Se-rich tea polysaccharide extracted by high hydrostatic pressure attenuated anaphylaxis by improving gut microbiota and metabolic regulation.

Selenium-rich tea polysaccharides (Se-TPS) were extracted via high hydrostatic pressure technology with a pressure of 400 MPa (200-500 MPa) for 10 min (3-20 min) at a material-to-solvent ratio of 1:40 (1:20-1:50). Subsequently, Se-TPS1-4 were isolated and purified, with Se-TPS3-4 as the main components. A spectral analysis proved that Se, which has antioxidant activity, existed. An in vitro study found that among Se-TPS, Se-TPS3-4 attenuated the release of ß-hexosaminidase, histamine, and interleukin (IL)-4. Furthermore, in vivo experiments revealed that treatment with Se-TPS downregulated IL-4 levels and upregulated TGF-ß and interferon-γ levels to improve imbalanced Th1/Th2 immunity in tropomyosin-sensitized mice. Moreover, Se-TPS promoted Lactobacillus and norank_f_Muribaculaceaek growth and upregulated metabolites such as genipin and coniferyl alcohol. Overall, these results showed the strong anti-allergy potential of Se-TPS by regulating mast cell-mediated allergic inflammatory responses and microbiota regulation, highlighting the potential of Se-TPS as a novel therapeutic agent to regulate allergy-associated metabolic disorders.

Transcriptomic analysis of epicardial adipose tissue reveals the potential crosstalk genes and immune relationship between type 2 diabetes mellitus and atrial fibrillation.

BACKGROUND: The complex relationship between atrial fibrillation (AF) and type 2 diabetes mellitus (T2DM) suggests a potential role for epicardial adipose tissue (EAT) that requires further investigation. This study employs bioinformatics and experimental approaches to clarify EAT's role in linking T2DM and AF, aiming to unravel the biological mechanisms involved. METHOD: Bioinformatics analysis initially identified common differentially expressed genes (DEGs) in EAT from T2DM and AF datasets. Pathway enrichment and network analyses were then performed to determine the biological significance and network connections of these DEGs. Hub genes were identified through six CytoHubba algorithms and subsequently validated biologically, with further in-depth analyses confirming their roles and interactions. Experimentally, db/db mice were utilized to establish a T2DM model. AF induction was executed via programmed transesophageal electrical stimulation and burst pacing, focusing on comparing the incidence and duration of AF. Frozen sections and Hematoxylin and Eosin (H&E) staining illuminated the structures of the heart and EAT. Moreover, quantitative PCR (qPCR) measured the expression of hub genes. RESULTS: The study identified 106 DEGs in EAT from T2DM and AF datasets, underscoring significant pathways in energy metabolism and immune regulation. Three hub genes, CEBPZ, PAK1IP1, and BCCIP, emerged as pivotal in this context. In db/db mice, a marked predisposition towards AF induction and extended duration was observed, with HE staining verifying the presence of EAT. Additionally, qPCR validated significant changes in hub genes expression in db/db mice EAT. In-depth analysis identified 299 miRNAs and 33 TFs as potential regulators, notably GRHL1 and MYC. GeneMANIA analysis highlighted the hub genes' critical roles in stress responses and leukocyte differentiation, while immune profile correlations highlighted their impact on mast cells and neutrophils, emphasizing the genes' significant influence on immune regulation within the context of T2DM and AF. CONCLUSION: This investigation reveals the molecular links between T2DM and AF with a focus on EAT. Targeting these pathways, especially EAT-related ones, may enable personalized treatments and improved outcomes.

Comparative genomics analysis of pheophorbide a oxygenase (PAO) genes in eight pyrus genomes and their regulatory role in multiple stress responses in Chinese pear (Pyrus bretschneideri).

Pyrus (pear) is among the most nutritious fruits and contains fibers that have great health benefits to humans. It is mostly cultivated in temperate regions globally and is highly subjected to biotic and abiotic stresses which affect its yield. Pheophorbide a oxygenase (PAO) is an essential component of the chlorophyll degradation system and contributes to the senescence of leaves. It is responsible for opening the pheophorbide a porphyrin macrocycle and forming the main fluorescent chlorophyll catabolite However, this gene family and its members have not been explored in Pyrus genomes. Here we report a pangenome-wide investigation has been conducted on eight Pyrus genomes: Cuiguan, Shanxi Duli, Zhongai 1, Nijisseiki, Yunhong No.1, d'Anjou, Bartlett v2.0, and Dangshansuli v.1.1. The phylogenetic history, their gene structure, conservation patterns of motifs, their distribution on chromosomes, and gene duplication are studied in detail which shows the intraspecific structural conservation as well as evolutionary patterns of Pyrus PAOs. Cis-elements, protein-protein interactions (PPI), and the Gene Ontology (GO) enrichment analyses show their potential biological functions. Furthermore, their expression in various tissues, fruit hardening conditions, and drought stress conditions is also studied. Based on phylogenetics, the identified PAOs were divided into four groups. The expansion of this gene family in Pyrus is caused by both tandem and segmental duplication. Moreover, positive and negative selection pressure equally directed the gene's duplication process. The Pyrus PAO genes were enriched in hormones-related, light, development, and stress-related elements. RNA-seq data analysis showed that PAOs have varied levels of expression under diseased and abiotic stress conditions. The 3D structures of PAOs are also predicted to get more insights into functional conservation. Our research can be used further to get a deeper knowledge of the PAO gene family in Pyrus and to guide future research on improving the genetic composition of Pyrus to enhance stress tolerance.

Gold core@CeO2 halfshell Janus nanocomposites catalyze targeted sulfate radical for periodontitis therapy.

The sulfate radical (SO4•-), known for its high reactivity and long lifespan, has emerged as a potent antimicrobial agent. Its exceptional energy allows for the disruption of vital structures and metabolic pathways in bacteria that are usually inaccessible to common radicals. Despite its promising potential, the efficient generation of this radical, particularly through methods involving enzymes and photocatalysis, remains a substantial challenge. Here, we capitalized on the peroxidase (POD)-mimicking activity and photocatalytic properties of cerium oxide (CeO2) nanozymes, integrating these properties with the enhanced concept of plasma gold nanorod (GNR) to develop a half-encapsulated core@shell GNRs@CeO2 Janus heterostructure impregnated with persulfate. Under near-infrared irradiation, the GNRs generate hot electrons, thereby boosting the CeO2's enzyme-like activity and initiating a potent reactive oxygen species (ROS) storm. This distinct nanoarchitecture facilitates functional specialization, wherein the heterostructure and efficient light absorption ensured continuous hot electron flow, not only enhancing the POD-like activity of CeO2 for the production of SO4•- effectively, but also contributing a significant photothermal effect, disrupting periodontal plaque biofilm and effectively eradicating pathogens. Furthermore, the local temperature elevation synergistically enhances the POD-like activity of CeO2. Transcriptomics analysis, as well as animal experiments of the periodontitis model, have revealed that pathogens undergo genetic information destruction, metabolic disorders, and pathogenicity changes in the powerful ROS system, and profound therapeutic outcomes in vivo, including anti-inflammation and bone preservation. This study demonstrated that energy transfer to augment nanozyme activity, specifically targeting ROS generation, constitutes a significant advancement in antibacterial treatment.

Microplastics change soil properties, plant performance, and bacterial communities in salt-affected soils.

Microplastics (MPs) are emerging contaminants found globally. However, their effects on soil-plant systems in salt-affected habitats remain unknown. Here, we examined the effects of polyethylene (PE) and polylactic acid (PLA) on soil properties, maize performance, and bacterial communities in soils with different salinity levels. Overall, MPs decreased soil electrical conductivity and increased NH4+-N and NO3--N contents. Adding NaCl alone had promoting and inhibitive effects on plant growth in a concentration-dependent manner. Overall, the addition of 0.2% PLA increased shoot biomass, while 2% PLA decreased it. Salinity increased Na content and decreased K/Na ratio in plant tissues (particularly roots), which were further modified by MPs. NaCl and MPs singly and jointly regulated the expression of functional genes related to salt tolerance in leaves, including ZMSOS1, ZMHKT1, and ZMHAK1. Exposure to NaCl alone had a slight effect on soil bacterial α-diversity, but in most cases, MPs increased ACE, Chao1, and Shannon indexes. Both MPs and NaCl altered bacterial community composition, although the specific effects varied depending on the type and concentration of MPs and the salinity level. Overall, PLA had more pronounced effects on soil-plant systems compared to PE. These findings bridge knowledge gaps in the risks of MPs in salt-affected habitats.

Targeting myocardial inflammation: investigating the therapeutic potential of atrial natriuretic peptide in atrial fibrosis.

BACKGROUND: Atrial Fibrillation (AF), a prevalent arrhythmic condition, is intricately associated with atrial fibrosis, a major pathological contributor. Central to the development of atrial fibrosis is myocardial inflammation. This study focuses on Atrial Natriuretic Peptide (ANP) and its role in mitigating atrial fibrosis, aiming to elucidate the specific mechanisms by which ANP exerts its effects, with an emphasis on fibroblast dynamics. METHODS AND RESULTS: The study involved forty Sprague-Dawley rats, divided into four groups: control, Angiotensin II (Ang II), Ang II + ANP, and ANP only. The administration of 1 µg/kg/min Ang II was given to Ang II and Ang II + ANP groups, while both Ang II + ANP and ANP groups received 0.1 µg/kg/min ANP intravenously for a duration of 14 days. Cardiac fibroblasts were used for in vitro validation of the proposed mechanisms. The study observed that rats in the Ang II and Ang II + ANP groups showed an increase in blood pressure and a decrease in body weight, more pronounced in the Ang II group. Diastolic dysfunction, a characteristic of the Ang II group, was alleviated by ANP. Additionally, ANP significantly reduced Ang II-induced atrial fibrosis, myofibroblast proliferation, collagen overexpression, macrophage infiltration, and the elevated expression of Interleukin 6 (IL-6) and Tenascin-C (TN-C). Transcriptomic sequencing indicated enhanced PI3K/Akt signaling in the Ang II group. Furthermore, in vitro studies showed that ANP, along with the PI3K inhibitor LY294002, effectively reduced PI3K/Akt pathway activation and the expression of TN-C, collagen-I, and collagen-III, which were induced by Ang II. CONCLUSIONS: The study demonstrates ANP's potential in inhibiting myocardial inflammation and reducing atrial fibrosis. Notably, ANP's effect in countering atrial fibrosis seems to be mediated through the suppression of the Ang II-induced PI3K/Akt-Tenascin-C signaling pathway. These insights enhance our understanding of AF pathogenesis and position ANP as a potential therapeutic agent for treating atrial fibrosis.

Experiences and perspectives on the optimal timing for initiating advance care planning in patients with mild to moderate dementia: A meta-synthesis.

BACKGROUND: Advance care planning is typically initiated during the last six months of a patient's life. However, due to the progressive decline in the decision-making process in individuals with dementia, their involvement in advance care planning is limited to the early stages of the disease. Currently, there is no consensus on the optimal timing for initiating advance care planning for people with dementia, and a comprehensive review of the literature addressing this matter is lacking. OBJECTIVE: To explore the experiences and perspectives of people with dementia, their family caregivers, and health care professionals with regard to the optimal timing for initiating advance care planning. DESIGN: A meta-synthesis was conducted. DATA SOURCE: The following eight electronic databases were searched: PubMed, Embase, Web of Science, Cochrane Library, CINAHL and CNKI, WanFang and Vip. REVIEW METHODS: This review uses thematic synthesis to systematically synthesize qualitative evidence and report findings according to The Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) and the Joanna Briggs Institute Manual for Evidence Synthesis. Study selection and data extraction were conducted independently by two researchers, and quality was evaluated using the Joanna Briggs Institute's Qualitative Research Standard Assessment tool. FINDINGS: Twenty-one studies were selected for this review. This review involved an overarching theme: The utilization of pivotal elements to transition from delayed initiation to comprehensive implementation. Three themes emerge, including the prerequisites for initiating advance care planning, not ready to start advance care planning and struggling along narrow roads. For health care professionals, the selection of an opportune moment to initiate advance care planning for people with dementia is not only a challenge but also a crucial prerequisite for the successful implementation of advance care planning. Health care professionals' experience, attitude toward advance care planning, trust relationship with patients, cultural differences among people with dementia and their caregivers, and economic disparities all influence health care professionals' judgment of the timing for initiating advance care planning. CONCLUSIONS: Determining the optimal timing for initiating advance care planning is a complex process that requires a comprehensive consideration of the realities faced by health care professionals, people with dementia and their caregivers. Therefore, it is imperative to provide relevant training to health care professionals to ensure the successful implementation of advance care planning.

Virtual reality-based dementia educational programmes for formal and informal caregivers of people with dementia: A scoping review.

AIM: To map evidence of the existing virtual reality-based dementia educational programmes and the effects of these educational programmes on dementia formal and informal caregivers. DESIGN: A scoping review. METHODS: A comprehensive search of nine databases was conducted to find studies from the inception of the databases to October 2023. Two authors independently screened the titles and abstracts related to the eligibility criteria. Full texts of potentially relevant studies were read by one author and checked by a second. Data extraction and synthesis using NVivo 12 were undertaken by one author and checked by two other authors. RESULTS: Nineteen studies published between 2002 and 2022. The four randomised controlled studies and five qualitative studies were of moderate to good methodological quality. The 10 quasi-experimental studies were of weak to moderate quality. Fifteen virtual reality-based educational programmes had a positive influence on formal and informal caregivers, including improving caregivers' perceptions changing attitudes towards people with dementia, while the nursing competence of formal caregivers did not improve in short term. Educational programmes that covered dementia-related information and care strategies better improved the knowledge level of dementia formal and informal caregivers. CONCLUSIONS: The qualitative and quantitative studies of moderate to good quality included in this study support the idea that virtual reality-based dementia educational programmes may be a safe and effective way and have potential benefits for improving knowledge, perceptions, attitudes and nursing competence. IMPACT: This scoping review will provide an emerging teaching model for formal and informal caregivers of people with dementia and help them better understand the types and the influence of virtual reality-based dementia educational programmes. REPORTING METHOD: PRISMA-ScR. NO PATIENT OR PUBLIC CONTRIBUTION: Not required as this review in accordance with the aim to map existing literature from the dementia formal and informal caregivers' perspective.

Multimodal joint deconvolution and integrative signature selection in proteomics.

Deconvolution is an efficient approach for detecting cell-type-specific (cs) transcriptomic signals without cellular segmentation. However, this type of methods may require a reference profile from the same molecular source and tissue type. Here, we present a method to dissect bulk proteome by leveraging tissue-matched transcriptome and proteome without using a proteomics reference panel. Our method also selects the proteins contributing to the cellular heterogeneity shared between bulk transcriptome and proteome. The deconvoluted result enables downstream analyses such as cs-protein Quantitative Trait Loci (cspQTL) mapping. We benchmarked the performance of this multimodal deconvolution approach through CITE-seq pseudo bulk data, a simulation study, and the bulk multi-omics data from human brain normal tissues and breast cancer tumors, individually, showing robust and accurate cell abundance quantification across different datasets. This algorithm is implemented in a tool MICSQTL that also provides cspQTL and multi-omics integrative visualization, available at https://bioconductor.org/packages/MICSQTL .

Inhibition of USP7 enhances CD8+ T cell activity in liver cancer by suppressing PRDM1-mediated FGL1 upregulation.

Lymphocyte activation gene 3 (LAG3), an immune checkpoint molecule expressed on activated T cells, functions as a negative regulator of immune responses. Persistent antigen exposure in the tumor microenvironment results in sustained LAG3 expression on T cells, contributing to T cell dysfunction. Fibrinogen-like protein 1 (FGL1) has been identified as a major ligand of LAG3, and FGL1/LAG3 interaction forms a novel immune checkpoint pathway that results in tumor immune evasion. In addition, ubiquitin-specific peptidase 7 (USP7) plays a crucial role in cancer development. In this study we investigated the role of USP7 in modulation of FGL1-mediated liver cancer immune evasion. We showed that knockdown of USP7 or treatment with USP7 inhibitor P5091 suppressed liver cancer growth by promoting CD8+ T cell activity in Hepa1-6 xenograft mice and in HepG2 or Huh7 cells co-cultured with T cells, whereas USP7 overexpression produced the opposite effect. We found that USP7 upregulated FGL1 in HepG2 and Huh7 cells by deubiquitination of transcriptional factor PR domain zinc finger protein 1 (PRDM1), which transcriptionally activated FGL1, and attenuated the CD8+ T cell activity, leading to the liver cancer growth. Interestingly, USP7 could be transcriptionally stimulated by PRDM1 as well in a positive feedback loop. P5091, an inhibitor of USP7, was able to downregulate FGL1 expression, thus enhancing CD8+ T cell activity. In an immunocompetent liver cancer mouse model, the dual blockade of USP7 and LAG3 resulted in a superior antitumor activity compared with anti-LAG3 therapy alone. We conclude that USP7 diminishes CD8+ T cell activity by a USP7/PRDM1 positive feedback loop on FGL1 production in liver cancer; USP7 might be a promising target for liver cancer immunotherapy.

Dignity-preserving care of people with dementia in different nursing environments: a qualitative systematic review.

AIMS: To systematically identify, evaluate and synthesize qualitative evidence about the dignity-related nursing experiences of people with dementia in families and nursing homes, summarize the similarities and differences and analyse the causes and influencing factors. METHODS: A synthesis of qualitative studies retrieved from eight databases that were published before September 2022. Two reviewers independently screened and selected studies. Inclusion criteria were established according to the PICOS principle. Quality assessment was guided by Joanna Briggs Institute's Qualitative Assessment and Review Instrument and the structured topic synthesis method was used to summarise studies eligible for inclusion. RESULTS: Three key themes were extracted from 14 included studies; the living environment, relationship needs and self-awareness, which focused on improving the dementia-centred nursing environment, meeting the needs of the relationship-centred nursing network, and finally, improving the self-awareness of people with dementia to promote dignity. CONCLUSION: This systematic review shows people with dementia need to integrate into society and maintain their dignity in a dementia-friendly environment that is respectful, inclusive environment that promotes freedom.

A fully digital workflow to design anterior guidance for an implant-supported single crown using a modified patient-specific motion technique.

Current methods for designing anterior guidance of anterior fixed prostheses are either complicated or lack accuracy. The article describes a fully digital workflow to design individualized anterior guidance of an implant-supported single crown by using a modified patient-specific motion technique. The technique aims to optimize the digital occlusal design workflow, thereby improving the occlusal fit and long-term stability of anterior fixed prostheses.

Life experience and identity of spousal caregivers of people with dementia: A qualitative systematic review.

BACKGROUND: The number of people with dementia is on the rise worldwide, and dementia care has become the focus of global health services. People with dementia are primarily cared for by informal caregivers, with spouses seen as a particularly vulnerable group. Focusing on the spousal caregiving experience and having a good caregiver identity contributes to group bonding and enhanced social support. OBJECTIVE: To explore the dynamic changes that occur in the caregiving experience of spouse caregivers and explicate the identity of spouses during this process alongside its causes. DESIGN: A qualitative systematic review. DATA SOURCE: The following eight electronic databases were searched: PubMed, Web of Science (Core Collection), The Cochrane Library, Embase, CINAHL and CNKI, WanFang and Vip. REVIEW METHODS: The Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) and Joanna Briggs Institute Reviewer's Manual criteria were used to report the results. Study screening and data extraction were conducted independently by two reviewers, and quality was assessed using the Joanna Briggs Institute's Qualitative Research Standard Assessment tool. Data synthesis was performed using thematic analysis. RESULTS: A total of 15 studies were included and synthesized into three analytical themes: (1) attitudes and emotions toward dementia, (2) emotional ups and downs in dementia care, and (3) who am "I". In binary care, patience and marital responsibilities are identified as facilitators, while care burden and social isolation are identified as hindrances. In addition, gender differences were identified as influencers of identity. CONCLUSIONS: In this review, spouse identity of people with dementia is complex and affects caregiving experience together with dementia cognition. Disease cognition, caregiving burden and social isolation are identified. Interventions for barriers are suggested to enhance social support.

Role of Platelet/Lymphocyte, Neutrophil/Lymphocyte, and Interleukin-37/Interleukin-17 Ratios in the Occurrence and Treatment of Rheumatoid Arthritis.

This study was designed to investigate the correlation of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and interleukin (IL)-37/IL-17 ratio with the incidence/treatment of rheumatoid arthritis (RA). Firstly, fifty-eight patients with RA treated at the first affiliated hospital of Xinjiang Medical University from January 2018 to January 2019 were selected as the RA group; forty-nine healthy volunteers were enrolled in the control group. RA patients were treated with disease-modifying anti-rheumatic drugs (DMARDs). Next, the NLR, PLR, IL-37, IL-17 and 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) were deleted in two groups. Subsequently, Spearman correlation analysis was adopted for the correlations of various indicators before and after treatment in two groups. According to the analysis results, the levels of NLR, PLR, IL-37, and IL-17 before treatment in the RA group were higher than those in the control group (P < .05), but the difference in the IL-37/IL-17 level between the two groups was not significant (P > .05). After treatment, NLR, PLR, and IL-37/IL-17 levels were significantly reduced in RA patients (P < .05). NLR and PLR were significantly positively correlated with DAS28-ESR, ESR and C-reactive protein (CRP), of which represented the disease activity of RA. NLP was strongly correlated with IL-37/IL-17. Collectively, NLR, PLR, IL-37, and IL-17 are closely related to the occurrence of RA. In addition, NLR and IL-37/IL-17 are more suitable than PLR in reflecting the therapeutic effect. Therefore, IL-37/IL-17 can be considered as a new indicator for reflecting the treatment effectiveness of RA.

Effect of PCI on ophthalmic artery hemodynamics in patients with acute coronary syndrome.

Purpose: We aimed to explore the effects of percutaneous coronary intervention (PCI) on the ophthalmic artery (OA) hemodynamics in patients with acute coronary syndrome (ACS). Methods: A total of 73 participants (Group0: healthy controls, Group1: Patients with ACS underwent PCI < 3 months, Group2: Patients with ACS underwent PCI ≥ 3 months) were enrolled. Computed tomographic angiography images were used to construct three-dimensional models of participants' OAs. Numerical simulations based on computational fluid dynamics were used to acquire hemodynamic parameters. Results: The angle between the OA and internal carotid artery in Group2 was significantly larger compared with Group0 and Group1 (P = 0.003 and P = 0.044). Hemodynamic simulation showed a significantly slower OA blood velocity in Group1 than in the control (P < 0.001) and Group2 (P = 0.033). Lower wall shear stress was found in Group1 than that in control (P = 0.040). Patients after PCI had a higher wall pressure than healthy controls (P = 0.012 and P = 0.004). Mass flow ratios were decreased in Group1 and Group2 (P = 0.021 and P = 0.002). The hemodynamic parameters of OA were correlated with several clinical indicators. Conclusions: The OA blood flow velocity of patients with ACS after PCI initially slowed down, which increased the risk of plaque formation, and then showed an increasing trend. There was a correlation between OA hemodynamic parameters and clinical indexes related to cardiac stress. Ischemia-reperfusion injury and changes in blood flow status after PCI may affect OA morphology and hemodynamics, leading to ocular lesions. Trial registration: ChiCTR2100050428.

Metagenomic analysis reveals gene taxonomic and functional diversity response to microplastics and cadmium in an agricultural soil.

Both microplastics (MPs) and heavy metals are common soil pollutants and can interact to generate combined toxicity to soil ecosystems, but their impact on soil microbial communities (e.g., archaea and viruses) remains poorly studied. Here, metagenomic analysis was used to explore the response of soil microbiome in an agricultural soil exposed to MPs [i.e., polyethylene (PE), polystyrene (PS), and polylactic acid (PLA)] and/or Cd. Results showed that MPs had more profound effects on microbial community composition, diversity, and gene abundances when compared to Cd or their combination. Metagenomic analysis indicated that the gene taxonomic diversity and functional diversity of microbial communities varied with MPs type and dose. MPs affected the relative abundance of major microbial phyla and genera, while their coexistence with Cd influenced dominant fungi and viruses. Nitrogen-transforming and pathogenic genera, which were more sensitive to MPs variations, could serve as the indicative taxa for MPs contamination. High-dose PLA treatments (10%, w/w) not only elevated nitrogen metabolism and pathogenic genes, but also enriched copiotrophic microbes from the Proteobacteria phylum. Overall, MPs and Cd showed minimal interactions on soil microbial communities. This study highlights the microbial shifts due to co-occurring MPs and Cd, providing evidence for understanding their environmental risks.

Diammonium Glycyrrhizinate Inhibited Inflammatory Response and Modulated Serum Metabolism in Poly(I:C)-induced Pneumonia Model Mice.

ABSTRACT: Currently, the coronavirus disease 2019 (COVID-19) is becoming a serious threat to human health worldwide. Therefore, there is a great need to develop effective drugs against viral pneumonia. Diammonium glycyrrhizinate (DG), derived from Glycyrrhiza glabra L., has been demonstrated with significant anti-inflammatory properties. However, the therapeutic effects and mechanisms of DG on pneumonia require further clarification. In this study, mice received intratracheal injection of polyinosinic-polycytidylic acid (poly(I:C)) to induce pneumonia and were treated with DG. First, we evaluated the therapeutic potential of DG on poly(I:C)-induced pneumonia. Second, the anti-inflammatory and anti-oxidative activities and the impact of DG on the Toll-like receptor 3 (TLR3) pathway were investigated. Third, the mechanism of DG was analyzed through untargeted metabolomics techniques. Our results revealed that DG intervention decreased permeability and reduced abnormal lung alterations in poly(I:C)-induced pneumonia model mice. DG intervention also downregulated cytokine levels in bronchoalveolar lavage fluid. Moreover, DG treatment inhibited the activation of TLR3 pathway. Furthermore, untargeted metabolomics analysis revealed that DG intervention could modulate serum metabolites involved in amino and nucleotide sugar metabolism, fructose and mannose metabolism, tyrosine metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis pathways. In conclusion, our study showed that DG could ameliorate poly(I:C)-induced pneumonia by inactivating the TLR3 pathway and affecting amino and nucleotide sugar, fructose and mannose metabolism, as well as tryptophan, phenylalanine, and tyrosine biosynthesis.

Breaking Iron Homeostasis: Iron Capturing Nanocomposites for Combating Bacterial Biofilm.

Given the scarcity of novel antibiotics, the eradication of bacterial biofilm infections poses formidable challenges. Upon bacterial infection, the host restricts Fe ions, which are crucial for bacterial growth and maintenance. Having coevolved with the host, bacteria developed adaptive pathways like the hemin-uptake system to avoid iron deficiency. Inspired by this, we propose a novel strategy, termed iron nutritional immunity therapy (INIT), utilizing Ga-CT@P nanocomposites constructed with gallium, copper-doped tetrakis (4-carboxyphenyl) porphyrin (TCPP) metal-organic framework, and polyamine-amine polymer dots, to target bacterial iron intakes and starve them. Owing to the similarity between iron/hemin and gallium/TCPP, gallium-incorporated porphyrin potentially deceives bacteria into uptaking gallium ions and concurrently extracts iron ions from the surrounding bacteria milieu through the porphyrin ring. This strategy orchestrates a "give and take" approach for Ga3+/Fe3+ exchange. Simultaneously, polymer dots can impede bacterial iron metabolism and serve as real-time fluorescent iron-sensing probes to continuously monitor dynamic iron restriction status. INIT based on Ga-CT@P nanocomposites induced long-term iron starvation, which affected iron-sulfur cluster biogenesis and carbohydrate metabolism, ultimately facilitating biofilm eradication and tissue regeneration. Therefore, this study presents an innovative antibacterial strategy from a nutritional perspective that sheds light on refractory bacterial infection treatment and its future clinical application.

Clinical practice guidelines for the nutrition of colorectal cancer patients: a systematic review.

PURPOSE: The aim of this study is to rigorously assess the methodological quality of published clinical practice guidelines (CPGs) related to nutrition among colorectal cancer patients, to compile consensus recommendations, and to evaluate the quality of the included CPGs. METHODS: The systematic search covered eight electronic databases, two relevant professional association websites, and six guideline websites from their inception up to January 22, 2023. The methodological quality of the eligible guidelines was evaluated using the Appraisal of Guidelines Research and Evaluation II (AGREE II) instrument, and then, consensus recommendations were synthesized. The scores for each domain were expressed as the mean ± standard deviation (SD). Using the mean score as the benchmark for comparison, they were subsequently ranked from highest to lowest. The included guidelines were then categorized as having "high," "moderate," or "low" quality based on their scores. RESULTS: The literature search yielded ten guidelines. The findings indicated that the "Clarity of presentation" domain had the highest mean score (65.2 ± 7.7). This demonstrates how the guidelines effectively articulate recommendations. Additionally, the "Scope and purpose" domain achieved a mean score of 60.7 ± 10.9, followed by "Rigor of development" (51.7 ± 15.7), "Editorial independence" (51.1 ± 21), "Stakeholder involvement" (48 ± 16.8), and "Applicability" domains (47.5 ± 17.3). Two CPGs received an overall rating of "high quality" and were recommended; four CPGs received an overall rating of "moderate" and were recommended with modifications; and four CPGs received an overall rating of "low quality" and were not recommended. Furthermore, this study compiled twenty consensus recommendations related to nine distinct clinical issues. CONCLUSION: This study identified disparities in the methodological quality of the included CPGs, particularly in the "Applicability" domain, thus emphasizing the need for advancement in clinical feasibility and implementation. Notably, there is few guidelines specifically targeting colorectal cancer nutrition. These synthesized findings provided an intuitive, convenient, and comprehensive reference for evaluating nutrition among colorectal cancer patients. When applying these results, users should make careful decisions based on their specific situations.

Anti-Wound Dehiscence and Antibacterial Dressing with Highly Efficient Self-Healing Feature for Guided Bone Regeneration Wound Closure.

Guided bone regeneration (GBR) is a well-established technique for preserving and enhancing alveolar ridge structures. Success in GBR relies on fulfilling the Primary wound closure, Angiogenesis, Space maintenance, and Stability (PASS) principles. Conventional methods, involving titanium meshes and sutures, have drawbacks, including the need for secondary removal and customization challenges. To address these issues, an innovative multifunctional GBR dressing (MGD) based on self-healing elastomer (PUIDS) is introduced. MGD provides sutureless wound closure, prevents food particle accumulation, and maintains a stable environment for bone growth. It offers biocompatibility, bactericidal properties, and effectiveness in an oral GBR model. In summary, MGD provides a reliable, stable osteogenic environment for GBR, aligning with PASS principles and promoting superior post-surgery bone regeneration.