Unraveling the impact of starch granule-associated proteins on the emulsifying ability of quinoa starch granules at multiple scales.

Total starch granule-associated proteins (tGAP), including granule-channel (GCP) and granule-surface proteins (GSP), alter the physicochemical properties of starches. Quinoa starch (QS) acts as an effective emulsifier in Pickering emulsion. However, the correlation between the tGAP and the emulsifying capacity of QS at different scales remains unclear. Herein, GCP and tGAP were selectively removed from QS, namely QS-C and QS-A. Results indicated that the loss of tGAP increased the water permeability and hydrophilicity of the starch particles. Mesoscopically, removing tGAP decreased the diffusion rate and interfacial viscous modulus. Particularly, GSP had a more profound impact on the interfacial modulus than GCP. Microscopically and macroscopically, the loss of tGAP endowed QS with weakened emulsifying ability in terms of emulsions with larger droplet size and diminished rheological properties. Collectively, this work demonstrated that tGAP played an important role in the structural and interfacial properties of QS molecules and the stability of QS-stabilized emulsions.

Dachengqi decoction dispensing granule ameliorates LPS-induced acute lung injury by inhibiting PANoptosis in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) is a serious health-threatening syndrome of intense inflammatory response in the lungs, with progression leading to acute respiratory distress syndrome (ARDS). Dachengqi decoction dispensing granule (DDG) has a pulmonary protective role, but its potential modulatory mechanism to alleviate ALI needs further excavation. AIM OF THE STUDY: This study aims to investigate the effect and potential mechanism of DDG on lipopolysaccharide (LPS)-induced ALI models in vivo and in vitro. MATERIALS AND METHODS: LPS-treated Balb/c mice and BEAS-2B cells were used to construct in vivo and in vitro ALI models, respectively. Hematoxylin-eosin (HE), Wet weight/Dry weight (W/D) calculation of lung tissue, and total protein and Lactic dehydrogenase (LDH) assays in BALF were performed to assess the extent of lung tissue injury and pulmonary edema. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-18 (IL-18) in BALF, serum, and cell supernatant. The qRT-PCR was used to detect inflammatory factors, Z-DNA binding protein 1 (ZBP1), and receptor-interacting protein kinase 1 (RIPK1) expression in lung tissues and BEAS-2B cells. Double immunofluorescence staining and co-immunoprecipitation were used to detect the relative expression and co-localization of ZBP1 and RIPK1. The effects of LPS and DDG on BEAS-2B cell activity were detected by Cell Counting Kit-8 (CCK-8). Western blot (WB) was performed to analyze the expression of PANoptosis-related proteins in lung tissues and BEAS-2B cells. RESULTS: In vivo, DDG pretreatment could dose-dependently improve the pathological changes of lung tissue in ALI mice, and reduce the W/D ratio of lung, total protein concentration, and LDH content in BALF. In vitro, DDG reversed the inhibitory effect of LPS on BEAS-2B cell viability. Meanwhile, DDG significantly reduced the levels of inflammatory factors in vitro and in vivo. In addition, DDG could inhibit the expression levels of PANoptosis-related proteins, especially the upstream key regulatory molecules ZBP1 and RIPK1. CONCLUSION: DDG could inhibit excessive inflammation and PANoptosis to alleviate LPS-induced ALI, thus possessing good anti-inflammatory and lung-protective effects. This study establishes a theoretical basis for the further development of DDG and provides a new prospect for ALI treatment by targeting PANoptosis.

Effects of fermentation with Lactobacillus plantarum on rice flour: The role of granular characteristics.

This study examined the effects of lactic acid bacteria fermentation on the physicochemical and functional properties of the flours from two rice varieties, Shindongjin (SF) and Hitomebore (HF), both with similar amylose content. Fermentation with Lactobacillus plantarum over 48 h resulted in significant changes. Protein content decreased substantially in both varieties, especially in SF, and amylose content increased. Swelling power and solubility also increased more in SF. The gel hardness of fermented SF increased by approximately 22 %, whereas HF showed minimal change. These differences are due to variations in granule rigidity and starch molecule leaching. SF granules maintained rigidity and a robust external network due to higher amylose leaching. In contrast, the lower initial rigidity and higher amylopectin leaching in HF hindered strong gel network formation. These findings offer insights into the structural and molecular mechanisms of rice fermentation with lactic acid bacteria.

Qingxin Jieyu Granule alleviates myocardial infarction through inhibiting neutrophil extracellular traps via activating ANXA1/FPR2 axis.

BACKGROUND: Myocardial infarction (MI), representing the most severe manifestation of coronary artery disease (CAD), stands as a primary concern in the prevention and management of cardiovascular diseases. Clinical evidence demonstrates that Qingxin Jieyu Granule (QXJYG) is efficacious in treatment of MI patients. However, the mechanisms underlying its therapeutic effects remain to be elucidated. PURPOSE: This study aimed to evaluate the effects of QXJYG on MI and investigate its underlying mechanisms. MATERIALS AND METHODS: The MI model in rats was developed through ligating the left anterior descending (LAD) artery. The effect of QXJYG on cardiac function impairment in MI rats was assessed by echocardiography, while the improvement of cardiomyocyte morphology and myocardial fibrosis after treatment with QXJYG was evaluated through hematoxylin-eosin (H&E) staining and Masson staining. The chemical constituents of QXJYG in blood were identified by using the UPLC-Q-TOF/MS technique. Furthermore, the molecular mechanism underlying the QXJYG therapeutic effect in MI was postulated based on the disease gene-drug target network analysis. Other technical methods such as ELISA, immunohistochemical staining, Western Blot analysis and application of pharmacological inhibitors were employed to verify the effectiveness of QXJYG in treating MI and explore its potential molecular targets. RESULTS: The cardiac function in experimental rats post-MI was significantly impaired, as evidenced by an enlarged infarction area, disordered arrangement of cardiomyocytes, and aggravated myocardial fibrosis. QXJYG treatment significantly enhanced the cardiac function and reduced the pathological damage of the cardiac tissue in MI rats. Through the network pharmacology analysis, we identified that FPR2 might be a potential target of QXJYG in its cardiac protection role. QXJYG markedly downregulated the level of neutrophil extracellular traps (NETs) in MI rats, specifically manifested as a significant reduction in the Histone-DNA level and expression of myeloperoxidase (MPO) and citrullinated histone H3 (CitH3) proteins. Furthermore, QXJYG upregulated the levels of ANXA1 and FPR2 proteins in MI rats. The level of FPR2 was markedly reduced in MI rats upon administration of WRW4, a specific inhibitor of FPR2, which was associated with exacerbated MI injury and an elevated level of NETs. When WRW4 was co-administered with QXJYG, the cardioprotective effects of QXJYG on MI were significantly diminished. However, the addition of DNase I did not result in significant changes of the outcomes in MI rats after QXJYG intervention. CONCLUSION: QXJYG treatment alleviates cardiac tissue injury in MI rats by inhibiting NETs through activating the ANXA1/FPR2 axis. The findings extend our understanding of the therapeutic effectiveness of QXJYG and offer a scientific foundation for the clinical utilization of QXJYG.

A novel isolation technique for sweetpotato starch and its application in thermal property characterization.

BACKGROUND: The utilization of sweetpotato starch in the food industry is significantly influenced by the granule size of the starch. To isolate sweetpotato starch fractions with different sizes, an efficient isolation method is in demand. The differences in thermal properties of starch fractions with different sizes from various sweetpotato varieties were revealed insufficiently. RESULTS: In this study, we devised a time-saving isolation technique to effectively isolate sweetpotato starch fractions based on granule sizes. The new technique was proved applicable for sweetpotato varieties with different flesh colors. The amylose contents of the isolated starch fractions were in the range 16.49-23.27%. A positive association was observed between amylose content, relative crystallinity of starch fractions and their granule size. Conversely, both the swelling power and water solubility at 95 °C displayed a consistent decline from more than 30 g g-1 to lower than 20 g g-1 as the granule size increased. Tp, To and Tc decreased gradually with an increase of starch granule size, while the medium- or small-sized starch fractions showed higher ΔH. In the first stage of thermogravimetric analysis curves, the weight of the small-sized starch fractions decreased the slowest, but no definite pattern was detected in the second or third stage. CONCLUSION: Therefore, the newly established technique and the results of this study will help better understand the properties of sweetpotato starch fractions with different sizes and certainly provide guidelines for the utilization of sweetpotato starch in food processing and product development. © 2024 Society of Chemical Industry.

Alterations of the gut microbiota and metabolites by ShenZhu TiaoPi granule alleviates hyperglycemia in GK rats.

ShenZhu TiaoPi granule (STG) is a compound prescription that is used in Chinese medicine for the treatment of type 2 diabetes mellitus (T2DM). Previous studies have indicated a hypoglycaemic effect, but the underlying mechanism remains unclear. Goto-Kakizaki (GK) rats were used to establish an in vivo T2DM model (Mod). The metformin (Met) and STG treatment time was 12 weeks. Fasting blood glucose (FBG) and insulin levels and the area under the glucose curve (GAUC) were measured. Intestinal pathology and permeability were observed. Microbial diversity analysis and metabolomics were used to investigate the underlying mechanisms. Compared with the Con group, the T2DM Mod group presented significant differences in weight, FBG, GAUC, and homeostasis model assessment-insulin resistance (HOMA-IR) indices (p < 0.01). Met and STG improved these indicators (p < 0.01). The pathological morphology and zonula occludens 1 protein levels in the intestines of the Mod group of rats were altered, leading to increases in the lipopolysaccharide (LPS) and interleukin-1ß (IL-1ß) levels. In the Met and STG groups, the intestinal conditions improved, and the LPS and IL-1ß levels significantly decreased (p < 0.01). Changes in the gut microbiota and metabolites occurred in the Mod group. In the STG group, the abundance of Intestinimonas increased, and the abundance of Eubacterium coprostanoligenes decreased significantly (p < 0.05). Moreover, STG also altered 2-deoxyglucose, beta-muricholic acid and dioxolithocholic acid production. In addition, the main metabolic pathways affected by STG were bile acid biosynthesis and cholesterol metabolism. Intestinimonas, D-maltose_and_alpha-lactose may be potential biomarkers for the effects of STG. STG alleviates hyperglycaemia via the gut microbiota and metabolites in GK rats.

Activation of arginine vasopressin receptor 1a reduces inhibitory synaptic currents at reciprocal synapses in the mouse accessory olfactory bulb.

Central arginine vasopressin (AVP) facilitates social recognition and modulates many complex social behaviors in mammals that, in many cases, recognize each other based on olfactory and/or pheromonal signals. AVP neurons are present in the accessory olfactory bulb (AOB), which is the first relay in the vomeronasal system and has been demonstrated to be a critical site for mating-induced mate recognition (olfactory memory) in female mice. The transmission of information from the AOB to higher centers is controlled by the dendrodendritic recurrent inhibition, i.e., inhibitory postsynaptic currents (IPSCs) generated in mitral cells by recurrent dendrodendritic inhibitory inputs from granule cells. These reports suggest that AVP might play an important role in regulating dendrodendritic inhibition in the AOB. To test this hypothesis, we examined the effects of extracellularly applied AVP on synaptic responses measured from mitral and granule cells in slice preparations from 23--36-day-old Balb/c mice. To evoke dendrodendritic inhibition in a mitral cell, depolarizing voltages of -70 to 0 mV (10 ms duration) were applied to a mitral cell using a conventional whole-cell configuration. We found that AVP significantly reduced the IPSCs. The suppressive effects of AVP on the IPSCs was diminished by an antagonist for vasopressin receptor 1a (V1aR) (Manning compound), but not by an antagonist for vasopressin receptor 1b (SSR149415). An agonist for V1aRs [(Phe2)OVT] mimicked the action of AVP on IPSCs. Additionally, AVP significantly suppressed voltage-activated currents in granule cells without affecting the magnitude of the response of mitral cells to gamma-aminobutyric acid (GABA). The present results suggest that V1aRs play a role in reciprocal transmission between mitral cells and granule cells in the mouse AOB by reducing GABAergic transmission through a presynaptic mechanism in granule cells.

Dense but not alpha granules of platelets are required for insulin secretion from pancreatic ß cells.

OBJECTIVES: Platelets, originally described for their role in blood coagulation, are now also recognized as key players in modulating inflammation, tissue regeneration, angiogenesis, and carcinogenesis. Recent evidence suggests that platelets also influence insulin secretion from pancreatic ß cells. The multifaceted functions of platelets are mediated by the factors stored in their alpha granules (AGs) and dense granules (DGs). AGs primarily contain proteins, while DGs are rich in small molecules, and both types of granules are released during blood coagulation. Specific components stored in AGs and DGs are implicated in various inflammatory, regenerative, and tumorigenic processes. However, the relative contributions of AGs and DGs to the regulation of pancreatic ß cell function have not been previously explored. METHODS: In this study, we utilized mouse models deficient in AG content (neurobeachin-like 2 (Nbeal2) -deficient mice) and models with defective DG release (Unc13d-deficiency in bone marrow-derived cells) to investigate the impact of platelet granules on insulin secretion from pancreatic ß cells. RESULTS: Our findings indicate that AG deficiency has little to no effect on pancreatic ß cell function and glucose homeostasis. Conversely, mice with defective DG release exhibited glucose intolerance and reduced insulin secretion. Furthermore, Unc13d-deficiency in hematopoietic stem cells led to a reduction in adipose tissue gain in obese mice. CONCLUSIONS: Obtained data suggest that DGs, but not AGs, mediate the influence of platelets on pancreatic ß cells, thereby modulating glucose metabolism.

Changes in the Cyto- and Fibroarchitectonics of the Cerebellar Cortex in Rats Subjected to Extreme Physical Activity.

Physical overexertion surpassing the functional capacity of the nervous system causes the hyperactivation of the neural structures of the cerebellum. In turn, it causes the depletion of intracellular resources and progressive structural changes in cerebellar cells and fibers. These degenerative changes may lead to cerebellar dysfunction, including the worsening of coordination, balance, and motor functions. In order to maintain the health and functioning of the cerebellum and the nervous system in general, one needs to avoid physical overexertion and have enough time to recover. Three major types of Purkinje cells were identified in control group animals. After the forced swimming test, animals had significant morphological changes in pyriform cells, granule cells, internuncial neurons, and neuroglial cells. In particular, the extreme degeneration of granule cells was manifested via their fusion into conglomerates. These changes demonstrate that neurodegeneration in the cerebellum takes place in response to physical overexertion.

Network Pharmacology-Based Strategy to Explore the Effect and Mechanism of Zhizhu Granule Improving Glucose-Lipid Metabolism in Rats with Metabolic Syndrome.

Objective: To explore the mechanism of the traditional Chinese medicine (TCM), Zhizhu granule (ZZG), in treating metabolic syndrome (MS) based on network pharmacology and pharmacodynamic experiment. Materials and Methods: Network pharmacology combined with a pharmacodynamic experiment was used to elucidate the therapeutic mechanism of ZZG in MS. Serum samples were collected from rats with MS, induced by a high-sugar-fat-salt diet (HSFSD) combined with streptozotocin (STZ), to measure the levels of biochemical markers. The glucose (GLU), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were detected. The liver tissue of rats was used for histological examination and Western blot analysis. Results: Network pharmacology analysis generated 69 drug-disease common targets and 10 hub genes closely related to ZZG against MS. KEGG pathway analysis revealed that the PI3K/AKT signaling pathway was the most potential pathway, which took part in the therapeutic mechanisms. In the animal experiments section, the therapeutic effect of ZZG on MS and the therapeutic pathway of ZZG on MS were verified. ZZG could significantly decrease the body weight, TC, TG, LDL-C and GLU levels in MS rats (all p<0.01), alleviate hepatocyte steatosis and decrease liver lipid droplet deposition. Western blot analysis indicated that compared with the model group, the expression levels of PI3K, AKT, and IRS-1 protein were significantly increased (all p<0.05), and the FOXO-1 was significantly decreased (all p<0.05) in the ZZG group. Conclusion: ZZG can improve glucose-lipid metabolism disorder in rats with metabolic syndrome. The reported results provide experimental evidence for ZZG in the treatment of MS.

Enhancement of Stress Granule Formation by a Chiral Compound Targeting G3BP1 via eIF2α Phosphorylation.

The chirality of a chemical differentiates it from its mirror-image counterpart. This unique property has significant implications in chemistry, biology, and drug discovery, where chiral chemicals display high selectivity and activity in achieving target specificity and reducing attrition rates in drug development. Stress granules (SGs) are dynamic assemblies of proteins and RNA that form in the cytoplasm of cells under stress conditions. Modulating their formation or disassembly could offer a novel approach to treating a wide range of diseases. This has led to significant interest in SGs as potential therapeutic targets. This study examined the NTF2-like domain of G3BP1 as a possible target for SG modulation. Molecular docking was used to simulate the interactions of compounds with the domain, and a potential candidate with a chiral structure was identified. The experiments showed that the compound induced the formation of SG-like granules. Importantly, the ability of this compound to modulate SG offers valuable insights into a new mechanism underlying the dynamics and promoting the assembly of SGs, and this new mechanism, in turn, holds potential for the development of drugs with diverse mechanisms of action and potentially synergistic effects.

Understanding of Wetting Mechanism Toward the Sticky Powder and Machine Learning in Predicting Granule Size Distribution Under High Shear Wet Granulation.

The granulation of traditional Chinese medicine (TCM) has attracted widespread attention, there is limited research on the high shear wet granulation (HSWG) and wetting mechanisms of sticky TCM powders, which profoundly impact the granule size distribution (GSD). Here we investigate the wetting mechanism of binders and the influence of various parameters on the GSD of HSWG and establish a GSD prediction model. Permeability and contact angle experiments combined with molecular dynamics (MD) simulations were used to explore the wetting mechanism of hydroalcoholic solutions with TCM powder. Machine learning (ML) was employed to build a GSD prediction model, feature importance explained the influence of features on the predictive performance of the model, and correlation analysis was used to assess the influence of various parameters on GSD. The results show that water increases powder viscosity, forming high-viscosity aggregates, while ethanol primarily acted as a wetting agent. The contact angle of water on the powder bed was the largest and decreased with an increase in ethanol concentration. Extreme Gradient Boosting (XGBoost) outperformed other models in overall prediction accuracy in GSD prediction, the binder had the greatest impact on the predictions and GSD, adjusting the amount and concentration of adhesive can control the adhesion and growth of granules while the impeller speed had the least influence on granulation. The study elucidates the wetting mechanism and provides a GSD prediction model, along with the impact of material properties, formulation, and process parameters obtained, aiding the intelligent manufacturing and formulation development of TMC.

Monitoring the Biochemical Activity of Single Anammox Granules with Microbarometers.

Granule-based anaerobic ammonium oxidation (Anammox) is a promising biotechnology for wastewater treatments with extraordinary performance in nitrogen removal. However, traditional analytical methods often delivered an average activity of a bulk sample consisting of millions and even billions of Anammox granules with distinct sizes and components. Here, we developed a novel technique to monitor the biochemical activity of individual Anammox granules in real-time by recording the production rate of nitrogen gas with a microbarometer in a sealed chamber containing only one granule. It was found that the specific activity of a single Anammox granule not only varied by tens of folds among different individuals with similar sizes (activity heterogeneity) but also revealed significant breath-like dynamics over time (temporal fluctuation). Statistical analysis on tens of individuals further revealed two subpopulations with distinct color and specific activity, which were subsequently attributed to the different expression levels of heme c content and hydrazine dehydrogenase activity. This study not only provides a general methodology for various kinds of gas-producing microbial processes but also establishes a bottom-up strategy for exploring the structural-activity relationship at a single sludge granule level, with implications for developing a better Anammox process.

Effect of cations on aerobic granulation for sidestream treatment.

Aerobic granular sludge (AGS) represents an aggregate of sludge formed through the self-immobilization of microorganisms under aerobic conditions. It is currently under scrutiny for its potential as a technology to reduce carbon emissions and promote sustainability. The practicality of AGS stems from its ability to encourage granule formation and enhance structural stability. In this study, a total of five cations (K+, Ca2+, Mg2+, Al3+, Fe3+) were introduced to facilitate stable structuring and the formation of granules for treating high-strength wastewater, such as side-stream treatment. As a result of the experiment, the loosely bound extracellular polymeric substances (LB-EPS) content in the cation-enhanced sludge witnessed a significant increase, leading to elevated total EPS content under all experimental conditions. Furthermore, the protein (PN)/polysaccharide (PS) ratio, a pivotal component of EPS influencing AGS's hydrophobicity and structural stability, exhibited a collective increase, with Mg2+ reaching the highest value of 1.7. The relationship between relative hydrophobicity and the PN/PS ratio was found to strongly impact sludge adhesion, with noteworthy results observed particularly for Mg2+, Al3+, and Fe3+. The viability of attached cells reached 96.8 %, the highest recorded in the case of Mg2+. In the context of treating high-strength wastewater, Mg2+ emerged as the optimal cation for accelerating AGS formation and enhancing structural stability.

Thermal Stress and Nuclear Transport.

Nuclear transport is the basis for the biological reaction of eukaryotic cells, as it is essential to coordinate nuclear and cytoplasmic events separated by nuclear envelope. Although we currently understand the basic molecular mechanisms of nuclear transport in detail, many unexplored areas remain. For example, it is believed that the regulations and biological functions of the nuclear transport receptors (NTRs) highlights the significance of the transport pathways in physiological contexts. However, physiological significance of multiple parallel transport pathways consisting of more than 20 NTRs is still poorly understood, because our knowledge of each pathway, regarding their substrate information or how they are differently regulated, is still limited. In this report, we describe studies showing how nuclear transport systems in general are affected by temperature rises, namely, thermal stress or heat stress. We will then focus on Importin α family members and unique transport factor Hikeshi, because these two NTRs are affected in heat stress. Our present review will provide an additional view to point out the importance of diversity of the nuclear transport pathways in eukaryotic cells.

Qian Yang Yu Yin Granule prevents hypertensive cardiac remodeling by inhibiting NLRP3 inflammasome activation via Nrf2.

ETHNOPHARMACOLOGICAL RELEVANCE: Qian Yang Yu Yin Granule (QYYYG), a traditional Chinese poly-herbal formulation, has been validated in clinical trials to mitigate cardiac remodeling (CR), and cardiac damage in patients with hypertension. However, the specific mechanism remains unclear. AIM OF THE STUDY: This study explored the potential effects and potential mechanisms of QYYYG on hypertensive CR by combining various experimental approaches. MATERIALS AND METHODS: Spontaneously hypertensive rats (SHRs) were used as a model of hypertensive CR, followed by QYYYG interventions. Blood pressure, cardiac function and structure, histopathological changes, and myocardial inflammation and oxidative stress were tested to assess the efficacy of QYYYG in SHRs. For in vitro experiments, a cell model of myocardial hypertrophy and injury was constructed with isoprenaline. Cardiomyocyte hypertrophy, oxidative stress, and death were examined after treatment with different concentrations of QYYYG, and transcriptomics analyses were performed to explore the underlying mechanism. Nrf2 and the ROS/NF-κB/NLRP3 inflammasome pathway were detected. Thereafter, ML385 and siRNAs were used to inhibit Nrf2 in cardiomyocytes, so as to verify whether QYYYG negatively regulates the NLRP3 inflammasome by targeting Nrf2, thereby ameliorating the associated phenotypes. Finally, high performance liquid chromatography (HPLC) was conducted to analyze the active ingredients in QYYYG, and molecular docking was utilized to preliminarily screen the compounds with modulatory effects on Nrf2 activities. RESULTS: QYYYG improved blood pressure, cardiac function, and structural remodeling and attenuated myocardial inflammation, oxidative stress, and cell death in SHRs. The transcriptomics results showed that the inflammatory response might be crucial in pathological CR and that Nrf2, which potentially negatively regulates the process, was upregulated by QYYYG treatment. Furthermore, QYYYG indeed facilitated Nrf2 activation and negatively regulated the ROS/NF-κB/NLRP3 inflammasome pathway, therefore ameliorating the associated phenotypes. In vitro inhibition or knockdown of Nrf2 weakened or even reversed the repressive effect of QYYYG on ISO-induced inflammation, oxidative stress, pyroptosis, and the NLRP3 inflammasome activation. Based on the results of HPLC and molecular docking, 30 compounds, including cafestol, genistein, hesperetin, and formononetin, have binding sites to Keap1-Nrf2 protein and might affect the activity or stability of Nrf2. CONCLUSION: In conclusion, the alleviatory effect of QYYYG on hypertensive CR is related to its regulation of Nrf2 activation. Specifically, QYYYG blocks the activation of the NLRP3 inflammasome by boosting Nrf2 signaling and depressing myocardial inflammation, oxidative stress, and pyroptosis, thereby effectively ameliorating hypertensive CR.

Differentiation stage-specific expression of transcriptional regulators for epithelial mesenchymal transition in dentate granule progenitors.

During the development of the mouse dentate gyrus (DG), granule neuronal progenitors (GNPs) arise from glial fibrillary acidic protein (GFAP)-expressing neural stem cells in the dentate notch. However, the transcriptional regulators that control their stepwise differentiation remain poorly defined. Since neurogenesis involves epithelial-to-mesenchymal transition (EMT)-like processes, we investigated the spatio-temporal expression profiles of the EMT transcription factors Zeb1, Scratch2 (Scrt2) and Nkx6-2 in relation to known GNP markers. Our results show that Zeb1 and Scrt2 exhibit sequential, but partially overlapping expression across embryonic and postnatal stages of GNP differentiation. Zeb1 is highly enriched in gfap-GFP+/Sox2+ neural stem/progenitor pools and subsets of Tbr2+/Prox1+/NeuroD+ intermediate GNPs, whereas Scrt2 predominates in Tbr2+/Prox1+/NeuroD+ GNPs. Strikingly, the neuronal EMT regulator Nkx6-2 shows selective expression in postnatal Tbr2+/Prox1+ GNPs, but it is excluded from embryonic counterparts. This temporally coordinated yet distinct expression of Zeb1, Scrt2 and Nkx6-2 reveals discrete transcriptional programs orchestrating GNP differentiation and neurogenic progression at embryonic versus postnatal stages of DG neurogenesis.

Identification of chemical constituents and pharmacokinetic characteristics of Xiaoyan Tuire Granule in rats.

Xiaoyan Tuire Granule is a type of Chinese patent medicine that has been proven effective in treating respiratory tract infections. However, while it has been successfully introduced into clinical use, more knowledge is still needed regarding its chemical components and pharmacokinetics. This study investigated the chemical profile in the medicine and rat plasma by ultra high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Orbitrap-MS/MS). Subsequently, it developed a validated ultra high-performance liquid chromatography coupled with quadrupole mass spectrometry (UHPLC-MS/MS) method for determining five components in rat plasma after oral administration of Xiaoyan Tuire Granule. As a result, a total of 106 constituents were inferred, including 9 terpenoids, 29 flavonoids, 33 organic acids, 12 phenylpropanoids and 23 other compounds. After administration, 86 compounds were inferred in rat plasma, including 73 prototypes and 13 metabolites. The metabolic pathways were primarily hydrogenation, glucuronic acid conjugation, sulfate conjugation, hydrolysis and methylation. The established method determined the contents of esculetin, esculin, isovitexin, caffeic acid and p-coumaric acid had a good separation, and all the legal verification met the requirements. The pharmacokinetic results indicate that the absorption rate of the five compounds in vivo was rapid, with a Tmax of less than 0.25 h, and the elimination rate was also fast, with a half-time (T1/2) ranging from 1.22 h to 2.19 h. It is worth noting that esculin and esculetin have similar half-time in vivo due to their structural similarities. Among these five compounds, the AUC0-∞ and MRT0-∞ of p-coumaric acid and esculetin were relatively higher, indicating higher exposure and longer residence time of both compounds in vivo. In conclusion, this paper researched the chemical constituents and pharmacokinetics of Xiaoyan Tuire Granule, which provided the reference for further study.

Daily oscillations of neuronal membrane capacitance.

Capacitance of biological membranes is determined by the properties of the lipid portion of the membrane as well as the morphological features of a cell. In neurons, membrane capacitance is a determining factor of synaptic integration, action potential propagation speed, and firing frequency due to its direct effect on the membrane time constant. Besides slow changes associated with increased morphological complexity during postnatal maturation, neuronal membrane capacitance is considered a stable, non-regulated, and constant magnitude. Here we report that, in two excitatory neuronal cell types, pyramidal cells of the mouse primary visual cortex and granule cells of the hippocampus, the membrane capacitance significantly changes between the start and the end of a daily light-dark cycle. The changes are large, nearly 2-fold in magnitude in pyramidal cells, but are not observed in cortical parvalbumin-expressing inhibitory interneurons. Consistent with daily capacitance fluctuations, the time window for synaptic integration also changes in pyramidal cells.

Genome binding properties of Zic transcription factors underlie their changing functions during neuronal maturation.

BACKGROUND: The Zic family of transcription factors (TFs) promote both proliferation and maturation of cerebellar granule neurons (CGNs), raising the question of how a single, constitutively expressed TF family can support distinct developmental processes. Here we use an integrative experimental and bioinformatic approach to discover the regulatory relationship between Zic TF binding and changing programs of gene transcription during postnatal CGN differentiation. RESULTS: We first established a bioinformatic pipeline to integrate Zic ChIP-seq data from the developing mouse cerebellum with other genomic datasets from the same tissue. In newborn CGNs, Zic TF binding predominates at active enhancers that are co-bound by developmentally regulated TFs including Atoh1, whereas in mature CGNs, Zic TF binding consolidates toward promoters where it co-localizes with activity-regulated TFs. We then performed CUT&RUN-seq in differentiating CGNs to define both the time course of developmental shifts in Zic TF binding and their relationship to gene expression. Mapping Zic TF binding sites to genes using chromatin looping, we identified the set of Zic target genes that have altered expression in RNA-seq from Zic1 or Zic2 knockdown CGNs. CONCLUSIONS: Our data show that Zic TFs are required for both induction and repression of distinct, developmentally regulated target genes through a mechanism that is largely independent of changes in Zic TF binding. We suggest that the differential collaboration of Zic TFs with other TF families underlies the shift in their biological functions across CGN development.