circCDK13-loaded small extracellular vesicles accelerate healing in preclinical diabetic wound models.

Chronic wounds are a major complication in patients with diabetes. Here, we identify a therapeutic circRNA and load it into small extracellular vesicles (sEVs) to treat diabetic wounds in preclinical models. We show that circCDK13 can stimulate the proliferation and migration of human dermal fibroblasts and human epidermal keratinocytes by interacting with insulin-like growth factor 2 mRNA binding protein 3 in an N6-Methyladenosine-dependent manner to enhance CD44 and c-MYC expression. We engineered sEVs that overexpress circCDK13 and show that local subcutaneous injection into male db/db diabetic mouse wounds and wounds of streptozotocin-induced type I male diabetic rats could accelerate wound healing and skin appendage regeneration. Our study demonstrates that the delivery of circCDK13 in sEVs may present an option for diabetic wound treatment.

Insomnia and anxiety among COVID-19 patients in China: the chain mediating effect of psychological capital and self-esteem.

BACKGROUND: The outbreak of Corona Virus Disease (COVID-19) in 2019 has continued until now, posing a huge threat to the public's physical and mental health, resulting in different degrees of mental health problems. As a vulnerable segment of the public, anxiety is one of the most common mental health problems among COVID-19 patients. Excessive anxiety aggravates the physical and psychological symptoms of COVID-19 patients, which is detrimental to their treatment and recovery, increases financial expenditure, affects family relations, and adds to the medical burden. OBJECTIVE: This study aimed to explore the role of psychological capital and self-esteem in the relationship between insomnia and anxiety, thereby shedding light on the mechanism of the effect of insomnia on anxiety in COVID-19 patients. METHODS: A cross-sectional study was conducted from April to May 2022 in Fangcang hospital in Shanghai, China. The self-administered questionnaires were distributed to 718 COVID-19 patients via cell phone using the Internet platform "Questionnaire Star", which included Athens Insomnia Scale, Psychological Capital Questionnaire, Self-esteem Scale, Self-Rating Anxiety Scale, gender, age, marital status, education. Data analysis was performed using descriptive analysis, independent-samples t-test, one-way analysis of variance, Pearson correlation analysis, ordinary least-squares regression, and bootstrap method. RESULTS: Education background had significant impact on anxiety in COVID-19 patients (F = 7.70, P < 0.001). Insomnia, psychological capital, self-esteem and anxiety were significantly correlated, respectively (P < 0.001). And Regression analysis showed that insomnia had a direct negative predictive effect on psychological capital (ß = -0.70, P < 0.001) and self-esteem (ß = -0.13, P < 0.001). Psychological capital had a direct positive predictive effect on self-esteem (ß = 0.12, P < 0.001). Insomnia had a direct positive predictive effect on anxiety (ß = 0.61, P < 0.001). Both psychological capital and self-esteem had significant negative predictive effects on anxiety (ß = -0.06, P < 0.05; ß = -0.72, P < 0.001). The results showed that the mediating effect of psychological capital and self-esteem was significant, and the mediating effect value was 0.21. First, the indirect effect consisting of insomnia - psychological capital - anxiety was 0.04, showing that psychological capital had a significant mediating effect. Second, the indirect effect consisting of insomnia-self-esteem-anxiety had a value of 0.10, indicating that self-esteem had a significant mediating effect. Third, the indirect effect consisting of insomnia-psychological capital-self-esteem-anxiety had a value of 0.06, suggesting that psychological capital and self-esteem had a significant chain mediating effect between insomnia and anxiety. CONCLUSIONS: Insomnia had a significant positive predictive effect on anxiety. Insomnia was first associated with a decrease in psychological capital, followed by a sequential decrease in self-esteem, which in turn was associated with increased anxiety symptoms in COVID-19 patients. Therefore, focusing on improving the psychological capital and self-esteem of patients can help alleviate the anxiety caused by insomnia in COVID-19 patients. It is recommended that patients and health care professionals increase the psychological capital and Self-esteem of COVID-19 patients through various methods to counter the effects of insomnia on anxiety.

MiR-141-3p-Functionalized Exosomes Loaded in Dissolvable Microneedle Arrays for Hypertrophic Scar Treatment.

Hypertrophic scar (HS) is a common fibroproliferative disease caused by abnormal wound healing after deep skin injury. However, the existing approaches have unsatisfactory therapeutic effects, which promote the exploration of newer and more effective strategies. MiRNA-modified functional exosomes delivered by dissolvable microneedle arrays (DMNAs) are expected to provide new hope for HS treatment. In this study, a miRNA, miR-141-3p, which is downregulated in skin scar tissues and in hypertrophic scar fibroblasts (HSFs), is identified. MiR-141-3p mimics inhibit the proliferation, migration, and myofibroblast transdifferentiation of HSFs in vitro by targeting TGF-ß2 to suppress the TGF-ß2/Smad pathway. Subsequently, the engineered exosomes encapsulating miR-141-3p (miR-141-3pOE -Exos) are isolated from adipose-derived mesenchymal stem cells transfected with Lv-miR-141-3p. MiR-141-3pOE -Exos show the same inhibitive effects as miR-141-3p mimics on the pathological behaviors of HSFs in vitro. The DMNAs for sustained release of miR-141-3pOE -Exos are further fabricated in vivo. MiR-141OE -Exos@DMNAs effectively decrease the thickness of HS and improve fibroblast distribution and collagen fiber arrangement, and downregulate the expression of α-SMA, COL-1, FN, TGF-ß2, and p-Smad2/3 in the HS tissue. Overall, a promising, effective, and convenient exosome@DMNA-based miRNA delivery strategy for HS treatment is provided.

Risk factors predisposing relapse of bullous pemphigoid at initial diagnosis: A retrospective cohort study of 205 patients.

BACKGROUND: Previous studies have revealed the factors associated with the relapse of bullous pemphigoid (BP). This study aims to assess the characteristics of BP patients at the time of initial diagnosis and a potential association with subsequent relapse occurrences. METHODS: A retrospective cohort study was conducted on 205 BP patients from January 2009 to May 2022 at the Peking Union Medical College Hospital in Beijing, China. The median follow-up duration was 2.7 years. We conducted univariate and multivariate analyses on various clinical indicators (e.g., lesional involvements and medical history) and laboratory test results. RESULTS: Among the 205 patients, 118 (57.6 %) relapsed during the follow-up period. Univariate analysis revealed several factors associated with relapse, which were greater age [Hazard Ratio (HR)1.018, 95 % confidence interval (CI) 1.004-1.032] (p = 0.010), a past medical history of thyroid diseases [HR 3.674, 95 % CI 1.472-9.167] (p = 0.005), hematological disease complications [HR 4.123, 95 % CI 1.301-13.061] (p = 0.016), negative C3 deposition in direct immunofluorescence [HR 0.574, 95 % CI 0.374-0.883] (p = 0.011) and prealbumin level less than 200 mg/L[HR 0.580, 95 % CI 0.351-0.957] (p = 0.033). Multivariate analysis demonstrated that patients with negative C3 deposition in direct immunofluorescence [HR 0.524, 95 % CI 0.296-0.927] (p = 0.026) and prealbumin levels below 200 mg/L [HR 0.541, 95 % CI 0.301-0.974] (p = 0.041) were associated with further relapses of BP. CONCLUSIONS: Negative C3 deposition in direct immunofluorescence and a prealbumin level below 200 mg/L at initial diagnosis served as predictive markers for future relapses of BP. Systemic evaluation of BP patients at initial diagnosis could be essential in helping prevent recurrences and achieve more effective disease management.

The relationship between bullous pemphigoid and renal disease and related treatments: a review of the current literature.

INTRODUCTION: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disorder in older adults. There is increasing evidence that BP has connections with renal diseases, such as glomerulopathy and neoplasm; it is also linked to the receipt of renal replacement therapy. AREAS COVERED: In this review, we summarize the current evidence that BP is a comorbidity of common renal diseases. Furthermore, our exploration of the characteristics and possible mechanisms underlying these connections provides insights that may facilitate the prevention, diagnosis, and management of BP. EXPERT OPINION: There is mounting proof that BP is not just a skin immunological disorder but rather a systemic immune-mediated illness. Quantities of case reports focused on BP as a renal disease comorbidity and the coexistence of them is not accidental. However, the underlying mechanisms are still needed to be investigated. Clinicians should be alert to the comorbidities in order to facilitate effective treatment and improve patient prognosis.

Severe acute respiratory syndrome coronavirus 2 infection in patients with autoimmune bullous diseases in China.

Patients with autoimmune bullous diseases (AIBDs) are considered to be immunocompromised and, consequently, they may be more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and have poorer outcomes. However, the risk and repercussions of SARS-CoV-2 infection in patients with AIBDs have not been fully understood. Therefore, we aimed to investigate the risk factors of SARS-CoV-2 infection and the impact of SARS-CoV-2 on patients with AIBDs. From December 2022 to January 2023, all patients with AIBDs who visited our clinic were enrolled in this study. Meanwhile, web-based questionnaires and telesurveys were used as supplements. Information about patients' demographics, comorbidities, SARS-CoV-2 infection, and vaccination, as well as AIBD status and treatments were collected and analyzed. The diagnosis of SARS-CoV-2 infection was based on a positive polymerase chain reaction test, and/or an antigen test, or the presence of typical symptoms in conjunction with an epidemiological history. Finally, 95 patients with AIBDs were enrolled, including 47 cases of pemphigus and 48 cases of pemphigoid cases, and 73 had symptoms consistent with coronavirus disease 2019. Common symptoms after SARS-CoV-2 infection were fever (80.8%), fatigue (75.0%), cough (71.2%), muscle/joint pain (49.3%), and sore throat (45.2%). No significant differences were found between SARS-CoV-2-infected and asymptomatic patients. Patients who had hypertension (p = 0.034), hyperlipidemia (p = 0.017), or more than two comorbidities (p = 0.011) were more likely to develop pneumonia after infection. Patients with pemphigus who did not achieve disease control (p = 0.045) or had an oral corticosteroid dose ≥15 mg/day (p = 0.024) and patients with pemphigoid with a disease duration ≥2 years (p = 0.037) were more prone to AIBDs aggravation. In conclusion, patients with AIBDs are generally susceptible to SARS-CoV-2 infection. Individuals with newly diagnosed AIBDs, uncontrolled disease, and a higher corticosteroid dose are more susceptible to disease exacerbation.

Recent Progress of Advanced Materials for Triboelectric Nanogenerators.

Triboelectric nanogenerators (TENGs) have received intense attention due to their broad application prospects in the new era of internet of things (IoTs) as distributed power sources and self-powered sensors. Advanced materials are vital components for TENGs, which decide their comprehensive performance and application scenarios, opening up the opportunity to develop efficient TENGs and expand their potential applications. In this review, a systematic and comprehensive overview of the advanced materials for TENGs is presented, including materials classifications, fabrication methods, and the properties required for applications. In particular, the triboelectric, friction, and dielectric performance of advanced materials is focused upon and their roles in designing the TENGs are analyzed. The recent progress of advanced materials used in TENGs for mechanical energy harvesting and self-powered sensors is also summarized. Finally, an overview of the emerging challenges, strategies, and opportunities for research and development of advanced materials for TENGs is provided.

Autophagosomes Defeat Ferroptosis by Decreasing Generation and Increasing Discharge of Free Fe2+ in Skin Repair Cells to Accelerate Diabetic Wound Healing.

Ferroptosis plays an essential role in the development of diabetes and its complications, suggesting potential therapeutic strategies targeting ferroptosis. Secretory autophagosomes (SAPs) carrying cytoplasmic cargoes have been recognized as novel nano-warrior to defeat diseases. Here, it is hypothesized that SAPs derived from human umbilical vein endothelial cells (HUVECs) can restore the function of skin repair cells by inhibiting ferroptosis to promote diabetic wound healing. High glucose (HG)-caused ferroptosis in human dermal fibroblasts (HDFs) is observed in vitro, which results in impaired cellular function. SAPs successfully inhibit ferroptosis in HG-HDFs, thereby improving their proliferation and migration. Further research show that the inhibitory effect of SAPs on ferroptosis resulted from a decrease in endoplasmic reticulum (ER) stress-regulated generation of free ferrous ions (Fe2+ ) in HG-HDFs and an increase in exosome release to discharge free Fe2+ from HG-HDFs. Additionally, SAPs promote the proliferation, migration, and tube formation of HG-HUVECs. Then the SAPs are loaded into gelatin-methacryloyl (GelMA) hydrogels to fabricate functional wound dressings. The results demonstrate the therapeutic effect of Gel-SAPs on diabetic wounds by restoring the normal behavior of skin repair cells. These findings suggest a promising SAP-based strategy for the treatment of ferroptosis-associated diseases.

Novel neutrophil extracellular trap-related mechanisms in diabetic wounds inspire a promising treatment strategy with hypoxia-challenged small extracellular vesicles.

Neutrophil extracellular traps (NETs) have been considered a significant unfavorable factor for wound healing in diabetes, but the mechanisms remain unclear. The therapeutic application of small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) has received considerable attention for their properties. Hypoxic preconditioning is reported to enhance the therapeutic potential of MSC-derived sEVs in regenerative medicine. Therefore, the aim of this study is to illustrate the detailed mechanism of NETs in impairment of diabetic wound healing and develop a promising NET-targeting treatment based on hypoxic pretreated MSC-derived sEVs (Hypo-sEVs). Excessive NETs were found in diabetic wounds and in high glucose (HG)-induced neutrophils. Further research showed that high concentration of NETs impaired the function of fibroblasts through activating endoplasmic reticulum (ER) stress. Hypo-sEVs efficiently promoted diabetic wound healing and reduced the excessive NET formation by transferring miR-17-5p. Bioinformatic analysis and RNA interference experiment revealed that miR-17-5p in Hypo-sEVs obstructed the NET formation by targeting TLR4/ROS/MAPK pathway. Additionally, miR-17-5p overexpression decreased NET formation and overcame NET-induced impairment in fibroblasts, similar to the effects of Hypo-sEVs. Overall, we identify a previously unrecognized NET-related mechanism in diabetic wounds and provide a promising NET-targeting strategy for wound treatment.

Immunomodulatory potential of mesenchymal stem cell-derived extracellular vesicles: Targeting immune cells.

Various intractable inflammatory diseases caused by disorders of immune systems have pressed heavily on public health. Innate and adaptive immune cells as well as secreted cytokines and chemokines are commanders to mediate our immune systems. Therefore, restoring normal immunomodulatory responses of immune cells is crucial for the treatment of inflammatory diseases. Mesenchymal stem cell derived extracellular vesicles (MSC-EVs) are nano-sized double-membraned vesicles acting as paracrine effectors of MSCs. MSC-EVs, containing a variety of therapeutic agents, have shown great potential in immune modulation. Herein, we discuss the novel regulatory functions of MSC-EVs from different sources in the activities of innate and adaptive immune cells like macrophages, granulocytes, mast cells, natural killer (NK) cells, dendritic cells (DCs) and lymphocytes. Then, we summarize the latest clinical trials of MSC-EVs in inflammatory diseases. Furthermore, we prospect the research trend of MSC-EVs in the field of immune modulation. Despite the fact that the research on the role of MSC-EVs in regulating immune cells is in infancy, this cell-free therapy based on MSC-EVs still offers a promising solution for the treatment of inflammatory diseases.

Associations between bullous pemphigoid and hematological diseases: Literature review on mechanistic connections and possible treatments.

Bullous pemphigoid is an autoimmune blistering disorder that primarily occurs in elderly patients. Reports indicate that BP coexists with various hematological diseases, including acquired hemophilia A, hypereosinophilic syndrome, aplastic anemia, autoimmune thrombocytopenia, and hematological malignancies. Early identification of these comorbidities contributes to a better control and reduced mortality. This article details the atypical clinical manifestations of BP when associated with hematological diseases, specific diagnostic strategies, underlying mechanistic connections, and possible treatments. Cross-reactivity between autoantibodies and exposed abnormal epitopes, shared cytokines and immune cells, together with genetic susceptibility are the most common connections between BP and hematological diseases. Patients were most often successfully treated with oral steroids combined with medications specifically targeting the hematological disorders. However, the individual comorbidities require specific considerations.

MiR146a-loaded engineered exosomes released from silk fibroin patch promote diabetic wound healing by targeting IRAK1.

Unhealable diabetic wounds need to be addressed with the help of newer, more efficacious strategies. Exosomes combined with biomaterials for sustained delivery of therapeutic agents are expected to bring new hope for chronic wound treatment. Here, the engineered exosomes modified for efficiently loading miR146a and attaching to silk fibroin patch (SFP) were demonstrated to promote diabetic wound healing. Silk fibroin binding peptide (SFBP) was screened through phage display, and SFBP-Gluc-MS2 (SGM) and pac-miR146a-pac fusion protein were constructed. The designed exosomes (SGM-Exos, miR146a-Exos, and SGM-miR146a-Exos) were isolated from the engineered placental mesenchymal stem cells (PMSCs) transduced with SGM or/and pac-miR146a-pac protein. Gluc signals indicated SGM-Exo@SFP markedly increased the binding rate and the stability of SGM-Exo. Moreover, the loading efficiency of miR146a in SGM-miR146a-Exos was ten-fold higher than that in miR146a-Exos. Superior to untreated, SGM-miR146a-Exo-only treated, and SFP-only treated groups, SGM-miR146a-Exo@SFP drived wound healing associated with less inflammation, collagen deposition, and neovascularization. The transcriptomics analysis suggested anti-inflammatory and regenerative effects with SGM-miR146a-Exo@SFP treatment. Here, we show efficient exosome@biomaterial-based miRNA delivery systems for regenerative medicine and tissue engineering.

Predictive model for early functional outcomes following acute care after traumatic brain injuries: A machine learning-based development and validation study.

INTRODUCTION: Few studies on early functional outcomes following acute care after traumatic brain injury (TBI) are available. The aim of this study was to develop and validate a predictive model for functional outcomes at discharge for TBI patients using machine learning methods. PATIENTS AND METHODS: In this retrospective study, data from 5281 TBI patients admitted for acute care who were identified in the Beijing hospital discharge abstract database were analysed. Data from 4181 patients in 52 tertiary hospitals were used for model derivation and internal validation. Data from 1100 patients in 21 secondary hospitals were used for external validation. A poor outcome was defined as a Barthel Index (BI) score ≤ 60 at discharge. Logistic regression, XGBoost, random forest, decision tree, and back propagation neural network models were used to fit classification models. Performance was evaluated by the area under the receiver operating characteristic curve (AUC), the area under the precision-recall curve (AP), calibration plots, sensitivity/recall, specificity, positive predictive value (PPV)/precision, negative predictive value (NPV) and F1-score. RESULTS: Compared to the other models, the random forest model demonstrated superior performance in internal validation (AUC of 0.856, AP of 0.786, and F1-score of 0.724) and external validation (AUC of 0.779, AP of 0.630, and F1-score of 0.604). The sensitivity/recall, specificity, PPV/precision, and NPV of the model were 71.8%, 69.2%, 52.2%, and 84.0%, respectively, in external validation. The BI score at admission, age, use of nonsurgical treatment, neurosurgery status, and modified Charlson Comorbidity Index were identified as the top 5 predictors for functional outcome at discharge. CONCLUSIONS: We established a random forest model that performed well in predicting early functional outcomes following acute care after TBI. The model has utility for informing decision-making regarding patient management and discharge planning and for facilitating health care quality assessment and resource allocation for TBI treatment.

The evolutionary characteristics and influencing factors of total carbon productivity: evidence from China.

In order to systematically understand the evolution of total factor carbon productivity and explore its influence mechanism, based on panel data of 30 Chinese provinces from 2005 to 2019, the slacks-based measure of directional distance functions model and the Luenberger index are used to estimate the evolution of total factor carbon productivity, and the SYS-GMM model is constructed to explore the drivers of total factor carbon productivity and its influence effect. The results show that from 2005 to 2019, the overall level of total factor carbon productivity was low, but its growth index and decomposition term both showed an increasing trend; the development of total factor carbon productivity has regional differences. Only the eastern, northern, and middle Yellow River economic regions experience positive growth in total factor carbon production. The downward trend of total factor carbon productivity is most significant in the northwest and southwest economic regions, with - 2.577% and - 1.463%, respectively; improvements in scale technology are the main reasons for improving total factor carbon productivity across time and regions; economic growth and environmental regulations contribute to total factor carbon productivity at 1% significance level, and industrial structure has a negative impact. Foreign direct investment inhibits total factor carbon productivity, but the effect is not significant. Based on these findings, this paper provides an effective reference for achieving the goal of low-carbon sustainable development and improving total factor carbon productivity.

Association between environmental chemicals co-exposure and peripheral blood immune-inflammatory indicators.

Chronic inflammation is closely related to chronic inflammatory diseases, autoimmune diseases and cancer. Few studies have evaluated the effects of exposure to multiple chemical combinations on immunoinflammatory related indicators and their possible molecular mechanisms. This study explored the effect of exposure to various chemicals on immune-inflammatory biomarkers and its molecular mechanism. Using data from 1,723 participants in the National Health and Nutrition Examination Survey (NHANES, 2011-2012), the aim was to determine the association between chemical mixtures and immunoinflammatory biomarkers [including White blood cell (Wbc), neutrophil (Neu), lymphocytes (Lym), and Neutrophil-to-lymphocyte ratio (NLR)] using linear regression model, weighted quantile sum regression (WQSR) model, and bayesian nuclear machine regression (BKMR) model. Meanwhile, functional enrichment analysis and protein-protein interaction network establishment were performed to explore the molecular mechanism of inflammation induced by high-weight chemicals. In the linear regression model established for each single chemical, the four immunoinflammatory biomarkers were positively correlated with polycyclic aromatic hydrocarbons (PAHs), negatively correlated with perfluoroalkyl substances (PFASs), and positively or negatively correlated with metallic and non-metallic elements. WQSR model showed that cadmium (Cd), perfluorooctane sulfonic acid (PFOS) and perfluorodecanoic acid (PFDE) had the highest weights. In BKMR analysis, the overall effect of chemical mixtures was significantly associated with Lym and showed an increasing trend. The hub genes in high-weight chemicals inflammation-related genes were interleukin-6 (IL6), tumor necrosis factor (TNF), and interleukin-1B (IL1B), etc. They were mainly enriched in inflammatory response, Cytokine-cytokine receptor interaction, Th17 cell differentiation and IL-17 signaling pathway. The above results show that exposure to environmental chemical cocktails primarily promotes an increase in Lym across the immune-inflammatory spectrum. The mechanism leading to the inflammatory response may be related to the activation of IL-6 amplifier by the co-exposure of environmental chemicals.

Standardized measurement of dielectric materials' intrinsic triboelectric charge density through the suppression of air breakdown.

Triboelectric charge density and energy density are two crucial factors to assess the output capability of dielectric materials in a triboelectric nanogenerator (TENG). However, they are commonly limited by the breakdown effect, structural parameters, and environmental factors, failing to reflect the intrinsic triboelectric behavior of these materials. Moreover, a standardized strategy for quantifying their maximum values is needed. Here, by circumventing these limitations, we propose a standardized strategy employing a contact-separation TENG for assessing a dielectric material's maximum triboelectric charge and energy densities based on both theoretical analyses and experimental results. We find that a material's vacuum triboelectric charge density can be far higher than previously reported values, reaching a record-high of 1250 µC m-2 between polyvinyl chloride and copper. More importantly, the obtained values for a dielectric material through this method represent its intrinsic properties and correlates with its work function. This study provides a fundamental methodology for quantifying the triboelectric capability of dielectric materials and further highlights TENG's promising applications for energy harvesting.

Development of Fluorescent Aptasensors Based on G-Quadruplex Quenching Ability for Ochratoxin A and Potassium Ions Detection.

G-quadruplexes have received significant attention in aptasensing due to their structural polymorphisms and unique binding properties. In this work, we exploited the fluorescence-quenching properties of G-quadruplex to develop a simple, fast, and sensitive platform for fluorescence detection of ochratoxin A (OTA) and potassium ions (K+) with a label-free fluorophore and quencher strategy. The quenching ability of G-quadruplex was confirmed during the recognition process after the formation of the G-quadruplex structure and the quenching of the labeled fluorescein fluorophore (FAM). The fluorescence-quenching mechanism was studied by introducing specific ligands of G-quadruplex to enhance the quenching effect, to show that this phenomenon is due to photo-induced electron transfer. The proposed fluorescence sensor based on G-quadruplex quenching showed excellent selectivity with a low detection limit of 0.19 nM and 0.24 µM for OTA and K+, respectively. Moreover, we demonstrated that our detection method enables accurate concentration determination of real samples with the prospect of practical application. Therefore, G-quadruplexes can be excellent candidates as quenchers, and the strategy implemented in the study can be extended to an aptasensor with G-quadruplex.

Design of a Quencher-Free Fluorescent Aptasensor for Ochratoxin A Detection in Red Wine Based on the Guanine-Quenching Ability.

This study describes a quencher-free fluorescent aptasensor for ochratoxin A (OTA) detection using the specific quenching ability of guanine for fluorescein (FAM) molecules based on photo-induced electron transfer (PIET). In this strategy, OTA is detected by monitoring the fluorescence change induced by the conformational change of the aptamer after target binding. A new shorter OTA aptamer compromising three guanine bases at the 5' end was used in this study. This new aptamer, named G3-OTAapt1-FAM (F1), was labeled with FAM on the 3' end as a fluorophore. In order to increase the binding affinity of the aptamer and OTA, G3-OTAapt2-FAM (F2) was designed; this added a pair of complementary bases at the end compared with F1. To prevent the strong self-quenching of F2, a complementary chain, A13, was added. Although the F1 aptasensor was simpler to implement, the sensitivity of the F2 aptasensor with A13 was better than that of F1. The proposed F1 and F2 sensors can detect OTA with a concentration as low as 0.69 nmol/L and 0.36 nmol/L, respectively.

Identification of Potential Biomarkers and Small Molecule Drugs for Cutaneous Melanoma Using Integrated Bioinformatic Analysis.

Background: Cutaneous melanoma (CM) is a type of skin cancer with a high fatality rate, and its pathogenesis has not yet been fully elucidated. Methods: We obtained the gene expression datasets of CM through the Gene Expression Omnibus (GEO) database. Subsequently, robust rank aggregation (RRA) method was used to identify differentially expressed genes (DEGs) between CM cases and normal skin controls. Gene functional annotation was performed to explore the potential function of the DEGs. We built the protein-protein interaction (PPI) network by the Interactive Gene database retrieval tool (STRING) and selected hub modules by Molecular Complexity Detection (MCODE). We furthered and validated our results using the TCGA-GTEX dataset. Finally, potential small molecule drugs were predicted by CMap database and verified by molecular docking method. Results: A total of 135 DEGs were obtained by RRA synthesis analysis. GMPR, EMP3, SLC45A2, PDZD2, NPY1R, DLG5 and ADH1B were screened as potential targets for CM. Furazolidone was screened as a potential small molecule drug for the treatment of CM, and its mechanism may be related to the inhibition of CM cell proliferation by acting on GMPR. Conclusion: We identified seven prognostic therapeutic targets associated with CM and furazolidone could be used as a potential drug for CM treatment, providing new prognostic markers, potential therapeutic targets and small molecule drugs for the treatment and prevention of CM.

Clinical Profile and Treatment Outcome in MOGAD: A Single-Center Case-Series Study in Guiyang, China.

Background: The clinical spectrum of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is expanding over time. However, the long-term management and prognosis of this disorder are still controversial. Therefore, this study aimed to report the clinical profiles and treatment outcomes of MOGAD in our center. Methods: This was a single-center case-series study. Clinical and para-clinical data, along with treatment outcomes of patients with MOGAD were analyzed. Results: A total of 27 patients were identified, of which 19 (70%) patients were women, and the median age at disease onset was 40 years (range 20-67). A total of 47 episodes were observed, with optic neuritis (53%) being the most frequent presentation and 60% of them were unilateral. Other presentations included rhombencephalitis (RE) (17%), limbic encephalitis (9%), simultaneous optic neuritis and myelitis (9%), acute disseminated encephalomyelitis (ADEM)-like presentation (6%), myelitis (4%), and ADEM (2%). One patient presenting with RE also met the diagnostic criteria of area postrema syndrome (APS). Another patient with RE presented with imaging characteristics of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). A total of 29 lumbar punctures were recorded, among which an elevated protein level was found in 34% of the samples, pleocytosis was found in 14% of the samples, and positive intrathecal oligoclonal bands were found in 19% of the patients. One patient was found to have anti-N-methyl-D-aspartate receptor antibodies both in his serum and cerebrospinal fluid. Intravenous methylprednisolone (IVMP) was administrated for 85% of the attacks while both IVMP and intravenous immunoglobulin were for 6% of the attacks. Moreover, nine patients received maintenance therapy. Among them, six patients were treated with mycophenolate mofetil, three patients were treated with prednisone, rituximab, and teriflunomide, respectively. The median follow-up period was 20 months (range 6-127). At follow-up, twelve (44%) patients experienced a relapsing course, and the median time to the first relapse was 9.5 months (range 2-120). The median Expanded Disability Status Scale score at nadir was 3.5 (range 2-8) and was 0 (range 0-3) at the last follow-up. Conclusion: The clinical spectrum of MOGAD is heterogenous, wherein APS and CLIPPERS-form can occur. The long-term outcome of MOGAD seems benign. Further studies are warranted to determine the risk factors of relapse and identify the optimal steroid-sparing agents.