The secondary visual cortex mediated the enhancement of associative learning on methamphetamine self-administration behaviors.

RATIONALE: Methamphetamine addiction is a persistent and intractable pathological learning and memory, whereas no approved therapeutics is available. However, few attentions have been paid to how associative learning participates in the formation of intractable memory related to drug addiction OBJECTIVES AND METHODS: To investigate the role of associative learning in methamphetamine addiction and the underlying neurobiological mechanism, methamphetamine self-administration, oral sucrose self-administration, chemogenetic neuromanipulation, and fiber photometry in mice were performed in this study. RESULTS: We reported that associative learning increased methamphetamine-induced self-administration, but not oral sucrose self-administration. In addition, the enhancement of methamphetamine-induced self-administration was independent of more methamphetamine consumption, and remained with higher drug-taking and motivation in the absence of visual cues, suggesting the direct effects of the associative learning that enhanced methamphetamine-induced self-administration. Moreover, chemogenetic inactivation of the secondary visual cortex (V2) reduced the enhancement of the drug-taking induced by associative learning but did not alter sucrose-taking. Further fiber photometry of V2 neurons demonstrated that methamphetamine-associative learning elicits V2 neuron excitation, and sucrose-associative learning elicits V2 neuron inhibition. CONCLUSIONS: Therefore, this study reveals the neurobiological mechanism of V2 excitability underlying how associative learning participates in the formation of intractable memory related to drug addiction, and gives evidence to support V2 as a promising target for stimulation therapy for methamphetamine addiction.

MiR-106a-5p targets PFKFB3 and improves sepsis through regulating macrophage pyroptosis and inflammatory response.

The enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3) is a critical regulator of glycolysis and plays a key role in modulating the inflammatory response, thereby contributing to the development of inflammatory diseases such as sepsis. Despite its importance, the development of strategies to target PFKFB3 in the context of sepsis remains challenging. In this study, we employed a miRNA-based approach to decrease PFKFB3 expression. Through multiple meta-analyses, we observed a downregulation of miR-106a-5p expression and an upregulation of PFKFB3 expression in clinical sepsis samples. These changes were also confirmed in blood monocytes from patients with early sepsis and from a mouse model of lipopolysaccharide (LPS)-induced sepsis. Overexpression of miR-106a-5p significantly decreased the LPS-induced increase in glycolytic capacity, inflammatory response, and pyroptosis in macrophages. Mechanistically, we identified PFKFB3 as a direct target protein of miR-106a-5p and demonstrated its essential role in LPS-induced pyroptosis and inflammatory response in macrophages. Furthermore, treatment with agomir-miR-106a-5p conferred a protective effect in an LPS mouse model of sepsis, but this effect was attenuated in myeloid-specific Pfkfb3 KO mice. These findings indicate that miR-106a-5p inhibits macrophage pyroptosis and inflammatory response in sepsis by regulating PFKFB3-mediated glucose metabolism, representing a potential therapeutic option for the treatment of sepsis.

Endothelial NLRP3 inflammasome regulation in atherosclerosis.

AIM: The activation of Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in endothelial cells (ECs) contributes to vascular inflammation in atherosclerosis. Considering the high glycolytic rate of ECs, we delineated whether and how glycolysis determines endothelial NLRP3 inflammasome activation in atherosclerosis. METHODS AND RESULTS: Our results demonstrated a significant upregulation of 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3 (PFKFB3), a key regulator of glycolysis, in human and mouse atherosclerotic endothelium, which positively correlated with NLRP3 levels. Atherosclerotic stimuli upregulated endothelial PFKFB3 expression via sterol regulatory element binding protein 2 (SREBP2) transactivation. EC-selective haplodeficiency of Pfkfb3 in Apoe-/- mice resulted in reduced endothelial NLRP3 inflammasome activation and attenuation of atherogenesis. Mechanistic investigations revealed that PFKFB3-driven glycolysis increased the NADH content and induced oligomerization of C-terminal binding protein 1 (CtBP1), an NADH-sensitive transcriptional co-repressor. The monomer form, but not the oligomer form, of CtBP1 was found to associate with the transcriptional repressor Forkhead box P1 (FOXP1) and acted as a transrepressor of inflammasome components, including NLRP3, caspase-1, and interleukin-1ß (IL-1ß). Interfering with NADH-induced CtBP1 oligomerization restored its binding to FOXP1 and inhibited the glycolysis-dependent upregulation of NLRP3, Caspase-1, and IL-1ß. Additionally, EC-specific overexpression of NADH-insensitive CtBP1 alleviates atherosclerosis. CONCLUSIONS: Our findings highlight the existence of a glycolysis-dependent NADH/CtBP/FOXP1-transrepression pathway that regulates endothelial NLRP3 inflammasome activation in atherogenesis. This pathway represents a potential target for selective PFKFB3 inhibitors or strategies aimed at disrupting CtBP1 oligomerization to modulate atherosclerosis.

Decreasing mitochondrial fission ameliorates HIF-1α-dependent pathological retinal angiogenesis.

Angiogenesis plays a critical role in many pathological processes, including irreversible blindness in eye diseases such as retinopathy of prematurity. Endothelial mitochondria are dynamic organelles that undergo constant fusion and fission and are critical signalling hubs that modulate angiogenesis by coordinating reactive oxygen species (ROS) production and calcium signalling and metabolism. In this study, we investigated the role of mitochondrial dynamics in pathological retinal angiogenesis. We showed that treatment with vascular endothelial growth factor (VEGF; 20 ng/ml) induced mitochondrial fission in HUVECs by promoting the phosphorylation of dynamin-related protein 1 (DRP1). DRP1 knockdown or pretreatment with the DRP1 inhibitor Mdivi-1 (5 µM) blocked VEGF-induced cell migration, proliferation, and tube formation in HUVECs. We demonstrated that VEGF treatment increased mitochondrial ROS production in HUVECs, which was necessary for HIF-1α-dependent glycolysis, as well as proliferation, migration, and tube formation, and the inhibition of mitochondrial fission prevented VEGF-induced mitochondrial ROS production. In an oxygen-induced retinopathy (OIR) mouse model, we found that active DRP1 was highly expressed in endothelial cells in neovascular tufts. The administration of Mdivi-1 (10 mg·kg-1·d-1, i.p.) for three days from postnatal day (P) 13 until P15 significantly alleviated pathological angiogenesis in the retina. Our results suggest that targeting mitochondrial fission may be a therapeutic strategy for proliferative retinopathies and other diseases that are dependent on pathological angiogenesis.

Direct exposure to CpG and specific antigens mitigate airway allergy through modulating dendritic cell properties.

BACKGROUND: CpG oligodeoxynucleotide (CpG-ODN; CpG, in short) has been employed as an adjuvant in allergen specific immunotherapy (AIT) to treat allergic diseases. The underlying mechanism needs to be further explained. The aim of this study is to examine the mechanism by which CpG and dust mite extracts (DME, a specific antigen) alleviate experimental airway allergy. METHODS: DME was used as the specific allergen to establish an airway allergy mouse model. The mice were directly exposed to DME and CpG through nasal instillations (the CpG.DME therapy). The response of DCs and allergic responses in the airways were assessed using immunological approaches. RESULTS: The airway allergy reaction was effectively suppressed by CpG.DME therapy. The administration of CpG or DME alone did not have any significant suppressive effects on the airway allergic response. Direct exposure to CpG.DME induced type 1 DCs (DC1s) and plasmacytoid DCs (pDCs), while CpG alone induced DC1s and DME alone induced DC2s in the airway tissues. Both DC1s and pDCs were required for the induction of type 1 regulatory T cells in the airway tissues by CpG.DME therapy. Depletion of either pDCs or DC1s abolished the induction of Tr1 cells, and abolished the suppressive effects on airway allergic response by the CpG.DME therapy. CONCLUSIONS: Direct exposure to CpG.DME induces DC1s and pDCs in the airway tissues. DC1s in synergy with pDCs induce type 1 regulatory T cells. The CpG.DME therapy is effective in suppressing allergic responses in mice with airway allergy.

Workshop environment heterogeneity shaped the microbiome and metabolome profiles during Xiasha round of Jiangxiangxing Baijiu.

Workshop with different fermentation years plays an essential role in the yield and quality of Baijiu. In actual production, the quality of base Baijiu in newly built workshop is inferior to the older one. In this study, the microbiota of workshop environment and fermentation process from two workshops namely N (ferment 2 years) and O (ferment 20 years) and flavor compounds were studied during Xiasha round. Results showed workshop O accumulated more environmental microorganisms and fungi including P. kudriavzevii, Wickerhamomyces anomalus and Saccharomyces sp mainly came from ground. Yeasts including Pichia, Cyberlindnera, Wickerhamomyces and Candida were responsible for flavor substances formation in O while Saccharopolyspora was in N. This study for the first time explored the reasons for the brewing differences among N and O workshop from perspectives of workshop environment, microbial community and flavor substances, providing new ideas for guiding production as well as improvement of Baijiu quality.

An optimized back propagation neural network on small samples spectral data to predict nitrite in water.

Accurate detection of pollutant levels in water bodies using fusion algorithms combined with spectral data has become a critical issue for water conservation. However, the number of samples is too small and the model is unstable, which often leads to poor prediction and fails to achieve the measurement goal well. To address these challenges, this paper proposes a practical and effective method to precisely predict the concentrations of nitrite pollution in aquatic environments. The proposed method consists of three steps. Firstly, the dimension of the spectral data is reduced using Kernel Principal Component Analysis (KPCA), followed by sample augmentation using Generative Adversarial Network (GAN) to reduce calculation cost and increase the diversity and scale of the data. Secondly, several improvement strategies, including multi-cluster competitive and adaptive parameter updating, are introduced to enhance the capability of the Particle Swarm Optimization (PSO) algorithm. The improved PSO algorithm is then applied to optimize the initialization weights and biases of the Back Propagation neural network, thereby improving the model fitting and training performance. Finally, the developed prediction model is employed to predict the test set samples. The result suggests that the R2, RMSE, and MAE values are 0.976290, 0.008626, and 0.006617, which outperform the state-of-the-art and provided a promising model for the prediction of nitrite concentration in water.

Glycolysis Promotes Angiotensin II-Induced Aortic Remodeling Through Regulating Endothelial-to-Mesenchymal Transition via the Corepressor C-Terminal Binding Protein 1.

BACKGROUND: Endothelial dysfunction plays a crucial role in aortic remodeling. Aerobic glycolysis and endothelial-to-mesenchymal transition (EndoMT) have, respectively, been suggested to contribute to endothelial dysfunction in many cardiovascular diseases. Here, we tested the hypothesis that glycolytic reprogramming is critical for EndoMT induction in aortic remodeling through an epigenetic mechanism mediated by a transcriptional corepressor CtBP1 (C-terminal binding protein 1), a sensor of glycolysis-derived NADH. METHODS: EndoMT program, aortic remodeling, and endothelial expression of the glycolytic activator PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3) were evaluated in Ang (angiotensin) II-infused mice. Mice with endothelial-specific Pfkfb3 deficiency or CtBP1 inactivation, immunoprecipitation, chromatin immunoprecipitation, and luciferase reporter assay were employed to elucidate whether and how PFKFB3/CtBP1 epigenetically controls EndoMT. RESULTS: The EndoMT program and increased endothelial PFKFB3 expression were induced in remodeled thoracic aortas. In TGF-ß (transforming growth factor-ß)-treated human endothelial cells, activated SMAD2/3 (SMAD Family Member 2/3) transcriptionally upregulated PFKFB3 expression. In turn, the TGF-ß/SMAD signaling and EndoMT were compromised by silencing or inhibition of PFKFB3. Mechanistic studies revealed that PFKFB3-mediated glycolysis increased NADH content and activated the NADH-sensitive CtBP1. Through interaction with the transcription repressor E2F4 (E2F Transcription Factor 4), CtBP1 enhanced E2F4-mediated transcriptional repression of SMURF2 (SMAD ubiquitin regulatory factor 2), a negative regulator of TGF-ß/SMAD2 signaling. Additionally, EC-specific Pfkfb3 deficiency or CtBP1 inactivation in mice led to attenuated Ang II-induced aortic remodeling. CONCLUSIONS: Our results demonstrate a glycolysis-mediated positive feedback loop of the TGF-ß signaling to induce EndoMT and indicate that therapeutically targeting endothelial PFKFB3 or CtBP1 activity could provide a basis for treating EndoMT-linked aortic remodeling.

Changes of stressful life events, coping strategies and mental health among youths in the pre- and post-coronavirus 2019 pandemic era: A cross-sectional study.

BACKGROUND: In the pandemic era, stressful life events (StressLEv) aggravated the impact on mental health. However, youths exhibited different responses to StressLEv because of diverse coping strategies, social support, and emotional intelligence before and after the pandemic. AIMS: To explore the changes in StressLEv and coping strategies before and after the coronavirus 2019 pandemic, as well as report the associations among mental health and related factors in a sample of Chinese youths experiencing the post-pandemic era. METHOD: A cross-sectional study using convenience sampling was conducted from July 1 to August 30, 2022, covering 3,038 youths aged 14 to 25 in China. Multiple logistic regression was conducted for crude odds ratios (ORs) and adjusted ORs. The relationships between lasso-selected variables was examined using structural equation modeling. RESULTS: More StressLEv and limited coping strategies were reported after the pandemic. In the post-pandemic era, BSI-positive youths (youths diagnosed as considered case by Brief Symptom Inventory, BSI) reported more StressLEv (BSI-positive: mean = 75.47; BSI-negative: mean = 28.69), less social support (BSI-positive: mean = 31.81; BSI-negative: mean = 39.22), and lower emotional intelligence (BSI-positive: mean = 75.34; BSI-negative: mean = 89.42). The willingness to engage in mental health counseling (OR: no vs. yes: 1.89; uncertain vs. yes: 4.42), being punished (OR: 1.27), adaptation problems (OR: 1.06), task-oriented coping (OR: 0.95), social diversion coping (OR: 0.90), objective support (OR: 0.90), utilization of social support (OR: 0.81), and regulation of emotion in oneself (OR: 0.94) were associated with mental health. Structural equation modeling supported our theoretical framework. CONCLUSIONS: Pandemic-induced mental health problems should not be ignored. The proposed response mechanisms could guide the development of effective interventions, which can help youths better cope with StressLEv and maintain good mental health.

The role of pulse indicator continuous cardiac output (PiCCO) and critical care ultrasound in volume status assessment during fluid resuscitation for and prognosis of septic shock patients.

Objectives: To investigate whether pulse index continuous cardiac output (PiCCO) and critical care ultrasound are highly consistent in volume status assessment during fluid resuscitation for septic shock patients and analyze their influence on the prognosis of septic shock. Methods: Eighty septic shock patients treated by Huizhou Central People's Hospital during December 2018 and December 2020 were included and divided into a study group and a control group by the presence of volume responsiveness, with each group having 40 patients. The control group was subject to PiCCO-guided fluid resuscitation therapy, while the study group was given fluid resuscitation therapy guided by critical care ultrasound. Cardiac output, cardiac function, and catheter-related infection (CRI) were documented for intergroup comparison to confirm whether these two techniques were consistent with each other regarding their effects on resuscitation for and prognosis of septic shock patients. Results: Mechanical ventilation duration (MVD) and intensive care unit (ICU) length of stay (LoS) were significantly shorter in the study group when compared with the control group, and the differences were statistically significant (p<0.05, respectively). In terms of blood pressure parameters, the two groups did not differ greatly in diastolic blood pressure (DBP), mean arterial pressure (MAP), systolic blood pressure (SBP), and central venous pressure (CVP) before resuscitation (p>0.05, respectively); at 6h(six hour) after resuscitation, DBP, MAP, SBP, and CVP were substantially increased in both groups as compared with the pre-resuscitation levels (all p<0.05), but the differences between the two groups lacked statistical significance (all p>0.05). Comparing urine volume and degrees of positive fluid balance at 6 h and 12 h after resuscitation, drastic increases in urine volume and positive fluid balance were observed in both groups at 12 h as compared with at 6 h (all p<0.05); nevertheless, the two groups showed no statistically significant difference in urine volume and positive fluid balance at 6 h or 12 h (p>0.05, respectively). With regards to prognosis, there was no statistically significant difference between the two groups in the number of cases of continuous renal replacement therapy (CRRT), dosage of vasoactive agents and 28-d mortality rate (all p>0.05). However, the incidence of CRI was markedly lower in the study group (0/40) as compared with the control group (5/40), and the difference was statistically significant (p<0.05). Conclusions: Both PiCCO and critical care ultrasound can help achieve favorable outcomes from resuscitation for septic shock patients. Compared with PiCCO, critical care ultrasound monitoring appears to be more effective in preventing CRI and reducing MVD and ICU LoS, thereby easing patients' medical burden.

Hsa_circ_0023984 Regulates Cell Proliferation, Migration, and Invasion in Esophageal Squamous Cancer via Regulating miR-1294/PI3K/Akt/c-Myc Pathway.

Circular RNAs (circRNAs) exert an essential function in the tumorigenesis and progression of esophageal squamous cancer (ESCC). Nonetheless, the role and potential mechanism of circ_0023984 in ESCC are blurred. circRNA expression profile data from Gene Expression Omnibus (GEO) database was applied to analyze circRNAs that were differentially expressed between ESCC tissues and paracancerous tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to analyze circ_0023984 expression and miR-1294 expression in ESCC tissues and cells. Then a series of functional experiments were executed to validate the role of circ_0023984 and miR-1294 in modulating the proliferation, migration, invasion, and cell cycle progression of ESCC cells. Luciferase reporter experiment was performed to confirm the targeting relationship between circ_0023984 and miR-1294. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out with DAVID database. Western blot assay was utilized to detect phosphorylated-Akt (p-Akt) expression and c-Myc expression. circ_0023984 was remarkably upmodulated in ESCC tumor tissues and cell lines. circ_0023984 overexpression was correlated with advanced clinical stage and lymph node metastasis of ESCC patients. circ_0023984 overexpression remarkably enhanced ESCC cell proliferation, migration, invasion, and cell cycle progression, while knockdown of circ_0023984 showed the opposite effect. circ_0023984 was the molecular sponge of miR-1294. miR-1294 could significantly inhibit ESCC cell proliferation, migration, invasion, and induce cell cycle arrest at G0/G1 phase. circ_0023984 affected ESCC progression through regulating miR-1294 expression. The target genes of miR-1294 were associated with cell cycle arrest and PI3K-Akt signaling pathway. circ_0023984 upregulated the expression of p-Akt and c-Myc by repressing miR-1294. circ_0023984 facilitates the malignant biological behaviors of ESCC cells through inhibiting miR-1294 and activating PI3K/Akt/c-myc pathway.

Real-World First-Line Treatment Patterns and Outcomes in Hormone Receptor-Positive Advanced Breast Cancer Patients: A Multicenter, Retrospective Study in China.

Background: Recent data on first-line treatment patterns administered to hormone receptor-positive (HR+) advanced breast cancer (ABC) patients in the real-world setting are limited. This study aimed to report the first-line treatment patterns and outcomes of HR+ ABC patients in China. Methods: This was a multicenter, noninterventional study. Eligible patients were cytologically or histologically confirmed to have HR+ ABC with ≥2 complete medical records and received first-line therapies between January 2015 and June 2019. Treatment patterns and outcomes were extracted from structured or unstructured electronic medical records. Progression-free survival (PFS) was analyzed with the Kaplan-Meier method. Results: In total, 1072 patients with HR+ ABC were enrolled at 6 treatment sites: 327 human epidermal growth factor receptor 2-positive (HER2+) patients, 696 HER2-negative (HER2-) patients and 49 HER2-unknown patients. Overall, 62.41% of patients received first-line chemotherapy (CT), 21.08% received targeted therapy (TT) and 15.49% received endocrine therapy (ET). For HR+/HER2+ patients, 65.14% received TT, 28.44% received CT, and 5.81% received ET. Compared with patients who received TT, patients who received CT alone, had a significantly worse median PFS (adjusted hazard ratio [HR] =2.59, 95% confidence interval [CI], 1.64-4.10, p<0.001). For HR+/HER2- patients, 77.01% received CT, 20.69% received ET and 1.15% received TT. Compared with patients who received ET, patients who received CT with maintenance therapy had a significantly prolonged median PFS (adjusted HR =0.57, 95% CI, 0.44-0.76, p<0.001). Among HR+/HER2- patients who received CT with maintenance treatment, those with maintenance ET had a longer median PFS than those with maintenance CT, but the difference was not significant (adjusted HR=0.92, 95% CI, 0.64-1.33, p=0.66). Conclusions: This real-world study demonstrates that CT remains the mainstream first-line treatment option for HR+ patients in China. Among patients with HR+/HER2+ ABC, the majority received first-line TT and experienced a PFS benefit. A high percentage of HR+/HER2- patients received CT as first-line therapy in clinical practice. PFS benefit was significantly longer in patients who received CT with maintenance therapy. Moreover, there was no obvious difference in PFS between maintenance ET and CT. Maintenance ET may be a better choice considering its lower toxicity and better quality of life.

Identifying periodontitis risk factors through a retrospective analysis of 80 cases.

OBJECTIVES: To investigate periodontitis risk factors and to establish a reference framework for identifying factors that place individuals at greater risk for periodontitis. METHODS: Clinical data from 80 periodontitis patients admitted in the Department of Stomatology at Hebei Provincial People's Hospital and treated between March 2020 and March 2021 were retrospectively analyzed. RESULTS: Univariate analysis showed that lower daily brushing frequencies, decreased tooth brushing duration, decreased scaling frequency, dietary habits, smoking and drinking, genetic factors, diabetes, hypertension, and obesity were more prevalent among periodontitis patients than healthy controls. Multivariate binary logistic analysis showed that daily brushing frequency, routine scaling, smoking, drinking, heredity, diabetes, hypertension, and obesity were all risk factors for periodontitis. CONCLUSIONS: There are many risk factors for periodontitis. Clinicians need to be aware of these factors for early detection and treatment of the disease.

Maneuvering Target Tracking Using Simultaneous Optimization and Feedback Learning Algorithm Based on Elman Neural Network.

Tracking maneuvering targets is a challenging problem for sensors because of the unpredictability of the target's motion. Unlike classical statistical modeling of target maneuvers, a simultaneous optimization and feedback learning algorithm for maneuvering target tracking based on the Elman neural network (ENN) is proposed in this paper. In the feedback strategy, a scale factor is learnt to adaptively tune the dynamic model's error covariance matrix, and in the optimization strategy, a corrected component of the state vector is learnt to refine the final state estimation. These two strategies are integrated in an ENN-based unscented Kalman filter (UKF) model called ELM-UKF. This filter can be trained online by the filter residual, innovation and gain matrix of the UKF to simultaneously achieve maneuver feedback and an optimized estimation. Monte Carlo experiments on synthesized radar data showed that our algorithm had better performance on filtering precision compared with most maneuvering target tracking algorithms.

TLR4 participates in sympathetic hyperactivity Post-MI in the PVN by regulating NF-κB pathway and ROS production.

Sympathetic nerve hyperactivity is a primary reason for fatal ventricular arrhythmias (VAs) following myocardial infarction (MI). Pro-inflammatory cytokines produced in the paraventricular nucleus (PVN) post-MI are associated with sympathetic overexcitation; however, the precise mechanism needs further investigation. Our aim was to explore the mechanism of toll-like receptor 4 (TLR4) and its downstream molecular pathway in mediating sympathetic activity post-MI within the PVN. A rat MI model was developed via left anterior descending coronary artery ligation. TLR4 was primarily localized in microglia and increased markedly within the PVN at 3 days in MI rats. Sympathoexcitation also increased, as indicated by high levels of renal sympathetic nerve activity (RSNA) and norepinephrine (NE) concentration. TLR4 knockdown via shRNA microinjection to the PVN resulted in decreased activation of Fos protein (+) neurons in the PVN and peripheral sympathetic nerve activity. TLR4 knockdown also exhibited a lower arrhythmia score following programmed electrical stimulation than those treated with MI surgery only, indicating that the knockdown of TLR4 decreased the incidence of malignant ventricular arrhythmias following MI. LPS-induced inflammatory response was analyzed to explore the underlying mechanism of TLR4 in sympathetic hyperactivity. High levels of NF-κB protein, the pro-inflammatory cytokines IL-1ß and TNF-α, and ROS production were observed in the LPS group. PVN-targeted injection of the NF-κB inhibitor PDTC attenuated NF-κB expression and sympathetic activity. Taken together, the results suggested that knockdown of microglial TLR4 within the PVN decreased sympathetic hyperactivity and subsequent VAs post-MI. The downstream NF-κB pathway and ROS production participated in the process. Interventions targeting TLR4 signaling in the PVN may be a novel approach to ameliorate the incidence of VAs post-MI.

Microglial Mincle receptor in the PVN contributes to sympathetic hyperactivity in acute myocardial infarction rat.

Malignant ventricular arrhythmias (VAs) following myocardial infarction (MI) is a lethal complication resulting from sympathetic nerve hyperactivity. Numerous evidence have shown that inflammation within the paraventricular nucleus (PVN) participates in sympathetic hyperactivity. Our aim was to explore the role of Macrophage-inducible C-type lectin (Mincle) within the PVN in augmenting sympathetic activity following MI,and whether NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome/IL-1ß axis is involved in this activity. MI was induced by coronary artery ligation. Mincle expression localized in microglia within the PVN was markedly increased at 24 hours post-MI together with sympathetic hyperactivity, as indicated by measurement of the renal sympathetic nerve activity (RSNA) and norepinephrine (NE) concentration. Mincle-specific siRNA was administrated locally to the PVN, which consequently decreased microglial activation and sympathetic nerve activity. The MI rats exhibited a higher arrhythmia score after programmed electric stimulation than that treated with Mincle siRNA, suggesting that the inhibition of Mincle attenuated foetal ventricular arrhythmias post-MI. The underlying mechanism of Mincle in sympathetic hyperactivity was investigated in lipopolysaccharide (LPS)-primed naïve rats. Recombinant Sin3A-associated protein 130kD (rSAP130), an endogenous ligand for Mincle, induced high levels of NLRP3 and mature IL-1ß protein. PVN-targeted injection of NLRP3 siRNA or IL-1ß antagonist gevokizumab attenuated sympathetic hyperactivity. Together, the data indicated that the knockdown of Mincle in microglia within the PVN prevents VAs by attenuating sympathetic hyperactivity and ventricular susceptibility, in part by inhibiting its downstream NLRP3/IL-1ß axis following MI. Therapeutic interventions targeting Mincle signalling pathway could constitute a novel approach for preventing infarction injury.

Effect of ILV6 Deletion and Expression of aldB from Lactobacillus plantarum in Saccharomyces uvarum on Diacetyl Production and Wine Flavor.

Diacetyl generates an aromatic off-flavor in wine at a high level. The present study expressed α-acetolactate decarboxylase (ALDB) from Lactobacillus plantarum and/or inactivated acetohydroxyacid synthase (Ilv6) in Saccharomyces uvarum, and the effects on diacetyl production and wine flavor in mutants were investigated through sequential fermentation and cofermentation in mixed cultures of S. uvarum and L. plantarum. The diacetyl content of WYDΔ6 (disrupted one ILV6 allele), WYSΔ6 ( ILV6 complete deletion), WYADΔ6 (disrupted one ILV6 allele with aldB expression), and WYASΔ6 ( ILV6 complete deletion with aldB expression) decreased by 25.71%, 41.30%, 47.77%, and 50.00%, respectively, after sequential fermentation and decreased by 15.15%, 26.72%, 35.26%, and 43.80%, respectively, after cofermentation, compared with that of the parental strain. In addition, Ilv6 inactivation not only decreased the acetic acid content but also balanced the flavor profile in wine effectively. This work provided a valuable insight into the metabolic pathway of diacetyl and wine flavor in S. uvarum.

Discrete 1 : 1 complexes and higher order assemblies formed from aminobenzene sulphonate anions and a tetraimidazolium "molecular box".

Use of isomeric aminobenzene sulphonate anions in conjunction with a tetraimidazolium "molecular box" leads to self-assembled embedded structures. Simple 1 : 1 complexes are formed at low concentrations in DMSO when the host : guest ratio is 1.0. Higher order species are seen as the concentration is increased or the host-guest ratio is perturbed. The assembly and disassembly of the supramolecular aggregates can be controlled by application of various external stimuli, including changes in concentration, temperature, and protonation state of the guest species.

[Influence Factors on Analyzing Transmission Time of Relative Blood Volume Based on Ultrasonic].

Ultrasound-based measurement of relative blood volume can be used to assess patient's dry weight during hemodialysis. The results of relative blood volume were calculated from the ultrasonic transmission time measurement in the arteriol pot, and the accuracy of transmission time measurement is directly related to the reliability of the results of relative blood volume. There are various factors which influence the travel time, this article analyzed patients themselves, measuring device and the external factors, and advised appropriate counter measures.