Genome-Wide Analysis of MYB Gene Family in Chrysanthemum ×morifolium Provides Insights into Flower Color Regulation.

MYBs constitute the second largest transcription factor (TF) superfamily in flowering plants with substantial structural and functional diversity, which have been brought into focus because they affect flower colors by regulating anthocyanin biosynthesis. Up to now, the genomic data of several Chrysanthemum species have been released, which provides us with abundant genomic resources for revealing the evolution of the MYB gene family in Chrysanthemum species. In the present study, comparative analyses of the MYB gene family in six representative species, including C. lavandulifolium, C. seticuspe, C. ×morifolium, Helianthus annuus, Lactuca sativa, and Arabidopsis thaliana, were performed. A total of 1104 MYBs, which were classified into four subfamilies and 35 lineages, were identified in the three Chrysanthemum species (C. lavandulifolium, C. seticuspe, and C. ×morifolium). We found that whole-genome duplication and tandem duplication are the main duplication mechanisms that drove the occurrence of duplicates in CmMYBs (particularly in the R2R3-MYB subfamily) during the evolution of the cultivated chrysanthemums. Sequence structure and selective pressure analyses of the MYB gene family revealed that some of R2R3-MYBs were subjected to positive selection, which are mostly located on the distal telomere segments of the chromosomes and contain motifs 7 and 8. In addition, the gene expression analysis of CmMYBs in different organs and at various capitulum developmental stages of C. ×morifolium indicated that CmMYBS2, CmMYB96, and CmMYB109 might be the negative regulators for anthocyanin biosynthesis. Our results provide the phylogenetic context for research on the genetic and functional evolution of the MYB gene family in Chrysanthemum species and deepen our understanding of the regulatory mechanism of MYB TFs on the flower color of C. ×morifolium.

The Regulatory Mechanism of Smilax China L. Saponins against Nonalcoholic Fatty Liver Is Revealed by Metabolomics and Transcriptomics.

This study was to investigate the effects of Smilax China L. saponins (SCS) on non-alcoholic fatty liver disease (NAFLD). Rats were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD, followed by SCS treatment for 8 weeks. The effect of SCS on liver injury was observed by H&E staining and the regulative mechanism of SCS on lipid formation was exposed by detecting Oil red O, insulin resistance (IR), and fatty acids synthesis (FAS). Furthermore, transcriptomics and metabolomics were performed to analyze the potential targets. The experimental results indicated that SCS exerted a positive curative effect in alleviating HFD-induced overweight, hepatic injury, steatosis, and lipid formation and accumulation in rats, and the preliminary mechanism studies showed that SCS could alleviate IR, inhibit FAS expression, and reduce Acetyl-CoA levels. Besides, the integrative analysis of transcriptomics and metabolomics exposed the targets of SCS to regulate lipid production likely being the sphingolipid metabolism and glycerophospholipid metabolism pathways. This study demonstrates that SCS significantly ameliorates lipid metabolic disturbance in rats with NAFLD by relieving insulin resistance, inhibiting the FAS enzymes, and regulating the sphingolipid and glycerophospholipid metabolism pathways.

Depression in Polycystic Ovary Syndrome: Focusing on Pathogenesis and Treatment.

Polycystic ovary syndrome (PCOS) is one of the most prevalent gynecological endocrine conditions affecting reproductive women. It can feature a variety of symptoms, such as obesity, insulin resistance, skin conditions, and infertility. Women with PCOS are susceptible to illnesses including mood disorders, diabetes, hypertension, and dyslipidemia. Among them, depression is the most common in PCOS and has a detrimental effect on quality of life. Depression may occasionally develop due to the pathological traits of PCOS, but its exact pathogenesis in PCOS have eluded researchers to date. Therefore, there is an urgent need to explore the pathogenesis and treatments of depression in PCOS. The present review discusses the epidemiology of depression in PCOS, potential pathogenic mechanisms underlying PCOS and depression, as well as some potential factors causing depression in PCOS, including obesity, insulin resistance, hyperandrogenism, inflammation, and infertility. Meanwhile, some common treatment strategies for depression in PCOS, such as lifestyle intervention, acupuncture, oral contraceptive pills, psychological intervention, and insulin-sensitizer, are also reviewed. To fully understand the pathogenesis and treatment of depression in PCOS, a need remains for future large-scale multi-center randomized controlled trials and in-depth mechanism studies. Appeared originally in Front Psychiatry 2022; 13:1001484.

Pathogenesis of gout: Exploring more therapeutic target.

Gout is a chronic metabolic and immune disease, and its specific pathogenesis is still unclear. When the serum uric acid exceeds its saturation in the blood or tissue fluid, it is converted to monosodium urate crystals, which lead to acute arthritis of varying degrees, urinary stones, or irreversible peripheral joint damage, and in severe cases, impairment of vital organ function. Gout flare is a clinically significant state of acute inflammation in gout. The current treatment is mostly anti-inflammatory analgesics, which have numerous side effects with limited treatment methods. Gout pathogenesis involves many aspects. Therefore, exploring gout pathogenesis from multiple perspectives is conducive to identifying more therapeutic targets and providing safer and more effective alternative treatment options for patients with gout flare. Thus, this article is of great significance for further exploring the pathogenesis of gout. The author summarizes the pathogenesis of gout from four aspects: signaling pathways, inflammatory factors, intestinal flora, and programmed cell death, focusing on exploring more new therapeutic targets.

Detonation Performance of Insensitive Nitrogen-Rich Nitroenamine Energetic Materials Predicted from First-Principles Reactive Molecular Dynamics Simulations.

Because of the excellent combination of high detonation and low sensitivity properties of the 1,1-diamino-2,2-dinitroethylene (FOX-7) energetic material (EM), it is useful to explore new energetic derivatives that start with the FOX-7 structure. However, most such derivatives are highly sensitive, making them unsuitable for EM applications. An exception is the new nitroenamine EM, 1,1-diamino-2-tetrazole-2-nitroethene (FOX-7-T) (synthesized by replacing a nitro group with a tetrazole ring), which exhibits good stability. Unfortunately, FOX-7-T shows an unexpected much lower detonation performance than FOX-7, despite its higher nitrogen content. To achieve an atomistic understanding of the insensitivity and detonation performance of FOX-7 and FOX-7-T, we carried out reactive molecular dynamics (RxMD) using the ReaxFF reactive force field and combined quantum mechanics MD (QM-MD). We found that the functional group plays a significant role in the initial decomposition reaction. For FOX-7, the initial decomposition involves only simple hydrogen transfer reactions at high temperature, whereas for FOX-7-T, the initial reaction begins at much lower temperature with a tetrazole ring breaking to form N2, followed by many subsequent reactions. Our first-principles-based simulations predicted that FOX-7-T has 34% lower CJ pressure, 15% lower detonation velocity, and 45% lower CJ temperature than FOX-7. This is partly because a larger portion of the FOX-7-T mass gets trapped into condensed phase carbon clusters at the CJ point, suppressing generation of gaseous CO2 and N2 final products, leading to reduced energy delivery. Our findings suggest that the oxygen balance is an important factor to be considered in the design of the next generation of high-nitrogen-containing EMs.

Melatonin improves influenza virus infection-induced acute exacerbation of COPD by suppressing macrophage M1 polarization and apoptosis.

BACKGROUND: Influenza A viruses (IAV) are extremely common respiratory viruses for the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), in which IAV infection may further evoke abnormal macrophage polarization, amplify cytokine storms. Melatonin exerts potential effects of anti-inflammation and anti-IAV infection, while its effects on IAV infection-induced AECOPD are poorly understood. METHODS: COPD mice models were established through cigarette smoke exposure for consecutive 24 weeks, evaluated by the detection of lung function. AECOPD mice models were established through the intratracheal atomization of influenza A/H3N2 stocks in COPD mice, and were injected intraperitoneally with melatonin (Mel). Then, The polarization of alveolar macrophages (AMs) was assayed by flow cytometry of bronchoalveolar lavage (BAL) cells. In vitro, the effects of melatonin on macrophage polarization were analyzed in IAV-infected Cigarette smoking extract (CSE)-stimulated Raw264.7 macrophages. Moreover, the roles of the melatonin receptors (MTs) in regulating macrophage polarization and apoptosis were determined using MTs antagonist luzindole. RESULTS: The present results demonstrated that IAV/H3N2 infection deteriorated lung function (reduced FEV20,50/FVC), exacerbated lung damages in COPD mice with higher dual polarization of AMs. Melatonin therapy improved airflow limitation and lung damages of AECOPD mice by decreasing IAV nucleoprotein (IAV-NP) protein levels and the M1 polarization of pulmonary macrophages. Furthermore, in CSE-stimulated Raw264.7 cells, IAV infection further promoted the dual polarization of macrophages accompanied with decreased MT1 expression. Melatonin decreased STAT1 phosphorylation, the levels of M1 markers and IAV-NP via MTs reflected by the addition of luzindole. Recombinant IL-1ß attenuated the inhibitory effects of melatonin on IAV infection and STAT1-driven M1 polarization, while its converting enzyme inhibitor VX765 potentiated the inhibitory effects of melatonin on them. Moreover, melatonin inhibited IAV infection-induced apoptosis by suppressing IL-1ß/STAT1 signaling via MTs. CONCLUSIONS: These findings suggested that melatonin inhibited IAV infection, improved lung function and lung damages of AECOPD via suppressing IL-1ß/STAT1-driven macrophage M1 polarization and apoptosis in a MTs-dependent manner. Melatonin may be considered as a potential therapeutic agent for influenza virus infection-induced AECOPD.

Adaptive Synaptic Scaling in Spiking Networks for Continual Learning and Enhanced Robustness.

Synaptic plasticity plays a critical role in the expression power of brain neural networks. Among diverse plasticity rules, synaptic scaling presents indispensable effects on homeostasis maintenance and synaptic strength regulation. In the current modeling of brain-inspired spiking neural networks (SNN), backpropagation through time is widely adopted because it can achieve high performance using a small number of time steps. Nevertheless, the synaptic scaling mechanism has not yet been well touched. In this work, we propose an experience-dependent adaptive synaptic scaling mechanism (AS-SNN) for spiking neural networks. The learning process has two stages: First, in the forward path, adaptive short-term potentiation or depression is triggered for each synapse according to afferent stimuli intensity accumulated by presynaptic historical neural activities. Second, in the backward path, long-term consolidation is executed through gradient signals regulated by the corresponding scaling factor. This mechanism shapes the pattern selectivity of synapses and the information transfer they mediate. We theoretically prove that the proposed adaptive synaptic scaling function follows a contraction map and finally converges to an expected fixed point, in accordance with state-of-the-art results in three tasks on perturbation resistance, continual learning, and graph learning. Specifically, for the perturbation resistance and continual learning tasks, our approach improves the accuracy on the N-MNIST benchmark over the baseline by 44% and 25%, respectively. An expected firing rate callback and sparse coding can be observed in graph learning. Extensive experiments on ablation study and cost evaluation evidence the effectiveness and efficiency of our nonparametric adaptive scaling method, which demonstrates the great potential of SNN in continual learning and robust learning.

Rheology and gelation of aqueous carboxymethylated curdlan solution: Impact of the degree of substitution.

Curdlan is a unique (1,3)-ß-D-glucan with bioactivity and exceptional gelling properties. By chemical functionalization such as carboxymethylation, the physicochemical properties of curdlan can be significantly tailored. However, how the carboxymethylation extent of curdlan affects its rheology and gelation characteristics has yet to be fully understood. Herein, we investigated the impact of the degree of substitution (DS, ranging from 0.04 to 0.97) on the rheological and gelation behavior of carboxymethylated curdlan (CMCD). It was found that CMCD with DS below 0.20, resembling native curdlan, still retained its gelling capability. As the DS increased beyond 0.36, there was a significant increase in its water solubility instead of gelation, resulting in transparent solutions with steady/complex viscosities adhering to the Cox-Merz rule. Moreover, CMCD with high DS demonstrated the ability to undergo in-situ gelation in the presence of metal ions, attributed to the nonspecific electrostatic binding. Additionally, in vitro cytocompatibility testing showed positive compatibility across varying DS in CMCD. This research offers a holistic understanding of the viscosifying and gelling behaviors of CMCD with varying DS, thereby fostering their practical application as thickeners and gelling agents in fields ranging from food and biomedicine to cosmetics and beyond.

Models of gouty nephropathy: exploring disease mechanisms and identifying potential therapeutic targets.

Gouty nephropathy (GN) is a metabolic disease with persistently elevated blood uric acid levels. The main manifestations of GN are crystalline kidney stones, chronic interstitial nephritis, and renal fibrosis. Understanding the mechanism of the occurrence and development of GN is crucial to the development of new drugs for prevention and treatment of GN. Currently, most studies exploring the pathogenesis of GN are primarily based on animal and cell models. Numerous studies have shown that inflammation, oxidative stress, and programmed cell death mediated by uric acid and sodium urate are involved in the pathogenesis of GN. In this article, we first review the mechanisms underlying the abnormal intrinsic immune activation and programmed cell death in GN and then describe the characteristics and methods used to develop animal and cell models of GN caused by elevated uric acid and deposited sodium urate crystals. Finally, we propose potential animal models for GN caused by abnormally high uric acid levels, thereby provide a reference for further investigating the methods and mechanisms of GN and developing better prevention and treatment strategies.

A new modular framework for high-level application development at HEPS.

As a representative of the fourth-generation light sources, the High Energy Photon Source (HEPS) in Beijing, China, utilizes a multi-bend achromat lattice to obtain an approximately 100 times emittance reduction compared with third-generation light sources. New technologies bring new challenges to operate the storage ring. In order to meet the beam commissioning requirements of HEPS, a new framework for the development of high-level applications (HLAs) has been created. The key part of the new framework is a dual-layer physical module to facilitate the seamless fusion of physical simulation models with the real machine, allowing for fast switching between different simulation models to accommodate the various simulation scenarios. As a framework designed for development of physical applications, all variables are based on physical quantities. This allows physicists to analytically assess measurement parameters and optimize machine parameters in a more intuitive manner. To enhance both extensibility and adaptability, a modular design strategy is utilized, partitioning the entire framework into discrete modules in alignment with the requirements of HLA development. This strategy not only facilitates the independent development of each module but also minimizes inter-module coupling, thereby simplifying the maintenance and expansion of the entire framework. To simplify the development complexity, the design of the new framework is implemented using Python and is called Python-based Accelerator Physics Application Set (Pyapas). Taking advantage of Python's flexibility and robust library support, we are able to develop and iterate quickly, while also allowing for seamless integration with other scientific computing applications. HLAs for both the HEPS linac and booster have been successfully developed. During the beam commissioning process at the linac, Pyapas's ease of use and reliability have significantly reduced the time required for the beam commissioning operators. As a development framework for HLA designed for the new-generation light sources, Pyapas has the versatility to be employed with HEPS, as well as with other comparable light sources, due to its adaptability.

The effects of exercise on insomnia disorders: An umbrella review and network meta-analysis.

OBJECTIVE: To summarize the evidence of various exercise modalities on population with insomnia disorders. METHOD: PubMed, Embase, Cochrane Library, and Web of Science were searched for eligible studies published from inception to October 2022 and updated on September 2023. Systematic reviews with meta-analyses and randomized controlled trials designed to investigate the effect of various exercise modalities on population with insomnia were eligible. RESULTS: A total of 4 SRs with (very) low methodological quality and 1034 participants in 10 network meta-analyses explored the association between different types and intensity exercise modalities with insomnia disorders. Various exercise modalities could significantly improve total sleep time and sleep quality and alleviate insomnia severity. Compared to passive control, moderate aerobic exercise, moderate aerobic exercise combined with light intensity strength and mind-body exercise can improve sleep efficiency and reduce wake after sleep onset by objectively measured. Moderate intensity strength, light intensity strength and mind-body exercise can improve sleep efficiency subjectively measured; mind-body exercise can reduce sleep onset latency and wake time after sleep onset, and increase total sleep time; moderate aerobic exercise can reduce sleep onset latency. Moderate intensity strength, light intensity strength, mind body exercise and moderate aerobic exercise combined with light intensity strength can the severity of insomnia and improv sleep quality. CONCLUSION: Exercise had a positive effect on relief insomnia and improve sleep quality. Moderate aerobic exercise, mind-body exercise and moderate aerobic exercise combined with light intensity strength play an important role in improving the sleep quality in people with insomnia disorders.

Deep-qGFP: A Generalist Deep Learning Assisted Pipeline for Accurate Quantification of Green Fluorescent Protein Labeled Biological Samples in Microreactors.

Absolute quantification of biological samples provides precise numerical expression levels, enhancing accuracy, and performance for rare templates. Current methodologies, however, face challenges-flow cytometers are costly and complex, whereas fluorescence imaging, relying on software or manual counting, is time-consuming and error-prone. It is presented that Deep-qGFP, a deep learning-aided pipeline for the automated detection and classification of green fluorescent protein (GFP) labeled microreactors, enables real-time absolute quantification. This approach achieves an accuracy of 96.23% and accurately measures the sizes and occupancy status of microreactors using standard laboratory fluorescence microscopes, providing precise template concentrations. Deep-qGFP demonstrates remarkable speed, quantifying over 2000 microreactors across ten images in just 2.5 seconds, with a dynamic range of 56.52-1569.43 copies µL-1 . The method demonstrates impressive generalization capabilities, successfully applied to various GFP-labeling scenarios, including droplet-based, microwell-based, and agarose-based applications. Notably, Deep-qGFP is the first all-in-one image analysis algorithm successfully implemented in droplet digital polymerase chain reaction (PCR), microwell digital PCR, droplet single-cell sequencing, agarose digital PCR, and bacterial quantification, without requiring transfer learning, modifications, or retraining. This makes Deep-qGFP readily applicable in biomedical laboratories and holds potential for broader clinical applications.

miR-223-3p Prevents Necroptotic Macrophage Death by Targeting Ripk3 in a Negative Feedback Loop and Consequently Ameliorates Advanced Atherosclerosis.

BACKGROUND: The formation of large necrotic cores results in vulnerable atherosclerotic plaques, which can lead to severe cardiovascular diseases. However, the specific regulatory mechanisms underlying the development of necrotic cores remain unclear. METHODS: To evaluate how the modes of lesional cell death are reprogrammed during the development of atherosclerosis, the expression levels of key proteins that are involved in the necroptotic, apoptotic, and pyroptotic pathways were compared between different stages of plaques in humans and mice. Luciferase assays and loss-of-function studies were performed to identify the microRNA-mediated regulatory mechanism that protects foamy macrophages from necroptotic cell death. The role of this mechanism in atherosclerosis was determined by using a knockout mouse model with perivascular drug administration and tail vein injection of microRNA inhibitors in Apoe-/- mice. RESULTS: Here, we demonstrate that the necroptotic, rather than the apoptotic or pyroptotic, pathway is more activated in advanced unstable plaques compared with stable plaques in both humans and mice, which closely correlates with necrotic core formation. The upregulated expression of Ripk3 (receptor-interacting protein kinase 3) promotes the C/EBPß (CCAAT/enhancer binding protein beta)-dependent transcription of the microRNA miR-223-3p, which conversely inhibits Ripk3 expression and forms a negative feedback loop to regulate the necroptosis of foamy macrophages. The knockout of the Mir223 gene in bone marrow cells accelerates atherosclerosis in Apoe-/- mice, but this effect can be rescued by Ripk3 deficiency or treatment with the necroptosis inhibitors necrostatin-1 and GSK-872. Like the Mir223 knockout, treating Apoe-/- mice with miR-223-3p inhibitors increases atherosclerosis. CONCLUSIONS: Our study suggests that miR-223-3p expression in macrophages protects against atherosclerotic plaque rupture by limiting the formation of necrotic cores, thus providing a potential microRNA therapeutic candidate for atherosclerosis.

Qingjie decoction attenuated E.coli-induced diarrhea by regulating energy metabolism and alleviating inflammation based on network analysis and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Diarrhea is a frequently encountered gastrointestinal complication in clinical practice, and E. coli is one of the main causative agents. Although Qingjie decoction (QJD) has been shown to be highly effective in treating diarrhea by eliminating heat-toxin, the underlying molecular mechanisms and pathways of QJD remain unclear. AIM OF REVIEW: The aim of this research was to explore the effects and fundamental mechanism of QJD on diarrhea induced by E.coli in rats. MATERIALS AND METHODS: Initially, we used UHPLC-MS/MS analysis to identify the chemical composition of QJD. Then, we constructed a visualization network using network pharmacology. Next, we utilized metabolomics to identify differentially expressed metabolites of QJD that are effective in treating diarrhea. RESULTS: The chemical composition of QJD was analyzed using UHPLC-MS/MS, which identified a total of 292 components. Using a network pharmacology approach, 127 bioactive compounds of QJD were screened, targeting 171 potential diarrhea treatment targets. TNF-α, IL-6, IL-1ß, and CAT were identified as important targets through visualizing the PPI network. Enrichment analysis demonstrated significant enrichment in the TNF signaling pathway, IL-17 signaling pathway, and PI3K-Akt signaling pathway. QJD showed beneficial effects, such as increased body weight, decreased fecal water content, and reduced inflammatory cell infiltration in the duodenum and colon, as well as maintaining the structure of the duodenum and colon. Metabolomic analysis revealed 32 differentially expressed metabolites in the control, model and QJD-H groups, including glucose, valine, and cysteine. Functional analysis indicated that differential metabolites were related to energy metabolism, including glucose metabolism, TCA cycle, and amino acid metabolism. CONCLUSION: QJD significantly increased body weight, decreased water content in feces, relieved inflammatory cell infiltration, maintained the structure of duodenum and colon. Combining network analysis and metabolomics, QJD exerted therapeutic effects by inhibiting inflammation and oxidative stress, regulating glucose metabolism, tricarboxylic acid metabolism, and amino acid metabolism.

A microRNA sponge, LINC02193, promotes neutrophil activation by upregulating ICAM1 and is correlated with ANCA-associated vasculitis.

OBJECTIVE: To investigate the pathogenic role and underlying mechanisms of lncRNAs in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). METHODS：: RNA-sequencing (RNA-seq) was applied to screen the expression profile of lncRNAs in peripheral leukocytes from 5 AAV patients and 5 healthy controls (HC). Candidate lncRNAs were preliminarily verified in peripheral leukocytes from 46 AAV patients and 35 HC by qRT-PCR. Then, the identified LINC02193 was further validated in peripheral neutrophils from 67 AAV patients, 45 HC and 64 disease controls. Correlation between LINC02193 levels and disease activity was analyzed. Then, a loss-of-function study was conducted to investigate the role of LINC02193 in neutrophils activation. Furthermore, bioinformatics analysis, dual luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to explore the mechanism of LINC02193 regulating neutrophils activation. RESULTS: A total of 467 upregulated and 412 downregulated lncRNAs were identified in AAV patients. From top 5 upregulated lncRNAs, an elevation of LINC02193 was validated in a larger sample of AAV patients, and positively correlated with disease activity. Knockdown of LINC02193 inhibited ROS and NO production, NETs release and adhesion to endothelial cells of differentiated human promyelocytic leukaemia HL­60 cells (dHL-60), whereas overexpression of ICAM1 counteracted these effects. Mechanistic analysis demonstrated that LINC02193 acted as a miR-485-5p sponge to relieve the repressive effect of miR-485-5p on ICAM1, thus promoting ICAM1 expression. CONCLUSION: LINC02193, a novel lncRNA identified in AAV could function as competing endogenous RNAs (ceRNA) for miR-485-5p to promote ICAM1 expression and neutrophils activation, suggesting its potential as a therapeutic target of AAV.

Insights into the structure of the pelagic microbial food web in the oligotrophic tropical Western Pacific: Examining trophic interactions and relationship with abiotic variables.

Microbial food webs (MFW) play an indispensable role in marine pelagic ecosystem, yet their composition and response to abiotic variables were poorly documented in the oligotrophic tropical Western Pacific. During winter of 2015, we conducted a survey to examine key components of MFW, including Synechococcus, Prochlorococcus, picoeukaryotes, heterotrophic prokaryotes (HP), heterotrophic/pigmented nanoflagellates and ciliates, across water column from surface to 2000 m. Each MFW component exhibited unique vertical distribution pattern, with abundance ratio varying over six and three orders of magnitude across Pico/Microplankton (1.6 ± 1.0 × 106) and Nano/Microplankton (3.2 ± 2.8 × 103), respectively. Furthermore, HP was main component for MFW in the bathypelagic (>1000 m) zone. Multivariate biota-environment analysis demonstrated that environmental variables, particularly temperature, significantly impacted MFW composition, suggesting that bottom-up control (resource availability) dominated the water column. Our study provides benchmark information for future environmental dynamics forcing on MFW in the oligotrophic tropical seas.

The onset of adenosine monophosphate-activated protein kinase activity on orthodontic tooth movement in rats with type 2 diabetes.

Adenosine monophosphate-activated protein kinase (AMPK) plays pivotal roles in metabolic diseases including type 2 diabetes. However, the specific role of AMPK for orthodontic tooth movement in type 2 diabetes is unclear. In this study, a diabetic rat model was established through dietary manipulation and streptozocin injection. Examinations were conducted to select qualified type 2 diabetic rats. Then, an orthodontic device was applied to these rats for 0, 3, 7, or 14 days. The distance of orthodontic tooth movement and parameters of alveolar bone were analyzed by micro-computed tomography. Periodontal osteoclastic activity, inflammatory status, and AMPK activity were measured via histological analyses. Next, we repeated the establishment of diabetic rats to investigate whether change of AMPK activity was associated with orthodontic tooth movement under type 2 diabetes. The results showed that diabetic rats exhibited an exacerbated alveolar bone resorption, overactive inflammation, and decreased periodontal AMPK activity during orthodontic tooth movement. Injection of the AMPK agonist alleviated type 2 diabetes-induced periodontal inflammation and alveolar bone resorption, thus normalizing distance of orthodontic tooth movement. Our study indicates that type 2 diabetes decreases periodontal AMPK activity, leading to excessive inflammation elevating osteoclast formation and alveolar bone resorption, which could be reversed by AMPK activation.

The tooth movement efficiency of different orthodontic thermoplastics for clear aligners: study protocol for a randomized controlled clinical trial.

INTRODUCTION: With regard to the esthetics and comfort of orthodontic treatment, the requirement for removable clear aligners (CAs) is increasing. Unlike conventional fixed orthodontic appliances, CAs were made of thermoplastic film by thermoforming on the personalized dental models. The construction of orthodontic thermoplastic is a critical factor for orthodontic tooth movement (OTM). Polyethylene terephthalate glycol-modified (PETG) and thermoplastic polyurethane (TPU) are the most commonly orthodontic thermoplastics; however, the evidence of the differences between different orthodontic thermoplastic are limited to vitro environment and the evidence in vivo environment is not available. Therefore, this trial aims to provide reliable evidence for orthodontists' personalized treatment plans whether the two most commonly used orthodontic thermoplastics of PETG and TPU have differences in the efficiency of OTM. METHODS AND ANALYSIS: This randomized controlled clinical study will recruit 44 orthodontic patients for orthodontic treatment. All the subjects will be randomized into two groups (PETG and TPU, n = 22 for each group). In the first stage (M0 to M1), clear aligners will be made of two orthodontic thermoplastics and move the maxillary first or second premolars 2 mm. In the second stage, patients will take the standard orthodontic treatments. The primary outcome will be the efficiency of clear aligners made of different materials on the digital models. The secondary outcome will be the efficiency of clear aligners made of different materials on the cone-beam computed tomography (CBCT). The efficiency will be calculated through the superimposition of the digital models and CBCT. DISCUSSION: The results from this trial will serve as evidence for orthodontists and manufacturers and clarify whether the difference in orthodontic thermoplastics significantly impacts the efficiency of OTM. TRIAL REGISTRATION NUMBER: ChiCTR2300070980. Registered on 27 April 2023. https://www.chictr.org.cn/showproj.html?proj=186253.

Functional evaluation of constructed pseudo-endogenous microRNA-targeted myocardial ultrasound nanobubble.

Background: Stem cell transplantation is one of the treatment methods for acute myocardial infarction (AMI). MicroRNA-1 contributes to the study of the essential mechanisms of stem cell transplantation for treating AMI by targeted regulating the myocardial microenvironment after stem cell transplantation at the post-transcriptional level. Thus, microRNA-1 participates in regulating the myocardial microenvironment after stem cell transplantation, a promising strategy for the Stem cell transplantation treatment of AMI. However, the naked microRNA-1 synthesized is extremely unstable and non-targeting, which can be rapidly degraded by circulating RNase. Herein, to safely and effectively targeted transport the naked microRNA-1 synthesized into myocardial tissue, we will construct pseudo-endogenous microRNA-targeted myocardial ultrasound nanobubble pAd-AAV-9/miRNA-1 NB and evaluate its characteristics, targeting, and function. Methods: The pAd-AAV-9/miRNA-1 gene complex was linked to nanobubble NBs by the "avidin-biotin bridging" method to prepare cardiomyocyte-targeted nanobubble pAd-AAV-9/miRNA-1 NB. The shape, particle size, dispersion, and stability of nanobubbles and the connection of pAd-AAV-9/miRNA-1 gene complex to nanobubble NB were observed. The virus loading efficiency was determined, and the myocardium-targeting imaging ability was evaluated using contrast-enhanced ultrasound imaging in vivo. The miRNA-1 expression level in myocardial tissue and other vital organs ex vivo of SD rats was considered by Q-PCR. Also, the cytotoxic effects were assessed. Results: The particle size of NBs was 504.02 ± 36.94 nm, and that of pAd-AAV-9/miRNA-1 NB was 568.00 ± 37.39 nm. The particle size and concentration of pAd-AAV-9/miRNA-1 NBs did not change significantly within 1 h at room temperature (p > 0.05). pAd-AAV-9/miRNA-1 NB had the highest viral load rate of 86.3 ± 2.2% (p < 0.05), and the optimum viral load was 5 µL (p < 0.05). pAd-AAV-9/miRNA-1 NB had good contrast-enhanced ultrasound imaging in vivo. Quantitative analysis of miRNA-1 expression levels in vital organs ex vivo of SD rats by Q-PCR showed that pAd-AAV-9/miRNA-1 NB targeted the myocardial tissue. Q-PCR indicated that the expression level of miRNA-1 in the myocardium of the pAd-AAV-9/miRNA-1 NB + UTMD group was significantly higher than that of the pAd-AAV-9/miRNA-1 NB group (p < 0.05). pAd-AAV-9/miRNA-1 NB had no cytotoxic effect on cardiomyocytes (p > 0.05). Conclusion: The pAd-AAV-9/miRNA-1 NB constructed in this study could carry naked miRNA-1 synthesized in vitro for targeted transport into myocardial tissue successfully and had sound contrast-enhanced imaging effects in vivo.

Isovitexin alleviates hepatic fibrosis by regulating miR-21-mediated PI3K/Akt signaling and glutathione metabolic pathway: based on transcriptomics and metabolomics.

BACKGROUND: Effective drugs for the treatment of hepatic fibrosis have not yet been identified. Isovitexin (IVT) is a promising hepatoprotective agent owing to its efficacy against acute liver injury. However, the role of IVT in liver fibrosis has not been reported. PURPOSE: To explore the effect of IVT on liver fibrosis both in vitro and in vivo. STUDY DESIGN AND METHODS: A mouse model of liver fibrosis induced by carbon tetrachloride (CCl4) and two types of hepatic stellate cell models induced by platelet-derived growth factor-BB (PDGF-BB) were established to evaluate the effect of IVT on hepatic fibrosis. Transcriptomics and metabolomics were used to predict the underlying targets of IVT and were validated by a combination of in vitro and in vivo experiments. Exploration of miRNA and N6-methyladenosine (m6A) modifications was also carried out to detect the key upstream targets of the above targets. RESULTS: IVT reduced collagen deposition and hepatic stellate cell activation to alleviate liver fibrosis. The transcriptomics and metabolomics analyses showed that phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling and the glutathione (GSH) metabolic pathway may be the main regulatory processes of IVT in hepatic fibrosis. Both the in vitro and in vivo experiments confirmed the inhibitory effect of IVT on the PTEN-PI3K-Akt-mTOR axis and activation of the GSH metabolic pathway. A miR-21 mimic inhibited the effects of IVT on these two pathways, suggesting that miR-21 is the hub for IVT regulation of PI3K-Akt signaling and the GSH metabolic pathway. IVT also increased pri-miR-21 level and reduced the m6A enrichment of pri-miR-21, demonstrating that IVT may regulate pri-miR-21 through m6A modification, thereby affecting the maturation of miR-21. CONCLUSION: This study is the first to propose a protective effect of IVT against liver fibrosis. The mechanism of IVT against hepatic fibrosis is based on the regulation of miR-21, targeting PTEN-Akt signaling and the GSH metabolic pathway, which is also a novel discovery.