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Branch retinal vein occlusion (BRVO) is the most prevalent retinal vascular disease that constitutes a threat to vision due to increased venous pressure caused by venous effluent in the space, leading to impaired visual function. Optical Coherence Tomography Angiography (OCTA) is an innovative non-invasive technique that offers high-resolution three-dimensional structures of retinal blood vessels. Most publicly available datasets are collected from single visits with different patients, encompassing various eye diseases for distinct tasks and areas. Moreover, due to the intricate nature of eye structure, professional labeling not only relies on the expertise of doctors but also demands considerable time and effort. Therefore, we have developed a BRVO-focused dataset named Soul (Source of ocular vascular) and propose a human machine collaborative annotation framework (HMCAF) using scrambled retinal blood vessels data. Soul is categorized into 6 subsets based on injection frequency and follow-up duration. The dataset comprises original images, corresponding blood vessel labels, and clinical text information sheets which can be effectively utilized when combined with machine learning.
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Aprendizado de Máquina , Oclusão da Veia Retiniana , Vasos Retinianos , Tomografia de Coerência Óptica , Humanos , Vasos Retinianos/diagnóstico por imagemRESUMO
BACKGROUND: Ethnic socialisation plays a vital role in the development of ethnic minority adolescents. However, the generalizability of research findings beyond the context of immigrant societies in the United States remains unclear. METHODS: Utilising a person-centred approach, this study analysed a sample of 2,600 ethnic minority adolescents in China (55.8% female, Mage = 14.93 ± 1.82) to explore ethnic socialisation patterns, and their correlations with depression. RESULTS: Latent profile analysis revealed four distinct ethnic socialisation profiles: low-frequency, moderate-frequency, high-frequency and proactive integration orientation. Adolescents with the high-frequency profile displayed the highest levels of depression, followed by those with the moderate-frequency profile, whereas adolescents with the low-frequency and proactive integration orientation profiles showed a lower risk of depression. CONCLUSIONS: Within the sociocultural context of China, ethnic minority families' ethnic socialisation practices demonstrate unique characteristics. Various ethnic socialisation messages are integrated in diverse patterns to exert influence on adolescents.
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Depressão , Humanos , China/etnologia , Adolescente , Feminino , Masculino , Depressão/etnologia , Minorias Étnicas e Raciais/estatística & dados numéricos , Grupos Minoritários/psicologia , Grupos Minoritários/estatística & dados numéricos , Etnicidade/estatística & dados numéricos , Etnicidade/psicologiaRESUMO
Oxidative stress caused by pregnancy-induced hypertension syndrome significantly affects the health of pregnant women. Hydrogen sulfide is a typical gaseous signal molecule against oxidative stress, and it is of profound significance to develop a detection method. In this study, a stimuli-responsive hydrogel was constructed based on the coordination and bonding principle of metal ions and chitosan (CS) to realize the quantitative detection of hydrogen sulfide (H2S). The chain of CS contains a large number of amino groups and hydroxyl groups, which can form the coordination structure with Cu2+, triggering CS to form a stable hydrogel. The hydrogel can be formed within about 5â s, which has the characteristics of rapid preparation. In the presence of target H2S, the cross-linking agent Cu2+ in the hydrogel can compete out, resulting in the collapse of the hydrogel and the release of the electrochemical probe. By detecting the concentration of the released electrochemical probe, the quantitative detection of H2S can be achieved. The prepared hydrogel has a good linear relationship with the concentration of H2S from 1â µM to 60â µm. At the same time, the hydrogel has good specificity and stability, and it can be applied to the detection of H2S in serum samples.
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Purpose: The purpose of the present study was to identify predictors of severe white matter hyperintensity (WMH) with obesity (SWO), and to build a prediction model for screening obese people with severe WMH without Nuclear Magnetic Resonance Imaging (MRI) examination. Patients subjects and methods: From September 2020 to October 2021, 650 patients with WMH were recruited consecutively. The subjects were divided into two groups, SWO group and non-SWO group. Univariate and Logistic regression analysis were was applied to explore the potential predictors of SWO. The Youden index method was adopted to determine the best cut-off value in the establishment of the prediction model of SWO. Each parameter had two options, low and high. The score table of the prediction model and nomogram based on the logistic regression were constructed. Of the 650 subjects, 487 subjects (75%) were randomly assigned to the training group and 163 subjects (25%) to the validation group. By resampling the area under the curve (AUC) of the subject's operating characteristics and calibration curves 1,000 times, nomogram performance was verified. A decision curve analysis (DCA) was used to evaluate the nomogram's clinical usefulness. By resampling the area under the curve (AUC) of the subject's operating characteristics and calibration curves 1,000 times, nomogram performance was verified. A decision curve analysis (DCA) was used to evaluate the nomogram's clinical usefulness. Results: Logistic regression demonstrated that hypertension, uric acid (UA), complement 3 (C3) and Interleukin 8 (IL-8) were independent risk factors for SWO. Hypertension, UA, C3, IL-8, folic acid (FA), fasting C-peptide (FCP) and eosinophil could be used to predict the occurrence of SWO in the prediction models, with a good diagnostic performance, Areas Under Curves (AUC) of Total score was 0.823 (95% CI: 0.760-0.885, p < 0.001), sensitivity of 60.0%, specificity of 91.4%. In the development group, the nomogram's AUC (C statistic) was 0.829 (95% CI: 0.760-0.899), while in the validation group, it was 0.835 (95% CI: 0.696, 0.975). In both the development and validation groups, the calibration curves following 1,000 bootstraps showed a satisfactory fit between the observed and predicted probabilities. DCA showed that the nomogram had great clinical utility. Conclusion: Hypertension, UA, C3, IL-8, FA, FCP and eosinophil models had the potential to predict the incidence of SWO. When the total score of the model exceeded 9 points, the risk of SWO would increase significantly, and the nomogram enabled visualization of the patient's WMH risk. The application prospect of our models mainly lied in the convenient screening of SWO without MRI examination in order to detect SWO and control the WMH hazards early.
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We use molecular dynamics (MD) simulation and nanofluidic experiments to probe the non-equilibrium transient physics of two nanochannel-confined polymers driven against a permeable barrier in a flow field. For chains with a persistence length P smaller than the channel diameter D, both simulation and experiment with dsDNA reveal nonuniform mixing of the two chains, with one chain dominating locally in what we term "aggregates." Aggregates undergo stochastic dynamics, persisting for a limited time, then disappearing and reforming. Whereas aggregate-prone mixing occurs immediately at sufficiently high flow speeds, chains stay segregated at intermediate flow for some time, often attempting to mix multiple times, before suddenly successfully mixing. Observation of successful mixing nucleation events in nanofluidic experiments reveal that they arise through a peculiar "back-propagation" mechanism whereby the upstream chain, closest to the barrier, penetrates and passes through the downstream chain (farthest from the barrier) moving against the flow direction. Simulations suggest that the observed back-propagation nucleation mechanism is favored at intermediate flow speeds and arises from a special configuration where the upstream chain exhibits one or more folds facing the downstream chain, while the downstream chain has an unfolded chain end facing upstream.
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Tumor-specific antigens (TSAs) are crucial for tumor-specific immune response that reduces tumor burden and thus serve as important targets for immunotherapy. Identification of novel TSAs can provide new strategies for immunotherapies. In this study, we demonstrated that the upstream open reading frame (uORF) of RNF10 encodes an antigenic peptide (RNF10 uPeptide), capable of eliciting a T cell-mediated anti-tumor immune response. We initially demonstrated the immunogenicity of the RNF10 uPeptide in a CT26 tumor mouse model, by showing that its epitope was specifically recognized by CD8+ T cells. Vaccination of mice with the long form of the RNF10 uPeptide conferred strong anti-tumor activity. Next, we proved that the human RNF10 uORF could be translated. In addition, we predicted the binding of an RNF10 uPeptide epitope to HLA-A∗02:01 (HLA-A2). This HLA-A2-restricted epitope of the RNF10 uPeptide induced a potent specific human T cell response. Finally, we showed that an HLA-A2-restricted cytotoxic T cell (CTL) clone, derived from a pancreatic cancer patient, recognized the RNF10 uPeptide epitope (RLFGQQQRA) and lysed HLA-A2+ pancreatic carcinoma cells expressing the RNF10 uPeptide. These results indicate that the RNF10 uPeptide could be a promising target for pancreatic carcinoma immunotherapy.
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We use molecular dynamics simulation to probe the non-equilibrium physics of two nanochannel-confined semiflexible polymers in a homogeneous flow field. We find that for sufficiently stiff chains the internal organization of the two chains takes the form of interwoven folds and circular coils. This organization can lead to mixing or demixing depending on chain stiffness and flow speed. At low and intermediate flow, the two chains adopt a folded configuration, which favours mixing. At high flow, the two chains adopt a predominantly coiled configuration. The coiled configuration results in demixing when the chains are compressed from an initially demixed condition and mixing when the chains are compressed from an initially mixed condition. We find that the mixing/demixing behaviour is governed by the ratio of the number of folded segments of one chain relative to the other at low flow and by the degree of coiling in both chains at high flow. For decreasing stiffness, the chains start to aggregate locally instead of mixing smoothly at low and intermediate flow. In the limit of completely flexible chains, the two chains either completely segregate at low flow, or adopt a locally demixed configuration consisting of large aggregates of one chain relative to the other that undergo complex stochastic dynamics, diffusing, disintegrating, and reforming at intermediate flow. The transition from complete segregation to the aggregate-dominated configuration occurs when the linear intra-chain ordering breaks down.
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Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases with genetic and clinical heterogeneity characterized by spasticity and weakness of the lower limbs. It includes four genetic inheritance forms: autosomal dominant inheritance (AD), autosomal recessive inheritance (AR), X-linked inheritance, and mitochondrial inheritance. To date, more than 82 gene loci have been found to cause HSP, and SPG15 (ZFYVE26) is one of the most common autosomal recessive hereditary spastic paraplegias (ARHSPs) with a thin corpus callosum (TCC), presents with early cognitive impairment and slowly progressive leg weakness. Here, we reported a homozygous pathogenic variant in ZFYVE26. A 19-year-old Chinese girl was admitted to our hospital presenting with a 2-year progressive bilateral leg spasticity and weakness; early cognitive impairment; corpus callosum dysplasia; chronic neurogenic injury of the medulla oblongata supplied muscles; and bilateral upper and lower limbs on electromyogram (EMG). Based on these clinical and electrophysiological features, HSP was suspected. Exome sequencing of the family was performed by high-throughput sequencing, and an analysis of the patient showed a ZFYVE26 NM_015346: c.7111dupA p.(M2371Nfs*51) homozygous mutation. This case reported a new ZFYVE26 pathogenic variant, which was different from the SPG15 gene mutation reported earlier.
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RATIONALE: Few reports of idiopathic hypereosinophilic syndrome exist presenting as ischemic cerebrovascular disease, and the majority are watershed infarction. We report the first case of idiopathic hypereosinophilic syndrome that has clinical features of capsular warning syndrome lasting 6 weeks. PATIENT CONCERNS: A 26-year-old man complained of recurrent right limb weakness, accompanying slurred speech, and right facial paresthesia. DIAGNOSES: The patient was diagnosed with idiopathic hypereosinophilic syndrome (IHES). INTERVENTIONS: Adequate glucocorticoid and anticoagulant treatments were given. OUTCOMES: The patient's motor ability improved, and he was discharged 2 weeks later. Muscle strength in the right-side extremities had fully recovered at a 3-month follow-up after discharge. LESSONS: This case suggests that idiopathic hypereosinophilic syndrome should be considered as a cause of capsular warning syndrome, and the dose of glucocorticoid and the efficacy evaluation index needs to be reevaluated for the treatment of ischemic cerebrovascular disease associated with idiopathic hypereosinophilic syndrome.
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Líquidos Corporais , Transtornos Cerebrovasculares , Síndrome Hipereosinofílica , Masculino , Humanos , Adulto , Glucocorticoides/uso terapêutico , Síndrome Hipereosinofílica/complicações , Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/tratamento farmacológico , AnticoagulantesRESUMO
Circular RNAs (circRNAs) are molecular sponges that are involved in regulation of multiple types of cancer. The present study aimed to screen and explore the key circRNA/microRNA (miRNA or miR)/mRNA interactions in head and neck squamous cell carcinoma (HNSCC) using bioinformatics. A total of six pairs of cancerous and adjacent healthy tissue were obtained from patients with HNSCC and genome-wide transcriptional sequencing was performed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on differentially expressed genes (DEGs). Moreover, expression levels of DEGs were verified in HNSCC cells and tissues using reverse transcription-quantitative (RT-q)PCR. A molecular regulatory network consisting of three circRNAs, seven miRNAs and seven mRNAs was constructed, resulting in identification of two signaling axes, hsa_circ_0035431/hsa-miR-940/fucosyltransferase 6 (FUT6) and hsa_circ_0035431/hsa-miR-940/cingulin-like 1 (CGNL1). FUT6 and CGNL1 were downregulated in HNSCC compared with adjacent healthy tissue and the expression levels of these genes were associated with tumor stage. Low FUT6 and CGNL1 expression levels were associated with lower overall survival rate and progression-free intervals in HNSCC. RT-qPCR demonstrated that hsa_circ_0035431, FUT6 and CGNL1 were downregulated in HNSCC cells and tissue and hsa-miR-940 was upregulated. Notably, these results were consistent with those obtained using high-throughput sequencing. In conclusion, hsa_circ_0035431 may participate in regulation of FUT6 and CGNL1 expression by sponging hsa-miR-940, thus, impacting the occurrence, development and prognosis of HNSCC.
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Bacteria have numerous large dsDNA molecules that freely interact within the cell, including multiple plasmids, primary and secondary chromosomes. The cell membrane maintains a micron-scale confinement, ensuring that the dsDNA species are proximal at all times and interact strongly in a manner influenced by the cell morphology (e.g. whether cell geometry is spherical or anisotropic). These interactions lead to non-uniform spatial organization and complex dynamics, including segregation of plasmid DNA to polar and membrane proximal regions. However, exactly how this organization arises, how it depends on cell morphology and number of interacting dsDNA species are under debate. Here, using an in vitro nanofluidic model, featuring a cavity that can be opened and closed in situ, we address how plasmid copy number and confinement geometry alter plasmid spatial distribution and dynamics. We find that increasing the plasmid number alters the plasmid spatial distribution and shortens the plasmid polar dwell time; sharper cavity end curvature leads to longer plasmid dwell times.
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DNA , DNA/genética , Plasmídeos/genética , Anisotropia , Membrana CelularRESUMO
Klotho gene was originally discovered as an anti-aging gene, Klotho protein encoded by Klotho gene is expressed in multiple human tissues, and its most prominent function is the regulation of phosphate homeostasis. Klotho protein possesses various activities, including inhibition of multiple signaling pathways, reducing oxidative stress and suppressing inflammation, and these activities are associated with cancer. Klotho protein is discovered as a universal tumor suppressor, and its expression is associated with tumorigenesis and prognosis of patients. Lung cancer is the most common malignancy tumor, and it is the leading cause of cancer deaths worldwide because of its high incidence and mortality. This article summarizes the research progress of the role of Klotho on pathogenesis, therapeutic effect and prognosis in lung cancer, in order to provide new biomarker and target for diagnosis, treatment and prognosis of lung cancer.â©.
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Neoplasias Pulmonares , Humanos , Carcinogênese , InflamaçãoRESUMO
The practical application of black phosphorus (BP) is limited by its low absorption characteristics. In this work, we propose a perfect absorber based on a BP and bowtie shaped cavity, which has high tunability and excellent optical performance. This absorber effectively increases the light-matter interaction and achieves perfect absorption by using a monolayer BP and a reflector to form a Fabry-Perot cavity. We study the influence of structural parameters on the absorption spectrum and realize the adjustment of frequency and absorption in a certain range. Applying an external electric field on the surface of BP by electrostatic gating, we can change its carrier concentration to control its optical properties. In addition, we can flexibly tune the absorption and Q-factor by varying the polarization direction of incident light. This absorber has promising applications in optical switches, sensing, and slow light, which provides a new perspective for the practical application of BP and a foundation for future research, offering possibilities for more applications.
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Despite the advent of precision medicine and immunotherapy, mortality due to lung cancer remains high. The sonic hedgehog (SHH) cascade and its key terminal factor, glioma-associated oncogene homolog 1 (GLI1), play a pivotal role in the stemness and drug resistance of lung cancer. Here, we investigated the molecular mechanism of non-canonical aberrant GLI1 upregulation. The SHH cascade was upregulated in stem spheres and chemo-resistant lung cancer cells and was accountable for drug resistance against multiple chemotherapy regimens. GLI1 and the long non-coding RNA SOX2OT were positively regulated, and the GLI1-SOX2OT loop mediated the proliferation of parental and stem-like lung cancer cells. Further mechanistic investigation revealed that SOX2OT facilitated METTL3/14/IGF2BP2-mediated m6A modification and stabilization of the GLI1 mRNA. Additionally, SOX2OT upregulated METTL3/14/IGF2BP2 by sponging miR-186-5p. Functional analysis corroborated that GLI1 acted as a downstream target of METTL3/14/IGF2BP2, and GLI1 silencing could block the oncogenicity of lung cancer stem-like cells. Pharmacological inhibition of the loop remarkably inhibited the oncogenesis of lung cancer cells in vivo. Compared with paired adjacent normal tissues, lung cancer specimens exhibited consistently upregulated GLI1/SOX2OT/METTL3/14/IGF2BP2. The m6A-modified GLI1-SOX2OT loop may serve as a potential therapeutic target and prognostic predictor for lung cancer therapy and diagnosis in the clinic.
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Patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) seropositive for autoantibodies against nodal and paranodal proteins display distinct clinical presentations. In the latest study, CIDP with autoantibodies against paranodal proteins was defined as autoimmune nodopathy (AN). We herein present a case of 39-year-old male with anti- neurofascin (NF) 155 and NF186 IgG4 antibody with gait disturbance and tremor, who was followed up for 4 months and demonstrated clinical improvements after apparently effective rituximab therapy. In addition, a literature review was conducted to investigate the clinical characteristics of anti-NF155/NF186-positive AN.
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OBJECTIVE: To explore the regulatory role of SOX2-OT in migration of lung squamous cell carcinoma H520 cells and the underlying mechanisms. METHODS: Wound- healing and Transwell migration assays were performed to examine the changes in migration and invasion capacity of lung squamous cell line H520, which expressed higher levels of SOX2-OT than other lung cancer cell lines, following RNA interference-mediated SOX2-OT knockdown. The transcription levels of epithelial-mesenchymal transition (EMT)-related components was detected by qRT-PCR and immunoblotting. Gli1 gain-of-function analysis was performed in H520 cells with SOX2-OT knockdown and the changes in EMT phenotype of the cells were examined. miR-200c mimic and inhibitor were used to analyze the mechanism by which SOX2-OT positively regulates Gli1 and the mediating role of SOX2. RESULTS: SOX2-OT knockdown significantly lowered the invasiveness and migration capacity of H520 cells and caused changes in EMT phenotype of the cells. Overexpression of Gli1, which was positively regulated by SOX2-OT, reversed the inhibitory effect of SOX2-OT knockdown on migration of H520 cells. Transfection of the cells with miR-200c inhibitor effectively reversed SOX2-OT knockdown-induced down-regulation of SOX2. CONCLUSION: The SOX2-OT/SOX2 axis positively regulates migration of lung squamous H520 cells via Gli1-mediated EMT.
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Neoplasias Pulmonares , MicroRNAs , Humanos , Transição Epitelial-Mesenquimal/genética , Proteína GLI1 em Dedos de Zinco/genética , Proteína GLI1 em Dedos de Zinco/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Invasividade Neoplásica/genética , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismoRESUMO
There is growing appreciation for the role phase transition based phenomena play in biological systems. In particular, self-avoiding polymer chains are predicted to undergo a unique confinement dependent demixing transition as the anisotropy of the confined space is increased. This phenomenon may be relevant for understanding how interactions between multiple dsDNA molecules can induce self-organized structure in prokaryotes. While recent in vivo experiments and Monte Carlo simulations have delivered essential insights into this phenomenon and its relation to bacteria, there are fundamental questions remaining concerning how segregated polymer states arise, the role of confinement anisotropy and the nature of the dynamics in the segregated states. To address these questions, we introduce an artificial nanofluidic model to quantify the interactions of multiple dsDNA molecules in cavities with controlled anisotropy. We find that two dsDNA molecules of equal size confined in an elliptical cavity will spontaneously demix and orient along the cavity poles as cavity eccentricity is increased; the two chains will then swap pole positions with a frequency that decreases with increasing cavity eccentricity. In addition, we explore a system consisting of a large dsDNA molecule and a plasmid molecule. We find that the plasmid is excluded from the larger molecule and will exhibit a preference for the ellipse poles, giving rise to a non-uniform spatial distribution in the cavity that may help explain the non-uniform plasmid distribution observed during in vivo imaging of high-copy number plasmids in bacteria.
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DNA , Polímeros , Anisotropia , DNA/química , Método de Monte Carlo , Polímeros/químicaRESUMO
We use molecular dynamics simulation to probe the nonequilibrium physics of single nanochannel-confined semiflexible polymers in a homogeneous flow field. The flow field compresses the polymer against the end of the nanochannel, simulating an experiment of a nanochannel confined chain compressed against a slit barrier. The flow-based compression gives rise to a packing of the chain against the channel end that possesses a striking organization, consisting of interweaving of folds and circular coils. For stiff chains at low flow, we find that the organization is dominated by repeated hairpin folds. For stiff chains at higher flow, we observe that circular coils arise along with the folds, with folding and coiling domains becoming interwoven at the highest flow speeds. Chain organization is retained even when the chain persistence length is on order of the channel width. We show that the global polymer organization, consisting of a number of defined folds and coiled loops, arises from the minimization of the total chain free energy.
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Objective: Patients treated with medication for rheumatoid arthritis (RA) often improve but continue to have active diseases. The study aims to investigate whether needle-warming moxibustion (NWM) plus multirehabilitation training can improve quality of life (QoL) and functional mobility of RA patients after medication. Methods: Eighty-four RA patients were selected as study participants, including 42 patients receiving medication (medication group) and 42 patients receiving NWM plus multirehabilitation training (NWM + MRT group). The scores of disease symptoms, pain (visual analogue scale (VAS)), sleep quality (Pittsburgh Sleep Quality Index (PSQI)), functional mobility (Fugl-Meyer assessment scale (FMAS)), self-rating anxiety scale (SAS), self-rating depression scale (SDS), and QoL (SF-36) were compared before and after treatment. When patients were discharged from the hospital, they were given a questionnaire for treatment satisfaction. Results: After treatment, decreases in the scores of the VAS, PSQI, SAS, and SDS were observed in both cohorts, especially in the NWM + MRT group (P < 0.05). The FMAS scores of upper limbs and lower limbs were increased after treatment, which were higher in the NWM + MRT group in comparison with the medication group (P < 0.05). Of note, patients in the NWM + MRT group scored higher in various dimensions of the SF-36 scale (P < 0.05), showing better QoL. The satisfaction survey showed that the NWM + MRT group had a higher proportion of patients being satisfied and a lower proportion of patients being dissatisfied (P < 0.05). Conclusion: NWM plus multirehabilitation training could significantly attenuate disease symptoms, improve QoL, recover functional mobility, and reduce the risk of anxiety and depression in RA patients.