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1.
Nat Immunol ; 22(9): 1127-1139, 2021 09.
Article in English | MEDLINE | ID: mdl-34413521

ABSTRACT

Follicular helper T (TFH) cells are a specialized subset of CD4+ T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of TFH cell survival remains unclear. Here we report that TFH cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the major lipid peroxidation scavenger and is necessary for TFH cell survival. The deletion of GPX4 in T cells selectively abrogated TFH cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased TFH cell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Our findings reveal the central role of the selenium-GPX4-ferroptosis axis in regulating TFH homeostasis, which can be targeted to enhance TFH cell function in infection and following vaccination.


Subject(s)
Ferroptosis/physiology , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Selenium/pharmacology , T Follicular Helper Cells/physiology , Adolescent , Adult , Animals , Cell Survival/immunology , Child , Female , Germinal Center/cytology , Germinal Center/immunology , Homeostasis/drug effects , Homeostasis/genetics , Humans , Immunity, Humoral/immunology , Influenza Vaccines/immunology , Lipid Peroxidation/physiology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitochondria/physiology , Ovalbumin , T Follicular Helper Cells/immunology , Vaccination , Young Adult
2.
Nature ; 616(7955): 77-83, 2023 04.
Article in English | MEDLINE | ID: mdl-37020008

ABSTRACT

Inorganic superionic conductors possess high ionic conductivity and excellent thermal stability but their poor interfacial compatibility with lithium metal electrodes precludes application in all-solid-state lithium metal batteries1,2. Here we report a LaCl3-based lithium superionic conductor possessing excellent interfacial compatibility with lithium metal electrodes. In contrast to a Li3MCl6 (M = Y, In, Sc and Ho) electrolyte lattice3-6, the UCl3-type LaCl3 lattice has large, one-dimensional channels for rapid Li+ conduction, interconnected by La vacancies via Ta doping and resulting in a three-dimensional Li+ migration network. The optimized Li0.388Ta0.238La0.475Cl3 electrolyte exhibits Li+ conductivity of 3.02 mS cm-1 at 30 °C and a low activation energy of 0.197 eV. It also generates a gradient interfacial passivation layer to stabilize the Li metal electrode for long-term cycling of a Li-Li symmetric cell (1 mAh cm-2) for more than 5,000 h. When directly coupled with an uncoated LiNi0.5Co0.2Mn0.3O2 cathode and bare Li metal anode, the Li0.388Ta0.238La0.475Cl3 electrolyte enables a solid battery to run for more than 100 cycles with a cutoff voltage of 4.35 V and areal capacity of more than 1 mAh cm-2. We also demonstrate rapid Li+ conduction in lanthanide metal chlorides (LnCl3; Ln = La, Ce, Nd, Sm and Gd), suggesting that the LnCl3 solid electrolyte system could provide further developments in conductivity and utility.

4.
Nat Immunol ; 17(10): 1187-96, 2016 10.
Article in English | MEDLINE | ID: mdl-27487330

ABSTRACT

During unresolved infections, some viruses escape immunological control and establish a persistant reservoir in certain cell types, such as human immunodeficiency virus (HIV), which persists in follicular helper T cells (TFH cells), and Epstein-Barr virus (EBV), which persists in B cells. Here we identified a specialized group of cytotoxic T cells (TC cells) that expressed the chemokine receptor CXCR5, selectively entered B cell follicles and eradicated infected TFH cells and B cells. The differentiation of these cells, which we have called 'follicular cytotoxic T cells' (TFC cells), required the transcription factors Bcl6, E2A and TCF-1 but was inhibited by the transcriptional regulators Blimp1, Id2 and Id3. Blimp1 and E2A directly regulated Cxcr5 expression and, together with Bcl6 and TCF-1, formed a transcriptional circuit that guided TFC cell development. The identification of TFC cells has far-reaching implications for the development of strategies to control infections that target B cells and TFH cells and to treat B cell-derived malignancies.


Subject(s)
Arenaviridae Infections/immunology , B-Lymphocytes/immunology , Epstein-Barr Virus Infections/immunology , HIV/immunology , Lymphocytic choriomeningitis virus/immunology , T-Lymphocytes, Cytotoxic/immunology , Animals , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Cell Differentiation , Cells, Cultured , Gene Expression Regulation , Germinal Center/pathology , Germinal Center/virology , Hepatocyte Nuclear Factor 1-alpha/genetics , Hepatocyte Nuclear Factor 1-alpha/metabolism , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Positive Regulatory Domain I-Binding Factor 1 , Proto-Oncogene Proteins c-bcl-6/genetics , Proto-Oncogene Proteins c-bcl-6/metabolism , Receptors, CXCR5/genetics , Receptors, CXCR5/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
5.
Immunity ; 49(4): 695-708.e4, 2018 10 16.
Article in English | MEDLINE | ID: mdl-30291027

ABSTRACT

B cells can present antigens to CD4+ T cells, but it is thought that dendritic cells (DCs) are the primary initiators of naive CD4+ T cell responses. Nanoparticles, including virus-like particles (VLPs), are attractive candidates as carriers for vaccines and drug delivery. Using RNA phage Qß-derived VLP (Qß-VLP) as a model antigen, we found that antigen-specific B cells were the dominant antigen-presenting cells that initiated naive CD4+ T cell activation. B cells were sufficient to induce T follicular helper cell development in the absence of DCs. Qß-specific B cells promoted CD4+ T cell proliferation and differentiation via cognate interactions and through Toll-like receptor signaling-mediated cytokine production. Antigen-specific B cells were also involved in initiating CD4+ T cell responses during immunization with inactivated influenza virus. These findings have implications for the rational design of nanoparticles as vaccine candidates, particularly for therapeutic vaccines that aim to break immune tolerance.


Subject(s)
Antigen-Presenting Cells/immunology , B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , Immunization/methods , Influenza Vaccines/immunology , Animals , Antigen Presentation/immunology , Antigens, Viral/chemistry , Antigens, Viral/immunology , Cell Differentiation/immunology , Cytokines/immunology , Cytokines/metabolism , Influenza A Virus, H1N1 Subtype/immunology , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Nanoparticles/chemistry , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Helper-Inducer/metabolism , Toll-Like Receptors/immunology , Vaccines, Inactivated/immunology
6.
Immunity ; 47(1): 159-170.e10, 2017 07 18.
Article in English | MEDLINE | ID: mdl-28723548

ABSTRACT

Clearance of pathogens or tumor cells by antibodies traditionally requires both Fab and Fc domains of IgG. Here, we show the Fc domain of IgG alone mediates recognition and clearance of herpes simplex virus (HSV1)-infected cells. The human natural killer (NK) cell surface is naturally coated with IgG bound by its Fc domain to the Fcγ receptor CD16a. NK cells utilize the Fc domain of bound IgG to recognize gE, an HSV1-encoded glycoprotein that also binds the Fc domain of IgG but at a site distinct from CD16a. The bridge formed by the Fc domain between the HSV1-infected cell and the NK cell results in NK cell activation and lysis of the HSV1-infected cell in the absence of HSV1-specific antibody in vitro and prevents fatal HSV1 infection in vivo. This mechanism also explains how bacterial IgG-binding proteins regulate NK cell function and may be broadly applicable to Fcγ-receptor-bearing cells.


Subject(s)
Antibodies, Viral/metabolism , Herpes Simplex/immunology , Immunoglobulin Fc Fragments/metabolism , Immunoglobulin G/metabolism , Killer Cells, Natural/immunology , Simplexvirus/immunology , Animals , Antibodies, Viral/immunology , Cells, Cultured , Cytotoxicity, Immunologic , Female , Humans , Immunoglobulin Fc Fragments/immunology , Immunoglobulin G/immunology , Lymphocyte Activation , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Protein Binding , Receptor Aggregation , Receptors, IgG/metabolism , Signal Transduction , Viral Proteins/immunology
7.
Mol Cell ; 72(3): 525-540.e13, 2018 11 01.
Article in English | MEDLINE | ID: mdl-30318443

ABSTRACT

Functions of many long noncoding RNAs (lncRNAs) depend on their ability to interact with multiple copies of specific RNA-binding proteins (RBPs). Here, we devised a workflow combining bioinformatics and experimental validation steps to systematically identify RNAs capable of multivalent RBP recruitment. This uncovered a number of previously unknown transcripts encoding high-density RBP recognition arrays within genetically normal short tandem repeats. We show that a top-scoring hit in this screen, lncRNA PNCTR, contains hundreds of pyrimidine tract-binding protein (PTBP1)-specific motifs allowing it to sequester a substantial fraction of PTBP1 in a nuclear body called perinucleolar compartment. Importantly, PNCTR is markedly overexpressed in a variety of cancer cells and its downregulation is sufficient to induce programmed cell death at least in part by stimulating PTBP1 splicing regulation activity. This work expands our understanding of the repeat-containing fraction of the human genome and illuminates a novel mechanism driving malignant transformation of cancer cells.


Subject(s)
Alternative Splicing/physiology , Heterogeneous-Nuclear Ribonucleoproteins/physiology , Polypyrimidine Tract-Binding Protein/physiology , RNA-Binding Proteins/physiology , Alternative Splicing/genetics , Cell Line , Cell Movement , Cell Nucleus , Cell Proliferation , Cell Survival , Computational Biology/methods , Exons , Heterogeneous-Nuclear Ribonucleoproteins/metabolism , Humans , Microsatellite Repeats/genetics , Microsatellite Repeats/physiology , Polypyrimidine Tract-Binding Protein/metabolism , Pyrimidines , RNA Splicing , RNA, Long Noncoding/physiology
8.
Proc Natl Acad Sci U S A ; 120(22): e2220148120, 2023 05 30.
Article in English | MEDLINE | ID: mdl-37216506

ABSTRACT

Exploring the potential lead compounds for Alzheimer's disease (AD) remains one of the challenging tasks. Here, we report that the plant extract conophylline (CNP) impeded amyloidogenesis by preferentially inhibiting BACE1 translation via the 5' untranslated region (5'UTR) and rescued cognitive decline in an animal model of APP/PS1 mice. ADP-ribosylation factor-like protein 6-interacting protein 1 (ARL6IP1) was then found to mediate the effect of CNP on BACE1 translation, amyloidogenesis, glial activation, and cognitive function. Through analysis of the 5'UTR-targetd RNA-binding proteins by RNA pulldown combined with LC-MS/MS, we found that FMR1 autosomal homolog 1 (FXR1) interacted with ARL6IP1 and mediated CNP-induced reduction of BACE1 by regulating the 5'UTR activity. Without altering the protein levels of ARL6IP1 and FXR1, CNP treatment promoted ARL6IP1 interaction with FXR1 and inhibited FXR1 binding to the 5'UTR both in vitro and in vivo. Collectively, CNP exhibited a therapeutic potential for AD via ARL6IP1. Through pharmacological manipulation, we uncovered a dynamic interaction between FXR1 and the 5'UTR in translational control of BACE1, adding to the understanding of the pathophysiology of AD.


Subject(s)
Alzheimer Disease , Animals , Mice , 5' Untranslated Regions , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Amyloid Precursor Protein Secretases/genetics , Amyloid Precursor Protein Secretases/metabolism , Aspartic Acid Endopeptidases/genetics , Aspartic Acid Endopeptidases/metabolism , Chromatography, Liquid , Fragile X Mental Retardation Protein/genetics , Protein Biosynthesis , Tandem Mass Spectrometry
9.
Plant Physiol ; 195(3): 2289-2308, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38466723

ABSTRACT

The production of glutamine (Gln) from NO3- and NH4+ requires ATP, reducing power, and carbon skeletons. Plants may redirect these resources to other physiological processes using Gln directly. However, feeding Gln as the sole nitrogen (N) source has complex effects on plants. Under optimal concentrations, Arabidopsis (Arabidopsis thaliana) seedlings grown on Gln have similar primary root lengths, more lateral roots, smaller leaves, and higher amounts of amino acids and proteins compared to those grown on NH4NO3. While high levels of Gln accumulate in Arabidopsis seedlings grown on Gln, the expression of GLUTAMINE SYNTHETASE1;1 (GLN1;1), GLN1;2, and GLN1;3 encoding cytosolic GS1 increases and expression of GLN2 encoding chloroplastic GS2 decreases. These results suggest that Gln has distinct effects on regulating GLN1 and GLN2 gene expression. Notably, Arabidopsis seedlings grown on Gln have an unexpected gene expression profile. Compared with NH4NO3, which activates growth-promoting genes, Gln preferentially induces stress- and defense-responsive genes. Consistent with the gene expression data, exogenous treatment with Gln enhances disease resistance in Arabidopsis. The induction of Gln-responsive genes, including PATHOGENESIS-RELATED1, SYSTEMIC ACQUIRED RESISTANCE DEFICIENT1, WRKY54, and WALL ASSOCIATED KINASE1, is compromised in salicylic acid (SA) biosynthetic and signaling mutants under Gln treatments. Together, these results suggest that Gln may partly interact with the SA pathway to trigger plant immunity.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Disease Resistance , Gene Expression Regulation, Plant , Glutamine , Plant Roots , Stress, Physiological , Arabidopsis/genetics , Arabidopsis/physiology , Arabidopsis/growth & development , Arabidopsis/drug effects , Glutamine/metabolism , Plant Roots/genetics , Plant Roots/growth & development , Plant Roots/metabolism , Stress, Physiological/genetics , Disease Resistance/genetics , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Plant Diseases/genetics , Plant Diseases/immunology , Seedlings/genetics , Seedlings/growth & development , Seedlings/drug effects , Glutamate-Ammonia Ligase/metabolism , Glutamate-Ammonia Ligase/genetics
10.
J Proteome Res ; 23(3): 939-955, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38364797

ABSTRACT

N-Linked glycosylation is one of the most essential post-translational modifications of proteins. However, N-glycan structural determination remains challenging because of the small differences in structures between isomers. In this study, we constructed a database containing collision-induced dissociation MSn mass spectra and chromatograms of high-performance liquid chromatography for the rapid identification of high-mannose and paucimannose N-glycan isomers. These N-glycans include isomers by breaking of arbitrary numbers of glycosidic bonds at arbitrary positions of canonical Man9GlcNAc2 N-glycans. In addition, some GlcMannGlcNAc2 N-glycan isomers were included in the database. This database is particularly useful for the identification of the N-glycans not in conventional N-glycan standards. This study demonstrated the application of the database to structural assignment for high-mannose N-glycans extracted from bovine whey proteins, soybean proteins, human mammary epithelial cells, and human breast carcinoma cells. We found many N-glycans that are not expected to be generated by conventional biosynthetic pathways of multicellular eukaryotes.


Subject(s)
Breast , Mannose , Humans , Animals , Cattle , Chromatography, High Pressure Liquid , Databases, Factual , Polysaccharides
11.
Plant Physiol ; 192(2): 1532-1547, 2023 05 31.
Article in English | MEDLINE | ID: mdl-36843191

ABSTRACT

Nutrient sensing and signaling are critical for plants to coordinate growth and development in response to nutrient availability. Plant ACT DOMAIN REPEAT (ACR) proteins have been proposed to serve as nutrient sensors, but their functions remain largely unknown. Here, we showed that Arabidopsis (Arabidopsis thaliana) ACR9 might function as a repressor in glucose (Glc) signaling pathways. ACR9 was highly expressed in the leaves, and its expression was downregulated by sugars. Interestingly, the acr9-1 and acr9-2 T-DNA insertion mutants were hypersensitive to Glc during seedling growth, development, and anthocyanin accumulation. Nitrogen deficiency increased the mutants' sensitivity to Glc. The expression of sugar-responsive genes was also significantly enhanced in the acr9 mutants. By contrast, the 35S:ACR9 and 35S:ACR9-GFP overexpression (OE) lines were insensitive to Glc during early seedling development. The Glc signaling pathway is known to interact with the plant hormone abscisic acid (ABA). Notably, the acr9 mutants were also hypersensitive to ABA during early seedling development. The Glc sensor HEXOKINASE1 (HXK1) and the energy sensor SUCROSE NON-FERMENTING1 (SNF1)-RELATED PROTEIN KINASE1 (SnRK1) are key components of the Glc signaling pathways. The acr9-1/hxk1-3 and acr9-1/snrk1 double mutants were no longer hypersensitive to Glc, indicating that functional HXK1 and SnRK1 were required for the acr9-1 mutant to be hypersensitive to Glc. Together, these results suggest that ACR9 is a repressor of the Glc signaling pathway, which may act independently or upstream of the HXK1-SnRK1 signaling module.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Glucose/metabolism , Arabidopsis Proteins/metabolism , Plant Growth Regulators/metabolism , Abscisic Acid/metabolism , Signal Transduction/physiology , Gene Expression Regulation, Plant , Protein Serine-Threonine Kinases/metabolism
12.
BMC Cancer ; 24(1): 538, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38678181

ABSTRACT

BACKGROUND: Patients with immunocompromise were suspected to encounter a high risk for severe coronavirus disease 2019 (COVID-19) infection on early period; however, data is lacking nowadays and immune response remain unclear. METHODS: In this retrospective study, internet questionnaire survey and medical records were acquired in pediatric hematology oncology patients. Clinical severity, immunological characteristics, and outcomes were analyzed from December 1, 2022 to January 31, 2023 at the 3rd year of pandemic in China. RESULTS: A total of 306 patients were included, with 21 patients (6.9%) asymptomatic, 262 (85.6%) mild severity, 17 (5.6%) moderate severity, 5 (1.6%) severe severity, and 1 (0.3%) critical severity. Seventy-eight (25.5%) patients were on intensive chemotherapy, and 32.0% children were on maintenance chemotherapy. Delays in cancer therapy occurred in 86.7% patients. Univariable analysis revealed active chemotherapy (P < 0.0001), long duration of symptom (P < 0.0001), low lymphocytes count (P = 0.095), low CD3 + and CD8 + T cell count (P = 0.013, P = 0.022), high percentage of CD4 + TCM (P = 0.016), and low percentage of transitional B cells (P = 0.045) were high risk factors for severe COVID-19 infection. Cox regression model showed that the absolute lymphocytes count (P = 0.027) and long duration of symptom (P = 0.002) were the independent factors for severity. Patients with CD8 + dominant and B cell depletion subtype wasn't related with severity, but had higher percentage of CD8 + effector memory T cells (TEM) and terminally differentiated effector memory T cells (TEMRA) (P < 0.001, P < 0.001), and a longer COVID-19 duration (P = 0.045). CONCLUSION: The severity was relatively mild in children with immunodeficiencies in the third year of COVID-19 pandemic. Low lymphocyte count and long duration of symptom were the independent risk factors with COVID-19 severity. Delays in cancer care remain a major concern and the long outcome is pending.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/immunology , COVID-19/epidemiology , COVID-19/complications , Child , Male , Female , Retrospective Studies , Child, Preschool , Adolescent , SARS-CoV-2/immunology , Immunophenotyping , China/epidemiology , Infant , Lymphocyte Count , Severity of Illness Index , Hematologic Neoplasms/immunology , Hematologic Neoplasms/complications , Neoplasms/immunology
13.
Mol Psychiatry ; 2023 Mar 13.
Article in English | MEDLINE | ID: mdl-36914810

ABSTRACT

Recent studies based on animal models of various neurological disorders have indicated that mitophagy, a selective autophagy that eliminates damaged and superfluous mitochondria through autophagic degradation, may be involved in various neurological diseases. As an important mechanism of cellular stress response, much less is known about the role of mitophagy in stress-related mood disorders. Here, we found that tumor necrosis factor-α (TNF-α), an inflammation cytokine that plays a particular role in stress responses, impaired the mitophagy in the medial prefrontal cortex (mPFC) via triggering degradation of an outer mitochondrial membrane protein, NIP3-like protein X (NIX). The deficits in the NIX-mediated mitophagy by TNF-α led to the accumulation of damaged mitochondria, which triggered synaptic defects and behavioral abnormalities. Genetic ablation of NIX in the excitatory neurons of mPFC caused passive coping behaviors to stress, and overexpression of NIX in the mPFC improved TNF-α-induced synaptic and behavioral abnormalities. Notably, ketamine, a rapid on-set and long-lasting antidepressant, reversed the TNF-α-induced behavioral abnormalities through activation of NIX-mediated mitophagy. Furthermore, the downregulation of NIX level was also observed in the blood of major depressive disorder patients and the mPFC tissue of animal models. Infliximab, a clinically used TNF-α antagonist, alleviated both chronic stress- and inflammation-induced behavioral abnormalities via restoring NIX level. Taken together, these results suggest that NIX-mediated mitophagy links inflammation signaling to passive coping behaviors to stress, which underlies the pathophysiology of stress-related emotional disorders.

14.
Mol Cell Biochem ; 479(4): 915-928, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37249813

ABSTRACT

Despite recent advances have been made in clinical treatments of breast cancer, the general prognosis of patients remains poor. Therefore, it is imperative to develop a more effective therapeutic strategy. Lysine demethylase 4B (KDM4B) has been reported to participate in breast cancer development recently, but its exact biological role in breast cancer remains unclear. Here, we observed that KDM4B was down-regulated in human primary BRCA tissues and the low levels of KDM4B expression were correlated with poor survival. Gain- and loss-of-function experiments showed that KDM4B inhibited the proliferation and metastasis of breast cancer cells. Besides, knockdown of KDM4B promoted the epithelial-mesenchymal transition (EMT) and cell stemness in breast cancer cells. Mechanistically, KDM4B down-regulates PHGDH by decreasing the enrichment of H3K36me3 on the promoter region of PHGDH. Knockdown of PHGDH could significantly reversed proliferation, migration, EMT, and cell stemness induced by KDM4B silencing in breast cancer cells. Collectively, we propose a model for a KDM4B/PHGDH axis that provides novel insight into breast cancer development, which may serve as a potential factor for predicting prognosis and a therapeutic target for breast cancer.


Subject(s)
Breast Neoplasms , Humans , Female , Up-Regulation , Down-Regulation , Breast Neoplasms/pathology , Cell Line, Tumor , Epithelial-Mesenchymal Transition , Jumonji Domain-Containing Histone Demethylases/genetics , Jumonji Domain-Containing Histone Demethylases/metabolism
15.
Int J Colorectal Dis ; 39(1): 121, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39085653

ABSTRACT

BACKGROUND: The relationship between fecal incontinence (FI) and type 2 diabetes (T2D) has been well recognized, but a comprehensive understanding of this relationship is lacking, taking into account demographic factors and lifestyle variables. METHODS: Using a cross-sectional approach, 13,510 adults aged 20 years and older were identified from the 2005-2010 National Health and Nutrition Examination Survey. Multivariate logistic regression models were used to calculate the adjusted odds ratios (ORs), and further subgroup analyses and propensity score analysis were performed to ensure stable results. RESULTS: Among 13,510 adults, 11.2% had T2D, and 8.8% had FI. We found a strong T2D-FI link (OR: 1.30; 95% CI: 1.09-1.54, P < 0.001), even after adjusting for covariates. Age > 45 was a critical factor, with a stronger T2D-FI association. Sedentary behavior (OR: 1.41; 95% CI: 1.15-1.73) in T2D patients were associated with FI. CONCLUSIONS: Our study highlights the significant T2D-FI link in US adults, especially in older T2D patients. Lifestyle changes may reduce FI risk. More research is needed for causality and mechanisms.


Subject(s)
Diabetes Mellitus, Type 2 , Fecal Incontinence , Humans , Fecal Incontinence/etiology , Fecal Incontinence/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Male , Female , Cross-Sectional Studies , Middle Aged , Adult , United States/epidemiology , Aged , Risk Factors , Sedentary Behavior , Odds Ratio , Nutrition Surveys , Young Adult
16.
Eur J Pediatr ; 183(4): 1901-1910, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38337095

ABSTRACT

The aim of the study was to determine the relationship between flatfoot morphology and body mass and height in children aged 6-12 years. A total of 6471 Chinese children (mean age 9.0 ± 1.9 years, 41% female) were assessed for foot morphometry, body height, and body mass index. Foot morphology, including foot length, width, girth, arch height, hallux valgus angle, and rearfoot valgus angle, was measured using a 3D laser scanner. Flatfoot evaluations were conducted using the Sztriter-Godunov index (KY) from footprints. All measurements were analyzed by age and sex using the mean values of the left and right sides. Comparisons were performed between flatfoot groups, between body mass index (BMI) groups, and between body height groups. The study revealed a significant decrease in the incidence of bipedal flatfoot with age (p < 0.001), whereas the prevalence of obesity remained consistent (p > 0.05). Bipedal flatfoot was associated with distinct morphological changes, including lower arches, reduced instep height, diminished ankle heights and a greater rearfoot valgus angle (p < 0.05). When comparing the BMI groups, overweight children had larger and thicker feet (p < 0.05), but no differences were found in arch height and ankle height (p > 0.05). When comparing the body height groups, short-statured children had a shorter feet girth, shorter arches, and shorter ankle height (p < 0.05), but no differences were found in the rearfoot valgus angle (p > 0.05). CONCLUSION: The main characteristics of flat feet include lower arches and instep heights and ankle heights but higher rearfoot valgus angles. In general, overweight children's feet do not have the common features of flat feet. In contrast, short children had similar features of flatfoot except for rearfoot valgus. Assessment of posture, such as rearfoot valgus, can be critical in identifying children with flat feet. WHAT IS KNOWN: • The morphology of children's feet is associated with body growth, but the relationship between flatfeet and body mass and height remains controversial. WHAT IS NEW: • Three-dimensional foot measurement shows that body mass is generally not associated with flatfeet, while short children have lower arches but no rearfoot valgus.


Subject(s)
Flatfoot , Child , Humans , Female , Male , Flatfoot/epidemiology , Flatfoot/complications , Overweight , Body Height , Foot/anatomy & histology , Obesity/complications
17.
Graefes Arch Clin Exp Ophthalmol ; 262(2): 519-526, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37594511

ABSTRACT

BACKGROUND: Corneal perforation is an ophthalmic emergency. The conventional management of corneal perforation can be associated with severe complications especially in patients with ocular surface disease. Endothelial keratoplasty has been suggested as an alternative surgical technique for the management of corneal perforations. We present a case series of nine patients with corneal perforation and ocular surface disease managed with secondary patch endothelial keratoplasty. METHODS: This is a retrospective case series of nine patch endothelial keratoplasties performed between 2016 and 2022 at a quaternary eye hospital in Australia. The surgical technique is similar to conventional endothelial keratoplasty except descemetorhexis was not performed. RESULTS: A total of 9 cases were treated during the review period. Eight of the nine cases had an improvement in visual acuity. One case failed to achieve corneal tectonic objective. CONCLUSION: Patch endothelial keratoplasty is a safe secondary procedure for the management of corneal perforations in patients with ocular surface disease.


Subject(s)
Corneal Diseases , Corneal Perforation , Corneal Transplantation , Humans , Corneal Perforation/diagnosis , Corneal Perforation/etiology , Corneal Perforation/surgery , Retrospective Studies , Corneal Transplantation/methods , Cornea/surgery , Visual Acuity , Keratoplasty, Penetrating/methods , Corneal Diseases/diagnosis , Corneal Diseases/etiology , Corneal Diseases/surgery
18.
Am J Respir Crit Care Med ; 207(7): 908-920, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36288294

ABSTRACT

Rationale: Emerging data support the existence of a microbial "gut-lung" axis that remains unexplored in bronchiectasis. Methods: Prospective and concurrent sampling of gut (stool) and lung (sputum) was performed in a cohort of n = 57 individuals with bronchiectasis and subjected to bacteriome (16S rRNA) and mycobiome (18S Internal Transcribed Spacer) sequencing (total, 228 microbiomes). Shotgun metagenomics was performed in a subset (n = 15; 30 microbiomes). Data from gut and lung compartments were integrated by weighted similarity network fusion, clustered, and subjected to co-occurrence analysis to evaluate gut-lung networks. Murine experiments were undertaken to validate specific Pseudomonas-driven gut-lung interactions. Results: Microbial communities in stable bronchiectasis demonstrate a significant gut-lung interaction. Multibiome integration followed by unsupervised clustering reveals two patient clusters, differing by gut-lung interactions and with contrasting clinical phenotypes. A high gut-lung interaction cluster, characterized by lung Pseudomonas, gut Bacteroides, and gut Saccharomyces, is associated with increased exacerbations and greater radiological and overall bronchiectasis severity, whereas the low gut-lung interaction cluster demonstrates an overrepresentation of lung commensals, including Prevotella, Fusobacterium, and Porphyromonas with gut Candida. The lung Pseudomonas-gut Bacteroides relationship, observed in the high gut-lung interaction bronchiectasis cluster, was validated in a murine model of lung Pseudomonas aeruginosa infection. This interaction was abrogated after antibiotic (imipenem) pretreatment in mice confirming the relevance and therapeutic potential of targeting the gut microbiome to influence the gut-lung axis. Metagenomics in a subset of individuals with bronchiectasis corroborated our findings from targeted analyses. Conclusions: A dysregulated gut-lung axis, driven by lung Pseudomonas, associates with poorer clinical outcomes in bronchiectasis.


Subject(s)
Bronchiectasis , Microbiota , Animals , Mice , Prospective Studies , RNA, Ribosomal, 16S/genetics , Lung/microbiology , Bronchiectasis/drug therapy
19.
BMC Ophthalmol ; 24(1): 259, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38880899

ABSTRACT

BACKGROUND: The anatomic structure of the anterior chamber (AC) helps to explain differences in refractive status in school-aged children and is closely associated with primary angle closure (PAC). The aim of this study was to quantify and analyze the anterior chamber and angle (ACA) characteristics in Chinese children with different refractive status by swept-source optical coherence tomography (SS-OCT). METHODS: In a cross-sectional observational study, 383 children from two primary schools in Shandong Province, China, underwent a complete ophthalmic examination. First, the anterior chamber depth (ACD), anterior chamber width (ACW), angle-opening distance (AOD), and trabecular-iris space area (TISA) were evaluated automatically using a CASIA2 imaging device. AOD and TISA were measured at 500, 750 µm nasal (N1 and N2, respectively), and temporal (T1 and T2, respectively) to the scleral spur (SS). Cycloplegic refraction and axial length (AL) were then measured. According to spherical equivalent refraction (SER), the children were assigned to hyperopic (SER > 0.50D), emmetropic (-0.50D < SER ≤ 0.50D), and myopic groups (SER ≤ -0.50D). RESULTS: Out of the 383 children, 349 healthy children (160 girls) with a mean age of 8.23 ± 1.06 years (range: 6-11 years) were included. The mean SER and AL were - 0.10 ± 1.57D and 23.44 ± 0.95 mm, respectively. The mean ACD and ACW were 3.17 ± 0.24 mm and 11.69 ± 0.43 mm. The mean AOD were 0.72 ± 0.25, 0.63 ± 0.22 mm at N1, T1, and 0.98 ± 0.30, 0.84 ± 0.27 mm at N2, T2. The mean TISA were 0.24 ± 0.09, 0.22 ± 0.09mm2 at N1, T1, and 0.46 ± 0.16, 0.40 ± 0.14mm2 at N2, T2. The myopic group had the deepest AC and the widest angle. Compared with boys, girls had shorter AL, shallower ACD, narrower ACW, and ACA (all p < 0.05). By Pearson's correlation analysis, SER was negatively associated with ACD, AOD, and TISA. AL was positively associated with ACD, ACW, AOD, and TISA. In the multiple regression analysis, AOD and TISA were associated with deeper ACD, narrower ACW, and longer AL. CONCLUSION: In primary school students, the myopic eyes have deeper AC and wider angle. ACD, ACW, AOD, and TISA all increase with axial elongation. ACA is highly correlated with deeper ACD.


Subject(s)
Anterior Chamber , Refraction, Ocular , Tomography, Optical Coherence , Humans , Tomography, Optical Coherence/methods , Cross-Sectional Studies , Child , Female , Male , Anterior Chamber/diagnostic imaging , Anterior Chamber/pathology , China/epidemiology , Refraction, Ocular/physiology , Glaucoma, Angle-Closure/physiopathology , Glaucoma, Angle-Closure/diagnosis , Glaucoma, Angle-Closure/ethnology , Refractive Errors/physiopathology , East Asian People
20.
Article in English | MEDLINE | ID: mdl-38909990

ABSTRACT

BACKGROUND: This study was designed to assess stress levels and related factors during the coronavirus disease 2019 (COVID-19) epidemic among individuals in centralized quarantine camps in Wenzhou, China. METHODS: The survey was conducted using a questionnaire. The questionnaire included questions on sociodemographic characteristics, life events related to the COVID-19 and stressful situations, as well as Perceived Stress Scale-14. Participants included close contacts of patients with COVID-19 or at-risk individuals in quarantine camps. Multivariate logistic regression was used to analyze different factors affecting perceived stress. RESULTS: The prevalence of high stress among quarantine camp participants was 37.45%. Of the 881 respondents, 51.99% were concerned about the difficulty of controlling the epidemic, 46.20% were concerned about the health of themselves and their family members and 39.61% were concerned about not being able to leave their homes. Multivariate logistic regression analysis revealed statistically significant differences in the prevalence of stress among different groups for certain variables, including occupation, education level and knowledge of COVID-19 (all P < 0.05). Our study found that at-risk individuals and close contacts experienced high levels of stress in quarantine camps during the COVID-19 pandemic. CONCLUSIONS: These findings suggest that centralized quarantine policies should be adapted and optimized to minimize negative psychological effects on quarantined individuals.

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