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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Open insufflation: a novel technique for identifying the intersegmental border.

Segmentectomy is gaining popularity for the treatment of lung cancer, especially in the early stages. Comprehensive understanding of segmental and subsegmental anatomy is required for the procedure to be successfully completed from a technical and oncological point of view. We hereby present a novel technique for delineating the intersegmental border, which can be widely reproduced because it is not time-consuming and does not require special equipment.

Uniportal Subxiphoid Video-Assisted Thoracoscopic Anatomical Segmentectomy: Technique and Results.

BACKGROUND: Performing sublobar resection for early stage non-small cell lung carcinoma is becoming increasingly popular, with studies suggesting equivalent outcomes to lobectomy when sufficient lymph node sampling is performed. Furthermore, there has been a move to minimally invasive thoracic surgery facilitating enhanced recovery and reduced postoperative morbidity. The subxiphoid video-assisted thoracic surgery (SVATS) approach is a novel technique that is becoming increasingly popular, with evidence of reduced postoperative pain. Here, we report experience and the technique of performing segmentectomy by the uniportal SVATS approach. METHODS: The uniportal SVATS approach was used to perform all possible segmentectomies. Specific instruments were designed to facilitate performing surgery through this approach, and the operative technique is described and demonstrated with videos. RESULTS: Between September 2014 and April 2017, 242 segmentectomies were performed by uniportal SVATS. Twenty-nine of the patients underwent bilateral procedures. The mean duration of surgery was 2.14 ± 0.78 hours. Lymph node stations were accessible, and a mean of 4.00 ± 1.00 lymph node stations and 10.64 ± 3.38 lymph nodes were sampled. The mean postoperative hospital length of stay was 4.67 ± 9.54 days. Only 4 cases required conversion to thoracotomy, and 3 required conversion to full lobectomy. There were no perioperative deaths, with 30-day survival of 100%. CONCLUSIONS: This report demonstrates that the uniportal SVATS approach can be safely and effectively utilized to perform pulmonary segmentectomies. Our series demonstrates that it is possible to access and resect all segments by this novel approach to VATS.

ClariVein™ - One year results of mechano-chemical ablation for varicose veins in a multi-ethnic Asian population from Singapore.

OBJECTIVES: This study assessed the effectiveness and patient experience of ClariVein for varicose veins and chronic venous insufficiency (CVI) in a multi-ethnic Asian population from Singapore. METHODS: A total of 121 patients underwent mechano-chemical ablation. Patients were reviewed at an interval of one week, and at 3, 6 and 12 months post procedure and underwent Duplex ultrasound with patient satisfaction assessment. RESULTS: At three months of follow-up, the great saphenous vein and short saphenous vein occlusion rates were 90.8% and 96.0%, respectively. At six months of follow-up, the GSV and short saphenous vein occlusion rates were 86.9% and 90.9%, respectively. At one year, great saphenous vein and short saphenous vein occlusion rates were 84.8% and 94.3%, respectively. CONCLUSIONS: Early results are similar to what is described so far in the mechano-chemical ablation literature but recurrences are more than expected at one year. This is disappointing but is tempered by the fact that the majority of patients were asymptomatic and required no reintervention.

Subxiphoid uniportal video-assisted thoracoscopic middle lobectomy and anterior anatomic segmentectomy (S3).

The video-assisted thoracoscopic surgery (VATS) approach for combined lobectomy and segmentectomy in the same lung is an infrequent procedure, rarely reported in the literature. Currently, Most of the surgeons still use 2-3 thoracic incisions for thoracoscopic anatomic resections. However, the uniportal approach is gaining worldwide acceptance in the recent years. The main advances of uniportal VATS during the last years are related to improvements in surgical technique by implementing new technology. The experience acquired with the uniportal technique allows expert uniportal VATS surgeons to explore new approaches in order to minimize even more the surgical invasiveness. Recently the aim to avoid the intercostal nerve damage created by the transthoracic incision has led to the creation of a novel procedure entitled uniportal VATS subxiphoid approach. Here we report the first case of a lobectomy combined with anatomic segmentectomy performed through a uniportal subxiphoid approach.

Uniportal video-assisted thoracoscopic bronchoplastic and carinal sleeve procedures.

Despite of the recent advanced with the video-assisted thoracoscopic surgery (VATS), the most common approach for bronchial and carinal resection is still the open surgery. The technical difficulties, the steep learning curve and the concerns about performing an oncologic and safe reconstruction in advanced cases, are the main reasons for the low adoption of VATS for sleeve resections. Most of the authors use 3-4 incisions for thoracoscopic sleeve procedures. However these surgical techniques can be performed by a single incision approach by skilled uniportal VATS surgeons. The improvements of the surgical instruments, high definition cameras and recent 3D systems have greatly contributed to facilitate the adoption of uniportal VATS techniques for sleeve procedures. In this article we describe the technique of thoracoscopic bronchial sleeve, bronchovascular and carinal resections through a single incision approach.