Cardiac regeneration: Pre-existing cardiomyocyte as the hub of novel signaling pathway.

In the mammalian heart, cardiomyocytes are forced to withdraw from the cell cycle shortly after birth, limiting the ability of the heart to regenerate and repair. The development of multimodal regulation of cardiac proliferation has verified that pre-existing cardiomyocyte proliferation is an essential driver of cardiac renewal. With the continuous development of genetic lineage tracking technology, it has been revealed that cell cycle activity produces polyploid cardiomyocytes during the embryonic, juvenile, and adult stages of cardiogenesis, but newly formed mononucleated diploid cardiomyocytes also elevated sporadically during myocardial infarction. It implied that adult cardiomyocytes have a weak regenerative capacity under the condition of ischemia injury, which offers hope for the clinical treatment of myocardial infarction. However, the regeneration frequency and source of cardiomyocytes are still low, and the mechanism of regulating cardiomyocyte proliferation remains further explained. It is noteworthy to explore what force triggers endogenous cardiomyocyte proliferation and heart regeneration. Here, we focused on summarizing the recent research progress of emerging endogenous key modulators and crosstalk with other signaling pathways and furnished valuable insights into the internal mechanism of heart regeneration. In addition, myocardial transcription factors, non-coding RNAs, cyclins, and cell cycle-dependent kinases are involved in the multimodal regulation of pre-existing cardiomyocyte proliferation. Ultimately, awakening the myocardial proliferation endogenous modulator and regeneration pathways may be the final battlefield for the regenerative therapy of cardiovascular diseases.

Identification and biotransformation analysis of volatile markers during the early stage of Salmonella contamination in chicken.

Salmonella is one of the most prevalent foodborne pathogens in poultry and its products. Its rapid detection based on volatile organic compounds (VOC) has been widely accepted. However, the variation in the VOCs of Salmonella-contaminated chicken during the early stage (48 h) remains uncertain. Headspace-SPME-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and headspace-gas chromatography-ion migration spectroscopy (HS-GC-IMS) were used to identify VOCs and their variations after the chicken meat was contaminated with Salmonella. Chemometric and KEGG enrichment analyses were performed to identify VOC markers and their potential metabolic pathways. A total of 64 volatile compounds were detected using HS-GC-IMS, which showed a better differentiation than HS-SPME-GC-MS (45 volatile compounds) based on principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). Fatty acid degradation was the main cause of VOC variation. 2-Propanol, hexadecane, 3-methylbutanol, acetic acid, propyl acetate, acetic acid methyl ester, and 3-butenenitrile were identified as VOC markers in the middle stage of decomposition, and 1-octen-3-ol was recognized as a VOC marker of Salmonella-contaminated chicken during the first 48 h of contamination. This provides a theoretical basis for the study of Salmonella contamination VOC markers in poultry meat.

Deciphering mechanisms of cardiomyocytes and non-cardiomyocyte transformation in myocardial remodeling of permanent atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, and it significantly increases the risk of cardiovascular complications and morbidity, even with appropriate treatment. Tissue remodeling has been a significant topic, while its systematic transcriptional signature remains unclear in AF. OBJECTIVES: Our study aims to systematically investigate the molecular characteristics of AF at the cellular-level. METHODS: We conducted single-nuclei RNA-sequencig (snRNA-seq) analysis using nuclei isolated from the left atrial appendage (LAA) of AF patients and sinus rhythm (SR). Pathological staining was performed to validate the key findings of snRNA-seq. RESULTS: A total of 30 cell subtypes were identified among 80, 592 nuclei. Within the LAA of AF, we observed a specific subtype of differentiated cardiomyocytes characterized by reduced expression of cardiac contractile proteins (TTN and TRDN) and heightened expression of extracellular-matrix related genes (COL1A2 and FBN1). Transcription factor prediction analysis revealed that gene expression patterns in dedifferentiated cardiomyocytes were primarily regulated by CEBPG and GISLI. Additionally, we identified a distinct subtype of endothelial progenitor cells (EPCs) demonstrating elevated expression of PROM1 and KDR, a population decreased within the LAA of AF. Epicardial adipocytes disclosed a reduced release of the anti-inflammatory and anti-fibrotic factor PRG4, and an augmented secretion of VEGF signals targeting cardiomyocytes. Additionally, we noted accumulation of M2-like macrophages and CD8+ T cells with high pro-inflammatory score in LAA of AF. Furthermore, the analysis of intercellular communication revealed specific pathways related to AF, such as inflammation, extracellular matrix, and vascular remodeling signals. CONCLUSIONS: This study has discovered the presence of de-differentiated myocardial cells, a decrease in endothelial progenitor cells, a shift in the secretion profile of fat cells, and an amplified inflammatory response in AF. These findings could offer crucial insights for future research on AF and serve as valuable references for investigating novel therapeutic approaches for AF.

Structurally Diverse Sesquiterpenoids with NO Production and α-Glucosidase Inhibitory Activities from the Fruits of Schisandra chinensis.

Chemical fractionation of the AcOEt partition, generated from the EtOH extract of the fruits of Schisandra chinensis, afforded a series of sesquiterpenyl constituents including two new cadinanes, a new eudesmane, two new widdranes (a handling artefact and a new natural product), a new bisabolane and two new natural cuparane enantiomers, along with 15 known structurally related analogs. Structures of the new compounds were unambiguously characterized by interpretation of detailed spectroscopic data including ESI-MS and 1D/2D NMR, with their absolute configurations being established by electronic circular dichroism (ECD) calculation and induced ECD experiment. The inhibitory effects of all the isolates against α-glucosidase and lipopolysaccharide (LPS) induced nitric oxide (NO) production in murine RAW264.7 macrophages, as well as their antibacterial and cytotoxic potential, were evaluated, with selective compounds showing moderate α-glucosidase and NO inhibitory activity. Notably, canangaterpene III exhibited the most significant NO inhibitory effect with an IC50 value of 31.50±1.49 µM.

Metabolomics reveals that PS-NPs promote lung injury by regulating prostaglandin B1 through the cGAS-STING pathway.

Nanoplastics have been widely studied as environmental pollutants, which can accumulate in the human body through the food chain or direct contact. Research has shown that nanoplastics can affect the immune system and mitochondrial function, but the underlying mechanisms are unclear. Lungs and macrophages have important immune and metabolic functions. This study explored the effects of 100 nm PS-NPs on innate immunity, mitochondrial function, and cellular metabolism-related pathways in lung (BEAS-2B) cells and macrophages (RAW264.7). The results had shown that PS-NPs exposure caused a decrease in mitochondrial membrane potential, intracellular ROS accumulation, and Ca2+ overload, and activated the cGAS-STING signaling pathway related to innate immunity. These changes had been observed at concentrations of PS-NPs as low as 60 µg/mL, which might have been comparable to environmental levels. Non-target metabolomics and Western Blotting results confirmed that PS-NPs regulated prostaglandin B1 and other metabolites to cause cell damage through the cGAS-STING pathway. Supplementation of prostaglandin B1 alleviated the immune activation and metabolic disturbance caused by PS-NPs exposure. This study identified PS-NPs-induced innate immune activation, mitochondrial dysfunction, and metabolic toxicity pathways, providing new insights into the potential for adverse outcomes of NPs in human life.

Alleviative effect of poly-ß-hydroxybutyrate on lipopolysaccharide-induced oxidative stress, inflammation and cell apoptosis in Cyprinus carpio.

In this study, the alleviative effects of poly-ß-hydroxybutyrate (PHB) in bioflocs on oxidative stress, inflammation and apoptosis of common carp (Cyprinus carpio) induced by lipopolysaccharide (LPS) were evaluated. Common carp were irregularity divided into 5 groups and fed five diets with 0 % (CK), 2 %, 4 %, 6 % and 8 % PHB. After 8-week feeding trial, LPS challenge was executed. Results showed that appropriate level of PHB enhanced serum immune function by reversing LPS-induced the decrease of C3, C4, IgM, AKP, ACP and LZM in serum, alleviated LPS-induced intestinal barrier dysfunction by decreasing the levels of 5-HT, D-LA, ET-1 and DAO in serum, increasing ZO-1, Occludin, Claudin-3 and Claudin-7 mRNA, improving intestinal morphology. Moreover, dietary PHB reversed LPS-induced the decrease of AST and ALT in hepatopancreas, while in serum exhibited the opposite trend. Suitable level of PHB reversed LPS-induced the reduction of GSH-PX, CAT, T-SOD and T-AOC in intestines and hepatopancreas, whereas MDA showed the opposite result. PHB alleviated LPS-induced the decrease of Nrf2, HO-1, CAT, SOD and GSH-PX mRNA, the increase of Keap1 mRNA. Appropriate level of PHB alleviated LPS-induced inflammation and apoptosis by up-regulating TGF-ß, IL-10 and Bcl-2 mRNA, down-regulating NF-κB, TNF-α, IL-6, Bax, Caspase-3, Caspase-8 and Caspase-9 mRNA. Furthermore, PHB inhibited activation of NLRP3 inflammasomes by reducing the levels of NLRP3, Caspase-1, ASC, IL-1ß and IL-18 mRNA and protein. In addition, the increases of dietary PHB linearly and quadratically affected LPS-induced adverse effects on common carp. Summary, this study suggested that appropriate level of dietary PHB alleviated LPS-induced oxidative stress, inflammation, apoptosis and the activation of NLRP3 inflammasome in common carp. And the appropriate level of PHB in common carp diets was 4 %.

Biochar amendment combined with partial root-zone drying irrigation alleviates salinity stress and improves root morphology and water use efficiency in cotton plant.

An adsorption experiment and a pot experiment were executed in order to explore the mechanisms by which biochar amendment in combination with reduced irrigation affects sodium and potassium uptake, root morphology, water use efficiency, and salinity tolerance of cotton plants. In the adsorption experiment, ten NaCl concentration gradients (0, 50, 100, 150, 200, 250, 300, 350, 400, and 500 mM) were set for testing isotherm adsorption of Na+ by biochar. It was found that the isotherms of Na+ adsorption by wheat straw biochar (WSP) and softwood biochar (SWP) were in accordance with the Langmuir isotherm model, and the Na+ adsorption ability of WSP (55.20 mg g-1) was superior to that of SWP (47.38 mg g-1). The pot experiment consisted three factors, viz., three biochar amendments (no biochar, WSP, and SWP), three irrigation strategies (deficit irrigation, partial root-zone drying irrigation - PRD, full irrigation), and two NaCl concentrations gradients (0 mM and 200 mM). The findings indicated that salinity stress lowered K+ concentration, root length, root surface area, and root volume (RV), but increased Na+ concentration, root average diameter, and root tissue density. However, biochar amendment decreased Na+ concentration, increased K+ concentration, and improved root morphology. In particular, the combination of WSP and PRD increased K+/Na+ ratio, RV, root weight density, root surface area density, water use efficiency, and partial factor productivity under salt stress, which can be a promising strategy to cope with drought and salinity stress in cotton production.

Targeting the opioid remifentanil: Protective effects and molecular mechanisms against organ ischemia-reperfusion injury.

Opioids are widely used in clinical practice by activating opioid receptors (OPRs), but their clinical application is limited by a series of side effects. Researchers have been making tremendous efforts to promote the development and application of opioids. Fortunately, recent studies have identified the additional effects of opioids in addition to anesthesia and analgesia, particularly in terms of organ protection against ischemia-reperfusion (I/R) injury, with unique advantages. I/R injury in vital organs not only leads to cell dysfunction and structural damage but also induces acute and chronic organ failure, even death. Early prevention and appropriate therapeutic targets for I/R injury are crucial for organ protection. Opioids have shown cardioprotective effects for over 20 years, especially remifentanil, a derivative of fentanyl, which is a new ultra-short-acting opioid analgesic widely used in clinical anesthesia induction and maintenance. In this review, we provide current knowledge about the physiological effects related to OPR-mediated organ protection, focusing on the protective effect and mechanism of remifentanil on I/R injury in the heart and other vital organs. Herein, we also explored the potential application of remifentanil in clinical I/R injury. These findings provide a theoretical basis for the use of remifentanil to inhibit or alleviate organ I/R injury during the perioperative period and provide insights for opioid-induced human organ protection and drug development.

Separable alginate gel spheres encapsulated with La-Fe modified biochar for efficient adsorption of Sb(III) with high capacity.

Sb and its compounds have been widely used in various industrial applications. Therefore, the preparation of Sb adsorbents with easy recovery and excellent adsorption levels is an urgent problem that must be resolved. By calcining and treating La/Fe metal-organic frameworks (MOF) biochar as a precursor, a loaded La-Fe-modified water hyacinth biochar was synthesised and used as a filler to synthesise iron alginate composite gel spheres, MBC/algFe. Through a series of static adsorption experiments, the effects of different filler addition ratios, solution pH, reaction time, coexisting ions, and other factors on the adsorption of Sb(III) were investigated. According to the Langmuir model, the maximum adsorption capacity of MBC/algFe at 25 â„ƒ was 277.8 mg·g-1. The adsorption mechanism mainly involved hydrogen bonding and metal-organic complexation interactions.

Elevated concentrations cause upright alpha-synuclein conformation at lipid interfaces.

The amyloid aggregation of α-synuclein (αS), related to Parkinson's disease, can be catalyzed by lipid membranes. Despite the importance of lipid surfaces, the 3D-structure and orientation of lipid-bound αS is still not known in detail. Here, we report interface-specific vibrational sum-frequency generation (VSFG) experiments that reveal how monomeric αS binds to an anionic lipid interface over a large range of αS-lipid ratios. To interpret the experimental data, we present a frame-selection method ("ViscaSelect") in which out-of-equilibrium molecular dynamics simulations are used to generate structural hypotheses that are compared to experimental amide-I spectra via excitonic spectral calculations. At low and physiological αS concentrations, we derive flat-lying helical structures as previously reported. However, at elevated and potentially disease-related concentrations, a transition to interface-protruding αS structures occurs. Such an upright conformation promotes lateral interactions between αS monomers and may explain how lipid membranes catalyze the formation of αS amyloids at elevated protein concentrations.

Impact of corrosion inhibitors on antibiotic resistance, metal resistance, and microbial communities in drinking water.

Corrosion inhibitors, including zinc orthophosphate, sodium orthophosphate, and sodium silicate, are commonly used to prevent the corrosion of drinking water infrastructure. Metals such as zinc are known stressors for antibiotic resistance selection, and phosphates can increase microbial growth in drinking water distribution systems (DWDS). Yet, the influence of corrosion inhibitor type on antimicrobial resistance in DWDS is unknown. Here, we show that sodium silicates can decrease antibiotic resistant bacteria (ARB) and antibiotic-resistance genes (ARGs), while zinc orthophosphate increases ARB and ARGs in source water microbial communities. Based on controlled bench-scale studies, zinc orthophosphate addition significantly increased the abundance of ARB resistant to ciprofloxacin, sulfonamides, trimethoprim, and vancomycin, as well as the genes sul1, qacEΔ1, an indication of resistance to quaternary ammonium compounds, and the integron-integrase gene intI1. In contrast, sodium silicate dosage at 10 mg/L resulted in decreased bacterial growth and antibiotic resistance selection compared to the other corrosion inhibitor additions. Source water collected from the drinking water treatment plant intake pipe resulted in less significant changes in ARB and ARG abundance due to corrosion inhibitor addition compared to source water collected from the pier at the recreational beach. In tandem with the antibiotic resistance shifts, significant microbial community composition changes also occurred. Overall, the corrosion inhibitor sodium silicate resulted in the least selection for antibiotic resistance, which suggests it is the preferred corrosion inhibitor option for minimizing antibiotic resistance proliferation in DWDS. However, the selection of an appropriate corrosion inhibitor must also be appropriate for the water chemistry of the system (e.g., pH, alkalinity) to minimize metal leaching first and foremost and to adhere to the lead and copper rule. IMPORTANCE Antibiotic resistance is a growing public health concern across the globe and was recently labeled the silent pandemic. Scientists aim to identify the source of antibiotic resistance and control points to mitigate the spread of antibiotic resistance. Drinking water is a direct exposure route to humans and contains antibiotic-resistant bacteria and associated resistance genes. Corrosion inhibitors are added to prevent metallic pipes in distribution systems from corroding, and the type of corrosion inhibitor selected could also have implications on antibiotic resistance. Indeed, we found that sodium silicate can minimize selection of antibiotic resistance while phosphate-based corrosion inhibitors can promote antibiotic resistance. These findings indicate that sodium silicate is a preferred corrosion inhibitor choice for mitigation of antibiotic resistance.

Astragalus Polysaccharide Protects Experimental Colitis Through An AhR-Dependent Autophagy Mechanism.

BACKGROUND AND PURPOSE: Disruption of intestinal barriers plays a vital role in the pathogenesis of colitis. The aryl hydrocarbon receptor (AhR) is a recognition sensor that mediates intestinal immune homeostasis and minimizes intestinal inflammation. Autophagy depends on AhR activation and might constitute a therapeutic target for colitis. Astragalus polysaccharide (APS) exerts pharmacological action in colitis; however, the mechanism has not been elucidated. We aimed to determine whether APS protects colitis through AhR-dependent autophagy. EXPERIMENTAL APPROACH: The symptoms of DSS-induced colitis mice involving intestinal barrier function and inflammatory injury were evaluated after APS administration. Intestinal-specific Becn1 conditional knockout mice (Becn1 cKO) were constructed and compared to WT mice. Autophagy and the therapeutic function of APS were investigated after the deactivation of AhR. The relationship between APS-induced AhR and autophagic Becn1 was investigated using a dual luciferase reporter system and ChIP-qPCR assay. Caco-2 cells investigated inflammatory response and AhR-dependent autophagy. KEY RESULTS: APS improved intestinal barrier function in the context of inflammatory injury in the colitis mice. APS triggered autophagic flow, however, knockout of the Becn1 in the gut increased susceptibility to colitis, leading to diminished epithelial barrier function and severe intestinal inflammation, furthermore impairing the protective effects of APS. Mechanistically, APS-triggered autophagy depends on AhR expression. Activated AhR bound to the promoter Becn1 to operate transcription of genes involved in anti-inflammation and intestinal barrier repair, while deactivation of AhR correlated with intestinal inflammation and the therapeutic function of APS. CONCLUSION AND IMPLICATIONS: APS protects colitis mice by targeting autophagy, especially that AhR stimulate the repair of damaged intestinal barrier functions.

OEEF-Driven Intramolecular Self-Redox of Superalkali Rb3BeB6Be'Rb'3: A High-Performance Candidate for NLO Molecular Switch.

To provide a novel intramolecular self-redox switch, a boron-based sandwich-like complex Rb3BeB6Be'Rb'3 is achieved by using theoretical computations. An applicable oriented external electric field (OEEF) can result in the occurrence of intramolecular self-redox (IMSR) with a long-range electron transfer from tetrahedral Be'Rb'3 to Rb3Be and subsequently [Rb3Be]3+[B6]6-[Be'Rb'3]3+ (D3d) changes to [Rb3Be]2+[B6]6-[Be'Rb'3]4+ (C3v), accompanying high-performance NLO switchable effect for both static and dynamic first hyperpolarizability (ß0). [Rb3Be]3+[B6]6-[Be'Rb'3]3+ (off-form) owns zero of dipole moment (µ0) and ß0, while [Rb3Be]2+[B6]6-[Be'Rb'3]4+ (on-form) exhibits a µ0 of 3.36 D and a ß0e of 2.18 × 105 au. The different dynamic first hyperpolarizabilities between [Rb3Be]3+[B6]6-[Be'Rb'3]3+ and [Rb3Be]2+[B6]6-[Be'Rb'3]4+ are also significant. This indicates that Rb3BeB6Be'Rb'3 is a potential candidate for an IMSR NLO switch.

The Intention of Inhaled Medication Adherence Scale (IMAS): The Development of a New Instrument for Assessing Inhaled Medication Adherence Among Patients with Chronic Obstructive Pulmonary Disease (COPD) Using Theory of Planned Behavior.

Purpose: Inhaled medication adherence is an important issue for patients with chronic obstructive pulmonary disease (COPD) because adhering to inhaled medications could substantially improve their health. However, patients with COPD may not be always adhere to the prescribed inhaled medications. Therefore, understanding the underlying reasons for patients with COPD adhering to inhaled medications is important. The present study used Theory of Planned Behavior (TPB) as a theoretical framework to develop the Intention of Inhaled Medication Adherence Scale (IMAS) and assess its psychometric properties. Patients and Methods: After reviewing papers using the TPB to design psychometric scales and the TPB scale development guidelines, 28 items were generated for expert evaluation. Eight experts reported that the 28 items all had good content validity (content validity index ranged from 0.88 to 1.00 at item-level; and from 0.981 to 0.987 at scale-level) comprising four factors. Following initial development, 235 patients with COPD (mean age 73.12 years; 93.6% males) completed the IMAS via interview with a respiratory therapist and a research assistant. The four-factor structure of the IMAS was evaluated using confirmatory factor analysis (CFA). Results: Nine IMAS items were removed because of low factor loadings or offending estimates. The 19-item IMAS was confirmed as having a four-factor structure supported by the CFA results (comparative fit index=1.00; Tucker-Lewis index=1.00; root mean square error of approximation=0.00; standardized root mean square residual=0.06). Conclusion: The 19-item IMAS had satisfactory psychometric properties in construct validity. The 19-item IMAS is an instrument that could help healthcare providers understand potential factors associated with adherence to inhaled medications among people with COPD.

A longitudinal resource for population neuroscience of school-age children and adolescents in China.

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank.

Necrostatin-1s Suppresses RIPK1-driven Necroptosis and Inflammation in Periventricular Leukomalacia Neonatal Mice.

Periventricular leukomalacia (PVL), a predominant form of brain injury in preterm survivors, is characterized by hypomyelination and microgliosis and is also the major cause of long-term neurobehavioral abnormalities in premature infants. Receptor-interacting protein kinase 1 (RIPK1) plays a pivotal role in mediating cell death and inflammatory signaling cascade. However, very little is known about the potential effect of RIPK1 in PVL and the underlying mechanism. Herein, we found that the expression level of RIPK1 was drastically increased in the brain of PVL neonatal mice models, and treatment of PVL neonatal mice with Necrostatin-1s (Nec-1s), an inhibitor of RIPK1, greatly ameliorated cerebral ischemic injury, exhibiting an increase of body weights, reduction of cerebral infarct size, neuronal loss, and occurrence of necrosis-like cells, and significantly improved the long-term abnormal neurobehaviors of PVL. In addition, Nec-1s significantly suppressed hypomyelination and promoted the differentiation of oligodendrocyte precursor cells (OPCs), as demonstrated by the increased expression levels of MBP and Olig2, the decreased expression level of GPR17, a significant increase in the number of CC-1-positive cells, and suppression of myelin ultrastructure impairment. Moreover, the mechanism of neuroprotective effects of Nec-1s against PVL is closely associated with its suppression of the RIPK1-mediated necrosis signaling molecules, RIPK1, PIPK3, and MLKL. More importantly, inhibition of RIPK1 could reduce microglial inflammatory injury by triggering the M1 to M2 microglial phenotype, appreciably decreasing the levels of M1 marker CD86 and increasing the levels of M2 markers Arg1 or CD206 in PVL mice. Taken together, inhibition of RIPK1 markedly ameliorates the brain injury and long-term neurobehavioral abnormalities of PVL mice through the reduction of neural cell necroptosis and reversing neuroinflammation.

A new type of cell related to organ movement for selfing in plants.

Many plants employ osmotic and hydrostatic pressure to generate movement for survival, but little is known about the cellular mechanisms involved. Here, we report a new cell type in angiosperms termed 'contractile cells' in the stigmas of the flowering plant Chirita pumila with a much-expanded rough endoplasmic reticulum (RER). Cryo-scanning electron microscopy and transmission electron microscopy analyses revealed that the RER is continuously distributed throughout the entirety of cells, confirmed by endoplasmic reticulum (ER)-specific fluorescent labeling, and is distinct from the common feature of plant ER. The RER is water-sensitive and extremely elongated with water absorption. We show that the contractile cells drive circadian stigma closing-bending movements in response to day-to-night moisture changes. RNA-seq analyses demonstrated that contractile cells have distinct molecular components. Furthermore, multiple microstructural changes in stigma movements convert an anti-selfing structure into a device promoting selfing-a unique cellular mechanism of reproductive adaptation for uncertain pollination environments.

Intermittent dietary carbohydrate restriction versus calorie restriction and cardiometabolic profiles: A randomized trial.

OBJECTIVE: The aim of this study was to investigate the effectiveness of an intermittent low-carbohydrate diet (ILCD) versus calorie restriction (ICR) in young populations and potential mechanisms. METHODS: Thirty-four participants aged 9 to 30 years with cardiometabolic risk were randomized to receive a self-administered 2-week ILCD (carbohydrate intake ≤ 50 g/d on seven nonconsecutive days) or ICR (500-600 kcal/d for two consecutive days per week). Differences in changes in obesity measures, glycemic and lipid profiles, gut microbiota composition, and three serum biomarkers were compared. RESULTS: The ILCD and ICR similarly reduced body weight, waist circumference, fasting glucose, insulin, postprandial glucose variation, monocyte chemoattractant protein-1, free fatty acid, and fibroblast growth factor 21, whereas ILCD produced significantly different alterations in the following outcomes compared with ICR: greater increases in low-density lipoprotein cholesterol and total cholesterol (-0.36 mmol/L, 95% CI: -0.68 to -0.04; -0.40 mmol/L, 95% CI: -0.73 to -0.06) and greater decrease in triglyceride (0.20 mmol/L, 95% CI: 0.04 to 0.37). Actinobacteria and Bifidobacterium reduced after ILCD but not ICR; and the reductions strongly correlated with changes in fasting glucose (both r = 0.84) and low-density lipoprotein cholesterol (r = -0.81 and -0.72). CONCLUSIONS: This study found no evidence of differences in changes from baseline in obesity measures, glucose regulation, and inflammation between ILCD and ICR, despite trends in reduction in those parameters. However, there seemed to be some differences in responses in lipids and gut microbiota.

A one-pot synthesis of 2,3-disubstituted-4(3H)-quinazolinone from o-aminobenzoic acid and DMF derivatives using imidazole hydrochloride as a promoter.

As a novel and environmentally friendly Brönsted acid, imidazole hydrochloride was used to promote the synthesis of 2,3-disubstituted-4(3H)-quinazolinone from o-aminobenzoic acid and DMF derivatives. The essence of this reaction is a multicomponent reaction, which constructs multiple chemical bonds between different components through the transamidation of imidazole hydrochloride. This protocol showed a wide range of functional group tolerance, and a series of quinazolinones were synthesized in low to moderate yields without metal catalysts, oxidants or other additives.