Explore the vast range of titles available.

Neural tube defects (NTDs), including spina bifida and anencephaly, represent the most severe and common malformations of the central nervous system affecting 0.7–3 per 1000 live births. They result from the failure of neural tube closure during the first few weeks of pregnancy. They have a complex etiology that implicate a large number of genetic and environmental factors that remain largely undetermined. Extensive studies in vertebrate models have strongly implicated the non-canonical Wnt/planar cell polarity (PCP) signaling pathway in the pathogenesis of NTDs. The defects in this pathway lead to a defective convergent extension that is a major morphogenetic process essential for neural tube elongation and subsequent closure. A large number of genetic studies in human NTDs have demonstrated an important role of PCP signaling in their etiology. However, the relative contribution of this pathway to this complex etiology awaits a better picture of the complete genetic architecture of these defects. The emergence of new genome technologies and bioinformatics pipelines, complemented with the powerful tool of animal models for variant interpretation as well as significant collaborative efforts, will help to dissect the complex genetics of NTDs. The ultimate goal is to develop better preventive and counseling strategies for families affected by these devastating conditions.

Purpose VEGF facilitates tumor angiogenesis, and bevacizumab targeting VEGF is used in anti-tumor therapy. It is meaningful to clarify the upstream regulatory mechanism of VEGF. BPTF is important in chromosomal remodeling, and promotes the progression of tumors. However, its role in promoting tumor angiogenesis by targeting VEGF has not been fully reported. This study aims to elucidate the expression regulation of VEGF by BPTF and its clinical significance in NSCLC. Methods 1. BPTF siRNA and shRNA plasmids were used to reduce the expression of BPTF by transfection in vivo and in vitro. BPTF, VEGF and CD144 expressions were examined by immunofluorescence and Western Blot. 2. The expressions of BPTF, VEGF, CD144 and CD31 were detected in lung adenocarcinoma samples by immunofluorescence, Western blot and immunohistochemical staining. 3. 26 lung adenocarcinoma patients treated by bevacizumab were divided into 2 groups according to the treatment efficacy. BPTF and VEGF expressions were analyzed. Results 1. BPTF knockdown inhibited the expression of VEGF and CD144 in vivo and in vitro. 2. Compared with para-cancer tissues, BPTF, VEGF, CD144 and CD31 were highly expressed in lung adenocarcinoma. 3. In 75 lung adenocarcinoma specimens, BPTF and VEGF overexpression was correlated with lymph node metastasis and clinical stage. The 5-year survival rate of patients with BPTF and VEGF low expression was higher, and BPTF expression was positively correlated with VEGF expression. 4. Among 26 patients treated with bevacizumab, the patients with BPTF overexpression are more sensitive to the treatment. Conclusions BPTF positively regulates VEGF expression and its high expression predicts a better efficacy of bevacizumab treatment in NSCLC.

As the main cause of visual function deficits in children and adolescents worldwide, amblyopia causes serious impairment of monocular visual acuity and stereopsis. The recovery of visual functions from amblyopia beyond the critical period is slow and incomplete due to the limited plasticity of the mature cortex; notably, visual stimulation training seems to be an effective therapeutic strategy in clinical practice. However, the precise neural basis and cellular mechanisms that underlie amblyopia and visual stimulation treatment remain to be elucidated. Using monocular deprivation in juvenile mice to model amblyopia, we employed two-photon calcium imaging and chemogenetic techniques to investigate the visual responses of individual excitatory neurons and parvalbumin (PV + ) interneurons in the primary visual cortex (V1) of amblyopic mice. We demonstrate that amblyopic mice exhibit an excitation/inhibition (E/I) imbalance. Moreover, visual stimulation decreases the response of PV + interneurons, reactivates the ocular dominance plasticity of excitatory neurons, and promotes vision recovery in adult amblyopic mice. Our results reveal a dynamic E/I balance between excitatory neurons and PV + interneurons that may underlie the neural mechanisms of amblyopia during cortical development and visual stimulation-mediated functional recovery from adult amblyopia, providing evidence for therapeutic applications that rely on reactivating adult cortical plasticity. A dynamic excitation and inhibition (E/I) balance between excitatory neurons and PV+ interneurons in the primary visual cortex underlying the neural mechanisms of amblyopia during cortical development and visual stimulation-mediated functional recovery from adult amblyopia.

AimsTo compare the baseline clinical characteristics and patterns of visual field defects between high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) in the Laser in Glaucoma and Ocular Hypertension (LiGHT) China subjects.MethodsAll patients (n=622) were recruited at Zhongshan Ophthalmic Center from 2015 to 2019. 1105 open-angle glaucoma eyes of 622 patients were classified as NTG (n=559) and HTG eyes (n=546) according to the baseline intraocular pressure (IOP) of 21 mm Hg. The mean deviation (MD), regional MD of the Glaucoma Hemifield Test regions and regional difference values were calculated. Daytime phasing IOP was recorded at 8:00, 10:00, 11:30, 14:30 and 17:00 hour. Multiple regression analyses were conducted for each regional difference.ResultsPatients with NTG were older, more likely to be female, hypertensive and suffer ischaemic heart disease than patients with HTG (p<0.05 for all comparisons). HTG showed higher mean daytime phasing IOP and higher daytime fluctuations than NTG (p<0.001 for all comparisons). HTG and NTG showed similar MD overall (p=0.665). NTG showed significantly greater hemifield asymmetry than HTG. The two arcuate regional differences in NTG were significantly associated with daytime IOP fluctuations (p<0.01 in both regions).ConclusionsIn the LiGHT China trial, NTG and HTG showed similar visual field defects severity at enrolment. However, NTG showed more severe hemifield asymmetry compared with HTG, and higher short-time IOP fluctuations might exacerbate this asymmetry in NTG.

Elevated temperatures at the transformer bushing cylinder head can precipitate failures, leading to significant power outages. In response, this study introduces a reversible temperature-indicating patch for the nuanced detection of thermal anomalies in the transformer bushing’s cylinder head. The patch, crafted through a melting process, utilizes a reversible discoloration material and is developed in two variants via an adsorption substrate method. Comprehensive evaluations of the patches’ color-changing characteristics, alongside their electrical and hydrophobic properties, were conducted using an automatic contact angle measuring instrument and an AC flashover test platform. The findings reveal that the temperature-indicating patch exhibits a discernible color transition within the range of 49~55 °C, with a color reversion temperature span of 45~55 °C, denoting marked sensitivity and robust reversibility. Additionally, it was observed that prolonged thermal aging correlates with a decrease in both the water contact angle and the discharge voltage per unit length across the surface of the patches, indicating a degradation in performance. Among the variants, the binder-based temperature-indicating patch demonstrated superior stability in electrical performance compared to its vacuum-based counterpart. The outcomes of this research offer valuable insights for the development of advanced diagnostic tools for the identification of thermal defects in transformer bushings, potentially enhancing reliability and safety in power distribution systems.

A waste biomass based hydrogel soybean residue-poly(acrylic acid) (SR–PAA) was prepared through a fast one-step reaction by UV radiation technology. SR–PAA was used to remove Cd(II) and Pb(II) ions from aqueous solutions. Effect of pH value, temperature, initial concentration, contact time, competitive ions in the solutions on metal ions adsorption and desorption/regeneration capacity of SR–PAA was discussed in detailed. It was found that the adsorption equilibrium was achieved within 20 min, and maximum adsorption for Cd(II) and Pb(II) ions were 1.43 and 2.04 mmol g −1 , respectively. Besides, adsorption thermodynamic analysis indicates that the process of Cd(II) and Pb(II) ions adsorption was spontaneous, feasible and exothermic in nature. And experimental data fitted the pseudo-second-order and Freundlich isotherm model well. Moreover, XPS spectra analysis proves that the metal ions were adsorbed on SR–PAA due to the interaction of carboxyl, hydroxyl and amine with these ions as ionic bond, coordination bond and electrostatic interaction.

Neurological disorders can be caused by viral infections. The association between viral infections and neuromyelitis optica spectrum disorder (NMOSD) has been well-documented for a long time, and this connection has recently come to attention with the occurrence of SARS-CoV-2 infection. However, the precise nature of the causal connection between NMOSD and COVID-19 infection remains uncertain. To investigate the causal relationship between COVID-19 and NMOSD, we utilized a two-sample Mendelian randomization (MR) approach. This analysis was based on the most extensive and recent genome-wide association study (GWAS) that included SARS-CoV-2 infection data (122616 cases and 2475240 controls), hospitalized COVID-19 data (32519 cases and 2062805 controls), and data on severe respiratory confirmed COVID-19 cases (13769 cases and 1072442 controls). Additionally, we incorporated a GWAS meta-analysis comprising 132 cases of AQP4-IgG-seropositive NMOSD (NMO-IgG+), 83 cases of AQP4-IgG-seronegative NMOSD (NMO-IgG-), and 1244 controls. The findings of our study indicate that the risk of developing NMO-IgG+ is elevated when there is a genetic predisposition to SARS-CoV-2 infection (OR = 5.512, 95% CI = 1.403-21.657, P = 0.014). Furthermore, patients with genetically predicted NMOSD did not exhibit any heightened susceptibility to SARS-CoV2 infection, COVID-19 hospitalization, or severity. our study using Mendelian randomization (MR) revealed, for the first time, that the presence of genetically predicted SARS-CoV2 infection was identified as a contributing factor for NMO-IgG+ relapses.

Background Targeted drugs are not quite effective for prolonging the survival of patients with gastric cancer due to off-target effects as well as tumor immune escape mechanisms. Circular RNAs widely exist in tumor regions as biomarkers and can be developed as effective drug targets. Methods Western blot, QRT-PCR, fluorescence in situ hybridization, and flow cytometry were used to investigate the function of hsa_circ_0136666 in promoting the proliferation of gastric cancer cells. Tissue immunofluorescence, enzyme-linked immunosorbent assay (ELISA), as well as flow cytometric analysis, was conducted to explore the process of tumor immune evasion in tumor-bearing mice. The differences of circRNA expression in clinical samples were analyzed through tissue microarray FISH. The effect of siRNA on improving the efficacy of anti-PDL1 drugs and suppressing the immune microenvironment was evaluated by the coadministration model. Results We demonstrated that hsa_circ_0136666 was widely and highly expressed in gastric cancer tissues and cells. Functionally, hsa_circ_0136666 promoted gastric cancer tumor proliferation and tumor microenvironment formation, leading to tumorigenesis immune escape, and this effect was dependent on CD8 + T cells. Mechanistically, we confirmed that hsa_circ_0136666 competitively upregulated PRKDC expression by sponging miR-375-3p, regulating immune checkpoint proteins, prompting phosphorylation of PD-L1 to preventing its degradation, driving PD-L1 aggregation and suppressing immune function, thereby impairing cancer immune responses. In terms of application, we found that LNP-siRNA effectively improved anti-PDL1 drug efficacy and inhibited immune escape. Conclusion Our results reveal an oncogenic role played by hsa_circ_0136666 in gastric cancer, driving PD-L1 phosphorylation via the miR-375/PRKDC signaling axis, prompting immune escape. This work proposes a completely new pathogenic mechanism of gastric cancer, uncovers a novel role for hsa_circ_0136666 as an immune target, and provides a rationale for enhancing the efficacy of anti-PD-L1 therapy for gastric cancer.

Age-related macular degeneration (AMD) is a retinal disorder that significantly impairs vision. This study investigates various machine learning models for predicting AMD risk, laying the groundwork for further research using big data and determining the most effective predictive model. Utilizing data from 8211 records with 39 features from the Fujian Eye Study, a cross-sectional epidemiological investigation, several machine learning models were developed and assessed. The models included logistic regression (LR), K-nearest neighbors (KNN), support vector machine (SVM), decision tree (DT), random forest (RF), light gradient boosting machine (LightGBM), and extreme gradient boosting (XGBoost). Data preprocessing, feature selection, and model training were all key components of the study. After evaluating multiple models, the logistic regression model emerged as the most accurate, achieving a balanced accuracy of 0.6364. Among the predictive features, educational background had the highest influence on the model's predictions, with an average SHAP (SHapley Additive exPlanations) value of 0.8199. Other significant factors included outdoor time and left eye spherical equivalent (OSSE), with SHAP values of 0.6474 and 0.6377, respectively. This study confirms that logistic regression is the most effective machine learning model for predicting AMD risk, with educational background identified as the most critical risk factor.

Alzheimer’s disease (AD) is one of the most common neurodegenerative disease and accumulating evidences suggest an active role of inflammation in the pathogenesis of AD. Inflammation resolution is an active process that terminates inflammation and facilitates the restoration of inflamed tissue to homeostasis. Resolution of inflammation has been shown to be conducted by a group of specialized pro-resolving lipid mediators (SPMs) including lipoxins, resolvins, protectins, and maresins (MaRs). Recent studies have demonstrated that failure of inflammation resolution can lead to chronic inflammation and, hence, contribute to AD progression. We have previously shown that MaR1 can improve neuronal survival and increase microglial phagocytosis of amyloid-β (Aβ). However, the effects of MaR1 on animal models of AD have not been reported. In this study, we aim to investigate the effects of MaR1 on behavioral deficits and pathological changes in a mouse model of AD. Mice received bilateral injections of Aβ42 protein into the hippocampus, followed by administration of MaR1 by intra-cerebroventricular injection. The behavioral changes in the mice were analyzed using Morris water maze. Immunohistochemistry, Fluoro-Jade B (FJB) staining, cytometric beads array (CBA), and western blot analysis were used to demonstrate molecular changes in the mice hippocampus and cortex. Our results showed that MaR1 treatment significantly improved the cognitive decline, attenuated microglia and astrocyte activation. In addition, we found that MaR1 decreased the pro-inflammatory cytokines TNF-α, IL-6, and MCP-1 production induced by Aβ42 and increased the anti-inflammatory cytokines IL-2, IL-10 secretion with or without Aβ42 stimulation. Moreover, western blot results showed that MaR1 up-regulated the levels of proteins related to survival pathway including PI3K/AKT, ERK and down-regulated the levels of proteins associated with inflammation, autophagy, and apoptosis pathways such as p38, mTOR and caspase 3. To conclude, MaR1 improved the cognitive decline, ameliorated pro-inflammatory glia cells activation via improving survival, enhancing autophagy, inhibiting inflammation and apoptosis pathways. In conclusion, this study shows that inflammation resolution may be a potential therapeutic target for AD.