The influence of electrode types to the visually induced gamma oscillations in mouse primary visual cortex.

The local field potential (LFP) is an extracellular electrical signal associated with neural ensemble input and dendritic signaling. Previous studies have linked gamma band oscillations of the LFP in cortical circuits to sensory stimuli encoding, attention, memory, and perception. Inconsistent results regarding gamma tuning for visual features were reported, but it remains unclear whether these discrepancies are due to variations in electrode properties. Specifically, the surface area and impedance of the electrode are important characteristics in LFP recording. To comprehensively address these issues, we conducted an electrophysiological study in the V1 region of lightly anesthetized mice using two types of electrodes: one with higher impedance (1 MΩ) and a sharp tip (10 µm), while the other had lower impedance (100 KΩ) but a thicker tip (200 µm). Our findings demonstrate that gamma oscillations acquired by sharp-tip electrodes were significantly stronger than those obtained from thick-tip electrodes. Regarding size tuning, most gamma power exhibited surround suppression at larger gratings when recorded from sharp-tip electrodes. However, the majority showed enhanced gamma power at larger gratings when recorded from thick-tip electrodes. Therefore, our study suggests that microelectrode parameters play a significant role in accurately recording gamma oscillations and responsive tuning to sensory stimuli.

Intervention of hypertension by acupuncture-related therapies: A network meta-analysis.

BACKGROUND: The prevalence of essential hypertension contributed significantly to morbidity and mortality rates. Acupuncture-related therapies were commonly employed in hypertension treatment. Nevertheless, a lack of conclusive evidence left uncertainties regarding the optimal strategies for managing hypertensive populations. OBJECTIVES: Conduct a comprehensive systematic review to evaluate the existing clinical evidence about the effectiveness of acupuncture and moxibustion-related therapies in managing hypertension, by employing network meta-analysis techniques. METHODS: A comprehensive electronic search was conducted across n of databases. This search covered studies available up to October 2022. Randomized controlled trials assessing acupuncture and moxibustion-related therapies in managing hypertension based on traditional Chinese medicine were screened. Primary outcome measures included the antihypertensive effectiveness rate, variations in blood pressure and the incorporation of Traditional Chinese Medicine (TCM) syndrome manifestations. The review follows the guidelines outlined in the PRISMA statement. RESULTS: We identified a total of 24 trials with 1867 patients, which evaluated the efficacy of various acupuncture-related therapies for hypertension management. Network meta-analysis showed that moxibustion and auricular point sticking combined with medication therapy had the best effect in terms of antihypertensive effective rate (medication + moxibustion + auricular pressure vs. medication = 1.29 [1.09, 1.54]; sucra = 85.9, p < .05) and hypertension symptom improvement (medication + moxibustion + auricular pressure vs. medication = -1.55 [-2.98, -0.13]; sucra = 96.1, p < .05). Acupuncture combined with moxibustion combined with medication therapy had the best effect in reducing systolic pressure (medication + moxibustion + acupuncture vs. medication = -8.50 [-10.19, -6.80]; sucra = 100, p < .05) and diastolic blood pressure (medication + moxibustion + acupuncture versus medication = -4.72 [-6.71, -2.72]; sucra = 99.71, p < 0.05). CONCLUSIONS: Network meta-analysis suggested that the combined use of moxibustion and auricular point application in conjunction with drug therapy showed the highest likelihood of being the most effective treatment in terms of antihypertensive efficiency rates and improvement in hypertension symptoms. Furthermore, the combination of acupuncture and moxibustion alongside drug treatment emerged as the most promising approach for reducing systolic blood pressure and diastolic blood pressure. Limited by the methodological quality and quantity of the included studies, the results need to be interpreted with caution. It is necessary to conduct more high-quality randomized controlled trials of acupuncture-related therapies for the adjuvant treatment of hypertension in the future. IMPLICATIONS FOR PRACTICE: Clinicians can use acupuncture-related therapies to inform their treatment decisions and potentially incorporate acupuncture-related therapies into their hypertension management protocols.

Tracing Oils and Gas Accumulation in Complex Petroleum Systems Based on Biomarkers, Light Hydrocarbons, and Diamondoids from Concomitant Crude Oils: A Case Study in the Shawan Sag of the Junggar Basin, NW China.

The Shawan Sag is one of the most promising blocks in the western Junggar Basin for natural gas and oil exploration. To date, the research and exploration degree here is still low, and there is limited understanding of the origin and migration of natural gas and oils, which seriously restricts future exploration and development. At least three oil charging episodes and one gas charging episode could be confirmed in the reservoirs on the western slope of the Shawan Sag based on the analysis of concentrations and ratios of hopanes and steranes, diamondoids, and light hydrocarbons. The first and second charging oils originated from the peak and late oil generation window stages of Lower Permian Fengcheng Formation (P1f) source rocks, respectively. The third charging oil originated from the late oil generation window stage of source rocks of the Middle Permian lower Wuerhe Formation (P2w). Combining the carbon isotopic compositions and the gas composition, the fourth charging gas was derived from the postmature source rocks of Carboniferous(C) and Lower Permian Jiamuhe Formation (P1j) and the high-postmature source rock of Lower Permian Fengcheng Formation (P1f). The preservation conditions of nature gas in the Mesozoic (T-K) cap rocks in the Shawan Sag, as indicated by methyladamantanes (MAs)/methyldiamantanes (MDs) ratio, are better than those in the Mahu Sag. In this study, the methyladamantane maturity parameters of oils in the reservoirs were proposed to evaluate the maturity and further determine the migration direction of late-charging natural gas. The results suggest that late postmatured natural gases were charged from the southern part to the northwest of the Shawan Sag. Therefore, the southeastern direction of Well SP1 is a favorable area for natural gas exploration in the Shawan Sag. Meanwhile the northern part of the sag is favorable for the exploration of high-mature oil generated from source rocks within the Middle Permian Lower Wuerhe Formation.

DNA methylation of skeletal muscle function-related secretary factors identifies FGF2 as a potential biomarker for sarcopenia.

BACKGROUND: Sarcopenia is characterized by progressive loss of muscle mass and function due to aging. DNA methylation has been identified to play important roles in the dysfunction of skeletal muscle. The aim of our present study was to explore the whole blood sample-based methylation changes of skeletal muscle function-related factors in patients with sarcopenia. METHODS: The overall DNA methylation levels were analysed by using MethlTarget™ DNA Methylation Analysis platform in a discovery set consistent of 50 sarcopenic older adults (aged ≥65 years) and 50 age- and sex-matched non-sarcopenic individuals. The candidate differentially methylated regions (DMRs) were further validated by Methylation-specific PCR (MSP) in another two independent larger sets and confirmed by pyrosequencing. Receiver operating characteristic (ROC) curve analysis was used to determine the optimum cut-off levels of fibroblast growth factor 2 (FGF2)_30 methylation best predicting sarcopenia and area under the ROC curve (AUC) was measured. The correlation between candidate DMRs and the risk of sarcopenia was investigated by univariate analysis and multivariate logistic regression analysis. RESULTS: Among 1149 cytosine-phosphate-guanine (CpG) sites of 27 skeletal muscle function-related secretary factors, 17 differentially methylated CpG sites and 7 differentially methylated regions (DMRs) were detected between patients with sarcopenia and control subjects in the discovery set. Further methylation-specific PCR identified that methylation of fibroblast growth factor 2 (FGF2)_30 was lower in patients with sarcopenia and the level was decreased as the severity of sarcopenia increased, which was confirmed by pyrosequencing. Correlation analysis demonstrated that the methylation level of FGF2_30 was positively correlated to ASMI (r = 0.372, P < 0.001), grip strength (r = 0.334, P < 0.001), and gait speed (r = 0.411, P < 0.001). ROC curve analysis indicated that the optimal cut-off value of FGF2_30 methylation level that predicted sarcopenia was 0.15 with a sensitivity of 84.6% and a specificity of 70.1% (AUC = 0.807, 95% CI = 0.756-0.858, P < 0.001). Multivariate logistic regression analyses showed that lower FGF2_30 methylation level (<0.15) was significantly associated with increased risk of sarcopenia even after adjustment for potential confounders including age, sex, and BMI (adjusted OR = 9.223, 95% CI: 6.614-12.861, P < 0.001). CONCLUSIONS: Our results suggest that lower FGF2_30 methylation is correlated with the risk and severity of sarcopenia in the older adults, indicating that FGF2 methylation serve as a surrogate biomarker for the screening and evaluation of sarcopenia.

The application of phenylboronic acid pinacol ester functionalized ROS-responsive multifunctional nanoparticles in the treatment of Periodontitis.

Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases.

Beyond Conventional Charge Density Wave for Strongly Enhanced 2D Superconductivity in 1H-TaS2 Superlattices.

Noncentrosymmetric transition metal dichalcogenide (TMD) monolayers offer a fertile platform for exploring unconventional Ising superconductivity (SC) and charge density waves (CDWs). However, the vulnerability of isolated monolayers to structural disorder and environmental oxidation often degrade their electronic coherence. Herein, an alternative approach is reported for fabricating stable and intrinsic monolayers of 1H-TaS2 sandwiched between SnS blocks in a (SnS)1.15TaS2 van der Waals (vdW) superlattice. The SnS block layers not only decouple individual 1H-TaS2 sublayers to endow them with monolayer-like electronic characteristics, but also protect the 1H-TaS2 layers from electronic degradation. The results reveal the characteristic 3 × 3 CDW order in 1H-TaS2 sublayers associated with electronic rearrangement in the low-lying sulfur p band, which uncovers a previously undiscovered CDW mechanism rather than the conventional Fermi surface-related framework. Additionally, the (SnS)1.15TaS2 superlattice exhibits a strongly enhanced Ising-like SC with a layer-independent Tc of ≈3.0 K, comparable to that of the isolated monolayer 1H-TaS2 sample, presumably attributed to their monolayer-like characteristics and retained Fermi states. These results provide new insights into the long-debated CDW order and enhanced SC of monolayer 1H-TaS2, establishing bulk vdW superlattices as promising platforms for investigating exotic collective quantum phases in the 2D limit.

Research on multi-model imaging machine learning for distinguishing early hepatocellular carcinoma.

OBJECTIVE: To investigate the value of differential diagnosis of hepatocellular carcinoma (HCC) and non-hepatocellular carcinoma (non-HCC) based on CT and MR multiphase radiomics combined with different machine learning models and compare the diagnostic efficacy between different radiomics models. BACKGROUND: Primary liver cancer is one of the most common clinical malignancies, hepatocellular carcinoma (HCC) is the most common subtype of primary liver cancer, accounting for approximately 90% of cases. A clear diagnosis of HCC is important for the individualized treatment of patients with HCC. However, more sophisticated diagnostic modalities need to be explored. METHODS: This retrospective study included 211 patients with liver lesions: 97 HCC and 124 non-hepatocellular carcinoma (non-HCC) who underwent CT and MRI. Imaging data were used to obtain imaging features of lesions and radiomics regions of interest (ROI). The extracted imaging features were combined to construct different radiomics models. The clinical data and imaging features were then combined with radiomics features to construct the combined models. Support Vector Machine (SVM), K-nearest Neighbor (KNN), RandomForest (RF), eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), Multilayer Perceptron (MLP) six machine learning models were used for training. Five-fold cross-validation was used to train the models, and ROC curves were used to analyze the diagnostic efficacy of each model and calculate the accuracy rate. Model training and efficacy test were performed as before. RESULTS: Statistical analysis showed that some clinical data (gender and concomitant cirrhosis) and imaging features (presence of envelope, marked enhancement in the arterial phase, rapid contouring in the portal phase, uniform density/signal and concomitant steatosis) were statistical differences (P < 0.001). The results of machine learning models showed that KNN had the best diagnostic efficacy. The results of the combined model showed that SVM had the best diagnostic efficacy, indicating that the combined model (accuracy 0.824) had better diagnostic efficacy than the radiomics-only model. CONCLUSIONS: Our results demonstrate that the radiomic features of CT and MRI combined with machine learning models enable differential diagnosis of HCC and non-HCC (malignant, benign). The diagnostic model with dual radiomic had better diagnostic efficacy. The combined model was superior to the radiomic model alone.

Nickel-Catalyzed Atroposelective C-H Alkylation Enabled by Bimetallic Catalysis with Air-Stable Heteroatom-Substituted Secondary Phosphine Oxide Preligands.

The catalytic asymmetric construction of axially chiral C-N atropisomers remains a formidable challenge due to their low rotational barriers and is largely reliant on toxic, cost-intensive, and precious metal catalysts. In sharp contrast, we herein describe the first nickel-catalyzed atroposelective C-H alkylation for the construction of C-N axially chiral compounds with the aid of a chiral heteroatom-substituted secondary phosphine oxide (HASPO)-ligated Ni-Al bimetallic catalyst. A wide range of alkenes, including terminal and internal alkenes, were well compatible with the reaction, providing a variety of benzimidazole derivatives in high yields and enantioselectivities (up to 97:3 e.r.). The key to success was the identification of novel HASPOs as highly effective chiral preligands. Mechanistic studies revealed the catalyst mode of action, and in-depth data science analysis elucidated the key features of the responsible chiral preligands in controlling the enantioselectivity.

Inhibition of EHMT1/2 rescues synaptic damage and motor impairment in a PD mouse model.

Epigenetic dysregulation that leads to alterations in gene expression and is suggested to be one of the key pathophysiological factors of Parkinson's disease (PD). Here, we found that α-synuclein preformed fibrils (PFFs) induced histone H3 dimethylation at lysine 9 (H3K9me2) and increased the euchromatic histone methyltransferases EHMT1 and EHMT2, which were accompanied by neuronal synaptic damage, including loss of synapses and diminished expression levels of synaptic-related proteins. Furthermore, the levels of H3K9me2 at promoters in genes that encode the synaptic-related proteins SNAP25, PSD95, Synapsin 1 and vGLUT1 were increased in primary neurons after PFF treatment, which suggests a linkage between H3K9 dimethylation and synaptic dysfunction. Inhibition of EHMT1/2 with the specific inhibitor A-366 or shRNA suppressed histone methylation and alleviated synaptic damage in primary neurons that were treated with PFFs. In addition, the synaptic damage and motor impairment in mice that were injected with PFFs were repressed by treatment with the EHMT1/2 inhibitor A-366. Thus, our findings reveal the role of histone H3 modification by EHMT1/2 in synaptic damage and motor impairment in a PFF animal model, suggesting the involvement of epigenetic dysregulation in PD pathogenesis.

Preparation of KHA/SA/MMT composites and their adsorption properties for Rhodamine B.

Two natural adsorbent materials, potassium humate (KHA) and montmorillonite (MMT), were successfully prepared by embedding them in sodium alginate (SA) gel spheres through physical cross-linking with CaCl2. And CaCO3 was used as a porogenic agent to prepare the porous composites, KHA/SA/MMT. The materials were characterized by using XRD, TGA, SEM, and N2 adsorption/desorption equipment. The results showed that MMT and KHA were successfully embedded in the SA gel; the introduction of MMT increased the thermal stability of the composites and the embedding of MMT, and the porogenic effect of CaCO3 increased the specific surface area of the composites substantially, which provided favorable conditions for adsorption and treatment of pollutants. In addition, a one-way exploratory experiment yielded a higher removal rate of Rhodamine B (RhB) at D = 0.6 g/L, pH = 5, C0 = 100 mg/L, and t = 360 min. The adsorption kinetics and adsorption isotherm conformed to the secondary kinetic model and Langmuir model, respectively, and the maximum adsorption of RhB by KHA/SA/MMT could reach up to 884.96 mg/g at 303 K. The adsorption mechanism for RhB was shown by FT-IR and XPS analyses to be possibly bound by non-covalent bonding forces. After seven consecutive adsorption-desorption cycles, the adsorption of RhB by KHA/SA/MMT still reached 80.75%. Therefore, the prepared gel spheres have the advantages of easy regeneration and efficient reuse and great potential for application in purifying RhB from wastewater.

Clinical experience sharing on gastric microneuroendocrine tumors: A case report.

BACKGROUND: The majority of gastric neuroendocrine tumors (G-NENs) are present in various lesions under endoscopy, and they can be polypoid uplifts, submucosal tumors or papules, erosions, and ulcers. The lesions are mostly confined to the mucosal or submucosal layer, usually less than 2 cm, and exclusively localized to the gastric body or fundus. In type 1 G-NENs, about 22% of cases have no visible lesions under an endoscope, and such lesions can only be detected via biopsies (microcarcinoids). CASE SUMMARY: A 67-year-old female patient with appetite loss for more than half a year and personal history of hyperthyroidism was admitted to our hospital. After admission, a random multi-point biopsy was performed on the gastric body, fundus, angle, and antrum through gastroscopy. Pathological examination showed chronic severe atrophic gastritis in the fundus and body of the stomach. The small curvature of the gastric body, the anterior wall of the gastric body, and the posterior wall of the gastric body displayed proliferation of intestinal chromaffin cells. The curvature of the gastric body showed neuroendocrine tumor G1 (carcinoid), while the antrum and angle of the stomach showed mild atrophic gastritis with mild intestinal metaplasia. Immunohistochemical examination showed that the greater curvature of the gastric body was Syn (+), CgA (+), and Ki-67 (+, approximately 1%), which is consistent with neuroendocrine tumors (grade 1). Regular gastroscopy and biopsy should be performed every one to two years to monitor G-NENs. CONCLUSION: In the case under study, the patient did not have any visible raised lesions under a gastroscope, and the lesions were found only after a random biopsy. This article combines the endoscopic manifestations and clinical features of the lesions in this case to improve the diagnosis of G-NENs.

Comparison of plasma aldosterone measured by chemiluminescence immunoassay and liquid chromatography-tandem mass spectrometry in screening test for primary aldosteronism.

Background: Whether chemiluminescence immunoassay (CLIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for plasma aldosterone concentration (PAC) measurement can be used interchangeably in primary aldosteronism (PA) screening is still controversial. The purpose of this study was to compare CLIA to LC-MS/MS for PAC measurement in PA screening. Methods: All participants underwent aldosterone-to-renin ratio (ARR) testing. PA was diagnosed by captopril challenge test or saline infusion test. PAC in screening test was measured with CLIA and LC-MS/MS. Plasma direct renin concentration in screening and confirmatory test was measured with CLIA. The concordance between CLIA and LC-MS/MS for PAC measurement in PA screening was analyzed. Results: Twenty-one healthy volunteers, 61 patients with essential hypertension (EH) and 43 PA patients were enrolled. Median PAC by CLIA was 84.7 % higher than that by LC-MS/MS in screening test (P < 0.001). A positive correlation of PAC was observed between the two assays (Pearson r coefficient 0.770, P < 0.001). When ARR was used in differentiating PA from EH, there was no difference in the area under the receiver operating characteristic curve between CLIA and LC-MS/MS for PAC measurement (0.968 vs 0.950, P = 0.249). Conclusion: CLIA and LC-MS/MS for PAC measurement exhibited high and comparable efficacy in PA screening. CLIA is a reliable and feasible alternative in PA screening test.

Deacetylase Sirtuin 1 mitigates type I IFN- and type II IFN-induced signaling and antiviral immunity.

Type I and type II IFNs are important immune modulators in both innate and adaptive immunity. They transmit signaling by activating JAK-STAT pathways. Sirtuin 1 (SIRT1), a class III NAD+-dependent deacetylase, has multiple functions in a variety of physiological processes. Here, we characterized the novel functions of SIRT1 in the regulation of type I and type II IFN-induced signaling. Overexpression of SIRT1 inhibited type I and type II IFN-induced interferon-stimulated response element activation. In contrast, knockout of SIRT1 promoted type I and type II IFN-induced expression of ISGs and inhibited viral replication. Treatment with SIRT1 inhibitor EX527 had similar positive effects. SIRT1 physically associated with STAT1 or STAT3, and this interaction was enhanced by IFN stimulation or viral infection. By deacetylating STAT1 at K673 and STAT3 at K679/K685/K707/K709, SIRT1 downregulated the phosphorylation of STAT1 (Y701) and STAT3 (Y705). Sirt1+/- primary peritoneal macrophages and Sirt1+/- mice exhibited enhanced IFN-induced signaling and antiviral activity. Thus, SIRT1 is a novel negative regulator of type I and type II IFN-induced signaling through its deacetylase activity.IMPORTANCESIRT1 has been reported in the precise regulation of antiviral (RNA and DNA) immunity. However, its functions in type I and type II IFN-induced signaling are still unclear. In this study, we deciphered the important functions of SIRT1 in both type I and type II IFN-induced JAK-STAT signaling and explored the potential acting mechanisms. It is helpful for understanding the regulatory roles of SIRT1 at different levels of IFN signaling. It also consolidates the notion that SIRT1 is an important target for intervention in viral infection, inflammatory diseases, or even interferon-related therapies.

Global trends in research of pseudomyxoma peritonei: a bibliometric and visualization analysis.

Objective: Pseudomyxoma peritonei (PMP) was a complex disease that had attracted increasing attention. However, there had been no bibliometric analysis of this disease so far. This study aimed to explore the current situation and frontier trend of PMP through bibliometric and visualization analysis, and to indicate new directions for future research. Methods: The original research articles and reviews related to the PMP research were downloaded from Web of Science Core Collection on September 11, 2023. CiteSpace (6.2.R4) and VOSviewer(1.6.18) were used to perform bibliometric analysis of the publications, and establish the knowledge map. The data collected was analyzed using the Online Analysis Platform of Bibliometric to evaluate the cooperation of countries in this field. Results: We identified 1449 original articles and reviews on PMP published between 1998 and 2023. The number of publications on PMP increased continuously. The United States, the United Kingdom and China were the top contributors. The most productive organization was the MedStar Washington Hospital Center. Sugarbaker, Paul H. was the most prolific author and the most cited. Keyword analysis showed that "Pseudomyxoma peritonei", "cancer", "cytoreductive surgery", and "hyperthermic intraperitoneal chemotherapy" were the most common keywords. The earliest and latest used keywords were "mucinous tumors" and "impact", respectively. "classification", "cytoreductive surgery", "appendiceal" were the top 3 strongest citation bursts. The reference "Carr NJ, 2016, AM J SURG PATHOL" had the highest co-citations. Conclusion: This bibliometric analysis showed an increasing trend in literature related to PMP. The research trends and hotspots identified in this study could guide the future research directions in this field, in order to promote the development of PMP.

DNA Methylation and Chromatin Accessibility Impact Subgenome Expression Dominance in the Common Carp (Cyprinus carpio).

DNA methylation and chromatin accessibility play important roles in gene expression, but their function in subgenome expression dominance remains largely unknown. We conducted comprehensive analyses of the transcriptome, DNA methylation, and chromatin accessibility in liver and muscle tissues of allotetraploid common carp, aiming to reveal the function of epigenetic modifications in subgenome expression dominance. A noteworthy overlap in differential expressed genes (DEGs) as well as their functions was observed across the two subgenomes. In the promoter and gene body, the DNA methylation level of the B subgenome was significantly different than that of the A subgenome. Nevertheless, differences in DNA methylation did not align with changes in homoeologous biased expression across liver and muscle tissues. Moreover, the B subgenome exhibited a higher prevalence of open chromatin regions and greater chromatin accessibility, in comparison to the A subgenome. The expression levels of genes located proximally to open chromatin regions were significantly higher than others. Genes with higher chromatin accessibility in the B subgenome exhibited significantly elevated expression levels compared to the A subgenome. Contrastingly, genes without accessibility exhibited similar expression levels in both subgenomes. This study contributes to understanding the regulation of subgenome expression dominance in allotetraploid common carp.

PFKFB3 facilitates cell proliferation and migration in anaplastic thyroid carcinoma via the WNT/ß-catenin signaling pathway.

PURPOSE: Despite the involvement of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase3 (PFKFB3) in the proliferation and metastasis of diverse tumor types, its biological functions and related molecular mechanisms in anaplastic thyroid carcinoma (ATC) remain largely unclear. METHODS: Datasets from the Gene Expression Omnibus, the Cancer Genome Atlas and immunohistochemistry (IHC) analyses were employed to measure the expression level of PFKFB3 in ATC. A series of assays were performed to analyze the role of PFKFB3 and its inhibitor KAN0438757 in ATC cell proliferation and migration. Furthermore, Western blotting (WB), IHC and luciferase reporter assay were conducted to investigate the potential mechanisms underlying the involvement of PFKFB3 and KAN0438757 in ATC. Additionally, we established a subcutaneous xenograft tumor model in nude mice to evaluate the in vivo tumor growth. RESULTS: PFKFB3 exhibited a significant increase in its expression level in ATC tissues. The overexpression of PFKFB3 resulted in the stimulation of ATC cell proliferation and migration. Furthermore, this overexpression was associated with the elevated expression levels of p-AKT (ser473), p-GSK3α/ß (ser21/9), nuclear ß-catenin, fibronectin1 (FN1), matrix metallopeptidase 9 (MMP-9) and cyclin D1. It also promoted the nuclear translocation of ß-catenin and the transcription of downstream molecules. Conversely, contrasting results were observed with the downregulation or KAN0438757-mediated inhibition of PFKFB3 in ATC cells. The selective AKT inhibitor MK2206 was noted to reverse the increased expression of p-AKT (ser473) and p-GSK3α/ß (ser21/9) induced by PFKFB3 overexpression. The level of lactate was increased in PFKFB3-overexpressing ATC cells, while the presence of KAN0438757 inhibited lactate production. Moreover, the simultaneous use of PFKFB3 downregulation and KAN0438757 was found to suppress subcutaneous tumor growth in vivo. CONCLUSION: PFKFB3 can enhance ATC cell proliferation and migration via the WNT/ß-catenin signaling pathway and plays a crucial role in the regulation of aerobic glycolysis in ATC cells.

Design, biological characteristics, and antibacterial mechanism of high therapeutic index antimicrobial peptides with PRRP as central axis.

As the important components of biological innate immunity, antimicrobial peptides (AMPs) were found in a variety of organisms including insects, plants, animals, bacteria, fungi, etc. However, high hemolytic activity, high toxicity, and poor stability of natural AMPs hinder serious their application as therapeutic agents. To overcome these problems, in this study we use PRRP as a central axis, and peptides were designed based on the sequence template XRRXXRXPRRPXRXXRRX-NH2, where X represents a hydrophobic amino acid like Phe (F), Ile (I), Val (V), and Leu (L). The designed peptides LR18, FR18, and IR18 showed effective antimicrobial activity against some Gram-positive bacteria and Gram-negative bacteria, low cytotoxicity to mammalian cells, and had a tendency to form α-helical structures in membrane-mimetic environments. Among them, peptide LR18 (X: L) showed the highest geometric mean average treatment index (GMTI = 42.7) against Gram-negative bacteria, and FR18 (X: L) showed the highest GMTI (22.86) against Gram-positive bacteria. LR18 and FR18 also showed better salt, temperature, pH, and trypsin stability. LR18 and FR18 exert their antimicrobial effects mainly through destroying bacteria cell membrane. Briefly, peptide LR18 and FR18 have the potential to serve as a therapeutic agent to reduce antibiotic resistance owing to its high therapeutic index and great stability.

RcMYB8 enhances salt and drought tolerance in rose (Rosa chinensis) by modulating RcPR5/1 and RcP5CS1.

Plant Myeloblastosis (MYB) proteins function crucially roles upon variegated abiotic stresses. Nonetheless, their effects and mechanisms in rose (Rosa chinensis) are not fully clarified. In this study, we characterized the effects of rose RcMYB8 under salt and drought tolerances. For induction of the RcMYB8 expression, NaCl and drought stress treatment were adopted. Rose plants overexpressing RcMYB8 displayed enhanced tolerance to salinity and drought stress, while silencing RcMYB8 resulted in decreased tolerance, as evidenced by lowered intra-leaf electrolyte leakage and callose deposition, as well as photosynthetic sustainment under stressed conditions. Here, we further show that RcMYB8 binds similarly to the promoters of RcPR5/1 and RcP5C51 in vivo and in vitro. Inhibiting RcP5CS1 by virus-induced gene silencing led to decreased drought tolerance through the reactive oxygen species (ROS) homeostatic regulation. RcP5CS1-silenced plants showed an increase in ion leakage and reduce of proline content, together with the content of malondialdehyde (MDA) increased, lowered activities of Catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD). Our study highlights the transcriptional modulator role of RcMYB8 in drought and salinity tolerances, which bridges RcPR5/1 and RcP5CS1 by promoting ROS scavenging. Besides, it is probably applicable to the rose plant engineering for enhancing their abiotic stress tolerances.

Amorphous bismuth and GO co-doped WO3 electrochromic film with fast-switching time and long-term stability.

The sol-gel process for fabricating electrochromic thin films is straightforward, offering advantages such as low cost and ease of compositional control. Herein we prepared GO-Bi-WO3 films with improved electrochromic performance using a simple sol-gel spin-coating method. The sample shows a fast-switching time (1.8 s for coloring and 1.8 s for bleaching), large optical modulation (85% at 630 nm), excellent stability (86.4% retention after 10 200 cycles), and high coloration efficiency (65.9 cm2 C-1). This work indicates the electrochromic performance of WO3-based films can be enhanced by incorporating GO, which provides an effective strategy for the rapid, safe, and efficient fabrication of electrochromic thin films.

Modulating the polarization phenotype of microglia - A valuable strategy for central nervous system diseases.

Central nervous system (CNS) diseases have become one of the leading causes of death in the global population. The pathogenesis of CNS diseases is complicated, so it is important to find the patterns of the disease to improve the treatment strategy. Microglia are considered to be a double-edged sword, playing both harmful and beneficial roles in CNS diseases. Therefore, it is crucial to understand the progression of the disease and the changes in the polar phenotype of microglia to provide guidance in the treatment of CNS diseases. Microglia activation may evolve into different phenotypes: M1 and M2 types. We focused on the roles that M1 and M2 microglia play in regulating intercellular dialogues, pathological reactions and specific diseases in CNS diseases. Importantly, we summarized the strategies used to modulate the polarization phenotype of microglia, including traditional pharmacological modulation, biological therapies, and physical strategies. This review will contribute to the development of potential strategies to modulate microglia polarization phenotypes and provide new alternative therapies for CNS diseases.