. Plasmid transferability of blaNDM-1 -producers was assayed by conjugation experiments. All ESBL strains carried the blaCTX-M-15 gene. Of these blaCTX-M-15 producing E. coli, four also carried blaNDM-1 located on transferable plasmids. All E. coli strains belonged to ST448 and displayed similar genetic features including genes for antimicrobial resistance, heavy metal, biocides and virulence. Genomic features of a multidrug-resistant (MDR) Ent. hormaechei were also reported for the first time in Pakistan. CONCLUSION: Our findings indicate that blaNDM-1 producing E. coli ST448 is a multidrug, heavy metals and biocides-resistant strain. Therefore, the screening of these isolates may be effective in limiting the MDR bacteria spread in hospitalized patients and within the community. SIGNIFICANCE AND IMPACT OF THIS STUDY: Spread of multi-drug-resistant ESBL-producing bacteria in the clinical settings of Pakistan is a serious challenge and further limiting treatment options in the country. WGS could be used as a tool in the nationwide antibiotic surveillance programme to explore insights of spread and outbreak.

Design of a Millimeter-Wave MIMO Antenna Array for 5G Communication Terminals.

This paper presents a design of multiple input multiple output (MIMO) antenna array for 5G millimeter-wave (mm-wave) communication systems. The proposed MIMO configuration consists of a two antenna arrays combination. Each antenna array consists of four elements which are arranged in an even manner, while two arrays are then assembled with a 90-degree shift with respect to each other. The substrate used is a 0.254 mm thick Rogers RT5880 with a dielectric constant of 2.2 and loss tangent of 0.0009, correspondingly. The proposed MIMO antenna array covers the 37 GHz frequency band, dedicated for 5G millimeter-wave communication applications. The proposed antenna element yields a gain of 6.84 dB, which is enhanced up to 12.8 dB by adopting a four elements array configuration. The proposed MIMO antenna array performance metrics, such as envelope correlation coefficient (ECC) and diversity gain (DG), are observed, which are found to be under the standard threshold. More than 85% of the radiation efficiency of the proposed MIMO antenna array is observed to be within the desired operating frequency band. All the proposed designs are simulated in computer simulation technology (CST) software. Furthermore, the measurements are carried out for the proposed MIMO antenna array, where a good agreement with simulated results is observed. Thus, the proposed design can be a potential candidate for 5G millimeter-wave communication systems.

Proteome-wide identification of S-sulphenylated cysteines in Brassica napus.

Deregulation of reduction-oxidation (redox) metabolism under environmental stresses results in enhanced production of intracellular reactive oxygen species (ROS), which ultimately leads to post-translational modifications (PTMs) of responsive proteins. Redox PTMs play an important role in regulation of protein function and cellular signalling. By means of large-scale redox proteomics, we studied reversible cysteine modification during the response to short-term salt stress in Brassica napus (B. napus). We applied an iodoacetyl tandem mass tags (iodoTMT)-based proteomic approach to analyse the redox proteome of B. napus seedlings under control and salt-stressed conditions. We identified 1,821 sulphenylated sites in 912 proteins from all samples. A great number of sulphenylated proteins were predicted to localize to chloroplasts and cytoplasm and GO enrichment analysis of differentially sulphenylated proteins revealed that metabolic processes such as photosynthesis and glycolysis are enriched and enzymes are overrepresented. Redox-sensitive sites in two enzymes were validated in vitro on recombinant proteins and they might affect the enzyme activity. This targeted approach contributes to the identification of the sulphenylated sites and proteins in B. napus subjected to salt stress and our study will improve our understanding of the molecular mechanisms underlying the redox regulation in response to salt stress.

Depth Hypotheses Fusion through 3D Weighted Least Squares in Shape from Focus.

In shape-from-focus (SFF) methods, a single focus measure is used to compute the focus volume. However, it seems that a single focus measure operator is not capable of computing accurate focus values for the images of diverse types of object shapes. Furthermore, most of the SFF methods try to improve the depth map without considering any additional structural or prior information. Consequently, the extracted shape of the object might lack important details. In this work, we address these problems and suggest a method in which depth hypotheses are combined for a more accurate 3D shape through 3D weighted least squares. First, depth hypotheses are obtained by applying a number of focus operators. Then, structural prior or guidance volume is extracted from the focus measure volumes. Finally, a 3D weighted least squares optimization technique is applied to the depth hypothesis volume, where weights are computed from the guidance volume. Thus, by inducing structural prior, an improved resultant depth map is obtained. The proposed method was tested using various image sequences of synthetic and microscopic real objects. Experimental results and comparative analysis demonstrated the effectiveness of the proposed method.

Real Time Multipurpose Smart Waste Classification Model for Efficient Recycling in Smart Cities Using Multilayer Convolutional Neural Network and Perceptron.

Urbanization is a big concern for both developed and developing countries in recent years. People shift themselves and their families to urban areas for the sake of better education and a modern lifestyle. Due to rapid urbanization, cities are facing huge challenges, one of which is waste management, as the volume of waste is directly proportional to the people living in the city. The municipalities and the city administrations use the traditional wastage classification techniques which are manual, very slow, inefficient and costly. Therefore, automatic waste classification and management is essential for the cities that are being urbanized for the better recycling of waste. Better recycling of waste gives the opportunity to reduce the amount of waste sent to landfills by reducing the need to collect new raw material. In this paper, the idea of a real-time smart waste classification model is presented that uses a hybrid approach to classify waste into various classes. Two machine learning models, a multilayer perceptron and multilayer convolutional neural network (ML-CNN), are implemented. The multilayer perceptron is used to provide binary classification, i.e., metal or non-metal waste, and the CNN identifies the class of non-metal waste. A camera is placed in front of the waste conveyor belt, which takes a picture of the waste and classifies it. Upon successful classification, an automatic hand hammer is used to push the waste into the assigned labeled bucket. Experiments were carried out in a real-time environment with image segmentation. The training, testing, and validation accuracy of the purposed model was 0.99% under different training batches with different input features.

The spinal microglial IL-10/ß-endorphin pathway accounts for cinobufagin-induced mechanical antiallodynia in bone cancer pain following activation of α7-nicotinic acetylcholine receptors.

BACKGROUND: Cinobufagin is the major bufadienolide of Bufonis venenum (Chansu), which has been traditionally used for the treatment of chronic pain especially cancer pain. The current study aimed to evaluate its antinociceptive effects in bone cancer pain and explore the underlying mechanisms. METHODS: Rat bone cancer model was used in this study. The withdrawal threshold evoked by stimulation of the hindpaw was determined using a 2290 CE electrical von Frey hair. The ß-endorphin and IL-10 levels were measured in the spinal cord and cultured primary microglia, astrocytes, and neurons. RESULTS: Cinobufagin, given intrathecally, dose-dependently attenuated mechanical allodynia in bone cancer pain rats, with the projected Emax of 90% MPE and ED50 of 6.4 µg. Intrathecal cinobufagin also stimulated the gene and protein expression of IL-10 and ß-endorphin (but not dynorphin A) in the spinal cords of bone cancer pain rats. In addition, treatment with cinobufagin in cultured primary spinal microglia but not astrocytes or neurons stimulated the mRNA and protein expression of IL-10 and ß-endorphin, which was prevented by the pretreatment with the IL-10 antibody but not ß-endorphin antiserum. Furthermore, spinal cinobufagin-induced mechanical antiallodynia was inhibited by the pretreatment with intrathecal injection of the microglial inhibitor minocycline, IL-10 antibody, ß-endorphin antiserum and specific µ-opioid receptor antagonist CTAP. Lastly, cinobufagin- and the specific α-7 nicotinic acetylcholine receptor (α7-nAChR) agonist PHA-543613-induced microglial gene expression of IL-10/ß-endorphin and mechanical antiallodynia in bone cancer pain were blocked by the pretreatment with the specific α7-nAChR antagonist methyllycaconitine. CONCLUSIONS: Our results illustrate that cinobufagin produces mechanical antiallodynia in bone cancer pain through spinal microglial expression of IL-10 and subsequent ß-endorphin following activation of α7-nAChRs. Our results also highlight the broad significance of the recently uncovered spinal microglial IL-10/ß-endorphin pathway in antinociception.

Core-Shell FeSe2 /C Nanostructures Embedded in a Carbon Framework as a Free Standing Anode for a Sodium Ion Battery.

Embedding the functional nanostructures into a lightweight nanocarbon framework is very promising for developing high performance advanced electrodes for rechargeable batteries. Here, to realize workable capacity, core-shell (FeSe2 /C) nanostructures are embedded into carbon nanotube (CNT) framework via a facile wet-chemistry approach accompanied by thermally induced selenization. The CNT framework offers 3D continuous routes for electronic/ionic transfer, while macropores provide adequate space for high mass loading of FeSe2 /C. However, the carbon shell not only creates a solid electronic link among CNTs and FeSe2 but also improves the diffusivity of sodium ions into FeSe2 , as well as acts as a buffer cushion to accommodate the volume variations. These unique structural features of CNT/FeSe2 /C make it an excellent host for sodium storage with a capacity retention of 546 mAh g-1 even after 100 cycles at 100 mA g-1 . Moreover, areal and volumetric capacities of 5.06 mAh cm-2 and 158 mAh cm-3 are also achieved at high mass loading 16.9 mg cm-2 , respectively. The high performance of multi-benefited engineered structure makes it a potential candidate for secondary ion batteries, while its easy synthesis makes it extendable to further complex structures with other morphologies (such as nanorods, nanowires, etc.) to meet the high energy demands.