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Social touch has a vital role in human development and psychological well-being. However, there is a lack of measures assessing individual differences in social touch experiences and attitudes, especially under Eastern cultures. This study developed the Social Touch Experiences and Attitudes Questionnaire - Chinese version (STEAQ-C) and examined its psychometric properties with healthy young Chinese adults. In Study 1, an item pool was generated and principal component analysis (PCA) was used to identify the factor structure of the STEAQ. Study 2 recruited an independent sample and examined its reliability and validity. Network analysis further explored the interrelations between social touch and a variety of subclinical traits and symptoms. PCA identified four factors of the STEAQ-C, relating to childhood touch experiences, current touch with intimate partners, with family and friends, and with unfamiliar people. Study 2 confirmed the four-factor structure and upheld its internal consistency and stability. Positive attitudes towards and greater experiences of social touch were negatively correlated with sensory over-responsiveness and sensory hyposensitivity, as well as childhood trauma particularly emotional neglect, supporting the convergent validity. Evidence of criterion-related validity was accrued via its concurrent and predictive associations with secure attachment style, higher levels of social competence, and lower levels of social anxiety. Network analysis highlighted altered perception of social touch may be a shared feature for psychiatric conditions with social dysfunctions (e.g., autism, social anxiety and negative schizotypy). The newly-developed STEAQ-C may be a timely tool in assessing social touch experiences and attitudes under Eastern cultures.
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Single-cell omics techniques have made it possible to analyze individual cells in biological samples, providing us with a more detailed understanding of cellular heterogeneity and biological systems. Accurate identification of cell types is critical for single-cell RNA sequencing (scRNA-seq) analysis. However, scRNA-seq data are usually high dimensional and sparse, posing a great challenge to analyze scRNA-seq data. Existing cell-type annotation methods are either constrained in modeling scRNA-seq data or lack consideration of long-term dependencies of characterized genes. In this work, we developed a Transformer-based deep learning method, scSwinFormer, for the cell-type annotation of large-scale scRNA-seq data. Sequence modeling of scRNA-seq data is performed using the smooth gene embedding module, and then, the potential dependencies of genes are captured by the self-attention module. Subsequently, the global information inherent in scRNA-seq data is synthesized using the Cell Token, thereby facilitating accurate cell-type annotation. We evaluated the performance of our model against current state-of-the-art scRNA-seq cell-type annotation methods on multiple real data sets. ScSwinFormer outperforms the current state-of-the-art scRNA-seq cell-type annotation methods in both external and benchmark data set experiments.
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Over the past two decades, metronomic chemotherapy has gained considerable attention and has demonstrated remarkable success in the treatment of cancer. Through chronic administration and low-dose regimens, metronomic chemotherapy is associated with fewer adverse events but still effectively induces disease control. The identification of its antiangiogenic properties, direct impact on cancer cells, immunomodulatory effects on the tumour microenvironment, and metabolic reprogramming ability has established the intrinsic multitargeted nature of this therapeutic approach. Recently, the utilization of metronomic chemotherapy has evolved from salvage treatment for metastatic disease to adjuvant maintenance therapy for high-risk cancer patients, which has been prompted by the success of several substantial phase III trials. In this review, we delve into the mechanisms underlying the antitumour effects of metronomic chemotherapy and provide insights into potential combinations with other therapies for the treatment of various malignancies. Additionally, we discuss health-economic advantages and candidates for the utilization of this treatment option.
Subject(s)
Administration, Metronomic , Neoplasms , Tumor Microenvironment , Humans , Neoplasms/drug therapy , Tumor Microenvironment/drug effects , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosageABSTRACT
Purpose: The aim of this study was to evaluate the surgical outcomes of proximal femoral bone cysts in pediatric patients. Methods: We retrospectively analyzed 41 pediatric patients (31 males and 10 females, mean age 7.47 ± 2.67 years, range 2.03-14.67 years) diagnosed with proximal femoral bone cysts treated at a single institute between March 2009 and November 2021. Data included demographics, preoperative details, intraoperative conditions, surgical techniques, postoperative outcomes, recurrence, and complications. Results: Of the participants, 68% presented with simple bone cysts and 32% with aneurysmal bone cysts. Prior to surgery, 32% exhibited pathological fractures. Surgical methods included lesion curettage, defect filling using allograft bone and Minimally-Invasive Injectable Graft ×3, and varied fixation techniques. Postoperative recurrence (17%) was associated with cyst location between the capital femoral epiphysis and the linea intertrochanterica (P = 0.010). At the final assessment (mean follow-up: 26.51 ± 18.99 months), all showed radiological bony union with 93% rated as "good" and 7% as 'fair' based on Ratliff hip scores. Complications arose in 20% of patients, significantly correlated with prior pathological fractures (P = 0.007) and their association with the linea intertrochanterica (P = 0.004). Those with fractures reported higher intraoperative blood loss (P = 0.015) and longer surgery durations (P = 0.012) compared to those without. Conclusion: Treating pediatric proximal femoral bone cysts using techniques such as lesion curettage, defect filling, and selective internal fixation yields favorable outcomes. The presence of pathological fractures can prolong surgical time, increase intraoperative blood loss, and elevate postoperative complication risks. Hence, early surgical intervention for these cysts is recommended to prevent fractures.
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Extracellular polymeric substances (EPS) are a critical influencing factor in sludge dewatering. Disrupting such EPS contributes to the release of bound water in sludge, enhancing the sludge dewatering performance. In This study, quaternized straw fibers that are destructive to the EPS structure and components in active sludge were prepared useing heterogeneous free radical graft polymerization. Straw fibers, dimethyl diallyl ammonium chloride (DMDAAC), ammonium persulfate (APS), and acrylamide (AM) were taken as the substrate, grafting monomer, catalyst, and cross-linking agent, respectively.The optimal processing conditions determined for the DMDAAC-based quaternization and graft modification of straw fibers were as follows: reaction temperature of 60 °C, reaction time of 5 h, 0.100 g of catalyst APS dosage per gram of straw, and 3.000 ml of DMDAAC dosage per gram of straw. The optimal processing conditions yielded 1.335 g of modified straw fibers per gram of straw, 33.67% grafting rate, and 31.70% substitution of the quaternary ammonium groups. The capillary suction time (CST) was conditioned from 243.3 ± 22.6 s in the original sludge to 134.5 ± 34.45 s. The specific resistance to filtration (SRF) was reduced from 8.82 ± 0.51 × 1012 m/kg in the original sludge to 4.59 ± 0.23 × 1012 m/kg.
Subject(s)
Sewage , Sewage/chemistry , Waste Disposal, Fluid/methods , Quaternary Ammonium Compounds/chemistry , Allyl Compounds/chemistryABSTRACT
This study explored the effectiveness of a short-term mindfulness-based intervention (MBI) on psychological distress, mindfulness levels, emotion regulation, and impulsivity among college students with non-suicidal self-injury (NSSI). Participants completed four questionnaires, including the Five Facet Mindfulness Questionnaire, the Depression Anxiety Stress Scale, the Emotion Regulation Questionnaire, and the Brief Barratt Impulsivity Scale, and two behavioral tasks, including an emotion regulation task and a stop signal task (SST), at three time points. Compared with the healthy group, the NSSI group had a significantly greater level of psychological distress and a lower level of mindfulness. Compared with the NSSI control group and the healthy group, the NSSI MBI group had significantly increased mindfulness levels and decreased psychological distress after the intervention. In the NSSI MBI group, regardless of which emotion regulation strategy was adopted when viewing negative pictures, the intensity of negative emotions during the emotion regulation task was significantly reduced. Moreover, in the NSSI MBI group, the effectiveness of the MBI on the mindfulness level, stress level, and emotion regulation process was maintained at the follow-up. The present study provided empirical support that short-term MBI has the potential to help individuals with NSSI by enhancing their emotion regulation.
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Aims: This study aims to assess the status and related factors among healthcare workers (HCWs) in designated quarantine-hospital-site (DQHS) based on the model of health ecology. Methods: The cross-sectional study was conducted from April to May, 2022, which included 351 valid samples. We measured sleep quality using the Pittsburgh Sleep Quality Index, which encompasses seven dimensions: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction. Each dimension is scored individually, contributing to an overall sleep quality score. Factors associated with the sleep quality of HCWs in DQHS were divided into individual, behavioral, interpersonal and social dimensions. Hierarchical linear regressions were conducted to identify the potential factors associated with sleep quality among HCWs in DQHS. Results: HCWs in DQHS had a statistically higher sleep quality than the Chinese national norm. HCWs who were female, afraid of Coronavirus disease, had more negative emotions, frequently worked overtime, were married, and had a higher income were more likely to experience worse sleep quality (p < 0.05), while those who worked between 51 and 70 h weekly, treated over 10 patients daily, and engaged in more health behaviors may have better sleep quality (p < 0.05). Conclusion: This study revealed a worrying level of sleep quality among HCWs in DQHS. The government, hospital managers, and families should collaborate to ensure the sleep quality of HCWs in DQHS.
Subject(s)
COVID-19 , Health Personnel , Quarantine , Sleep Quality , Humans , Cross-Sectional Studies , Male , Female , China/epidemiology , COVID-19/epidemiology , Quarantine/psychology , Adult , Health Personnel/statistics & numerical data , Health Personnel/psychology , Middle Aged , Surveys and Questionnaires , Sleep Wake Disorders/epidemiology , Hospitals/statistics & numerical data , PandemicsABSTRACT
Pueraria lobata (Willd.) Ohwi, known as kudzu and used as a "longevity powder" in China, is an edible plant which is rich in flavonoids and believed to be useful for regulating blood sugar and treating diabetes, although the modes of action are unknown. Here, a total of 53 flavonoids including 6 novel compounds were isolated from kudzu using multidimensional preparative liquid chromatography. The flavonoid components were found to lower blood sugar levels, promote urine sugar levels in mice, and reduce the urine volume. Molecular docking and in vitro assays suggested that the antidiabetic effect of kudzu was attributed to at least three targets: sodium-dependent glucose transporter 2 (SGLT2), protein tyrosine phosphatase-1B (PTP1B), and alpha-glucosidase (AG). This study suggests a possible mechanism for the antidiabetic effect that may involve the synergistic action of multiple active compounds from kudzu.
Subject(s)
Flavonoids , Hypoglycemic Agents , Plant Extracts , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Pueraria , Pueraria/chemistry , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Flavonoids/chemistry , Animals , Mice , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism , Humans , Plant Extracts/chemistry , Plant Extracts/pharmacology , Molecular Docking Simulation , Male , alpha-Glucosidases/metabolism , alpha-Glucosidases/chemistry , Blood Glucose/metabolism , Plants, Edible/chemistryABSTRACT
BACKGROUND: Breast cancer is the most common malignancy in women, with its prognosis varying greatly according to its subtype. Triple-negative breast cancer (TNBC) has the worst prognosis among all subtypes. Glycosylation is a critical factor influencing the prognosis of patients with TNBC. Our aim is to develop a tumor prognosis model by analyzing genes related to glycosylation to predict patient outcomes. METHODS: The dataset used in this study was downloaded from the Cancer Genome Atlas Program (TCGA) database, and predictive genes were identified through Cox one-way regression analysis. The model genes with the highest risk scores among the 18 samples were obtained by lasso regression analysis to establish the model. We analyzed the pathways affecting the progression of TNBC and discovered key genes for subsequent research. RESULTS: Our model was constructed using data from TCGA database and validated through Kaplan-Meier curve analysis and Receiver Operating Characteristic (ROC) curve assessment. Our analysis revealed that a high expression of tumor-related chemokines in the high-risk group may be associated with poor tumor prognosis. Furthermore, we conducted a random survival forest analysis and identified two significant genes, namely DPM2 and PINK1, which have been selected for further investigation. CONCLUSION: The prognostic analysis model, developed based on the glycosylation genes in TNBC, exhibits excellent validation efficacy. This model is valuable for the prognostic analysis of patients with TNBC.
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Neuroinflammation plays important roles in retinal ganglion cell (RGC) degeneration in glaucoma. MicroRNA-146 (miR-146) has been shown to regulate inflammatory response in neurodegenerative diseases. In this study, whether and how miR-146 could affect RGC injury in chronic ocular hypertension (COH) experimental glaucoma were investigated. We showed that in the members of miR-146 family only miR-146a-5p expression was upregulated in COH retinas. The upregulation of miR-146a-5p was observed in the activated microglia and Müller cells both in primary cultured conditions and in COH retinas, but mainly occurred in microglia. Overexpression of miR-146a-5p in COH retinas reduced the levels pro-inflammatory cytokines and upregulated the levels of anti-inflammatory cytokines, which were further confirmed in the activated primary cultured microglia. Transfection of miR-146a-5p mimic increased the percentage of anti-inflammatory phenotype in the activated BV2 microglia, while transfection of miR-146a-5p inhibitor resulted in the opposite effects. Transfection of miR-146a-5p mimic/agomir inhibited the levels of interleukin-1 receptor associated kinase (IRAK1) and TNF receptor associated factor 6 (TRAF6) and phosphorylated NF-κB subunit p65. Dual luciferase reporter gene assay confirmed that miR-146a-5p could directly target IRAK1 and TRAF6. Moreover, downregulation of IRAK1 and TRAF6 by siRNA techniques or blocking NF-κB by SN50 in cultured microglia reversed the miR-146a-5p inhibitor-induced changes of inflammatory cytokines. In COH retinas, overexpression of miR-146a-5p reduced RGC apoptosis, increased RGC survival, and partially rescued the amplitudes of photopic negative response. Our results demonstrate that overexpression of miR-146a-5p attenuates RGC injury in glaucoma by reducing neuroinflammation through downregulating IRAK1/TRAF6/NF-κB signaling pathway in microglia.
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Background: There remains a pressing need to identify biomarkers capable of reliably predicting prognostic outcomes for colorectal cancer (CRC) patients. As several body composition parameters have recently been reported to exhibit varying levels of prognostic significance in particular cancers, the present study was devised to assess the ability of body composition to predict long-term outcomes for CRC patients with different stages of disease. Methods: In total, this retrospective analysis enrolled 327 stage I-III CRC patients whose medical records were accessed for baseline demographic and clinical data. Primary outcomes for these patients included disease-free and overall survival (DFS and OS). The prognostic performance of different musculature, visceral, and subcutaneous fat measurements from preoperative computed tomography (CT) scans was assessed. Results: Over the course of follow-up, 93 of the enrolled patients experienced recurrent disease and 39 died. Through multivariate Cox regression analyses, the visceral/subcutaneous fat area (V/S) ratio was found to be independently associated with patient DFS (HR=1.93, 95% CI: 1.24-3.01, P=0.004), and the skeletal muscle index (SMI) as an independent predictor for OS (HR=0.43, 95% CI: 0.21-0.89, P=0.023). Through subgroup analyses, higher V/S ratios were found to be correlated with reduced DFS among patients with stage T3/4 (P=0.011), lymph node metastasis-positive (P=0.002), and TNM stage III (P=0.002) disease, whereas a higher SMI was associated with better OS in all T stages (P=0.034, P=0.015), lymph node metastasis-positive cases (P=0.020), and in patients with TNM stage III disease (P=0.020). Conclusion: Both the V/S ratio and SMI offer potential utility as clinical biomarkers associated with long-term CRC patient prognosis. A higher V/S ratio and a lower SMI are closely related to poorer outcomes in patients with more advanced disease.
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Acidic nitrification, as a novel process for treating wastewater without sufficient alkalinity, has received increasing attention over the years. In this study, a continuous-flow reactor with aerobic granular sludge was successful operated at low pH (<6.5) performing high-rate acidic nitrification. Volumetric ammonium oxidation rate of 0.4-1.2 kg/(m3·d) were achieved with the specific biomass activities of 5.8-13.9 mg N/(gVSS·h). Stable partial nitritation with nitrite accumulation efficiency over 85% could be maintained at pH above 6 with the aid of residual ammonium, whereas the nitrite accumulation disappeared when pH was below 6. Interestingly, the granule morphology significantly improved during the acidic operation. The increased secretion of extracellular polymeric substances (especially polysaccharides) suggested a self-protective behavior of microbes in the aerobic granules against acidic stress. 16S rRNA gene sequencing analyses indicated that Candidatus Nitrospira defluvii was always the dominant nitrite-oxidizing bacteria, while the dominant ammonia-oxidizing bacteria shifted from Nitrosomonas europaea to Nitrosomonas mobilis. This study, for the first time, demonstrated the improved stability of aerobic granules under acidic conditions, and also highlighted aerobic granules as a useful solution to achieve high-rate acidic nitrification.
Subject(s)
Bioreactors , Nitrification , Sewage , Hydrogen-Ion Concentration , Sewage/microbiology , Wastewater/chemistry , Waste Disposal, Fluid/methods , RNA, Ribosomal, 16S , Nitrites/metabolism , Oxidation-ReductionABSTRACT
N 6-Methyladenosine (m6A) is a prevalent and highly regulated RNA modification essential for RNA metabolism and normal brain function. It is particularly important in the hippocampus, where m6A is implicated in neurogenesis and learning. Although extensively studied, its presence in specific cell types remains poorly understood. We investigated m6A in the hippocampus at a single-cell resolution, revealing a comprehensive landscape of m6A modifications within individual cells. Through our analysis, we uncovered transcripts exhibiting a dense m6A profile, notably linked to neurological disorders such as Alzheimer's disease. Our findings suggest a pivotal role of m6A-containing transcripts, particularly in the context of CAMK2A neurons. Overall, this work provides new insights into the molecular mechanisms underlying hippocampal physiology and lays the foundation for future studies investigating the dynamic nature of m6A RNA methylation in the healthy and diseased brain.
Subject(s)
Adenosine , Hippocampus , Single-Cell Analysis , Hippocampus/metabolism , Adenosine/analogs & derivatives , Adenosine/metabolism , Animals , Single-Cell Analysis/methods , Mice , Neurons/metabolism , RNA Processing, Post-Transcriptional , Methylation , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics , RNA/metabolism , RNA/genetics , Humans , RNA MethylationABSTRACT
The accurate measurement of pH in highly alkaline environments is critical for various industrial applications but remains a complex task. This paper discusses the development of novel Fe-doped SrCoOx-based FET sensors for the detection of extreme alkaline pH levels. Through a comprehensive investigation of the effects of Fe doping on the structure, electrical properties, and sensing performance of SrCoOx, we have identified the optimal doping level that significantly enhances the sensor's performance in highly alkaline conditions. With a Fe doping level of 5 mol %, the sensitivity of the sensor improves to 0.86 lg(Ω)/pH while maintaining the response rate. Further increasing the Fe doping to 10 mol % results in a sensor that demonstrates favorable response time, a suitable pH range, and a linear correlation between lg(R) and pH. The combination of X-ray photoelectron spectroscopy and X-ray diffraction analysis provides insight into the regulation mechanisms of Fe doping on the crystal structure, electronic structure, and oxygen vacancy concentration of SrCoOx. Our findings indicate that Fe doping leads to an increase in oxygen vacancy concentration and a decrease in the energy barrier for oxygen ion migration, which contributes to the improved sensing performance of the Fe-doped SrCoOx sensors. Additionally, the study highlights the influence of oxygen vacancy concentration on the electrical properties of SrCoOx. Precise control over the concentration of oxygen vacancies is crucial for optimizing the sensitivity and response speed of SrCoOx FET sensors under extreme alkalinity conditions.
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Traditional Chinese medicines (TCMs) are popular in clinic because of their safety and efficacy. They contain abundant natural active compounds, which are important sources of new drug discovery. However, how to efficiently identify active compounds from complex ingredients remains a challenge. In this study, a method combining UHPLC-MS/MS characterization and in silico screening was developed to discover compounds with dopamine D2 receptor (D2R) activity in Stephania epigaea (S. epigaea). By combining the compounds identified in S. epigaea by UHPLC-MS/MS with reported compounds, a virtual library of 80 compounds was constructed for in silico screening. Potentially active compounds were chosen based on screening scores and subsequently tested for in vitro activity on a transfected cell line CHO-K1-D2 model using label-free cellular phenotypic assay. Three D2R agonists and five D2R antagonists were identified. (-)-Asimilobine, N-nornuciferine and (-)-roemerine were reported for the first time as D2R agonists, with EC50 values of 0.35 ± 0.04⯵M, 1.37 ± 0.10⯵M and 0.82 ± 0.22⯵M, respectively. Their target specificity was validated by desensitization and antagonism assay. (-)-Isocorypalmine, (-)-tetrahydropalmatine, (-)-discretine, (+)-corydaline and (-)-roemeroline showed strong antagonistic activity on D2R with IC50 values of 92 ± 9.9â¯nM, 1.73 ± 0.13⯵M, 0.34 ± 0.02⯵M, 2.09 ± 0.22⯵M and 0.85 ± 0.08⯵M, respectively. Their kinetic binding profiles were characterized using co-stimulation assay and they were both D2R competitive antagonists. We docked these ligands with human D2R crystal structure and analyzed the structure-activity relationship of aporphine-type D2R agonists and protoberberine-type D2R antagonists. These results would help to elucidate the mechanism of action of S. epigaea for its analgesic and sedative efficacy and benefit for D2R drug design. This study demonstrated the potential of integrating UHPLC-MS/MS with in silico and in vitro screening for accelerating the discovery of active compounds from TCMs.
Subject(s)
Cricetulus , Receptors, Dopamine D2 , Stephania , Tandem Mass Spectrometry , Tandem Mass Spectrometry/methods , CHO Cells , Animals , Chromatography, High Pressure Liquid/methods , Stephania/chemistry , Receptors, Dopamine D2/metabolism , Computer Simulation , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Dopamine D2 Receptor Antagonists/pharmacology , Dopamine D2 Receptor Antagonists/chemistry , Drug Discovery/methods , Dopamine Agonists/pharmacology , Dopamine Agonists/chemistry , Humans , Medicine, Chinese Traditional/methods , Liquid Chromatography-Mass SpectrometryABSTRACT
Neurofeedback, a non-invasive intervention, has been increasingly used as a potential treatment for major depressive disorders. However, the effectiveness of neurofeedback in alleviating depressive symptoms remains uncertain. To address this gap, we conducted a comprehensive meta-analysis to evaluate the efficacy of neurofeedback as a treatment for major depressive disorders. We conducted a comprehensive meta-analysis of 22 studies investigating the effects of neurofeedback interventions on depression symptoms, neurophysiological outcomes, and neuropsychological function. Our analysis included the calculation of Hedges' g effect sizes and explored various moderators like intervention settings, study designs, and demographics. Our findings revealed that neurofeedback intervention had a significant impact on depression symptoms (Hedges' g = -0.600) and neurophysiological outcomes (Hedges' g = -0.726). We also observed a moderate effect size for neurofeedback intervention on neuropsychological function (Hedges' g = -0.418). As expected, we observed that longer intervention length was associated with better outcomes for depressive symptoms (ß = -4.36, P < 0.001) and neuropsychological function (ß = -2.89, P = 0.003). Surprisingly, we found that shorter neurofeedback sessions were associated with improvements in neurophysiological outcomes (ß = 3.34, P < 0.001). Our meta-analysis provides compelling evidence that neurofeedback holds promising potential as a non-pharmacological intervention option for effectively improving depressive symptoms, neurophysiological outcomes, and neuropsychological function in individuals with major depressive disorders.
Subject(s)
Depressive Disorder, Major , Neurofeedback , Neurofeedback/methods , Humans , Depressive Disorder, Major/therapy , Depressive Disorder, Major/physiopathology , Treatment Outcome , Electroencephalography/methodsABSTRACT
Dendritic cells (DCs) present an ideal target for delivering immunogenic cargo due to their potent antigen-presenting capabilities. This targeting approach holds promise in vaccine development by enhancing the efficiency of antigen recognition and capture by DCs. To identify a high-affinity targeting peptide binding to rabbit DCs, rabbit monocyte-derived DCs (raMoDCs) were isolated and cultured, and a novel peptide, HS (HSLRHDYGYPGH), was identified using a phage-displayed peptide library. Alongside HS, two other DC-targeting peptides, KC1 and MY, previously validated in our laboratory, were employed to construct recombinant Lactgobacillus reuteri fusion-expressed rabbit hemorrhagic disease virus (RHDV) capsid protein VP60. These recombinant Lactobacillus strains were named HS-VP60/L. reuteri, KC1-VP60/L. reuteri, and MY-VP60/L. reuteri. The ability of these recombinant Lactobacillus to bind rabbit DCs was evaluated both in vivo and in vitro. Results demonstrated that the DC-targeting peptide KC1 significantly enhanced the capture efficiency of recombinant Lactobacillus by raMoDCs, promoted DC maturation, and increased cytokine secretion. Furthermore, oral administration of KC1-VP60/L. reuteri effectively induced SIgA and IgG production in rabbits, prolonged rabbit survival post-challenge, and reduced RHDV copies in organs. In summary, the DC-targeting peptide KC1 exhibited robust binding to raMoDCs, and recombinant Lactobacillus expressing KC1-VP60 protein antigens efficiently induced systemic and mucosal immune responses in rabbits, conferring protective efficacy against RHDV. This study offers valuable insights for the development of novel RHDV vaccines.
Subject(s)
Dendritic Cells , Hemorrhagic Disease Virus, Rabbit , Limosilactobacillus reuteri , Peptides , Animals , Dendritic Cells/immunology , Rabbits , Hemorrhagic Disease Virus, Rabbit/immunology , Hemorrhagic Disease Virus, Rabbit/genetics , Limosilactobacillus reuteri/genetics , Limosilactobacillus reuteri/immunology , Peptides/immunology , Peptides/genetics , Caliciviridae Infections/prevention & control , Caliciviridae Infections/immunology , Reoviridae Infections/prevention & control , Reoviridae Infections/immunology , Capsid Proteins/genetics , Capsid Proteins/immunology , Viral Vaccines/immunology , Viral Vaccines/genetics , Lactobacillus/genetics , Lactobacillus/immunologyABSTRACT
Myasthenia gravis with positive MuSK antibody often involves the bulbar muscles and is usually refractory to acetylcholinesterase inhibitors. For MuSK-MG patients who experience acute exacerbations and do not respond to conventional treatments, there is an urgent need to find more suitable treatment options. With the advent of biologic agents, efgartigimod has shown promising results in the treatment of MG. We report a 65-year-old MuSK-MG patient who presented with impaired eye movements initially, and the symptoms rapidly worsened within a week, affecting the limbs and neck muscles, and had difficulties in chewing and swallowing. Lymphoplasmapheresis did not achieve satisfactory results, but after a cycle of efgartigimod treatment, the patient's symptoms gradually improved and remained in a good clinical state for several months.
Subject(s)
Myasthenia Gravis , Receptors, Cholinergic , Humans , Myasthenia Gravis/drug therapy , Aged , Receptors, Cholinergic/immunology , Treatment Outcome , Receptor Protein-Tyrosine Kinases/immunology , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Autoantibodies/immunology , Autoantibodies/blood , Male , FemaleABSTRACT
Introduction: Psoriasis is a chronic skin disease characterized by unique scaling plaques. However, during the acute phase, psoriatic lesions exhibit eczematous changes, making them difficult to distinguish from atopic dermatitis, which poses challenges for the selection of biological agents. This study aimed to identify potential diagnostic genes in psoriatic lesions and investigate their clinical significance. Methods: GSE182740 datasets from the GEO database were analyzed for differential analysis; machine learning algorithms (SVM-RFE and LASSO regression models) are used to screen for diagnostic markers; CIBERSORTx is used to determine the dynamic changes of 22 different immune cell components in normal skin lesions, psoriatic non-lesional skin, and psoriatic lesional skin, as well as the expression of the diagnostic genes in 10 major immune cells, and real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry are used to validate results. Results: We obtained 580 differentially expressed genes (DEGs) in the skin lesion and non-lesion of psoriasis patients, 813 DEGs in mixed patients between non-lesions and lesions, and 96 DEGs in the skin lesion and non-lesion of atopic dermatitis, respectively. Then 144 specific DEGs in psoriasis via a Veen diagram were identified. Ultimately, UGGT1, CCNE1, MMP9 and ARHGEF28 are identified for potential diagnostic genes from these 144 specific DEGs. The value of the selected diagnostic genes was verified by receiver operating characteristic (ROC) curves with expanded samples. The the area under the ROC curve (AUC) exceeded 0.7 for the four diagnosis genes. RT-qPCR results showed that compared to normal human epidermis, the expression of UGGT1, CCNE1, and MMP9 was significantly increased in patients with psoriasis, while ARHGEF28 expression was significantly decreased. Notably, the results of CIBERSORTx showed that CCNE1 was highly expressed in CD4+ T cells and neutrophils, ARHGEF28 was also expressed in mast cells. Additionally, CCNE1 was strongly correlated with IL-17/CXCL8/9/10 and CCL20. Immunohistochemical results showed increased nuclear expression of CCNE1 in psoriatic epidermal cells relative to normal. Conclusion: Based on the performance of the four genes in ROC curves and their expression in immune cells from patients with psoriasis, we suggest that CCNE1 possess higher diagnostic value.