METTL14 is decreased and regulates m6 A modification of α-synuclein in Parkinson's disease.

N6-methyladenosine (m6A), an emerging modification of messenger RNA, has been implicated in many biological processes. However, its role in Parkinson's disease (PD) remains largely unknown. Here, we investigated the role of m6A modification and its underlying mechanism in PD. First, 86 individuals with PD and 86 healthy controls were recruited from a pilot multicenter cohort. Levels of m6A and its modulators in peripheral blood mononuclear cells of patients with PD and controls were measured using an m6A RNA methylation quantification kit and quantitative real-time PCR. The underlying mechanism of m6A modification in PD was investigated in vitro through RNA immunoprecipitation assay, RNA stability assay, gene silencing or overexpression, western blot, and confocal immunoassay. The results show that mRNA levels of m6A, METTL3, METTL14, and YTHDF2 in patients with PD were significantly lower than in healthy controls, and METTL14 was the main factor involved in abnormal m6A modification. Area under the curve (AUC) analysis suggests METTL14 may provide excellent diagnostic capability for PD, especially when combined with plasma α-synuclein (α-syn). Spearman correlation analysis identified that METTL14 was moderately negatively correlated with plasma α-syn and the motor function of PD. Mechanistic experiments demonstrated that Mettl14 targets and regulates the expression of the α-syn gene using its methylation function. Overexpression of Mettl14 dramatically increased m6 A modification of α-syn mRNA and weakened its stability. Further results suggest that α-syn mRNA was modified by Mettl14 binding of an m6 A motif in the coding region of α-syn mRNA, while the reading protein Ythdf2 was involved in recognizing m6 A-modified α-syn mRNA. Taken together, our results reveal the potential of METTL14 as a novel diagnostic biomarker for PD and identify modification of pathogenic α-syn protein by METTL14 via an m6 A-YTHDF2-dependent mechanism.

Current Challenges and Routes Forward for Nonaqueous Lithium-Air Batteries.

Nonaqueous lithium-air batteries have garnered considerable research interest over the past decade due to their extremely high theoretical energy densities and potentially low cost. Significant advances have been achieved both in the mechanistic understanding of the cell reactions and in the development of effective strategies to help realize a practical energy storage device. By drawing attention to reports published mainly within the past 8 years, this review provides an updated mechanistic picture of the lithium peroxide based cell reactions and highlights key remaining challenges, including those due to the parasitic processes occurring at the reaction product-electrolyte, product-cathode, electrolyte-cathode, and electrolyte-anode interfaces. We introduce the fundamental principles and critically evaluate the effectiveness of the different strategies that have been proposed to mitigate the various issues of this chemistry, which include the use of solid catalysts, redox mediators, solvating additives for oxygen reaction intermediates, gas separation membranes, etc. Recently established cell chemistries based on the superoxide, hydroxide, and oxide phases are also summarized and discussed.

Uncoupling protein-2 regulates M1 macrophage infiltration of gingiva with periodontitis.

Periodontitis is an inflammatory disease accompanied by alveolar bone loss. Moreover, M1 macrophages play a critical role in the development of periodontal disease. Uncoupling protein-2 (UCP2) is a mitochondrial transporter protein that controls M1 macrophage activation by modulating reactive oxygen species (ROS) production. We investigated the role of UCP2 in M1 macrophage infiltration in gingival tissues with periodontitis. We found that the expression of UCP2 was upregulated in M1 macrophages infiltrating human periodontal tissues with periodontitis. Macrophage-specific knockout of UCP2 could increase the infiltration of macrophage and exacerbate inflammatory response in a mouse gingiva affected with periodontitis, induced by Porphyromonas gingivalis-LPS (Pg-LPS) injection. The loss of UCP2 may contribute to the enhanced abilities of proliferation, migration, pro-inflammatory cytokine secretion, and ROS production in Pg-LPS-treated macrophages. Our results indicate that UCP2 has an important role in M1 macrophage polarization in the periodontal tissue with periodontitis. It might be helpful to provide theoretical basis for design of new therapeutic strategies for periodontitis.

Comparison of Clinical Outcomes and Radiographic Measurements in 4 Different Treatment Modalities for Osteoporotic Compression Fractures: Retrospective Analysis.

STUDY DESIGN: We conducted a retrospective analysis of a prospectively collected database in a tertiary hospital over 10 years. OBJECTIVE: Treatment for vertebral compression fractures remains an area of controversy with respect to timing and type of surgical management. We analyzed the clinical outcomes and radiographic measurements of 4 different modalities of treatment for these fractures. SUMMARY OF BACKGROUND DATA: From 2001 to 2011, we analyzed a total of 363 patients after failure of 30 days of conservative management. These patients were then further managed either conservatively or with vertebroplasty, balloon kyphoplasty, or sky bone expander. Outcomes were assessed by using self-report measures: Visual Analog Score; functional measures: Oswestry Disability Index and Short-Form 36; and physiological measures: preoperative and postoperative radiographs. METHODS: The outcome measures were assessed for 6 months for those treated conservatively and up till 2 years for those treated surgically. Radiographic measurements of the spine were correlated with the clinical outcomes. RESULTS: A total of 62 patients (12.1%) were treated conservatively, 148 (40.8%) with vertebroplasty, 97 (26.7%) with balloon kyphoplasty, and 56 (15.4%) with sky bone expander. We found significant improvements in Visual Analog Score, Oswestry Disability Index, and Short-Form-36 scores for all groups after 1-month follow-up (P<0.05), with the surgical groups demonstrating a greater improvement in pain scores after the first postoperative day (P<0.0001) when compared with the conservative group. The improvements in outcomes in those treated surgically were sustained for up to 2 years with no significant difference (P>0.05) among the surgical groups. We also found significant improvement (P<0.005) in anterior vertebral and kyphotic wedge angle after surgical intervention. CONCLUSIONS: We have shown that early surgical intervention allows for quicker pain relief compared with conservative treatment, with similar improvements in anterior vertebral height and kyphotic wedge angle between all 3 groups of surgical management.

Comparison of the effectiveness and safety of one-stage versus two-stage bilateral total knee arthroplasty.

This study aims to evaluate the effectiveness and safety of the patients receiving simultaneous bilateral TKA (BTKA). A total of 93 consecutive patients with bilateral knee degenerative osteoarthritis from January 2008 to November 2013 were divided into two groups--one-stage group (bilateral TKA under a single anesthetic, n = 54) and two-stage group (bilateral TKA performed during two separate admissions, n = 39). The patients in the both group have a similar incidence of postoperative complications (p = 0.544). The one-stage BTKA can significantly (p < 0.05) decrease the operative time, length of stay, and hospital charges, when compared to two-stage BTKA. The patients in one-stage group have a significantly (p < 0.05) higher postoperative drainage, amount of hidden blood loss, amount of blood loss, allogeneic transfusion and rate of blood transfusion, compared with those in two-stage group. Patients in both groups had a similar KSS (p = 0.839) and ROM (p = 0.383). The findings suggests that one-stage BTKA may be safely performed with similar knee function to those of two-stage procedure, and has the added benefit of single anaesthetic, reduced costs and decreased hospital stay when compared to two-stage BTKA.

A novel fluorinated polyimide surface with petal effect produced by electrospinning.

Superhydrophobic surfaces with strong adhesion to water droplets are drawing great attention due to their unique applications. In this communication, we propose a method to construct such surfaces with considerably strong solid-water adhesion. A novel fluorinated polyimide (FPI), was electrospun into dented nano and/or micro bowl-like particles linked with nanofibers. Surfaces consisting of such structures present robust superhydrophobicity as well as ultra high adhesion. A physical model is built to explain the generation of high adhesion on the revolutionary electrospun structures.

Spectral assemblage using light emitting diodes to obtain specified lighting characteristics.

Light emitting diodes (LEDs) are considered next-generation light sources. Because of their narrow emission spectrum, easy adjustment, and various other characteristics, LEDs can be used in many situations, especially those that require dimming or spectral assemblage. In this paper we discuss spectral assemblage with LEDs. We cover possible valid arrangements in a spectrum from 400 to 700 nm by an exhaustive and genetic algorithm, calculate the highest luminous efficacy of a source for each correlated color temperature and color-rendering index, and present the corresponding energy distribution.

Pompon mum-like ionic covalent organic framework nanocomposites for efficient solid-phase extraction of nonsteroidal anti-inflammatory drugs.

Molecularly imprinted ionic covalent organic framework nanocomposites (MI-IC-COF@SnO2) were prepared as potential adsorbents for the enhanced adsorption of nonsteroidal anti-inflammatory drugs (NSAIDs) from aqueous solution. The resulting material exhibited a pompon mum-like structure, featuring a large surface area, and well-defined mesopores. The presence of uniform positive ions within the three-dimensional skeleton of MI-IC-COF@SnO2 facilitated a rapid adsorption rate and high adsorption capacity for target analytes. Thermodynamic fitting revealed the adsorption process of NSAIDs to be feasible, endothermic, and spontaneous. Additionally, the adsorbent material exhibited respectable selectivity, as evidenced by imprinting factor values ranging from 2.8 to 6.7. Utilizing MI-IC-COF@SnO2 as the sorbent, a solid-phase extraction method coupled with high-performance liquid chromatography-ultraviolet detection (SPE-HPLC-UV) was developed and optimized. The proposed method demonstrated good linear range with determination coefficients of 0.998-0.999, and low limit of detection (0.18-1.35 µg L-1). Recoveries of NSAIDs in urine and river water samples were 78.1 %-106.1 %, with relative standard deviations lower than 12.5 %. This rapid and sensitive method enables the determination of NSAIDs at trace levels in complex matrices, providing reliable and reproducible results.

The potential protective role of Parkinson's disease against hypothyroidism: co-localisation and bidirectional Mendelian randomization study.

Background: The association between hypothyroidism and Parkinson's disease (PD) has sparked intense debate in the medical community due to conflicting study results. A better understanding of this association is crucial because of its potential implications for both pathogenesis and treatment strategies. Methods: To elucidate this complex relationship, we used Bayesian co-localisation (COLOC) and bidirectional Mendelian randomization (MR) analysis. COLOC was first used to determine whether hypothyroidism and PD share a common genetic basis. Subsequently, genetic variants served as instrumental variables in a bidirectional MR to explore causal interactions between these conditions. Results: COLOC analysis revealed no shared genetic variants between hypothyroidism and PD, with a posteriori probability of hypothesis 4 (PPH4) = 0.025. Furthermore, MR analysis indicated that hypothyroidism does not have a substantial causal effect on PD (OR = 0.990, 95% CI = 0.925, 1.060, p = 0.774). Conversely, PD appears to have a negative causal effect on hypothyroidism (OR = 0.776, 95% CI = 0.649, 0.928, p = 0.005). Conclusion: Our findings suggest the absence of shared genetic variants between hypothyroidism and PD. Interestingly, PD may inversely influence the risk of developing hypothyroidism, a finding that may inform future research and clinical approaches.

Flexible circumferential bioelectronics to enable 360-degree recording and stimulation of the spinal cord.

The spinal cord is crucial for transmitting motor and sensory information between the brain and peripheral systems. Spinal cord injuries can lead to severe consequences, including paralysis and autonomic dysfunction. We introduce thin-film, flexible electronics for circumferential interfacing with the spinal cord. This method enables simultaneous recording and stimulation of dorsal, lateral, and ventral tracts with a single device. Our findings include successful motor and sensory signal capture and elicitation in anesthetized rats, a proof-of-concept closed-loop system for bridging complete spinal cord injuries, and device safety verification in freely moving rodents. Moreover, we demonstrate potential for human application through a cadaver model. This method sees a clear route to the clinic by using materials and surgical practices that mitigate risk during implantation and preserve cord integrity.

Recent Progress in Developing a LiOH-Based Reversible Nonaqueous Lithium-Air Battery.

The realization of practical nonaqueous lithium-air batteries (LABs) calls for novel strategies to address their numerous theoretical and technical challenges. LiOH formation/decomposition has recently been proposed as a promising alternative route to cycling LABs via Li2 O2 . Herein, the progress in developing LiOH-based nonaqueous LABs is reviewed. Various catalytic systems, either soluble or solid-state, that can activate a LiOH-based electrochemistry are compared in detail, with emphasis in providing an updated understanding of the oxygen reduction and evolution reactions in nonaqueous media. We identify the key factors that can switch the cell chemistry between Li2 O2  and LiOH and highlight the debate around these routes, as well as rationalize potential causes for these opposing opinions. The identities of the reaction intermediates, activity of redox mediators and additives, location of reaction interfaces, causes of parasitic reactions, as well as the effect of CO2  on the LiOH electrochemistry, all play a critical role in altering the relative rates of a series of interconnected reactions and all warrant further investigation.

The emerging role of circular RNAs in Parkinson's disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease and the most common movement disorder. It involves a gradual loss of dopaminergic neurons in the substantia nigra. Although many studies have been conducted, the underlying molecular pathways of PD remain largely unknown. Circular RNAs (circRNAs), a novel class of non-coding RNAs with a covalently closed loop structure, are common in the brain. They are stable, conserved molecules that are widely expressed in eukaryotes in tissue-, cell-, and development-specific patterns. Many circRNAs have recently been identified in nervous system diseases, and some circRNA expression profiles have been linked to PD. Given that recent research has indicated the essential roles of various circRNAs in the development and progression of neurodegenerative diseases, the identification of individual circRNAs may be a promising strategy for finding new treatment targets for PD. Moreover, the search for circRNAs with high specificity and sensitivity will open up new avenues for the early diagnosis and treatment of PD. Herein, we address the biogenesis, properties, and roles of circRNAs and review their potential utility as biomarkers and therapeutic targets in PD.

Synthesis and Characterization of Photo-Cross-Linkable Silk Fibroin Methacryloyl Hydrogel for Biomedical Applications.

Photo-cross-linkable hydrogels have recently gained increased interest in the field of biomedical applications. In this study, silk fibroin was derivatized with methacrylic anhydride (MA) to obtain silk fibroin methacryloyl (SFMA), forming hydrogel under UV light exposure in 1 min. The SFMA sol-gel transition did not involve significant structural change at the early stage. Then, the formation of the irreversible ß-sheet was confirmed after 24 h. The resulting SFMA hydrogel showed a homogeneous porous structure with pore sizes ranging from 400 to 700 µm, depending on the content. In addition, these hydrogels demonstrated a lower swelling capacity, higher rheological properties and compressive modulus, and slow degradation behavior at higher content, likely due to the higher degree of cross-linking. An experiment with cells indicated the good cell compatibility of these hydrogels, as revealed by Cell Counting Kit-8 (CCK-8) assays. As a tissue-engineered material, this photo-cross-linkable SFMA is expected to have a wide range of applications in the biomedical field.

Coupling Water-Proof Li Anodes with LiOH-Based Cathodes Enables Highly Rechargeable Lithium-Air Batteries Operating in Ambient Air.

Realizing an energy-dense, highly rechargeable nonaqueous lithium-oxygen battery in ambient air remains a big challenge because the active materials of the typical high-capacity cathode (Li2 O2 ) and anode (Li metal) are unstable in air. Herein, a novel lithium-oxygen full cell coupling a lithium anode protected by a composite layer of polyethylene oxide (PEO)/lithium aluminum titanium phosphate (LATP)/wax to a LiOH-based cathode is constructed. The protected lithium is stable in air and water, and permits reversible, dendrite-free lithium stripping/plating in a wet nonaqueous electrolyte under ambient air. The LiOH-based full cell reaction is immune to moisture (up to 99% humidity) in air and exhibits a much better resistance to CO2 contamination than Li2 O2 , resulting in a more consistent electrochemistry in the long term. The current approach of coupling a protected lithium anode with a LiOH-based cathode holds promise for developing a long-life, high-energy lithium-air battery capable of operating in the ambient atmosphere.

Rare giant corneal keloid presenting 26 years after trauma: A case report.

BACKGROUND: Corneal keloid is a rare clinical disease with an unknown etiology, which is easily misdiagnosed. Surgery is the most effective treatment but is rarely reported in the literature. Herein, we report the clinical features, histopathology, and surgical outcome of a giant corneal keloid with trophoblastic vessels and discuss the genesis of the mass. CASE SUMMARY: A 36-year-old young man was admitted to the hospital because of a large mass on the surface of the left cornea. The patient had suffered an injury to his left eye at the age of 6-years-old; however, as the injury did not cause cornea perforation, he did not undergo treatment. Slit lamp exam showed a large, elevated, opaque lesion that covered the entire cornea and protruded from the surface of the eyeball. Anterior segment optical coherence tomography (AS-OCT) revealed a lesion of irregular density involving the anterior stroma. We suspected a secondary corneal fibroproliferative mass based on the clinical history, and slit lamp and AS-OCT findings. The patient subsequently underwent a superficial keratectomy and keratoplasty, and the final diagnosis of corneal keloid was confirmed by intraoperative histopathological examination. CONCLUSION: Non-penetrating corneal trauma damages corneal epithelium basement membrane, initiating stromal fibrosis and causing corneal keloids. AS-OCT and biopsy confirm diagnosis.

The Potential Circular RNAs Biomarker Panel and Regulatory Networks of Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease. It has been reported that circular RNAs (circRNAs) play important roles in several neurological diseases. However, the role and regulatory networks of circRNAs in PD are still largely unclear. In this study, we first compared the global expression level of circRNAs from patients with PD and controls using microarray, then the candidate circRNAs were validated in another PD cohort. The possible functions of these candidate circRNAs were analyzed using Gene Ontology (GO) analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and the regulatory networks of these candidate circRNAs were constructed through circRNA-miRNA-mRNA regulatory networks, protein-protein interaction (PPI) networks, and transcription factor-circRNA networks. The results indicated that hsa_circRNA_101275, hsa_circRNA_103730, and hsa_circRNA_038416 were significantly more highly expressed in patients with PD, while hsa_circRNA_102850 was lower expressed in patients with PD when compared with controls. A circRNA panel combining the four differentially expressed circRNA showed a high diagnostic ability to distinguish patients with PD from controls (AUC = 0.938). Furthermore, GO and KEGG analysis showed these candidate circRNAs were enriched in PI3K-Akt and MAPK signaling pathways. We established circRNA-miRNA-mRNA regulatory networks and identified 10 hub genes (ESR1, PTEN, SHC1, IGF1R, SMAD2, KRAS, MDM2, HIF1A, BMP4, and ACVR2B) were closely related to PD by using PPI network analysis. Besides, these circRNAs were predicted to be regulated through tyrosine hydroxylase (TH)-relevant transcription factors such as GATA2 and GATA3. In conclusion, our results suggest that the circRNA panel and the established circRNA-miRNA-mRNA regulation networks might provide potential novel biomarkers and therapeutic targets for PD.

Surgical Treatment for the Cluster Headache: Clinical Experience.

BACKGROUND: Cluster headache (CH) refers to the most painful primary headache that sometimes leads to poor quality of life and associated disability. So far, no treatment has been found to cure CHs. In this study, we introduce a novel and effective surgery for CH. METHODS: We studied 6 patients with CH diagnosed according to the criteria of the Headache Classification Committee of the IHS, third edition, who were eligible for surgical treatment on the basis of strong requirements. All of them underwent temporal craniectomy and transection of the greater superficial petrosal nerve and deep petrosal nerve pathway to the sphenopalatine ganglion. RESULTS: All 6 patients had the surgery for CH and follow-up per 3 months. We significantly cured their pain and autonomic dysfunction. In the follow-up process none of the patients had reoccurring alacrimia. All of them had reduction of secretion of nasal, oral mucosa, and parotid and were satisfied with the surgery. CONCLUSIONS: All 6 patients with CH received surgery by transection greater superficial petrosal nerve and deep petrosal nerve pathway to the sphenopalatine ganglion and were completely cured, and adverse events and serious complications did not occur.

Prognostic role of PHYH for overall survival (OS) in clear cell renal cell carcinoma (ccRCC).

This study attempts to evaluate the prognostic role of PHYH for overall survival (OS) in clear cell renal cell carcinoma (ccRCC) by means of publicly available data from The Cancer Genome Atlas (TCGA). Clinical pathologic features and PHYH expression were downloaded from the TCGA database and relationships between them were analyzed by univariate and multivariate Cox regression analyses. Gene Set Enrichment Analysis (GSEA) and gene-gene interactions were also performed between tissues with different PHYH expression levels. PHYH expression levels were significantly lower in patient with ccRCC compared with normal tissues (p = 1.156e-19). Kaplan-Meier survival analysis showed that high expression of PHYH had a better prognosis than low expression (p = 9e-05). Moreover, PHYH expression was also significantly associated with high grade (G2-4, p = 0.025), high stage (StageIII & IV, p = 5.604e-05), and high level of stage_T (T3-4, p = 4.373e-05). Univariate and multivariate Cox regression analyses indicated that PHYH could be acted as an independent prognostic factor (p < 0.05). Nomogram including clinical pathologic features and PHYH expression were also provided. GSEA revealed that butanoate metabolism, histidine metabolism, propanoate metabolism, pyruvate metabolism, tryptophan metabolism, PPAR signalling pathway, and renin-angiotensin system were differentially enriched in PHYH high-expression phenotype. ICGC database was utilized to verify the expression level and survival benefit of PHYH (both p < 0.05). We suspect that elevated PHYH expression may be served as a potential prognostic molecular marker of better survival in ccRCC. Besides, alpha-oxidation was closely regulated by PHYH, and PPAR signalling, pyruvate metabolism, butanoate metabolism, and RAS might be the key pathways regulated by PHYH in CCRC.

Uric acid increases fibronectin synthesis through upregulation of lysyl oxidase expression in rat renal tubular epithelial cells.

Urate is produced as the major end product of purine metabolism. In the last decade, the incidence of hyperuricemia increased markedly, and similar trends in the epidemiology of metabolic syndrome have been observed. Hyperuricemia is associated with renal disease, and recent studies have reported that mild hyperuricemia results in hypertension, intrarenal vascular disease, and renal injury. This has led to the hypothesis that uric acid may contribute to renal fibrosis and progressive renal disease. Our purpose was to investigate the relationship between uric acid and renal tubular injury. We applied the method of intraperitoneal injection of uric acid to generate the hyperuricemic mouse model. Compared with the saline injection group, the expression of lysyl oxidase (LOX) and fibronectin in kidneys was increased significantly in hyperuricemic groups. In vitro, uric acid significantly induced NRK-52E cells to express the ECM marker fibronectin, as well as LOX, which plays a pivotal role in ECM maturation, in a time- and dose-dependent manner. Upregulation of the urate transporter URAT1, which is located in the apical membrane of proximal tubules, sensitized the uric acid-induced fibronectin and LOX induction, while both knocking down URAT1 expression in tubular epithelial cells by RNA interference and inhibiting URAT1 function pharmacologically attenuated LOX and fibronectin expression. Furthermore, knockdown of LOX expression by a small interfering RNA strategy led to a decrease in fibronectin abundance induced by uric acid treatment. In addition, evidence of a uric acid-induced activation of the NF-kappaB signaling cascade was observed. Our findings highlight a need for carefully reevaluating our previous view on the pathological roles of hyperuricemia in the kidney and nephropathy induced by uric acid in clinical practice.