Emerging evidence of context-dependent synapse elimination by phagocytes in the CNS.

Precise synapse elimination is essential for the establishment of a fully developed neural circuit during brain development and higher function in adult brain. Beyond immune and nutrition support, recent groundbreaking studies have revealed that phagocytic microglia and astrocytes can actively and selectively eliminate synapses in normal and diseased brains, thereby mediating synapse loss and maintaining circuit homeostasis. Multiple lines of evidence indicate that the mechanisms of synapse elimination by phagocytic glia are not universal but rather depend on specific contexts and detailed neuron-glia interactions. The mechanism of synapse elimination by phagocytic glia is dependent on neuron-intrinsic factors, many innate immune and local apoptosis related molecules. During development, microglial synapse engulfment in the visual thalamus is primarily influenced by the classic complement pathway, whereas in the barrel cortex, the fractalkine pathway is dominant. In Alzheimer's disease, microglia employ complement-dependent mechanisms for synapse engulfment in tauopathy and early ß-amyloid pathology. But microglia are not involved in synapse loss at late ß-amyloid stages. Phagocytic microglia also engulfment synapses in complement dependent way in schizophrenia, anxiety and stress. Besides, phagocytic astrocytes engulf synapses in a MEGF10 dependent way during visual development, memory and stroke. Furthermore, the mechanism of a phenomenon that phagocytes selectively eliminating excitatory and inhibitory synapses is also emphasized in this review. We hypothesize that elucidating context-dependent synapse elimination by phagocytic microglia and astrocytes may reveal the molecular basis of synapse loss in neural disorders and provide a rationale for developing novel candidate therapies that target synapse loss and circuit homeostasis.

Epidemiology of malignant tumors in patients with pemphigus: an analysis of trends from 1955 to 2021.

BACKGROUND: The incidence of malignant tumors has increased in patients with non-paraneoplastic pemphigus, although there has been no systematic analysis of global epidemiology. OBJECTIVE: To explore the epidemiology of various types of non-paraneoplastic pemphigus associated with malignant tumors. METHODS: Five databases from establishment through October 20, 2023, were searched. STATA SE 17 was used for the data analysis. Subgroup, meta-regression, and sensitivity analyses were used to evaluate the heterogeneity of pooled studies. RESULTS: A total of 6679 participants were included in our meta-analysis from 16 studies. The aggregated prevalence of tumors in patients diagnosed with pemphigus was 8%. The prevalence was 7% in patients with pemphigus vulgaris, 10% in those with pemphigus foliaceus, and 12% in individuals diagnosed with other types of pemphigus. The prevalence was 8% in Asia, 11% in Europe, and 8% in North America. From a country-specific perspective, patients with pemphigus from Israel, Greece, and Germany exhibited a higher prevalence of tumors at 11%. Furthermore, when categorized by the duration of the study period, the highest prevalence was observed in studies spanning 10 to 20 years, at 11%. CONCLUSION: These findings demonstrate the incidence and prevalence of malignant tumors in patients with non-paraneoplastic pemphigus, which may achieve early detection and intervention, and then reduce mortality rates.

The effect of PAP on UACR and metabolic indexes in patients with MS and OSAHS.

PURPOSE: To investigate the effects of positive airway pressure (PAP) device on urinary albumin to creatinine ratio (UACR) and metabolic indexes in patients with metabolic syndrome (MS) and obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: This study is a retrospective cohort study. Grouped according to whether to use PAP treatment, there were 25 cases in the PAP group and 44 cases in the no OSAHS treatment group. The PAP group received positive airway pressure device and routine treatment of MS. The no OSAHS treatment group received routine treatment of OSAHS and MS. The treatment period is 3 months. RESULTS: 1. The PAP group demonstrated significant reductions in Body Mass Index (BMI), Waist circumference (WC), Neck circumference (NC), Visceral fat area (VFA), Fasting C peptide (FCP), high-sensitivity C-reactive protein (hs-CRP), and UACR compared to the no OSAHS treatment group, with significant differences (P all <0.05). Among them, the UACR in the PAP group decreased significantly (from 86.05(52.55,131.61)mg/g to 16.76(8.70,25.12)mg/g, P<0.001). 2. Linear regression analysis using the decrease in UACR values as the dependent variable demonstrated a positive linear relationship with the decrease in BMI, VFA, fasting insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR). Furthermore, multiple linear regression analysis indicated that the decrease in VFA (B=0.537 [95% confidence interval, 0.084 to 0.989]; P = 0.021) and HOMA-IR (B=1.000 [95% confidence interval, 0.082 to 1.917]; P = 0.033) values independently correlated with decrease in UACR values. CONCLUSIONS: PAP treatment can reduce UACR in patients with MS and OSAHS, and has the effect of improving metabolic disorders. The decrease of UACR in patients may be related to the decrease of visceral fat and the improvement of insulin resistance.

Sevoflurane postconditioning ameliorates cerebral hypoxia/reoxygenation injury in zebrafish involving the Akt/GSK-3ß pathway activation and the microtubule-associated protein 2 promotion.

Sevoflurane postconditioning has been shown to provide neuroprotection against cerebral hypoxia-ischemia injury, but the mechanisms remain elusive. Microtubule-associated protein 2 (MAP2) is implicated in early neuronal hypoxia-ischemia injury. This study aimed to investigate whether the neuroprotective effects of sevoflurane postconditioning are related to the Akt/GSK-3ß pathway and its downstream target MAP2 in zebrafish hypoxia/reoxygenation (H/R) model. Sevoflurane postconditioning or GSK-3ß inhibitor TDZD-8 were used to treat H/R zebrafish. The cerebral infarction, neuronal apoptosis, and mitochondrial changes were evaluated using TTC staining, TUNEL staining, and transmission electron microscopy, respectively. The distribution of MAP2 in the brain was determined by immunofluorescence imaging. The levels of Akt, p-Akt, GSK-3ß, p-GSK-3ß, and MAP2 proteins were evaluated by Western blotting. The neurobehavioral recovery of zebrafish was assessed based on optokinetic response behavior. Our results indicated that sevoflurane postconditioning and TDZD-8 significantly reduced the cerebral infarction area, suppressed cell apoptosis, and improved mitochondrial integrity in zebrafish subjected to H/R. Furthermore, sevoflurane postconditioning and TDZD-8 elevated the ratios of p-Akt/Akt and p-GSK-3ß/GSK-3ß. However, the neuroprotective effect of sevoflurane postconditioning was effectively abolished upon suppression of MAP2 expression. In conclusion, sevoflurane postconditioning ameliorated cerebral H/R injury and facilitated the restoration of neurobehavioral function through the activation of Akt/GSK-3ß pathway and promotion of MAP2 expression.

Sustained increase in suspended sediments near global river deltas over the past two decades.

River sediments play a critical role in sustaining deltaic wetlands. Therefore, concerns are raised about wetlands' fate due to the decline of river sediment supply to many deltas. However, the dynamics and drivers of suspended sediment near deltaic coasts are not comprehensively assessed, and its response to river sediment supply changes remains unclear. Here we examine patterns of coastal suspended sediment concentration (SSC) and river sediment plume area (RPA) for 349 deltas worldwide using satellite images from 2000 to 2020. We find a global increase in SSC and RPA, averaging +0.46% and +0.48% yr-1, respectively, with over 59.0% of deltas exhibiting an increase in both SSC and RPA. SSC and RPA increases are prevalent across all continents, except for Asia. The relationship between river sediment supply and coastal SSCs varies between deltas, with as much as 45.2% of the deltas showing opposing trends between river sediments and coastal SSCs. This is likely because of the impacts of tides, waves, salinity, and delta morphology. Our observed increase in SSCs near river delta paints a rare promising picture for wetland resilience against sea-level rise, yet whether this increase will persist remains uncertain.

Activation of astrocytes by ANXA2-derived extracellular vesicles from lung cancer cells affects aggressiveness, immunotherapy response and microenvironment of lung cancer.

Background: ANXA2 has been extensively documented in relation to cancer. Nevertheless, the involvement of ANXA2 in lung carcinoma remains uncertain. Methods: Data from The Cancer Genome Atlas (TCGA) database was downloaded using open-access methods. The examination of publicly available data was conducted utilizing the R software. The mRNA level of specific molecules was detected using Real-time Quantitative PCR (qPCR). The protein level of specific molecules was detected using the Western blot assay. The cell proliferation ability of cancer cells was assessed using the CCK8 assay. The invasion and migration capability of cancer cells was assessed using the Transwell assay. Validation of exosomes extraction was conducted using electron microscopy and particle size analysis. Results: In this study, based on series experiments, we found that ANXA2 can promote the activation of neuroastrocytes cells CP-H122 through the exosome pathway. Also, we found that ANXA2 can be transmitted from A549 cells to CP-H122 through the exosomes pathway and further promote the activation of CP-H122. Activated CP-H122 cells further enhance the proliferation, invasion and metastasis of A549 cells. Meanwhile, we performed transcriptome sequencing to explore the downstream genes of ANXA2 to screen potential targets for follow-up studies. Analysis based on public data showed that ANXA2 was related to the worse survival performance and clinical features of lung cancer. Gene set enrichment analysis based on the Hallmark gene set indicated that the patient with high ANXA2 expression might have a higher activity of the apical surface, reactive oxygen species pathway, angiogenesis, TGF-ß signaling, MYC target, but lower activity of pancreas-ß cells. More important, our results showed that ANXA2 can affects immunotherapy response and reshape immune microenvironment of lung cancer. Conclusions: This study demonstrates that ANXA2 activates CP-H122 cells, affects A549 cell behavior, and impacts lung cancer prognosis and immunotherapy response.

Multidrivers of energy-related carbon emissions and its decoupling with economic growth in Northwest China.

Northwest China has great natural resource endowment to develop its economy, but factors such as geographic remoteness and technological backwardness result in lower economic levels and higher carbon emissions. This study calculated the energy-related carbon emissions of five provinces in this region, and the evolutionary characteristics of energy-related carbon emissions were analysed from the spatiotemporal perspective. The Kaya identity was applied to decompose the factors influencing energy-related carbon emissions, and the logarithmic mean divisia index (LMDI) and refined Laspeyres index were combined to calculate the role of each influencing factor on energy-related carbon emissions. Finally, the Tapio and LMDI models were used to analyse the evolution of the decoupling relationship between energy-related carbon emissions and economic growth and the role of various influencing factors. The energy-related carbon emissions in Northwest China showed an increasing trend. In terms of influencing factors, economic growth and urban expansion had the highest contributions to carbon emissions and decoupling inhibition, whereas population agglomeration had the opposite effect. Northwest China showed great decoupling trends between energy-related carbon emissions and economic growth.

Qinzhuliangxue mixture ameliorates psoriasis by restraining apoptosis in psoriasis via downregulating the MDA-5 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is characterized by hyperkeratosis that produces the classic silvery scales, and the pathogenesis of psoriasis involves abnormal proliferation of keratinocytes. Emerging evidence supports that apoptosis regulates keratinocyte proliferation and formation of stratum corneum, which maintains the homeostasis of the skin. Qinzhuliangxue mixture (QZLX) is a representative formula for the treatment of psoriasis, which was earliest recorded in the classic Chinese medicine book Xia's Surgery. In our previous clinical studies, QZLX demonstrated 83.33% efficacy with few side effects in the treatment of psoriasis. Furthermore, our published basic research has also proved that the QZLX mixture effectively inhibits the hyperproliferation of keratinocytes, thus exerting therapeutic effects on psoriasis. However, whether QZLX mixture can regulate keratinocytes apoptosis requires further clarification. OBJECTIVE OF THE STUDY: To investigate the mechanism of QZLX in the treatment of psoriasis from the perspective of keratinocyte apoptosis. MATERIALS AND METHODS: First, psoriasis-like mice with imiquimod (IMQ)-induced were given QZLX intragastric administration and Psoriasis Area Severity Index (PASI) scores were recored for 11 consecutive days to appraise the efficacy. Then, tissue samples were collected for transcriptome analysis. The DEseq2 method detected significantly differentially expressed genes (DEGs), Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway databases were used to analyze the functions and pathway enrichment of DEGs. After that, the therapeutic mechanisms of QZLX in intervening with psoriasis were explored using TUNEL, immunohistochemical staining, and western blotting. RESULTS: QZLX ameliorated the symptoms and pathological characteristics of IMQ-induced psoriasis in mice. The epidermal cell hyperplasia in the skin was inhibited, in accordance with the suppressed expression of PCNA and Ki67 after treatment. Transcriptome sequencing showed that melanoma differentiation associated gene-5 (MDA-5) was downregulated. GO and KEGG enrichment analysis of the signaling pathways indicated that the differentially expressed genes were significantly enriched in apoptosis pathways. Besides, QZLX treatment decreased the apoptosis of keratinocyte as shown by reduced TUNEL-positive cells. As MDA-5 protein levels decreased, so did the expression of the downstream protein Caspase-8, which indicates that the apoptotic pathway was triggered. Furthermore, QZLX therapy might also help to balance the apoptotic Bcl-2 family expression. CONCLUSION: QZLX restrains the apoptosis of keratinocyte in psoriasis-like mice by downregulating the MDA-5 pathway. The restoration of the balance between cell apoptosis and proliferation in the skin may lead to considerable psoriasis relief. Our study reveals the possible molecular processes behind the effects of QZLX therapy on the skin lesions of psoriasis, and lends support to its clinical efficacy.

KGRT peptide incorporated hydrogel with antibacterial activity for wound healing by optimizing cellular functions via ERK/eNOS signaling.

Bacterial infected wounds, which is characterized by easy infection, multiple inflammation and slow healing, is a complex symptom, resulting from metabolic disorder of the wound microenvironment. In this study, a series of self-healing double-network hydrogels based on KGRT peptide (Lys-Gly-Arg-Thr) with antibacterial, anti-inflammatory and optimizing cellular functions were designed to promote the healing of infected wounds with full-thickness skin defects. Moreover, the dextran hydrogelintroduces a large number of side chains, which are entangled with each other in the Schiff base network to form an interpenetrating structure. The hydrogel might regulate cell metabolism, differentiation and vascular endothelial growth factor (VEGF) function. Importantly, both in vitro and in vivo data showed that hydrogel not only has good antibacterial properties (99.8 %), but also can eradicate bacterial biofilm, effectively reduce inflammation (down-regulated IL-1ß, TNF-α and ROS) and accelerate chronic wound healing process by speeding-up wound closure, increasing granulation tissue thickness, collagen deposition, angiogenesis (up-regulated CD31). The hydrogel could up-regulate mRNA expression of PI3K, AKT, ERK, eNOS, HIF-1α and VEGF, which were correlated with wound healing. Consistently, the hydrogel could promote infected wounds healing and inhibit inflammation through ERK/eNOS signaling pathway. Collectively, hydrogel has excellent clinical application potential for promoting infected wound healing.

Lifestyle intervention in children with obesity and nonalcoholic fatty liver disease (NAFLD): study protocol for a randomized controlled trial in Ningbo city (the SCIENT study).

BACKGROUND: The increasing prevalence of childhood obesity has become an urgent public health problem, evidence showed that intervention for childhood obesity bring enormous health benefits. However, an effective individualized intervention strategy remains to be developed, and the accompanying remission of related complications, such as nonalcoholic fatty liver disease (NAFLD), needs to be assessed. This study aimed to develop an m-Health-assisted lifestyle intervention program targeting overweight/obese children and assess its effectiveness on indicators of adiposity and NAFLD. METHODS: This is a cluster-randomized controlled trial that conducted in children with overweight/obesity in Ningbo city, Zhejiang Province, China. Students in Grade 3 (8-10 years old) were recruited from six primary schools, with three be randomized to intervention group and three to usual practice group. The intervention program will last for one academic year and consists of health education, dietary guidance, and physical activity reinforcement. This program is characterized by encouraging four stakeholders, including School, Clinic, famIly, and studENT (SCIENT), to participate in controlling childhood obesity, assisted by m-Health technology. Assessments will be conducted at baseline and 3 months, 9 months, 24 months, and 36 months after baseline. The primary outcome will be the differences between the two groups in students' body mass index and fatty liver index at the end of the intervention (9 months after baseline). During the implementation process, quality control methods will be adopted. DISCUSSION: The program will test the effectiveness of the m-Health-assisted lifestyle intervention on children with obesity and NAFLD. The results of this study will provide evidence for establishing effective lifestyle intervention strategy aimed at childhood obesity and NAFLD and may help develop guidelines for the treatment of obesity and NAFLD in Chinese children. TRIAL REGISTRATION: Clinicaltrials.gov NCT05482191. Registered on July 2022.

[Dynamic Analysis on Carbon Metabolism of the Northern Region of China Under the Background of Carbon Emission Trading Policy].

The launch of the national carbon emissions trading market in China is a policy to carry out the Beautiful China initiative and to establish a low-carbon economic development system that promotes carbon emission and waste reduction. In order to detect the carbon metabolic processes of the pilot and nonpilot municipalities or provinces in the northern region of China， the theory of urban carbon metabolism and the methods of input-output analysis and ecological network analysis were introduced and used. The results showed that the direct carbon emissions of Beijing and Tianjin had decreased， but their embodied carbon emissions had increased since 2012. The direct and embodied carbon emissions of the pilot sectors in Beijing and Tianjin had the same trend； specifically， the emissions of the sectors of mining and washing of coal， extraction of petroleum and natural gas， and manufacture of non-metallic mineral products decreased significantly， but the sectors of production and supply of electric power and steam with high carbon emission increased. The same trend of the embodied carbon emission intensities of sectors with that of their embodied carbon emissions verified that the embodied added values were not growing with the promotion of the carbon emission trading market. Subsequently， the embodied carbon emission of the pilot sectors in all the municipalities and provinces of the northern region were all contributed mainly by the emissions embodied by a path length less than 6； therefore， it showed that more attention should be paid to the trade among sectors with a path length less than 6 and reducing their carbon emissions. Furthermore， from 2007 to 2012， products or service trading among sectors mostly concentrated on sectors within one municipality or province， and these products or services had the characteristics of low carbon emission. Since 2012， the integration development of the Beijing-Tianjin-Hebei urban agglomeration and the new regional economic patterns established in the northern region both promoted the trading across provinces and across sectors. This research is based on the background of the carbon emission trading policy and aims to build a methodology to identify the key actors and paths in a metabolic system. This could provide a scientific basis for regional policy implementation and regional long-term sustainable development.

Visceral adiposity index as a predictor of type 2 diabetes mellitus risk: A systematic review and dose-response meta-analysis.

AIMS: Considering the positive association between visceral adiposity index (VAI) and type 2 diabetes mellitus (T2DM), no comprehensive assessment on the summarized and dose-response relationship between VAI and T2DM has yet been reported. Therefore, we performed a meta-analysis, including dose-response analysis, to quantitively elucidate this association. DATA SYNTHESIS: MEDLINE via PubMed and Embase databases were searched for relevant articles up to December 14, 2021. Random-effects generalized least squares regression models were used to assess the quantitative association between VAI and T2DM risk across studies. Restricted cubic splines were used to model the dose-response association. A total of 9 prospective cohort studies and 5 cross sectional studies were included in our review. Based on the meta-analysis, the pooled RR of T2DM was 2.05 (95% CI 1.74-2.41) for the highest versus reference VAI category. We found that the risk of T2DM was increased by 44% (RR, 1.44; 95% CI, 1.23-1.68) with each 1-unit increment of VAI. While, we found no evidence of a nonlinear dose-response association of VAI and T2DM (Pnon-linearity = 0.428). With the linear cubic spline model, when compared to population with VAI at 0.6, for those with VAI at 2.0, the risk of T2DM was increased by 81% (RR, 1.81; 95% CI 1.55-2.12). CONCLUSIONS: Our meta-analysis provides quantitative data suggesting that VAI is associated with an increased risk of T2DM. Public health strategies focusing on weight loss among obesity, especially the people characterized by the thin-on-the-outside--fat-on-the-inside phenotype could possibly reduce a substantial risk of T2DM. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022372666.

Therapeutic effects of the Qingre-Qushi recipe on atopic dermatitis through the regulation of gut microbiota and skin inflammation.

Accumulating evidence has highlighted a strong association between gut microbiota and the occurrence, development, prevention, and treatment of atopic dermatitis (AD). The regulation of gut microbial dysbiosis by oral traditional Chinese medicine (TCM) has garnered significant attention. In the treatment of AD, the TCM formula Qingre-Qushi Recipe (QRQS) has demonstrated clinical efficacy. However, both the therapeutic mechanisms of QRQS and its impact on gut microbiota remain unclear. Thus, our study aimed to assess the efficacy of QRQS and evaluate its influence on the composition and diversity of gut microbiota in AD animal models. First, we investigated the therapeutic effect of QRQS on AD using two animal models: filaggrin-deficient mice (Flaky tail, ft/ft) and MC903-induced AD-like mice. Subsequently, we explored its influence on the composition and diversity of gut microbiota. Our results demonstrated that QRQS treatment ameliorated the symptoms in both ft/ft mice and MC903-induced AD-like mice. It also reduced the levels of serum IgE and pro-inflammatory cytokines, including IL-1ß, IL-4, IL-5, IL-9, IL-13, IL-17A, and TNF-α. Furthermore, QRQS remarkably regulated gut microbiota diversity by increasing Lactobacillaceae and decreasing Bacteroidales. The inflammatory factors in peripheral serum of ft/ft mice showed a close correlation with gut microbiota, as determined using the Spearman correlation coefficient. Additionally, PICRUSt analysis revealed an enrichment in ascorbate and aldarate metabolism, fatty acid metabolism and biosynthesis, and propanoate metabolism in the QRQS group compared to the ft/ft group. Finally, we identified liquiritin as the primary active ingredient of QRQS using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). Our findings revealed that QRQS improved AD-like symptoms and alleviated skin inflammation in ft/ft and MC903-induced mice. This suggests that modulating the gut microbiota may help elucidate its anti-inflammation activation mechanism, highlighting a new therapeutic strategy that targets the intestinal flora to prevent and treat AD.

Gender differences in symptom burden among people living with HIV/AIDS receiving antiretroviral therapy in Yunnan, China.

ABSTRACTLittle is known about gender differences in the symptom burden of people living with HIV/AIDS (PLWHA) on antiretroviral therapy in China. This study was conducted based on a biopsychosocial-medical model to describe gender differences in symptom burden among 1035 PLWHA in Yunnan Province, China. After propensity score matching, 798 PLWHA were included in this analysis. Feeling stressed, poor sleep, and memory loss were the most burdensome symptoms among men, while feeling stressed, memory loss, and dizziness were the most burdensome symptoms among women. Among men PLWHA, factors associated with symptom burden were being of the ethnic minority, CD4 count ≥ 500 cells/mm3, physical functioning, and social support. Among women PLWHA, factors associated with symptom burden were being an inpatient, physical functioning, psychological functioning, and social support. Our findings suggest that healthcare providers need to take into account gender differences when developing optimal prevention, treatment, and care programs that provide individualized care to reduce patients' symptom burden.

Lysine demethylase KDM3A alleviates hyperoxia-induced bronchopulmonary dysplasia in mice by promoting ETS1 expression.

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease among neonates, with increasing morbidity and mortality. This study aims to investigate the effect and mechanism of lysine demethylase 3A (KDM3A) on hyperoxia-induced BPD. Hyperoxia-induced BPD mouse and alveolar epithelial cell models were constructed. The effects of hyperoxia on lung development were evaluated by histological and morphological analysis. The levels of KDM3A, E26 transformation specific-1 (ETS1), H3 lysine 9 dimethylation (H3K9me2), and endoplasmic reticulum (ER) stress-related indexes were quantified by RT-qPCR, Western blot, and IF staining. Cell apoptosis was assessed by flow cytometry and TUNEL staining. Transfection of oe-ETS1, oe-KDM3A, and sh-ETS1 was applied in hyperoxia-induced alveolar epithelial cells to explore the mechanism of the KDM3A/ETS1 axis in hyperoxia-induced apoptosis. KDM3A inhibitor IOX1 was applied to validate the in vivo effect of KDM3A in hyperoxia-induced BPD mice. The results displayed that hyperoxia-induced BPD mice showed reduced body weight, severe destruction of alveolar structure, decreased radial alveolar count (RAC), and increased mean linear intercept (MLI) and mean alveolar diameter (MAD). Further, hyperoxia induction down-regulated ETS1 expression, raised ER stress levels, and increased apoptosis rate in BPD mice and alveolar epithelial cells. However, transfection of oe-ETS1 improved the above changes in hyperoxia-induced alveolar epithelial cells. Moreover, transfection of oe-KDM3A up-regulated ETS1 expression, down-regulated H3K9me2 expression, inhibited ER stress, and reduced apoptosis rate in hyperoxia-induced alveolar epithelial cells. In addition, transfection of sh-ETS1 reversed the inhibitory effect of KDM3A on hyperoxia-induced apoptosis by regulating ER stress. In vivo experiments, KDM3A inhibitor IOX1 intervention further aggravated BPD in newborn mice. In a word, KDM3A alleviated hyperoxia-induced BPD in mice by promoting ETS1 expression.

Hemodynamic assessment for intracranial atherosclerosis from angiographic images: a clinical validation study.

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is one of the leading causes of ischemic stroke. Conventional anatomical analysis by CT angiography, MRI, or digital subtraction angiography can provide valuable information on the anatomical changes of stenosis; however, they are not sufficient to accurately evaluate the hemodynamic severity of ICAS. The goal of this study was to assess the diagnostic performance of the pressure ratio across intracranial stenoses (termed as fractional flow (FF)) derived from cerebral angiography for the diagnosis of hemodynamically significant ICAS defined by pressure wire-derived FF. METHODS: This retrospective study represents a feasible and reliable method for calculating the FF from cerebral angiography (AccuFFicas). Patients (n=121) who had undergone wire-based measurement of FF and cerebral angiography were recruited. The accuracy of the computed pressure ratio was evaluated using wire-based FF as the reference standard. RESULTS: The mean value of wire-based FF was 0.78±0.19, while the computed AccuFFicas had an average value of 0.79±0.18. Good correlation (Pearson's correlation coefficient r=0.92, P<0.001) between AccuFFicas and FF was observed. Bland-Altman analysis showed that the mean difference between AccuFFicas and FF was -0.01±0.07, indicating good agreement. The area under the curve (AUC) of AccuFFicas in predicting FF≤0.70, FF≤0.75, and FF≤0.80 was 0.984, 0.986, and 0.962, respectively. CONCLUSION: Angiography-based FF computed from cerebral angiographic images could be an effective computational tool for evaluating the hemodynamic significance of ICAS.

A rare case report of infratentorial cisternal angiolipoma with review of literature.

Angiolipomas are slow-growing benign mesenchymal-derived tumors consisting of mature adipocytes and thin-walled blood vessels. While the majority of angiolipomas are found in subcutaneous tissues, rarely there are case reports of intracranial lesions. We present a case of cisternal angiolipoma in a 10-year-old female. She presented with vague symptoms like dizziness without neurological deficits and radiological evaluation confirmed a left-sided infratentorial cisternal partially enhancing mass. She underwent craniotomy and had complete resection of the mass, which was histologically composed of mature adipocytes and blood vessels, consistent with angiolipoma. A review of the literature found only 18 cases of intracranial angiolipoma ever reported with our case representing the first case of infratentorial cisternal region.

Exendin-4 increases the firing activity of hippocampal CA1 neurons through TRPC4/5 channels.

The central neuropeptide GLP-1 is synthesized by preproglucagon (PPG) neurons in the brain. GLP-1 receptors are widely distributed in central nervous system. Hippocampus is a key component of the limbic system which is involved in learning, memory, and cognition. Previous studies have shown that overexpression of GLP-1 receptors in the hippocampus could improve the process of learning and memory. However, up to now, the direct electrophysiological effects and possible molecular mechanisms of GLP-1 in hippocampal CAl neurons remain unexplored. The present study aims to evaluate the effects and mechanisms of GLP-1 on the spontaneous firing activity of hippocampal CAl neurons. Employing multibarrel single-unit extracellular recordings, the present study showed that micro-pressure administration of GLP-1 receptor agonist, exendin-4, significantly increased the spontaneous firing rate of hippocampal CA1 neurons in rats. Furthermore, application of the specific GLP-1 receptor antagonist, exendin(9-39), alone significantly decreased the firing rate of CA1 neurons, suggesting that endogenous GLP-1 modulates the firing activity of CA1 neurons. Co-application of exendin(9-39) completely blocked exendin-4-induced excitation of hippocampal CA1 neurons. Finally, the present study demonstrated for the first time that the transient receptor potential canonical 4 (TRPC4)/TRPC5 channels may be involved in exendin-4-induced excitation. The present studies may provide a rationale for further investigation of the modulation of GLP-1 on learning and memory as well as its possible involvement in Alzheimer's disease.

Mediating Triple Ions Migration Behavior via a Fluorinated Separator Interface toward Highly Reversible Aqueous Zn Batteries.

Rampant dendrite growth, electrode passivation and severe corrosion originate from the uncontrolled ions migration behavior of Zn2+ , SO4 2- , and H+ , which are largely compromising the aqueous zinc ion batteries (AZIBs) performance. Exploring the ultimate strategy to eliminate all the Zn anode issues is challenging but urgent at present. Herein, a fluorinated separator interface (PVDF@GF) is constructed simply by grafting the polyvinylidene difluoride (PVDF) on the GF surface to realize high-performance AZIBs. Experimental and theoretical studies reveal that the strong interaction between C─F bonds in the PVDF and Zn2+ ions enables evenly redistributed Zn2+ ions concentration at the electrode interface and accelerates the Zn transportation kinetics, leading to homogeneous and fast Zn deposition. Furthermore, the electronegative separator interface can spontaneously repel the SO4 2- and anchor H+ ions to alleviate the passivation and corrosion. Accordingly, the Zn|Zn symmetric cell with PVDF@GF harvests a superior cycling stability of 500 h at 10 mAh cm-2 , and the Zn|VOX full cell delivers 76.8% capacity retention after 1000 cycles at 2 A g-1 . This work offers an all-round solution and provides new insights for the design of advanced separators with ionic sieve function toward stable and reversible Zn metal anode chemistry.