ABSTRACT
Objective: The cingulate sulcus sign (CSS) has been observed in patients with idiopathic normal pressure hydrocephalus (iNPH), suggesting potential disruptions in cerebrospinal fluid circulation and compromised glymphatic system. Although there are similarities in the underlying mechanisms between cerebral small vessel disease (CSVD) and iNPH, the relationship between CSS and CSVD remains unclear. This study aimed to investigate the prevalence and potential mechanisms of CSS in patients with CSVD. Methods: Data from patients diagnosed with CSVD at Shengjing Hospital of China Medical University between January 2020 and October 2022 were retrospectively collected, including general information, global cognitive function [assessed by measuring Mini-Mental State Examination (MMSE)], and four CSVD magnetic resonance imaging (MRI) markers [(white matter hyperintensity (WMH), cerebral microbleeds (CMBs), lacunes, and enlarged perivascular spaces (EPVS)], CSS and the Evan's index (EI). Results: A total of 308 patients were included, and CSS was detected in 80 patients (26%). Univariate analysis revealed that MMSE scores in the CSS group were significantly lower compared to the non-CSS group (p < 0.001). Multivariable analysis showed an independent correlation between CSS and the presence of lacunes (odds ratio [OR] 0.358, 95% confidence interval [CI] 0.193-0.663, p = 0.001), presence of lobar dominant CMBs (OR 2.683, 95%CI 1.385-5.195, p = 0.003), periventricular WMH Fazekas score (OR 1.693, 95% CI 1.133-2.529, p = 0.01), and EI (OR 1.276, 95% CI 1.146-1.420, p < 0.001). Conclusion: This preliminary study showed that CSS can be observed in some patients with CSVD. The presence of CSS may represent different mechanisms of CSVD pathogenesis and reflect differences in the degree of cerebrospinal fluid (CSF)/interstitial fluid (ISF) stasis.
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AIMS: To systematically evaluate the predictive efficacy of clinical frailty scale (CFS) for postoperative mortality older surgical patients, and to evaluate the prevalence of frailty in the included studies. DESIGN: A systematic review and meta-analysis of observational studies was conducted, utilizing the MOOSE guidelines for the evaluation of both. Quality assessment of the articles was also performed. DATA SOURCES: The protocol was registered (CRD42023423552). Relevant English and Chinese language studies published until October 20th, 2023 were retrieved from PubMed, Web of Science, Embase, Medline, CINAHL,Cochrane, WAN FANG DATA, VIP Information, CNKI, and SinoMed databases. REVIEW METHODS: Study were included in which frailty was measured by the CFS and postoperative mortality was reported for older surgery patients. A meta-analysis to predict postoperative mortality and frailty prevalence was performed using STATA 17.0 software. RESULTS: Sixteen cohort studies were included (5,864 participants) from 1,513 records. All studies' Newcastle-Ottawa Scale (NOS) scores were above 6 points. It was found that the prevalence of surgical frailty in the older was 0.36(CI 0.20-0.52). Patients assessed as frail by the CFS were associated with higher all-cause mortality (OR:4.01; CI 2.59-6.23). Subgroup analysis shows that frailty was associated with1-month mortality (OR:3.85; CI 1.11-13.45) and 1-year mortality (OR:4.43; CI 2.18-8.99). CONCLUSIONS: The prevalence of frailty is high in older surgical patients, and CFS can effectively predict the mortality of older surgical patients with frailty.
ABSTRACT
Understanding how numerous quantitative trait loci (QTL) shape phenotypic variation is an important question in genetics. To address this, we established a permanent population of 18,421 (18K) rice lines with reduced population structure. We generated reference-level genome assemblies of the founders and genotyped all 18K-rice lines through whole-genome sequencing. Through high-resolution mapping, 96 high-quality candidate genes contributing to variation in 16 traits were identified, including OsMADS22 and OsFTL1 verified as causal genes for panicle number and heading date, respectively. We identified epistatic QTL pairs and constructed a genetic interaction network with 19 genes serving as hubs. Overall, 170 masking epistasis pairs were characterized, serving as an important factor contributing to genetic background effects across diverse varieties. The work provides a basis to guide grain yield and quality improvements in rice.
Subject(s)
Epistasis, Genetic , Genome, Plant , Oryza , Quantitative Trait Loci , Oryza/genetics , Whole Genome Sequencing , Chromosome Mapping , Genes, Plant , Genotype , Gene Regulatory Networks , PhenotypeABSTRACT
Zirconia abutments and restorations have improved the aesthetic appeal of implant restoration, yet peri-implantitis poses a significant threat to long-term success. The soft tissue surrounding implants is a crucial biological barrier against inflammation and subsequent bone loss. Peri-implantitis, akin to periodontitis, progresses rapidly and causes extensive tissue damage. Variations in tissue structure significantly influence disease progression, particularly the lower vascular density in peri-implant connective tissue, compromising its ability to combat infection and provide essential nutrients. Blood vessels within this tissue are vital for healing, with angiogenesis playing a key role in immune defense and tissue repair. Enhancing peri-implant soft tissue angiogenesis holds promise for tissue integration and inflammation control. Microgroove surfaces have shown potential in guiding vessel growth, but using subtractive technologies to carve microgrooves on zirconia surfaces may compromise mechanical integrity. In this study, we utilized inkjet printing to prepare bioactive silk fibroin microgrooves (SFMG) coating with different sizes on zirconia surfaces. SFMG coating, particularly with 90 µm width and 10 µm depth, effectively directed human umbilical vein endothelial cells (HUVECs) along microgrooves, promoting their proliferation, migration, and tube formation. The expression of vascular endothelial growth factor A and fibroblast growth factor in HUVECs growing on SFMG coating was upregulated. Additionally, the SFMG coating activated the PI3K-AKT pathway and increased glycolytic enzyme gene expression in HUVECs. In conclusion, SFMG coating enhances HUVEC growth and angiogenesis potential by activating the PI3K-AKT pathway and glycolysis, showing promise for improving tissue integration and mitigating inflammation in zirconia abutments and restorations.
ABSTRACT
The use of zirconia has significantly enhanced the aesthetic outcomes of implant restorations. However, peri-implantitis remains a challenge to long-term functionality of implants. Unlike the perpendicularly arranged collagen fibers in periodontal tissue, those in peri-implant tissue lie parallel to the abutment surface and contain fewer fibroblasts, making them more prone to inflammation. Studies have shown that microgroove structures on implant abutments could improve surrounding soft tissue structure. However, creating precise microgrooves on zirconia without compromising its mechanical integrity is technically challenging. In this study, we applied inkjet printing, an additive manufacturing technique, to create stable silk fibroin microgroove (SFMG) coatings of various dimensions on zirconia substrates. SFMG significantly improved the hydrophilicity of zirconia and showed good physical and chemical stability. The SFMG with 90 µm interval and 10 µm depth was optimal in promoting the proliferation, alignment, and extracellular matrix production of human gingival fibroblasts (HGFs). Moreover, the in vitro results revealed that SFMG stimulated key glycolytic enzyme gene expression in HGFs via the PI3K-AKT-mTOR pathway. Additionally, the in vivo results of histological staining of peri-abutments soft tissue showed that SFMG promoted the vertical alignment of collagen fibers relative to the abutment surface, improving connective tissue sealing around the zirconia abutment. Our results indicated that SFMG on zirconia can enhance HGF proliferation, migration and collagen synthesis by regulating glycolysis though PI3K-AKT-mTor pathway, thereby improving connective tissue sealing.
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Objectively In objective terms, the return of rural labor force shortens the spatial distance with parents, leading to changes in caregiving support, emotional support, and financial support for parents, thereby affecting the health status of parents. This article, using data from the Chinese Family Panel Studies, analyzes the characteristics of the health status of parents with and without returning migrant children. By employing multiple linear regression models, PSM models, and IV-2SLS methods to address endogeneity bias, the study preliminarily explores the impact of rural labor force return on parental health. The results show that: (1) among the 5,760 older adult individuals, 1866 of them have returning migrant chil-dren, while the remaining 3,894 do not have returning migrant children. (2) Parents' health status generally follows a normal distribution, with a small proportion of parents having very poor or very good health. The proportions of parents with relatively poor, fair, and relatively good health status range between 20 and 40%. Among parents with returning chil-dren, 40.12% have relatively poor health status, 45.01% have fair health status, and a small proportion have very poor or very good health status. In contrast, among parents without returning children, the proportions of parents with relatively poor, fair, and rela-tively good health status are 21.69, 33.21, and 38.45%, respectively. When parents tran-sition from not having returning children to having returning children, their health status decreases by 0.541 levels, indicating a negative impact of rural labor force return on par-ents' health. Based on the analysis results, this article provides policy recommendations from three aspects: how to increase the income of returning labor force, improve the rural pension system, and enhance the concept of children supporting their parents.
Subject(s)
Health Status , Parents , Rural Population , Humans , China , Parents/psychology , Female , Rural Population/statistics & numerical data , Male , Middle Aged , Adult , Transients and Migrants/statistics & numerical data , Return to Work/statistics & numerical data , Employment/statistics & numerical data , AgedABSTRACT
Bilateral facial palsy with paresthesia (FDP) is a rare variant of GBS, characterized by simultaneous bilateral facial palsy and paresthesia of the distal limbs. Mounting evidence indicates that the presence of anti-GT1a IgG has a pathogenic role as an effector molecule in the development of cranial nerve palsies in certain patients with GBS, whereas anti-GT1a antibody is rarely presented positive in FDP. Here, we report the case of a 33-year-old male diagnosed with FDP presented with acute onset of bilateral facial palsy and slight paresthesias at the feet as the only neurological manifestation. An antecedent infection with no identifiable reason for the fever or skin eruptions was noted in the patient. He also exhibited cerebrospinal fluid albuminocytologic dissociation and abnormal nerve conduction studies. Notably, the testing of specific serum anti-gangliosides showed positive anti-GT1a IgG/IgM Ab. The patient responded well to intravenous immunoglobulin therapy. This case brings awareness to a rare variant of GBS, and provides the first indication that anti-GT1a antibodies play a causative role in the development of FDP. The case also suggests that prompt management with IVIG should be implemented if FDP is diagnosed.
Subject(s)
Autoantibodies , Facial Paralysis , Gangliosides , Paresthesia , Humans , Male , Adult , Paresthesia/immunology , Paresthesia/diagnosis , Paresthesia/etiology , Facial Paralysis/diagnosis , Facial Paralysis/etiology , Facial Paralysis/immunology , Autoantibodies/immunology , Autoantibodies/blood , Gangliosides/immunology , Immunoglobulins, Intravenous/therapeutic use , Immunoglobulin G/immunology , Immunoglobulin G/blood , Guillain-Barre Syndrome/diagnosis , Guillain-Barre Syndrome/immunologyABSTRACT
Multi-modal combination therapy is regarded as a promising approach to cancer treatment. Combining chemotherapy and phototherapy is an essential multi-modal combination therapy endeavor. Ivermectin (IVM) is a potent antiparasitic agent identified as having potential antitumor properties. However, the fact that it induces protective autophagy while killing tumor cells poses a challenge to its further application. IR780 iodide (IR780) is a near-infrared (NIR) dye with outstanding photothermal therapy (PTT) and photodynamic therapy (PDT) effects. However, the hydrophobicity, instability, and low tumor uptake of IR780 limit its clinical applications. Here, we have structurally modified IR780 with hydroxychloroquine, an autophagy inhibitor, to synthesize a novel compound H780. H780 and IVM can form H780-IVM nanoparticles (H-I NPs) via self-assembly. Using hyaluronic acid (HA) to modify the H-I NPs, a novel nano-delivery system HA/H780-IVM nanoparticles (HA/H-I NPs) was synthesized for chemotherapy-phototherapy of colorectal cancer (CRC). Under NIR laser irradiation, HA/H-I NPs effectively overcame the limitations of IR780 and IVM and exhibited potent cytotoxicity. In vitro and in vivo experiment results showed that HA/H-I NPs exhibited excellent anti-CRC effects. Therefore, our study provides a novel strategy for CRC treatment that could enhance chemo-phototherapy by modulating autophagy.
Subject(s)
Autophagy , Colorectal Neoplasms , Drug Repositioning , Ivermectin , Nanoparticles , Autophagy/drug effects , Animals , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/therapy , Humans , Mice , Nanoparticles/chemistry , Ivermectin/pharmacology , Ivermectin/chemistry , Cell Line, Tumor , Indoles/chemistry , Indoles/pharmacology , Mice, Inbred BALB C , Mice, Nude , Photochemotherapy/methods , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Phototherapy/methods , Hyaluronic Acid/chemistry , Hydroxychloroquine/pharmacology , Hydroxychloroquine/chemistry , Photothermal Therapy/methodsABSTRACT
Maize (Zea mays subspecies mays) is an important commercial crop across the world, and its flowering time is closely related to grain yield, plant cycle and latitude adaptation. FKF1 is an essential clock-regulated blue-light receptor with distinct functions on flowering time in plants, and its function in maize remains unclear. In this study, we identified two FKF1 homologs in the maize genome, named ZmFKF1a and ZmFKF1b, and indicated that ZmFKF1a and ZmFKF1b independently regulate reproductive transition through interacting with ZmCONZ1 and ZmGI1 to increase the transcription levels of ZmCONZ1 and ZCN8. We demonstrated that ZmFKF1b underwent artificial selection during modern breeding in China probably due to its role in geographical adaptation. Furthermore, our data suggested that ZmFKF1bHap_C7 may be an elite allele, which increases the abundance of ZmCONZ1 mRNA more efficiently and adapt to a wider range of temperature zone than that of ZmFKF1bHap_Z58 to promote maize floral transition. It extends our understanding of the genetic diversity of maize flowering. This allele is expected to be introduced into tropical maize germplasm to enrich breeding resources and may improve the adaptability of maize at different climate zones, especially at temperate region.
Subject(s)
Flowers , Gene Expression Regulation, Plant , Plant Proteins , Zea mays , Zea mays/genetics , Zea mays/physiology , Plant Proteins/genetics , Plant Proteins/metabolism , Flowers/genetics , Flowers/physiology , Adaptation, Physiological/genetics , Reproduction/genetics , Reproduction/physiology , Geography , AllelesABSTRACT
Colon cancer affects people of all ages. However, its frequency, as well as the related morbidity and mortality, are high among older adults. The complex physiological changes in the aging gut substantially limit the development of cancer therapies. Here, we identify a potentially unique intestinal microenvironment that is linked with an increased risk of colon cancer in older adults. Our findings show that aging markedly influenced persistent fucosylation of the apical surfaces of intestinal epithelial cells, which resulted in a favorable environment for tumor growth. Furthermore, our findings shed light on the importance of the host-commensal interaction, which facilitates the dysregulation of fucosylation and promotes tumor growth as people get older. We analyzed colonic microbial populations at the species level to find changes associated with aging that could contribute to the development of colon cancer. Analysis of single-cell RNA-sequencing data from previous publications identified distinct epithelial cell subtypes involved in dysregulated fucosylation in older adults. Overall, our study provides compelling evidence that excessive fucosylation is associated with the development of colon cancer, that age-related changes increase vulnerability to colon cancer, and that a dysbiosis in microbial diversity and metabolic changes in the homeostasis of older mice dysregulate fucosylation levels with age.
Subject(s)
Colonic Neoplasms , Humans , Mice , Animals , Aged , Colonic Neoplasms/metabolism , Glycosylation , Epithelial Cells/metabolism , Intestinal Mucosa/pathology , Tumor MicroenvironmentABSTRACT
RATIONALE: During the past 3 years of the corona virus disease 2019 (COVID-19) pandemic, COVID-19 has been recognized to cause various neurological complications, including rare posterior reversible encephalopathy syndrome (PRES). In previously reported cases of PRES associated with COVID-19, the majority of patients had severe COVID-19 infection and known predisposing factors for PRES, such as uncontrolled hypertension, renal dysfunction, and use of immunosuppressants. It remains unclear whether these risk factors or infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contributes to the development of PRES in these patients. Here we report a special case of PRES associated with COVID-19 without any known risk factors for PRES, indicating the SARS-CoV-2's direct role in the pathogenesis of PRES associated with COVID-19. PATIENT CONCERNS: An 18-year-old female patient presented to the emergency department with abdominal pain. Preliminary investigations showed no abnormalities, except for positive results in novel coronavirus nucleic acid tests using oropharyngeal swabs. However, the patient subsequently developed tonic-clonic seizures, headaches, and vomiting on the second day. Extensive investigations have been performed, including brain MRI and lumbar puncture. Brain MRI showed hypointense T1-weighted and hyperintense T2-weighted lesions in the bilateral occipital, frontal, and parietal cortices without enhancement effect. Blood and cerebrospinal fluid analyses yielded negative results. The patient had no hypertension, renal insufficiency, autoimmune disease, or the use of immunosuppressants or cytotoxic drugs. DIAGNOSES: PRES was diagnosed based on the clinical features and typical MRI findings of PRES. INTERVENTIONS: Symptomatic treatments such as anticonvulsants were administered to the patients. OUTCOMES: The patient fully recovered within 1 week. The initial MRI abnormalities also disappeared completely on a second MR examination performed 11 days later, supporting the diagnosis of PRES. The patient was followed up for 6 months and remained in a normal state. LESSONS: The current case had no classical risk factors for PRES, indicating that although the cause of PRES in COVID-19 patients may be multifactorial, the infection of SARS-CoV-2 may play a direct role in the pathogenesis of PRES associated with COVID-19.
Subject(s)
COVID-19 , Hypertension , Posterior Leukoencephalopathy Syndrome , Female , Humans , Adolescent , Posterior Leukoencephalopathy Syndrome/complications , SARS-CoV-2 , COVID-19/complications , Seizures/complications , Hypertension/complications , Immunosuppressive Agents/therapeutic useABSTRACT
Viroporins constitute a class of viral membrane proteins with diverse roles in the viral life cycle. They can self-assemble and form pores within the bilayer that transport substrates, such as ions and genetic material, that are critical to the viral infection cycle. However, there is little known about the oligomeric state of most viroporins. Here, we use native mass spectrometry in detergent micelles to uncover the patterns of oligomerization of the full-length SARS-CoV-2 envelope (E) protein, poliovirus VP4, and HIV Vpu. Our data suggest that the E protein is a specific dimer, VP4 is exclusively monomeric, and Vpu assembles into a polydisperse mixture of oligomers under these conditions. Overall, these results revealed the diversity in the oligomerization of viroporins, which has implications for the mechanisms of their biological functions as well as their potential as therapeutic targets.
Subject(s)
COVID-19 , HIV Infections , Poliovirus , Humans , SARS-CoV-2/metabolism , Viroporin Proteins , Viral Regulatory and Accessory Proteins , Human Immunodeficiency Virus Proteins/chemistry , Human Immunodeficiency Virus Proteins/metabolismABSTRACT
The dual role of CD8+ T cells in influenza control and lung pathology is increasingly appreciated. To explore whether protective and pathological functions can be linked to specific subsets, we dissected CD8+ T responses in influenza-infected murine lungs. Our single-cell RNA-sequencing (scRNA-seq) analysis revealed notable diversity in CD8+ T subpopulations during peak viral load and infection-resolved state. While enrichment of a Cxcr3hi CD8+ T effector subset was associated with a more robust cytotoxic response, both CD8+ T effector and central memory exhibited equally potent effector potential. The scRNA-seq analysis identified unique regulons regulating the cytotoxic response in CD8+ T cells. The late-stage CD8+ T blockade in influenza-cleared lungs or continuous CXCR3 blockade mitigated lung injury without affecting viral clearance. Furthermore, adoptive transfer of wild-type CD8+ T cells exacerbated influenza lung pathology in Cxcr3-/- mice. Collectively, our data imply that CXCR3 interception could have a therapeutic effect in preventing influenza-linked lung injury.
Subject(s)
Influenza, Human , Lung Injury , Animals , Humans , Mice , CD8-Positive T-Lymphocytes , Lung , Mice, Inbred C57BL , Mice, Knockout , Receptors, ChemokineABSTRACT
Coxsackievirus B3 (CVB3) is a non-enveloped, single-stranded, positive RNA virus known for its role in provoking inflammatory diseases that affect the heart, pancreas, and brain, leading to conditions such as myocarditis, pancreatitis, and meningitis. Currently, there are no FDA-approved drugs treating CVB3 infection; therefore, identifying potential molecular targets for antiviral drug development is imperative. In this study, we examined the possibility of activating the cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway, a cytosolic DNA-sensing pathway that triggers a type-I interferon (IFN) response, in inhibiting CVB3 infection. We found that activation of the cGAS-STING pathway through the application of cGAS (poly dA:dT and herring testes DNA) or STING agonists (2'3'-cGAMP and diamidobenzimidazole), or the overexpression of STING, significantly suppresses CVB3 replication. Conversely, gene-silencing of STING enhances viral replication. Mechanistically, we demonstrated that cGAS-STING activation combats CVB3 infection by inducing IFN response. Notably, we discovered that knockdown of IFN-α/ß receptor, a key membrane receptor in type-I IFN signaling, or inhibition of the downstream JAK1/2 signaling with ruxolitinib, mitigates the effects of STING activation, resulting in increased viral protein production. Furthermore, we investigated the interplay between CVB3 and the cGAS-STING pathway. We showed that CVB3 does not trigger cGAS-STING activation; instead, it antagonizes STING and the downstream TBK1 activation induced by cGAMP. In summary, our results provide insights into the interaction of an RNA virus and the DNA-sensing pathway, highlighting the potential for agonist activation of the cGAS-STING pathway in the development of anti-CVB3 drugs.
Subject(s)
Immunity, Innate , Interferon Type I , Signal Transduction/genetics , Nucleotidyltransferases/genetics , Nucleotidyltransferases/metabolism , Interferon Type I/metabolism , DNAABSTRACT
The explosive amount of multi-omics data has brought a paradigm shift both in academic research and further application in life science. However, managing and reusing the growing resources of genomic and phenotype data points presents considerable challenges for the research community. There is an urgent need for an integrated database that combines genome-wide association studies (GWAS) with genomic selection (GS). Here, we present CropGS-Hub, a comprehensive database comprising genotype, phenotype, and GWAS signals, as well as a one-stop platform with built-in algorithms for genomic prediction and crossing design. This database encompasses a comprehensive collection of over 224 billion genotype data and 434 thousand phenotype data generated from >30 000 individuals in 14 representative populations belonging to 7 major crop species. Moreover, the platform implemented three complete functional genomic selection related modules including phenotype prediction, user model training and crossing design, as well as a fast SNP genotyper plugin-in called SNPGT specifically built for CropGS-Hub, aiming to assist crop scientists and breeders without necessitating coding skills. CropGS-Hub can be accessed at https://iagr.genomics.cn/CropGS/.
Subject(s)
Crops, Agricultural , Databases, Genetic , Genomics , Genotype , Phenotype , Crops, Agricultural/genetics , Genome , Genome-Wide Association Study , Polymorphism, Single Nucleotide , InternetABSTRACT
OBJECTIVE: The study investigates the impact of preoperative rehabilitation on the surgical prognosis of frail older patients. METHOD: The effect sizes of all studies retrieved and included by the nine databases were analyzed and expressed as RR and WMD. RESULTS: 8 studies with 902 participants met the criteria for inclusion. A significant reduction in total complications (RR = 0.84, 95 % CI = 0.73 to 0.97, P = 0.021) and the 6MWT after surgery (WMD = 74.76, 95 % CI = 44.75 to 104.77, P = 0.000) was observed in the prehabilitation group. But it had no differences in mortality(RR = 1.89, 95 % CI = 0.75 to 4.72, P = 0.176), readmission rates(RR = 1.04, 95 % CI = 0.56 to 1.91, P = 0.906) and LOS(WMD = -0.24, 95 % CI = -1.00 to 0.52, P = 0.540). CONCLUSIONS: Prehabilitation had positive effect on postoperative complications and functional recovery in frail older patients.
Subject(s)
Frail Elderly , Preoperative Exercise , Humans , Aged , Postoperative Complications/prevention & control , Postoperative Complications/etiology , Prognosis , Recovery of FunctionABSTRACT
Benefiting from the biocompatibility, adhesiveness, and natural extracellular matrix-mimicking ability, hydrogels have received increasing research in recent years. In this study, a hydrogel system composed of dopamine, quaternized ammoniated chitosan (QCS), and polyvinylpyrrolidone was reported to exhibit fast hemostatic properties in Sprague-Dawley rat tail amputation and liver bleeding models. The results showed that this hydrogel had good hemostatic properties. The designed hydrogel showed high swelling ratios in H2O, PBS, and 0.9 % NaCl solution, indicating its capability to absorb tissue residual exudate and form a stable hydrogel. Compared with the control group, the blood loss in Sprague-Dawley rat tail amputation and liver bleeding were reduced by nearly 78 % and 76 %, respectively. Interestingly, dopamine endowed the hydrogel with antioxidant properties, thus holding a great application promise in inflammatory wounds. Furthermore, the designed hydrogel demonstrated good and reversible adhesion properties (12.23 ± 0.22 kPa-24.31 ± 0.55 kPa), ensuring its firm attachment to bleeding wounds of pig skin in wet environments. This research points out a novel path for designing chitosan-based hydrogels for biomedical applications.
Subject(s)
Chitosan , Hemostatics , Rats , Animals , Swine , Chitosan/pharmacology , Antioxidants/pharmacology , Hydrogels/pharmacology , Dopamine , Rats, Sprague-Dawley , Tissue Adhesions , Hemostatics/pharmacology , Hemostasis , Anti-Bacterial AgentsABSTRACT
The upper respiratory tract (nasopharynx or NP) is the first site of influenza replication, allowing the virus to disseminate to the lower respiratory tract or promoting community transmission. The host response in the NP regulates an intricate balance between viral control and tissue pathology. The hyper-inflammatory responses promote epithelial injury, allowing for increased viral dissemination and susceptibility to secondary bacterial infections. However, the pathologic contributors to influenza upper respiratory tissue pathology are incompletely understood. In this study, we investigated the role of interleukin IL-17 recetor A (IL-17RA) as a modulator of influenza host response and inflammation in the upper respiratory tract. We used a combined experimental approach involving IL-17RA-/- mice and an air-liquid interface (ALI) epithelial culture model to investigate the role of IL-17 response in epithelial inflammation, barrier function, and tissue pathology. Our data show that IL-17RA-/- mice exhibited significantly reduced neutrophilia, epithelial injury, and viral load. The reduced NP inflammation and epithelial injury in IL-17RA-/- mice correlated with increased resistance against co-infection by Streptococcus pneumoniae (Spn). IL-17A treatment, while potentiating the apoptosis of IAV-infected epithelial cells, caused bystander cell death and disrupted the barrier function in ALI epithelial model, supporting the in vivo findings.
Subject(s)
Influenza, Human , Animals , Mice , Humans , Influenza, Human/complications , Interleukin-17/genetics , Interleukin-17/metabolism , Inflammation/complications , Streptococcus pneumoniae/metabolism , InterleukinsABSTRACT
PURPOSE: Sequenced Protein-Protein Interaction (PPI) prediction represents a pivotal area of study in biology, playing a crucial role in elucidating the mechanistic underpinnings of diseases and facilitating the design of novel therapeutic interventions. Conventional methods for extracting features through experimental processes have proven to be both costly and exceedingly complex. In light of these challenges, the scientific community has turned to computational approaches, particularly those grounded in deep learning methodologies. Despite the progress achieved by current deep learning technologies, their effectiveness diminishes when applied to larger, unfamiliar datasets. RESULTS: In this study, the paper introduces a novel deep learning framework, termed DL-PPI, for predicting PPIs based on sequence data. The proposed framework comprises two key components aimed at improving the accuracy of feature extraction from individual protein sequences and capturing relationships between proteins in unfamiliar datasets. 1. Protein Node Feature Extraction Module: To enhance the accuracy of feature extraction from individual protein sequences and facilitate the understanding of relationships between proteins in unknown datasets, the paper devised a novel protein node feature extraction module utilizing the Inception method. This module efficiently captures relevant patterns and representations within protein sequences, enabling more informative feature extraction. 2. Feature-Relational Reasoning Network (FRN): In the Global Feature Extraction module of our model, the paper developed a novel FRN that leveraged Graph Neural Networks to determine interactions between pairs of input proteins. The FRN effectively captures the underlying relational information between proteins, contributing to improved PPI predictions. DL-PPI framework demonstrates state-of-the-art performance in the realm of sequence-based PPI prediction.
Subject(s)
Deep Learning , Protein Interaction Mapping , Protein Interaction Mapping/methods , Neural Networks, Computer , Amino Acid Sequence , Proteins/metabolismABSTRACT
Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC-reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level. Infection expands the pool of CD74+ PCs, whose number correlates with auto or allogeneic inflammatory disease progressions in mice. Similar correlation was found in human inflammatory disease tissues. Infection-stimulated cytokines increase production of reactive oxygen species (ROS) and expression of a PC-specific mucosal pentraxin (Mptx2) in activated PCs. A PC-specific ablation of MyD88 reduced CD74+ PC population, thus ameliorating pathogen-induced systemic disease. A similar phenotype was also observed in mice lacking Mptx2. Thus, infection stimulates expansion of a PC subset that influences disease progression.