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Contains fulltext : 291437.pdf (Publisher’s version ) (Open Access) Successful treatment of infected bone defects caused by multi-drug resistant bacteria (MDR) has become a major clinical challenge, stressing the urgent need for effective antibacterial bone graft substitutes. Mesoporous bioactive glass nanoparticles (MBGNs), a rapidly emerging class of nanoscale biomaterials, offer specific advantages for the development of biomaterials to treat bone infection due to endowed antibacterial features. Herein, we propose a facile post-modification sol-gel strategy to synthesize effective antibacterial MBGNs doped with copper ions (Cu-PMMBGNs). In this strategy, amine functional groups as chelating agents were introduced to premade mesoporous silica nanoparticles (MSNs) which further facilitate the incorporation of high content of calcium (∼17 mol%) and copper ions (∼8 mol%) without compromising nanoparticle shape, mesoporosity, and homogeneity. The resulting nanoparticles were degradable and showed rapidly induce abundant deposition of apatite crystals on their surface upon soaking in simulated body fluids (SBF) after 3 days. Cu-PMMBGNs exhibited a dose-dependent inhibitory effect on Methicillin-resistant Staphylococcus aureus (MRSA) bacteria, which are common pathogens causing severe bone infections. Most importantly, the nanoparticles containing 5 mol% copper ions at concentrations of 500 and 1000 μg.mL(-1) showed highly effective antibacterial performance as reflected by a 99.9 % reduction of bacterial viability. Nanoparticles at a concentration of 500 μg.mL(-1) showed no significant cytotoxicity toward preosteoblast cells (∼85-89 % cell viability) compared to the control group. In addition, the nanoscale properties of synthesized Cu-PMMBGNs (∼100 nm in size) facilitated their internalization into preosteoblast cells, which highlights their potential as intracellular carriers in combating intracellular bacteria. Therefore, these copper-doped nanoparticles hold strong promise for use as an antibacterial component in antibacterial bone substitutes such as hydrogels, nanocomposites, and coatings. 01 januari 2023

The Pediatric Perioperative Outcomes Group (PPOG) is an international collaborative of clinical investigators and clinicians within the subspecialty of pediatric anesthesiology and perioperative care which aims to use COMET (Core Outcomes Measures in Effectiveness Trials) methodology to develop core outcome setsfor infants, children and young people that are tailored to the priorities of the pediatric surgical population.Focusing on four age-dependent patient subpopulations determined a priori for core outcome set development: i) neonates and former preterm infants (up to 60 weeks postmenstrual age); ii) infants (60 weeks postmenstrual age -1 year); iii) toddlers and school age children (1-13 years); and iv) adolescents (13-18 years), we conducted a systematic review of outcomes reported in perioperative studies that include participants within age-dependent pediatric subpopulations. Our review of pediatric perioperative controlled trials published from 2008 to 2018 identified 724 articles reporting 3192 outcome measures. The proportion of published trials and the most frequently reported outcomes varied across pre-determined age groups. Outcomes related to patient comfort, particularly pain and analgesic requirement, were the most frequent domain for infants, children and adolescents. Clinical indicators, particularly cardiorespiratory or medication-related adverse events, were the most common outcomes for neonates and infants60 weeks and were the second most frequent domain at all other ages. Neonates and infants60 weeks of age were significantly under-represented in perioperative trials. Patient-centered outcomes, heath care utilization, and bleeding/transfusion related outcomes were less often reported. In most studies, outcomes were measured in the immediate perioperative period, with the duration often restricted to the post-anesthesia care unit or the first 24 postoperative hours. The outcomes identified with this systematic review will be combined with patient centered outcomes identified through a subsequent stakeholder engagement study to arrive at a core outcome set for each age-specific group.

Yanyan Tian, Shuguan Xia, Mingde Ma, Yonggang Zuo Department of Thyroid and Breast Surgery, Huaihe Hospital of Henan University, Kaifeng 475000, People’s Republic of ChinaCorrespondence: Yanyan TianDepartment of Thyroid and Breast Surgery, Huaihe Hospital of Henan University, No.8 Baobei Road, Gulou District, Kaifeng 475000, People’s Republic of ChinaEmail tianyanyantanyy@163.comBackground: Recent studies revealed that long non-coding RNAs (lncRNA) play crucial roles in cancer initiation and progression. However, the function and underlying mechanism of lncRNAs in triple-negative breast cancer (TNBC) are little investigated.Methods: qRT-PCR was used to investigate LINC00096 expression in TNBC tissues and cells. Function assays were used to test the effects of LINC00096 on TNBC cells progression. In addition, luciferase reporter and qRT-PCR assays were used to determine the underlying mechanism of LINC00096 on TNBC progression.Results: In our present study, we identify LINC00096 as one of the most upregulated lncRNA in TNBC progression by using microarray screening. High LINC00096 expression was obviously related to advanced tumor stage, metastasis, poor prognosis of patients. Loss-of-function assays showed that LINC00096 suppression reduced TNBC cells proliferation and invasive abilities in vitro. Mechanistically, we demonstrated that LINC00096 directly interacted with miR-383-5p, subsequently acted as a miRNA sponge to increase RBM3 expression.Conclusion: In the present study, we indicated that LINC00096 might promote the proliferation and invasion through regulating the miR-383-5p/RBM3 pathway in TNBC, which providing a novel therapeutic target for cancer treatment.Keywords: LINC00096, miR-383-5p, RBM3, triple-negative breast cancer

Tin-based compounds are promising anode materials for sodium-ion batteries (SIBs), owing to their high theoretical capacities and relatively low sodiation potential. However, their high-rate performance and cycle life-span are severely impeded by the inherent sluggish reaction kinetics and large structural change during charging and discharging. Herein, we report a composite anode consisting of SnO2/SnSe2 heterostructure nanoparticles uniformly encapsulated in N-doped carbon nanotubes (SnO2/SnSe2@C) for high-performance SIBs. The hollow tube nano-architecture not only accommodates the volume expansion of SnO2/SnSe2, but also facilitates the electrolyte penetration and shortens Na+ pathways. Meanwhile, the N-doped carbon shells provide highways for electron transport and contribute to the total capacity. More importantly, the construction of heterostructures boosts the charge transfer kinetics and further stabilizes the electrode structure by the additional confining effects of the increased crystalline boundaries. Benefiting from the synergistic effects between the elaborately-designed electrode architecture and the incorporation of heterostructures, the SnO2/SnSe2@C composite delivered a superior rate capability (322 mAh g−1 at 4 A g−1) and remarkable cycling stability with a capacity retention of 87.7% after 1000 cycles at 2 A g−1.

Background In recent years, more and more research evidence indicates that the causes of various neurodegeneration diseases are related to neuroinflammation in the brain, Aβ1–42 may be a key factor in the development of neuroinflammation in neurodegenerative diseases. Therefore, it is urgent to find an effective and targeted alleviation of neuroinflammation caused by Aβ1–42. Methods Our study found that exogenous administration of Aβ1–42 has a very obvious polarizing effect on microglia in the brain compared with the PBS-treated group. After the intervention of Aβ1–42, we obtained the mesenchymal stem cells derived exosome by ultracentrifugation. Microglia were treated with MSC-Exo in vivo and in vitro. Results The MSC-Exo were found have the effect of inhibiting microglial polarization in vivo and in vitro experiments. It was further found that its target gene was TLR2 on the surface of microglial cells to inhibit the expression of the downstream protein MYD88/NF-κB and inhibit the microglia polarization and the development of neuroinflammation. Conclusion MSC-Exo can significantly inhibited the Aβ1–42 induced microglia polarization by TLR2/MYD88/NF-κb pathway.

MotivationFusarium langsethiaeis a T-2 and HT-2 mycotoxins producingFusariumspecies firstly characterised in 2004. It is commonly isolated from oats in Northern Europe. T-2 and HT-2 mycotoxins exhibit immunological and haemotological effects in animal health mainly through inhibition of protein, RNA and DNA synthesis. The development of a high-quality and comprehensively annotated assembly for this species is therefore essential in providing the molecular understanding and the mechanism of T-2 and HT-2 biosynthesis inF. langsethiaeto help develop effective control strategies.ResultsTheF. langsethiaeassembly was produced using PacBio long reads, which were then assembled independently using Canu, SMARTdenovo and Flye; producing a genome assembly total length of 59Mb and N50 of 3.51Mb. A total of 19,336 coding genes were identified using RNA-Seq informedab-initiogene prediction. Finally, predicting genes were annotated using the basic local alignment search tool (BLAST) against the NCBI non-redundant (NR) genome database and protein hits were annotated using InterProScan. Genes with blast hits were functionally annotated with Gene Ontology.Contactf.mohareb@cranfield.ac.ukData availabilityRaw sequence reads and assembled genome can be downloaded from: GenBank under the accession JAFFKB000000000

Displays are basic building blocks of modern electronics1,2. Integrating displays into textiles offers exciting opportunities for smart electronic textiles—the ultimate goal of wearable technology, poised to change the way in which we interact with electronic devices3,4,5,6. Display textiles serve to bridge human–machine interactions7,8,9, offering, for instance, a real-time communication tool for individuals with voice or speech difficulties. Electronic textiles capable of communicating10, sensing11,12 and supplying electricity13,14 have been reported previously. However, textiles with functional, large-area displays have not yet been achieved, because it is challenging to obtain small illuminating units that are both durable and easy to assemble over a wide area. Here we report a 6-metre-long, 25-centimetre-wide display textile containing 5 × 105 electroluminescent units spaced approximately 800 micrometres apart. Weaving conductive weft and luminescent warp fibres forms micrometre-scale electroluminescent units at the weft–warp contact points. The brightness between electroluminescent units deviates by less than 8 per cent and remains stable even when the textile is bent, stretched or pressed. Our display textile is flexible and breathable and withstands repeated machine-washing, making it suitable for practical applications. We show that an integrated textile system consisting of display, keyboard and power supply can serve as a communication tool, demonstrating the system’s potential within the ‘internet of things’ in various areas, including healthcare. Our approach unifies the fabrication and function of electronic devices with textiles, and we expect that woven-fibre materials will shape the next generation of electronics.

In this work, a numerical model is proposed to study chloride transport in alkali-activated materials. This model is based on multiple-relaxation-time lattice Boltzmann method, where particle distribution function is introduced to simulate the chloride binding and diffusion. This model takes into account diffusion, homogenous reaction between chloride ions and diffusive solid, and heterogeneous reaction between chloride ions and non-diffusive solid. The accuracy of the model is confirmed by a benchmark simulation of transient reactive transport problem. As a demonstration, this model is then applied to simulate chloride transport in alkali-activated slag paste with varying alkaline activators. The influence of alkali content, silica content, curing age and chloride binding on the chloride transport property is briefly discussed.

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is associated with congenital absence of the uterus, cervix, and the upper part of the vagina; it is a sex-limited trait. Disrupted development of the Müllerian ducts (MD)/Wölffian ducts (WD) through multifactorial mechanisms has been proposed to underlie MRKHS. In this study, exome sequencing (ES) was performed on a Chinese discovery cohort (442 affected subjects and 941 female control subjects) and a replication MRKHS cohort (150 affected subjects of mixed ethnicity from North America, South America, and Europe). Phenotypic follow-up of the female reproductive system was performed on an additional cohort of PAX8-associated congenital hypothyroidism (CH) (n = 5, Chinese). By analyzing 19 candidate genes essential for MD/WD development, we identified 12 likely gene-disrupting (LGD) variants in 7 genes: PAX8 (n = 4), BMP4 (n = 2), BMP7 (n = 2), TBX6 (n = 1), HOXA10 (n = 1), EMX2 (n = 1), and WNT9B (n = 1), while LGD variants in these genes were not detected in control samples (p = 1.27E−06). Interestingly, a sex-limited penetrance with paternal inheritance was observed in multiple families. One additional PAX8 LGD variant from the replication cohort and two missense variants from both cohorts were revealed to cause loss-of-function of the protein. From the PAX8-associated CH cohort, we identified one individual presenting a syndromic condition characterized by CH and MRKHS (CH-MRKHS). Our study demonstrates the comprehensive utilization of knowledge from developmental biology toward elucidating genetic perturbations, i.e., rare pathogenic alleles involving the same loci, contributing to human birth defects. © 2020 American Society of Human Genetics

In addition to increased aberrant protein aggregation, inflammation has been proposed as a key element in the pathogenesis and progression of Alzheimer’s disease. How inflammation interacts with other disease pathways and how protein aggregation increases during disease are not clear. We used single molecule imaging approaches and membrane permeabilisation assays to determine the effect of chronic exposure to TNF, a master proinflammatory cytokine, on protein aggregation in human induced pluripotent stem cell-derived neurons harbouring monogenic Alzheimer’s disease mutations. We report that exposure of Alzheimer’s disease, but not control, neurons to TNF induces substantial production of extracellular protein aggregates. Aggregates from Alzheimer’s disease neurons are composed of amyloid-β and α-synuclein and induce significant permeabilisation of lipid membranes in an assay of pathogenicity. These findings provide support for a causal relationship between two crucial processes in Alzheimer’s disease pathogenesis, and suggest that targeting inflammation, particularly TNF, may have beneficial downstream effects on ameliorating aberrant protein aggregation and accumulation.

Cost-effective material with a rational design is significant for both sodium-ion batteries (SIBs) and electromagnetic wave (EMW) absorption. Herein, we report an elaborate yolk-shell FeS2@C nanocomposite as a promising material for application in both SIBs and EMW absorption. When applied as an anode material in SIBs, the yolk-shell structure not only facilitates a fast electron transport and shortens Na ion diffusion paths but also eases the huge volume change of FeS2 during repeated discharge/charge processes. The as-developed FeS2@C exhibits a high specific capacity of 616 mA h g-1 after 100 cycles at 0.1 A g-1 with excellent rate performance. Furthermore, owing to the significant cavity and interfacial effects enabled by yolk-shell structuring, the FeS2@C nanocomposite delivers excellent EMW absorption properties with a strong reflection loss (-45 dB with 1.45 mm matching thickness) and a broad 15.4 GHz bandwidth. This work inspires the development of high-performance bifunctional materials.