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Protein adsorption preferentially occurs and significantly affects the physicochemical reactions once the biodegradable magnesium alloys as bone replacements have been implanted. To date, interactions mechanisms between Mg implants and proteins remain unclear at a molecular level. Thereby, a combination of molecular dynamic (MD) simulations and experimental exploration is used to investigate the adsorption behavior and conformational change of bovine serum albumin (BSA), a representative protein of blood plasma, upon the surface of micro-arc oxidation (MAO) coated Mg alloy AZ31. The influences of absorbed proteins on the cytocompatibility of MAO coating are evaluated by virtue of cytotoxicity assay. Results indicate that the negatively charged O atoms (BSA) exhibit strong interaction with Mg2+ ions of Mg(OH)2, revealing that BSA molecules are ionically adsorbed on the AZ31 surface. Interestingly, MD simulation reveals that MAO coating demonstrates superior ability to capture BSA molecules during the process of adsorption owing to strong electric attraction between the negatively charged O atoms in BSA molecules with Mg atoms of MgO in MAO coating. Moreover, the α-helix part of absorbed BSA molecules on AZ31 substrate and MAO coating markedly decreases with an increase in β-sheet, β-turn and unordered contents, which is attributed to the reduction in the number of hydrogen bonds in BSA molecules. Furthermore, the adsorbed BSA molecules improve the cytocompatibility of MAO coating since the positively charged -NH3+ group and β-sheet content of absorbed BSA molecules mediate the cell adhesion by interacting with the negatively charged cell membrane.

Implant-associate infection (IAI) is a major cause of failure of bone implant materials, and one of the significant challenges in clinical managements. A synergistic coating strategy combining montmorillonite (MMT) sustained release, adsorption of bacteria and gentamicin (GS) bactericidal is proposed herein to tackle infection issues. Surface morphology, microstructure and chemical composition of the samples were investigated using SEM, XRD, FT-IR and XPS. Electrochemical experiments and immersion experiments reveal that corrosion resistance of Mg samples with GS/MMT coatings was higher than that of bare Mg alloy substrate in DMEM solution. In vitro studies demonstrated that the GS/MMT coating had a significant inhibitory effect on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The viability of MC3T3-E1 cells was 92.7% after a co-culturing for 72 h. After a subcutaneous transplantation of 90 days, the survival rate was 100% for GS/MMT-coated Mg alloy specimens with no infection at the implantation sites and no toxic damage to liver, kidney and local muscles pathological sections. This study provides a novel method for the preparation of sustained-release antimicrobial coatings on biodegradable Mg alloys as promising candidates for orthopedic implant materials.

List of differentially expressed genes after SRSF3-KO in GSCs

This files contains supplemental figures related to Figures 1-3, 4, and 6, and four supplemental tables, and supplemental materials and methods.

List of SRSF3-affected AS events in GSCs

List of SRSF3-affected and -correlated AS events in GSCs

Primers and gRNA sequences

Misregulated alternative RNA splicing (AS) contributes to the tumorigenesis and progression of human cancers, including glioblastoma (GBM). Here, we showed that a major splicing factor, serine and arginine rich splicing factor 3 (SRSF3), was frequently upregulated in clinical glioma specimens and that elevated SRSF3 was associated with tumor progression and a poor prognosis for patients with glioma. In patient-derived glioma stem-like cells (GSC), SRSF3 expression promoted cell proliferation, self-renewal, and tumorigenesis. Transcriptomic profiling identified more than 1,000 SRSF3-affected AS events, with a preference for exon skipping in genes involved with cell mitosis. Motif analysis identified the sequence of CA(G/C/A)CC(C/A) as a potential exonic splicing enhancer for these SRSF3-regulated exons. To evaluate the biological impact of SRSF3-affected AS events, four candidates were selected whose AS correlated with SRSF3 expression in glioma tissues, and their splicing pattern was modified using a CRISPR/Cas9 approach. Two functionally validated AS candidates were further investigated for the mechanisms underlying their isoform-specific functions. Specifically, following knockout of SRSF3, transcription factor ETS variant 1 (ETV1) gene showed exon skipping at exon 7, while nudE neurodevelopment protein 1 (NDE1) gene showed replacement of terminal exon 9 with a mutually exclusive exon 9′. SRSF3-regulated AS of these two genes markedly increased their oncogenic activity in GSCs. Taken together, our data demonstrate that SRSF3 is a key regulator of AS in GBM and that understanding mechanisms of misregulated AS could provide critical insights for developing effective therapeutic strategies against GBMs.Significance:SRSF3 is a significant regulator of glioma-associated alternative splicing, implicating SRSF3 as an oncogenic factor that contributes to the tumor biology of GBM.

Background Long noncoding RNAs (lncRNAs) regulate the etiology of complex diseases and cancers, including glioblastoma (GBM). However, lncRNA-based therapies are limited because the mechanisms of action of many lncRNAs with their binding partners are not completely understood. Methods We used transcriptomic and genomic data to analyze correlations between LINC02283 and PDGFRA (platelet-derived growth factor receptor A). The biological functions of the novel lncRNA were assessed in vivo using patient-derived glioma stem-like cells (GSCs), and orthotopic GBM xenografts. Immunoblotting, qRT-PCR, RNA pull down, crosslinked RNA immunoprecipitation, fluorescence in situ hybridization, and antisense oligo-mediated knockdown were performed to explore the regulation of LINC02283 on PDGFRA signaling. Expression of LINC02283 in clinical samples was assessed using pathologically diagnosed GBM patient samples. Results We identified a novel oncogenic lncRNA, LINC02283, that is highly expressed in the PDGFRA mutation-driven cohort of glioma patients and associated with worse prognosis. LINC02283 gene co-amplifies with the PDGFRA locus and shows high correlation with PDGFRA expression. Deprivation of LINC02283 in GSCs with PDGFRA amplification mutation, attenuated tumorigenicity and enhanced survival in orthotopic GBM xenograft models, while overexpression of LINC02283 in GSCs with wild-type PDGFRA, enhances PDGFRA signaling, and decreases survival. Further, LINC02283 interacts with PDGFRA to enhance its signaling and that of its downstream targets AKT and ERK, thus promoting oncogenesis in GBM. Conclusions Our results provide strong evidence of LINC02283 as a regulator of PDGFRA oncogenic activity and GBM malignancy and support the potential of lncRNAs as possible therapeutic targets.

Topiramate (TPM) is widely used as monotherapy or add-on therapy in adults and children (aged 2 to 16 years) with primary generalized tonic-clonic seizures or focal-onset seizures. TPM has also expanded its treatment spectrum to other seizure types and epileptic encephalopathies. Moreover, TPM has beneficial effects in some comorbidities of epilepsy such as migraine/headache and obesity. Interestingly, it also exhibited neuroprotective effects in several preclinical studies. The most common side effects of TPM are generally mild to moderate, including somnolence, dizziness, fatigue, insomnia and weight loss, which may be reduced through starting with a low dose and slowing titration to effective dosages. The mechanisms underlying the antiepileptic effect and adverse reactions of TPM have been extensively studied in the past 14 years since the last comprehensive review of TPM. Multiple mechanisms including but not limited to: (1) blockade of voltage-gated Na

Mg alloys possess biodegradability, suitable mechanical properties, and biocompatibility, which make them possible to be used as biodegradable implants. However, the uncontrollable degradation of Mg alloys limits their general applications. In addition to the factors from the metallic materials themselves, like alloy compositions, heat treatment process and microstructure, some external factors, relating to the test/service environment, also affect the degradation rate of Mg alloys, such as inorganic salts, bioorganic small molecules, bioorganic macromolecules. The influence of bioorganic molecules on Mg corrosion and its protection has attracted more and more attentions. In this work, the cutting-edge advances in the influence of bioorganic molecules (i.e., protein, glucose, amino acids, vitamins and polypeptide) and their coupling effect on Mg degradation and the formation of protection coatings were reviewed. The research orientations of biomedical Mg alloys in exploring degradation mechanisms in vitro were proposed, and the impact of bioorganic molecules on the protective approaches were also explored.

Smart polymeric coatings with early corrosion self-warning and damage self-repairing characteristics have garnered tremendous interest due to their ability to sense corrosion reactions and repair coating defects. However, tracking the repair process and its underlying protection mechanism is highly challenging. Herein, we report the construction of a novel composite coating by incorporating multifunctional nanosensors (graphene oxide-zeolitic imidazole frameworks loaded with 1,10-phenanthroline) into a thermo-responsive polyurethane. Under damaging events, the localized acidity derived from metal corrosion stimulates the decomposition of the nanosensors to produce 1,10-phenanthroline and benzimidazole. The generated ferrous ions are rapidly sensed by the released 1,10-phenanthroline to produce a conspicuous red color, which warns of the corrosion occurrence. In profiting from the photothermal effect of graphene oxide, the composite coating exhibits efficient crack closure behavior under near-infrared light irradiation. Morphology observation indicates that a coating scratch (about 30 μm wide) almost closed with 20 s of irradiation. The photothermally activated crack closure combined with benzimidazole inhibition endows the prepared coating with superior self-repairing performance. Interestingly, the change in color intensity around the coating defect can assist in tracking the repair process. Therefore, this work provides a novel strategy to visualize microscopic behaviors during damage and repair processes.

BackgroundThe immune-inflammatory response has been widely considered to be involved in the pathogenesis of post-stroke depression (PSD), but there is ambiguity about the mechanism underlying such association.MethodsAccording to Diagnostic and Statistical Manual of Mental Disorders (5th edition), depressive symptoms were assessed at 2 weeks after stroke onset. 15 single nucleotide polymorphisms (SNPs) in genes of indoleamine 2,3-dioxygenase (IDO, including IDO1 and IDO2) and its inducers (including pro-inflammatory cytokines interferon [IFN]-γ, tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-2 and IL-6) were genotyped using SNPscan™ technology, and serum IDO1 levels were detected by double-antibody sandwich enzyme-linked immune-sorbent assay.ResultsFifty-nine patients (31.72%) were diagnosed with depression at 2 weeks after stroke onset (early-onset PSD). The IDO1 rs9657182 T/T genotype was independently associated with early-onset PSD (adjusted odds ratio [OR] = 3.008, 95% confidence interval [CI] 1.157-7.822, p = 0.024) and the frequency of rs9657182 T allele was significantly higher in patients with PSD than that in patients with non-PSD (χ2 = 4.355, p = 0.037), but these results did not reach the Bonferroni significance threshold (p > 0.003). Serum IDO1 levels were also independently linked to early-onset PSD (adjusted OR = 1.071, 95% CI 1.002-1.145, p = 0.044) and patients with PSD had higher serum IDO1 levels than patients with non-PSD in the presence of the rs9657182 T allele but not homozygous C allele (t = -2.046, p = 0.043). Stroke patients with the TNF-α rs361525 G/G genotype had higher serum IDO1 levels compared to those with the G/A genotype (Z = -2.451, p = 0.014).ConclusionsOur findings provided evidence that IDO1 gene polymorphisms and protein levels were involved in the development of early-onset PSD and TNF-α polymorphism was associated with IDO1 levels, supporting that IDO1 which underlie strongly regulation by cytokines may be a specific pathway for the involvement of immune-inflammatory mechanism in the pathophysiology of PSD.

BackgroundHomocysteine (Hcy) has been indicated to be involved in pathophysiology of post stroke depression (PSD). There is a lack of research to study the relationship between Hcy metabolism genes and PSD. Our study aims to investigate the relationship among Hcy metabolism genes, Hcy, and early-onset PSD.Materials and methodsWe recruited 212 patients with stroke and collected their peripheral blood sample, clinical data, and laboratory test on admission. 12 single nucleotide polymorphisms (SNPs) in methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), and methionine synthase (MTR) genes were genotyped by high-resolution melt analysis. PSD was diagnosed by DSM-V at 2 weeks after stroke. Binary logistic regression and haplotype analysis were used to examine the association between Hcy metabolism genes and PSD. Mediation analysis was performed to clarify whether the SNPs exerted their effect on PSD by affecting the Hcy level.Results81 patients were diagnosed with PSD, and the incidence rate was 38.2%. Hcy level in PSD group was significantly higher than it in non-PSD group (p = 0.019). MTHFR rs1801133 AA genotype an A allele were associated with an elevated risk of PSD after adjustment for some confounding factors (OR = 4.021, 95% CI: 1.459∼11.080, p = 0.007 for AA genotype; OR = 1.808, 95% CI: 1.172∼2.788, p = 0.007 for A allele). Furthermore, the effect of MTHFR rs1801133 AA genotype on PSD was mediated by Hcy (OR = 1.569, 95% CI: 0.013∼3.350, p < 0.05).ConclusionMTHFR rs1801133 and Hcy were associated with PSD, and MTHFR rs1801133 may exert an effect on PSD via mediating Hcy level. This offers a new perspective for treating PSD and understanding the mechanism of PSD.

Many inflammatory skin diseases are characterized by altered epidermal differentiation. Whether this altered differentiation promotes inflammatory responses has been unknown. Here, we show that IRAK2, a member of the signaling complex downstream of IL-1 and IL-36, correlates positively with disease severity in both atopic dermatitis and psoriasis. Inhibition of epidermal IRAK2 normalizes differentiation and inflammation in two mouse models of psoriasis- and atopic dermatitis-like inflammation. Specifically, we demonstrate that IRAK2 ties together proinflammatory and differentiation-dependent responses and show that this function of IRAK2 is specific to keratinocytes and acts through the differentiation-associated transcription factor ZNF750. Taken together, our findings suggest that IRAK2 has a critical role in promoting feed-forward amplification of inflammatory responses in skin through modulation of differentiation pathways and inflammatory responses.

The novel coronavirus 2019 (COVID-19) pandemic represents one of the biggest global health threats in the last two decades, so researchers around the world are searching for solutions and treatments for COVID-19. At the time of writing, there are no specific drugs that have demonstrated suitable effectiveness in treating COVID-19. The current challenge involves designing tools for the prevention, rapid and accurate diagnosis, drug delivery, and effective treatment of this novel coronavirus. In this short review, we discuss how nanotechnology offers new ways to combat COVID-19, and how nanomaterials can be applied to control the COVID-19 outbreak. We also summarize relevant studies regarding the use of nanomaterials for preventing viral spread, preparing vaccines, and diagnosing coronavirus, as well as studies that show how nanoparticles can be used as drug delivery systems for the treatment of viral infections. Research on nanotechnology-based diagnosis, drug delivery, and antiviral therapy is currently in the early stages. However, the unique chemical properties of some nanomaterials highlight the broad prospect of nanomaterials in the future, and we propose that they will play an important role in the fight against COVID-19.新型冠状病毒-2019(COVID-19)大流行是过去20年最大的全球健康威胁之一, 因此世界各地的研究人员正在寻找COVID-19的解决方案和治疗方法。截至到撰写本文的时候, 研究人员发现还没有有效治疗COVID-19的特定药物。现阶段研究人员所面临的主要挑战是设计预防这种新型冠状病毒、快速准确诊断、药物传递和有效治疗的纳米工具。我们在这篇简短的综述中讨论了纳米技术如何为抗击COVID-19提供新方法, 还讨论了纳米材料如何应用于控制COVID-19爆发。同时, 我们还总结了纳米材料在预防COVID-19病毒传播、制备疫苗、诊断冠状病毒等方面的相关研究, 以及纳米材料作为药物递送系统治疗该病毒感染的研究。现阶段, 基于纳米技术的诊断、药物传递和抗病毒治疗的研究还处于早期阶段。然而, 一些纳米材料独特的化学性质凸显了纳米材料在未来的广阔前景, 我们认为它们将在抗击COVID-19中发挥十分重要的作用。.

The Audio Deep Synthesis Detection (ADD) Challenge has been held to detect generated human-like speech. With our submitted system, this paper provides an overall assessment of track 1 (Low-quality Fake Audio Detection) and track 2 (Partially Fake Audio Detection). In this paper, spectro-temporal artifacts were detected using raw temporal signals, spectral features, as well as deep embedding features. To address track 1, low-quality data augmentation, domain adaptation via finetuning, and various complementary feature information fusion were aggregated in our system. Furthermore, we analyzed the clustering characteristics of subsystems with different features by visualization method and explained the effectiveness of our proposed greedy fusion strategy. As for track 2, frame transition and smoothing were detected using self-supervised learning structure to capture the manipulation of PF attacks in the time domain. We ranked 4th and 5th in track 1 and track 2, respectively., 7 pages, 1 figures, Accecpted by Proceedings of the 1st International Workshop on Deepfake Detection for Audio Multimedia

Current state-of-the-art automatic speaker verification (ASV) systems are vulnerable to presentation attacks, and several countermeasures (CMs), which distinguish bona fide trials from spoofing ones, have been explored to protect ASV. However, ASV systems and CMs are generally developed and optimized independently without considering their inter-relationship. In this paper, we propose a new spoofing-aware ASV back-end module that efficiently computes a combined ASV score based on speaker similarity and CM score. In addition to the learnable fusion function of the two scores, the proposed back-end module has two types of attention components, scaled-dot and feed-forward self-attention, so that intra-relationship information of multiple enrollment utterances can also be learned at the same time. Moreover, a new effective trials-sampling strategy is designed for simulating new spoofing-aware verification scenarios introduced in the Spoof-Aware Speaker Verification (SASV) challenge 2022., Accepted by InterSpeech2022

The microstructure and chemical compositions of the solid solution-treated Mg-3Nd-1Li-0.2Zn alloy were characterized using optical microscope, scanning electron microscope (SEM), transmission electron microscope (TEM), electron probe micro-analyzer (EPMA) and X-ray photoelectron spectroscopy (XPS). The corrosion behaviour of the alloy was investigated via electrochemical polarization, electrochemical impedance spectroscopy (EIS), hydrogen evolution test and scanning Kelvin probe (SKP). The results showed that the microstructure of the as-extruded Mg-3Nd-1Li-0.2Zn alloy contained α-Mg matrix and nanometric second phase Mg41Nd5. The grain size of the alloy increased significantly with the increase in the heat-treatment duration, whereas the volume fraction of the second phase decreased after the solid solution treatment. The surface film was composed of oxides (Nd2O3, MgO, Li2O and ZnO) and carbonates (MgCO3 and Li2CO3), in addition to Nd. The as-extruded alloy exhibited the best corrosion resistance after an initial soaking of 10 min, whereas the alloy with 4h-solution-treatment possessed the lowest corrosion rate after a longer immersion (1 h). This can be attributed to the formation of Nd-containing oxide film on the alloys and a dense corrosion product layer. The dealloying corrosion of the second phase was related to the anodic Mg41Nd5 with a more negative Volta potential relative to α-Mg phase. The preferential corrosion of Mg41Nd5 is proven by in-situ observation and SEM. The solid solution treatment of Mg-3Nd-1Li-0.2Zn alloy led to a shift in corrosion type from pitting corrosion to uniform corrosion under long-term exposure.

Honoured as the second genome in humans, the gut microbiota is involved in a constellation of physiological and pathological processes, including those related to the central nervous system. The communication between the gut microbiota and the brain is realized by a complex bidirectional connection, known as the "microbiota-gut-brain axis", via neuroendocrine, immunological, and direct neural mechanisms. Recent studies indicate that gut dysfunction/dysbiosis is presumably involved in the pathogenesis of and susceptibility to epilepsy. In addition, the reconstruction of the intestinal microbiome through, for example, faecal microbiota transplantation, probiotic intervention, and a ketogenic diet, has exhibited beneficial effects on drug-resistant epilepsy. The purposes of this review are to provide a brief overview of the microbiota–gut–brain axis and to synthesize what is known about the involvement of the gut microbiota in the pathogenesis and treatment of epilepsy, to bring new insight into the pathophysiology of epilepsy and to present a preliminary discussion of novel therapeutic options for epilepsy based on the gut microbiota.

A hydrothermal deposition method was utilized to fabricate Ca-P composite coating induced by the layer-by-layer (LbL) assembled polyvinylpyrrolidone/deoxyribonucleic acid (PVP/DNA)20 multilayer on AZ31 alloy. The surface morphology and compositions were characterized by SEM, EDS, FTIR and XRD. Besides, the corrosion resistance and degradation behavior of the coating were tested via electrochemical polarization, impedance spectroscopy and immersion measurements. Results show that the main components of Ca-P coatings are hydroxyapatite, Ca3(PO4)2 and Mg3(PO4)2·nH2O. The LbL-assembled DNA and PVP promote the adsorption of Ca-P deposits on the sample surface, and structures and functional groups of the polyelectrolyte in the outermost layer are the primary influencing factor for the induction of the Ca-P coating. Carboxyl groups have the best biomineralization effect among all related functional groups. The enhanced corrosion resistance and adhesion highlight a promising use of (PVP/DNA)20-induced Ca-P coatings in the field of biomedical magnesium alloys.

Hydrophobic Mg(OH)2/calcium myristate (Ca[CH3(CH2)12COO]2, CaMS) and Mg(OH)2/magnesium myristate (Mg[CH3(CH2)12COO]2, MgMS) composite coatings were prepared on the alkali-treated AZ31 substrates via both electrodeposition and dipping methods. The morphologies, compositions, and constitutes of the coatings were investigated by using field-emission scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectrometry (FTIR) together with X-ray diffractometer (XRD). Furthermore, electrochemical (polarization and impedance spectroscopy) and hydrogen evolution tests were applied to evaluate the corrosion resistance. The wettability and adhesive strength of the composite coatings were characterized through water static contact angle (CA), sliding angle (SA), and nano-scratch tests. Results indicated that the better super-hydrophobicity, corrosion resistance, and adhesion were achieved via an electrodeposited process. The corrosion current density (icorr) and hydrogen evolution rate (HER) of the electrodeposited coating were three and one orders of magnitude smaller than the substrate, implying a significantly improved corrosion resistance. This scenario was ascribed to the super-hydrophobicity of electrodeposited composite coating with a contact angle (CA) and slide angle (SA) of 159.2° ± 0.8° and 5.2° ± 0.8°, respectively. However, the dipped composite coating was adverse to the improvement of corrosion resistance and adhesion due to the dissolution of the underlying Mg(OH)2 layer and smooth surface with less organic fatty acid salt (MgMS)

Exosomes derived from mesenchymal stem cells (MSC-Exo) are effective in modulating immunity. However, the role of MSC-Exo in clear cell renal cell carcinoma (ccRCC) is unclear. Our study was performed to identify if exosomal microRNA (miRNA) can be used as potential noninvasive biomarkers for ccRCC therapy. An orthotopic ccRCC mouse model was established, followed by MSC-Exo injection (1 mL, 20 μg/mL). The metastases of tumors were observed using HE staining, while number of dendritic cells, natural killing (NK) T cells and CD8(+) T cells was measured using flow cytometry. It was observed that MSC-Exo treatment significantly inhibited metastasis and growth of tumors, and improved immune response in vivo. As for in vitro assay, naive T cells were treated with MSC-Exo, followed by detection of T cell proliferation using EdU staining and CFSE assay. Results also showed that MSC-Exo facilitated sensitivity of ccRCC cells to NK T cells. Our experimental data further showed that miR-182 could be delivered by MSC-Exo in ccRCC, which targeted vascular endothelial growth factor A (VEGFA), as dual-luciferase reporter assays validated. In conclusion, miR-182 contained in MSC-Exo promoted immune response of T cells by suppressing VEGFA expression, thus alleviating ccRCC development.

This work reports the design and preparation of novel organic (polyvinyl alcohol, PVA)-inorganic (neodymium nitrate, Nd(NO

Tape stripping is a minimally invasive, nonscarring method that can be utilized to assess gene expression in the skin but is infrequently used given technical constraints. By comparing different tape stripping technologies and full-thickness skin biopsy results of lesional and nonlesional psoriatic skin from the same patients, we demonstrate that tape stripping with optimized high-resolution transcriptomic profiling can be used to effectively assess and characterize inflammatory responses in the skin. Upon comparison with single-cell RNA-sequencing data from psoriatic full-thickness skin biopsies, we illustrate that tape-stripping efficiently captures the transcriptome of the upper layers of the epidermis with sufficient resolution to assess the molecular components of the feed-forward immune amplification pathway in psoriasis. Notably, nonlesional psoriatic skin sampled by tape stripping demonstrates activated, proinflammatory changes when compared to healthy control skin, suggesting a prepsoriatic state, which is not captured on full-thickness skin biopsy transcriptome profiling. This work illustrates an approach to assess inflammatory response in the epidermis by combining noninvasive sampling with high throughput RNA-sequencing, providing a foundation for biomarker discoveries and mechanism of action studies for inflammatory skin conditions.

Magnesium (Mg) and its alloys are considered as ideal biodegradable materials due to their excellent mechanical properties and biocompatibility. In order to improve the surface properties to allow better adaptation to the surrounding tissue of the body, surface modification has played a significant role in satisfying multiple clinical requirements such as corrosion resistance, biocompatibility, and antibacterial ability. Here, layer-by-layer (LbL) self-assembly, which can be applied for biodegradable Mg alloys due to its extensive choice of usable units, holds great promise among all the surface techniques. In this review, the mechanisms of the driving force (i.e., electrostatic interaction, hydrogen bonding, charge transfer interaction and covalent bonding), cutting-edge advances in preparation methods (e.g., dipping, spraying, and spinning) and the functional properties (corrosion resistance, antibacterial activity, and biocompatibility) that could be achieved by the LbL coatings are summarized. A reasonable trend of the potential development of LbL for bio-Mg alloys is also proposed at the end of this article.

To investigate the impact of the COVID-19 outbreak on the behaviours, mental health and seizure control of adult patients with epilepsy (PWE) and to identify the correlation of seizure increase and the COVID-19 outbreak to guide the medical care of individuals with epilepsy during a public health crisis.This study was conducted at 28 centres from February 2020 to April 2020. Participants filled out a 62-item online survey including sociodemographic, COVID-19-related, epilepsy-related and psychological variables and were divided into two groups based on whether their seizure frequency increased during the COVID-19 pandemic. Chi-square tests and t-tests were used to test differences in significant characteristics. Multiple logistic regression analyses were used to identify risk factors for seizure worsening.A total of 1,237 adult PWE were enrolled for analysis. Of this sample, 31 (8.33%) patients experienced an increase in seizures during the pandemic. Multivariate logistic regression suggested that feeling nervous about the pandemic (P0.05), poor quality of life (P = 0.001), drug reduction/withdrawal (P = 0.032), moderate anxiety during the COVID-19 outbreak (P = 0.046) and non-seizure free before the COVID-19 outbreak (P0.05) were independently related to seizure increase during the pandemic.During the COVID-19 pandemic, PWE with poor quality of life and mental status, as well as AED reduction/withdrawal, were more likely to experience seizure increase. This observation highlights the importance of early identification of the population at high risk of seizure worsening and implementation of preventive strategies during the pandemic.

The observed incidence of psoriasis has been gradually increasing over time (J Am Acad Dermatol, 03, 2009, 394), but the underlying pathogenic factors have remained unclear. Recent studies suggest the importance of epigenetic modification in the pathogenesis of psoriasis. Aberrant epigenetic patterns including changes in DNA methylation, histone modifications and non-coding RNA expression are observed in psoriatic skin. Reversing these epigenetic mechanisms has showed improvement in psoriatic phenotypes, making epigenetic therapy a potential avenue for psoriasis treatment. Here, we summarize relevant evidence for epigenetic dysregulation contributing to psoriasis susceptibility and pathogenesis, and the factors responsible for epigenetic modifications, providing directions for potential future clinical avenues.

Background This study group has previously identified IL-9–producing mucosal mast cell (MMC9) as the primary source of IL-9 to drive intestinal mastocytosis and experimental IgE-mediated food allergy. However, the molecular mechanisms that regulate the expansion of MMC9s remain unknown. Objectives This study hypothesized that IL-4 regulates MMC9 development and MMC9-dependent experimental IgE-mediated food allergy. Methods An epicutaneous sensitization model was used and bone marrow reconstitution experiments were performed to test the requirement of IL-4 receptor α (IL-4Rα) signaling on MMC9s in experimental IgE-mediated food allergy. Flow cytometric, bulk, and single-cell RNA-sequencing analyses on small intestine (SI) MMC9s were performed to illuminate MMC9 transcriptional signature and the effect of IL-4Rα signaling on MMC9 function. A bone marrow–derived MMC9 culture system was used to define IL-4–BATF signaling in MMC9 development. Results Epicutaneous sensitization– and bone marrow reconstitution–based models of IgE-mediated food allergy revealed an IL-4 signaling-dependent cell-intrinsic effect on SI MMC9 accumulation and food allergy severity. RNA-sequencing analysis of SI-MMC9s identified 410 gene transcripts reciprocally regulated by IL-4 signaling, including Il9 and Batf. In silico analyses identified a 3491-gene MMC9 transcriptional signature and identified 2 transcriptionally distinct SI MMC9 populations enriched for metabolic or inflammatory programs. Employing an in vitro MMC9-culture model system showed that generation of MMC9-like cells was induced by IL-4 and this was in part dependent on BATF. Conclusions IL-4Rα signaling directly modulates MMC9 function and exacerbation of experimental IgE-mediated food allergic reactions. IL-4Rα regulation of MMC9s is in part BATF-dependent and occurs via modulation of metabolic transcriptional programs.

Diabetic retinopathy (DR) is a common microvascular complication that may cause severe visual impairment and blindness in patients with type 2 diabetes mellitus (T2DM). Early detection of DR will expand the range of potential treatment options and enable better control of disease progression. Epigenetic dysregulation has been implicated in the pathogenesis of microvascular complications in patients with T2DM. We sought to explore the diagnostic value of 5-hydroxymethylcytosines (5hmC) in circulating cell-free DNA (cfDNA) for DR, taking advantage of a highly sensitive technique, the 5hmC-Seal. The genome-wide 5hmC profiles in cfDNA samples from 35 patients diagnosed with DR and 35 age-, gender-, diabetic duration-matched T2DM controls were obtained using the 5hmC-Seal, followed by a case-control analysis and external validation. The genomic distribution of 5hmC in cfDNA from patients with DR reflected potential gene regulatory relevance, showing co-localization with histone modification marks for active expression (e.g., H3K4me1). A three-gene signature (MESP1, LY6G6D, LINC01556) associated with DR was detected using the elastic net regularization on the multivariable logistic regression model, showing high accuracy to distinguish patients with DR from T2DM controls (AUC [area under curve] = 91.4%; 95% CI [confidence interval], 84.3– 98.5%), achieving a sensitivity of 88.6% and a specificity of 91.4%. In an external testing set, the 5hmC model detected 5 out of 6 DR patients and predicted 7 out of 8 non-DR patients with other microvascular complications. Circulating cfDNA from patients with DR contained 5hmC information that could be exploited for DR detection. As a novel non-invasive approach, the 5hmC-Seal holds the promise to be an integrated part of patient care and surveillance tool for T2DM patients.

Mitral valve prolapse (MVP), known as balloon mitral valve, accounts for 2-4% of cases in the general population and is associated with several cardiac sequelae. A few studies have shown suboptimal results using electrocardiographic (ECG) machine learning to identify MVP in middle- or old-aged individuals; however, no studies have focused on young adults. The aim of this study is to develop an ECG-based system through machine learning to predict MVP in young adults. In a large military population of 2,206 males, aged 17–43 years, support vector machine (SVM), logistic regression (LR) and multilayer perceptron (MLP) classifiers are used as machine learning techniques for 26 ECG features and additional 6 simple biological parameters to link the output of MVP compared with a traditional ECG criterion of a negative T-axis in inferior limb leads. In the parasternal long-axis view of echocardiography, MVP is defined as a displacement of the anterior or posterior leaflet of the mitral valve to the mid portions of the annular hinge point >2 mm. The values of the area under the receiver operating characteristic curve are 74.59%, 74.16% and 73.02% in the proposed SVM, LR and MLP classifiers, respectively, which are better than 38.13% in the traditional ECG criterion for MVP. Our machine learning system provides a novel tool for screening MVP among young male adults. The proposed method can be an adjuvant to the physical findings for early detection of MVP prior to a confirmation by echocardiography for young male adults.

Probabilistic linear discriminant analysis (PLDA) or cosine similarity have been widely used in traditional speaker verification systems as back-end techniques to measure pairwise similarities. To make better use of multiple enrollment utterances, we propose a novel attention back-end model, which can be used for both text-independent (TI) and text-dependent (TD) speaker verification, and employ scaled-dot self-attention and feed-forward self-attention networks as architectures that learn the intra-relationships of the enrollment utterances. In order to verify the proposed attention back-end, we conduct a series of experiments on CNCeleb and VoxCeleb datasets by combining it with several sate-of-the-art speaker encoders including TDNN and ResNet. Experimental results using multiple enrollment utterances on CNCeleb show that the proposed attention back-end model leads to lower EER and minDCF score than the PLDA and cosine similarity counterparts for each speaker encoder and an experiment on VoxCeleb indicate that our model can be used even for single enrollment case.