ABSTRACT
Chronic inflammation is a common feature of obesity, with elevated cytokines such as interleukin-1 (IL-1) in the circulation and tissues. Here, we report an unconventional IL-1R-MyD88-IRAK2-PHB/OPA1 signaling axis that reprograms mitochondrial metabolism in adipocytes to exacerbate obesity. IL-1 induced recruitment of IRAK2 Myddosome to mitochondria outer membranes via recognition by TOM20, followed by TIMM50-guided translocation of IRAK2 into mitochondria inner membranes, to suppress oxidative phosphorylation and fatty acid oxidation, thereby attenuating energy expenditure. Adipocyte-specific MyD88 or IRAK2 deficiency reduced high-fat-diet-induced weight gain, increased energy expenditure and ameliorated insulin resistance, associated with a smaller adipocyte size and increased cristae formation. IRAK2 kinase inactivation also reduced high-fat diet-induced metabolic diseases. Mechanistically, IRAK2 suppressed respiratory super-complex formation via interaction with PHB1 and OPA1 upon stimulation of IL-1. Taken together, our results suggest that the IRAK2 Myddosome functions as a critical link between inflammation and metabolism, representing a novel therapeutic target for patients with obesity.
Subject(s)
Adipocytes/immunology , Inflammation/immunology , Interleukin-1 Receptor-Associated Kinases/metabolism , Interleukin-1/metabolism , Mitochondrial Membranes/metabolism , Obesity/immunology , Adipocytes/pathology , Animals , Cells, Cultured , Humans , Interleukin-1 Receptor-Associated Kinases/genetics , Male , Mice , Mice, Knockout , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/metabolism , Oxidative Phosphorylation , Prohibitins , Protein Transport , Receptors, Interleukin-1/metabolism , Signal TransductionABSTRACT
Chromothripsis is a catastrophic cellular event recently described in cancer in which chromosomes undergo massive deletion and rearrangement. Here, we report a case in which chromothripsis spontaneously cured a patient with WHIM syndrome, an autosomal dominant combined immunodeficiency disease caused by gain-of-function mutation of the chemokine receptor CXCR4. In this patient, deletion of the disease allele, CXCR4(R334X), as well as 163 other genes from one copy of chromosome 2 occurred in a hematopoietic stem cell (HSC) that repopulated the myeloid but not the lymphoid lineage. In competitive mouse bone marrow (BM) transplantation experiments, Cxcr4 haploinsufficiency was sufficient to confer a strong long-term engraftment advantage of donor BM over BM from either wild-type or WHIM syndrome model mice, suggesting a potential mechanism for the patient's cure. Our findings suggest that partial inactivation of CXCR4 may have general utility as a strategy to promote HSC engraftment in transplantation.
Subject(s)
Chromosomal Instability , Immunologic Deficiency Syndromes/genetics , Warts/genetics , Animals , Chromosomes, Human , Disease Models, Animal , Haploinsufficiency , Hematopoietic Stem Cells/metabolism , Humans , Lymphocytes/metabolism , Male , Mice , Middle Aged , Mosaicism , Mutation , Myeloid Cells/metabolism , Primary Immunodeficiency Diseases , Receptors, CXCR4/genetics , Remission, SpontaneousABSTRACT
Act1 is an essential adaptor in interleukin 17 (IL-17)-mediated signaling and is recruited to the receptor for IL-17 after stimulation with IL-17. Here we found that Act1 was a 'client' protein of the molecular chaperone hsp90. The D10N variant of Act1 (Act1(D10N)) that is linked to susceptibility to psoriasis was defective in its interaction with hsp90, which resulted in a global loss of Act1 function. Act1-deficient mice modeled the mechanistic link between loss of Act1 function and susceptibility to psoriasis. Although Act1 was necessary for IL-17-mediated inflammation, Act1-deficient mice had a hyperactive response of the T(H)17 subset of helper T cells and developed spontaneous IL-22-dependent skin inflammation. In the absence of IL-17 signaling, IL-22 was the main contributor to skin inflammation, which provides a molecular mechanism for the association of Act1(D10N) with psoriasis susceptibility.
Subject(s)
Connexin 43/metabolism , HSP90 Heat-Shock Proteins/metabolism , Molecular Chaperones/metabolism , Peptide Fragments/metabolism , Psoriasis/immunology , Th17 Cells/immunology , Animals , Cell Line , Connexin 43/genetics , Connexin 43/immunology , Disease Models, Animal , Genetic Predisposition to Disease , Humans , Interleukin-17/metabolism , Mice , Mice, Knockout , Molecular Chaperones/genetics , Mutation/genetics , Peptide Fragments/genetics , Peptide Fragments/immunology , Polymorphism, Genetic , Protein Binding/genetics , Protein Binding/immunology , Psoriasis/genetics , Signal TransductionABSTRACT
WHIM syndrome is an autosomal dominant immunodeficiency disorder caused by gain-of-function mutations in chemokine receptor CXCR4 that promote severe panleukopenia because of retention of mature leukocytes in the bone marrow (BM). We previously reported that Cxcr4-haploinsufficient (Cxcr4+/o) hematopoietic stem cells (HSCs) have a strong selective advantage for durable hematopoietic reconstitution over wild-type (Cxcr4+/+) and WHIM (Cxcr4+/w) HSCs and that a patient with WHIM was spontaneously cured by chromothriptic deletion of the disease allele in an HSC, suggesting that WHIM allele inactivation through gene editing may be a safe genetic cure strategy for the disease. We have developed a 2-step preclinical protocol of autologous hematopoietic stem and progenitor cell (HSPC) transplantation to achieve this goal. First, 1 copy of Cxcr4 in HSPCs was inactivated in vitro by CRISPR/Cas9 editing with a single guide RNA (sgRNA) that does not discriminate between Cxcr4+/w and Cxcr4+/+ alleles. Then, through in vivo natural selection, WHIM allele-inactivated cells were enriched over wild-type allele-inactivated cells. The WHIM allele-inactivated HSCs retained long-term pluripotency and selective hematopoietic reconstitution advantages. To our knowledge, this is the first example of gene therapy for an autosomal dominant gain-of-function disease using a disease allele inactivation strategy in place of the less efficient disease allele repair approach.
Subject(s)
Immunologic Deficiency Syndromes , Warts , Mice , Animals , Alleles , CRISPR-Cas Systems , RNA, Guide, CRISPR-Cas Systems , Immunologic Deficiency Syndromes/genetics , Immunologic Deficiency Syndromes/therapy , Warts/genetics , Warts/therapy , Genetic Therapy , Receptors, CXCR4/geneticsABSTRACT
Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is an ultra-rare combined primary immunodeficiency disease caused by heterozygous gain-of-function mutations in the chemokine receptor CXCR4. WHIM patients typically present with recurrent acute infections associated with myelokathexis (severe neutropenia due to bone marrow retention of mature neutrophils). Severe lymphopenia is also common, but the only associated chronic opportunistic pathogen is human papillomavirus and mechanisms are not clearly defined. In this study, we show that WHIM mutations cause more severe CD8 than CD4 lymphopenia in WHIM patients and WHIM model mice. Mechanistic studies in mice revealed selective and WHIM allele dose-dependent accumulation of mature CD8 single-positive cells in thymus in a cell-intrinsic manner due to prolonged intrathymic residence, associated with increased CD8 single-positive thymocyte chemotactic responses in vitro toward the CXCR4 ligand CXCL12. In addition, mature WHIM CD8+ T cells preferentially home to and are retained in the bone marrow in mice in a cell-intrinsic manner. Administration of the specific CXCR4 antagonist AMD3100 (plerixafor) in mice rapidly and transiently corrected T cell lymphopenia and the CD4/CD8 ratio. After lymphocytic choriomeningitis virus infection, we found no difference in memory CD8+ T cell differentiation or viral load between wild-type and WHIM model mice. Thus, lymphopenia in WHIM syndrome may involve severe CXCR4-dependent CD8+ T cell deficiency resulting in part from sequestration in the primary lymphoid organs, thymus, and bone marrow.
Subject(s)
Agammaglobulinemia , Heterocyclic Compounds , Immunologic Deficiency Syndromes , Lymphopenia , Neutropenia , Humans , Animals , Mice , Immunologic Deficiency Syndromes/genetics , Hematopoietic Stem Cell Mobilization/adverse effects , Agammaglobulinemia/complications , Agammaglobulinemia/genetics , Neutropenia/genetics , CD8-Positive T-Lymphocytes , Receptors, CXCR4/geneticsABSTRACT
Junctional adhesion molecular 3 (JAM3) is downregulated by hypermethylation in cancers but is unclear in cholangiocarcinoma. The JAM3 expression level was checked in cholangiocarcinoma cell lines and tissues. Methylated JAM3 was detected in cell lines, tissues and plasma cell-free DNAs (cfDNA). The roles of JAM3 in cholangiocarcinoma were studied by transfection of siRNA and pCMV3-JAM3. The survival analysis was based on the Gene Set Cancer Analysis (GSCA) database. JAM3 was downregulated in HCCC-9810 and HuCCT1 cell lines and tissues by hypermethylation. Methylated JAM3 was detected in cfDNAs with 53.3% sensitivity and 96.6% specificity. Transfection of pCMV3-JAM3 into HCCC-9810 and HuCCT1 induced apoptosis and suppressed cell proliferation, migration and invasion. The depletion of JAM3 in RBE cells using siRNA decreased apoptosis and increased cell proliferation, migration and invasion. Hypermethylation of JAM3 was associated with tumour differentiation, metastasis and TNM stage. Downregulation and hypermethylation of JAM3 were related to poor progression-free survival. Junctional adhesion molecular 3 may function as a tumour suppressor in cholangiocarcinoma. Methylated JAM3 DNA may represent a non-invasive molecular marker for the early detection of cholangiocarcinoma and prognosis.
Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Humans , Down-Regulation/genetics , Cholangiocarcinoma/diagnosis , Cholangiocarcinoma/genetics , Cholangiocarcinoma/metabolism , Biomarkers , Cell Proliferation/genetics , Bile Ducts, Intrahepatic/metabolism , Bile Duct Neoplasms/diagnosis , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/metabolism , RNA, Small Interfering/genetics , Cell Line, Tumor , Cell Movement/genetics , Gene Expression Regulation, Neoplastic , Cell Adhesion Molecules/genetics , Cell Adhesion Molecules/metabolismABSTRACT
BACKGROUND: R2R3-MYB transcription factors belong to one of the largest gene subfamilies in plants, and they are involved in diverse biological processes. However, the role of R2R3-MYB transcription factor subfamily genes in the response of rice (Oryza sativa L.) to salt stress has been rarely reported. RESULTS: In this study, we performed a genome-wide characterization and expression identification of rice R2R3-MYB transcription factor subfamily genes. We identified a total of 117 R2R3-MYB genes in rice and characterized their gene structure, chromosomal location, and cis-regulatory elements. According to the phylogenetic relationships and amino acid sequence homologies, the R2R3-MYB genes were divided into four groups. qRT-PCR of the R2R3-MYB genes showed that the expression levels of 10 genes significantly increased after 3 days of 0.8% NaCl treatment. We selected a high expression gene OsMYB2-115 for further analysis. OsMYB2-115 was highly expressed in the roots, stem, leaf, and leaf sheath. OsMYB2-115 was found to be localized in the nucleus, and the yeast hybrid assay showed that OsMYB2-115 has transcriptional activation activity. CONCLUSION: This result provides important information for the functional analyses of rice R2R3-MYB transcription factor subfamily genes related to the salt stress response and reveals that OsMYB2-115 may be an important gene associated with salt tolerance in rice.
Subject(s)
Gene Expression Regulation, Plant , Oryza , Phylogeny , Plant Proteins , Salt Stress , Transcription Factors , Oryza/genetics , Oryza/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Salt Stress/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Genome, Plant , Multigene Family , Gene Expression Profiling , Chromosomes, Plant/geneticsABSTRACT
We investigate optical transmission in cavity magnon polaritons and discover a complex multi-window magnetically induced transparency and a bistability with magnetic and optical characteristics. With the regulation of Kerr nonlinear effects and driven fields, a complex multi-window resonant transmission with fast and slow light effects appears, which includes transparency and absorption windows. The magnetically induced transparency and absorption can be explained by the destructive and constructive interference between different excitation pathways. Moreover, we demonstrate the bistability of magnons and photons with a hysteresis loop, where magnetic and optical bistabilities can induce and control each other. Our results pave a new way, to the best of our knowledge, for implementing a room-temperature multiband quantum memory.
ABSTRACT
PURPOSE: Dysphagia, a serious symptom of oral cancer, is also the most common. Further, patients who are more uncertain regarding their illness tend to catastrophize, which may affect their rehabilitation and long-term survival rate. Considering this relationship, this study aimed to investigate the occurrence of dysphagia in Chinese patients with oral cancer and explore the correlation between catastrophic cognition, illness uncertainty, and dysphagia. METHODS: Applying a cross-sectional design, convenience sampling was used to recruit 180 patients with oral cancer. Advanced statistical methods were employed to analyze the mediating effects of catastrophic cognition on illness uncertainty and dysphagia. RESULTS: Chinese patients with oral cancer had a mean dysphagia score of 52.88 ± 10.95. Catastrophic cognition and illness uncertainty in patients with oral cancer were significantly positively correlated (r = 0.447, P < 0.001). There was a significant negative correlation between dysphagia score and catastrophic cognition (r = -0.385, P < 0.001), and between dysphagia and illness uncertainty (r = -0.522, P < 0.001). Bootstrapping results indicated that the mediating effect of catastrophic cognition between illness uncertainty and dysphagia was -0.07 (95% CI: [-0.15, -0.03]) and significant, and the mediation effect accounted for 15.6% of the total effect. CONCLUSIONS: Chinese patients with oral cancer have poor swallowing function. Results suggest that catastrophic cognition partially mediated the relationship between illness uncertainty and dysphagia in patients with oral cancer. Medical staff can improve patients' swallowing function by reducing the level of catastrophic cognition via decreasing the level of illness uncertainty.
Subject(s)
Catastrophization , Cognition , Deglutition Disorders , Mouth Neoplasms , Adult , Aged , Female , Humans , Male , Middle Aged , China/epidemiology , Cross-Sectional Studies , Deglutition Disorders/etiology , Deglutition Disorders/psychology , East Asian People , Mouth Neoplasms/complications , Mouth Neoplasms/psychology , Surveys and Questionnaires , UncertaintyABSTRACT
AIM: WHIM (warts, hypogammaglobulinaemia, infections and myelokathexis) syndrome is a rare combined primary immunodeficiency disease caused by gain-of-function (GOF) mutations in the chemokine receptor CXCR4 and includes severe neutropenia as a common feature. Neutropenia is a known risk factor for periodontitis; however, a detailed periodontal evaluation of a WHIM syndrome cohort is lacking. This study aimed to establish the evidence base for the periodontal status of patients with WHIM syndrome. MATERIALS AND METHODS: Twenty-two adult WHIM syndrome patients and 22 age- and gender-matched healthy volunteers (HVs) were evaluated through a comprehensive medical and periodontal examination. A mouse model of WHIM syndrome was assessed for susceptibility to naturally progressing or inducible periodontitis. RESULTS: Fourteen patients with WHIM syndrome (63.6%) and one HV (4.5%) were diagnosed with Stage III/IV periodontitis. No WHIM patient presented with the early onset, dramatic clinical phenotypes typically associated with genetic forms of neutropenia. Age, but not the specific CXCR4 mutation or absolute neutrophil count, was associated with periodontitis severity in the WHIM cohort. Mice with a Cxcr4 GOF mutation did not exhibit increased alveolar bone loss in spontaneous or ligature-induced periodontitis. CONCLUSIONS: Overall, WHIM syndrome patients presented with an increased severity of periodontitis despite past and ongoing neutrophil mobilization treatments. GOF mutations in CXCR4 may be a risk factor for periodontitis in humans.
Subject(s)
Immunologic Deficiency Syndromes , Neutropenia , Periodontal Diseases , Periodontitis , Primary Immunodeficiency Diseases , Warts , Adult , Humans , Animals , Mice , Immunologic Deficiency Syndromes/complications , Immunologic Deficiency Syndromes/genetics , Immunologic Deficiency Syndromes/diagnosis , Primary Immunodeficiency Diseases/complications , Primary Immunodeficiency Diseases/genetics , Warts/genetics , Warts/therapy , Neutropenia/complications , Neutropenia/genetics , Periodontal Diseases/complications , Periodontal Diseases/genetics , Periodontitis/complications , Periodontitis/geneticsABSTRACT
BACKGROUND: Regulatory B cells (Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs (miRNAs), miR-29a-3p also inhibits translation by degrading the target mRNA, and yet the relationship between Bregs and miR-29a-3p has not yet been fully explored. This study aimed to investigate the impact of miR-29a-3p on the regulation of differentiation and immunosuppressive functions of memory Bregs (mBregs) and ultimately provide potentially effective therapies in inducing immune tolerance after liver transplantation. METHODS: Flow cytometry was employed to determine the levels of Bregs in peripheral blood mononuclear cells. TaqMan low-density array miRNA assays were used to identify the expression of different miRNAs, electroporation transfection was used to induce miR-29a-3p overexpression and knockdown, and dual luciferase reporter assay was used to verify the target gene of miR-29a-3p. RESULTS: In patients experiencing acute rejection after liver transplantation, the proportions and immunosuppressive function of mBregs in the circulating blood were significantly impaired. miR-29a-3p was found to be a regulator of mBregs differentiation. Inhibition of miR-29a-3p, which targeted nuclear factor of activated T cells 5 (NFAT5), resulted in a conspicuous boost in the differentiation and immunosuppressive function of mBregs. The inhibition of miR-29a-3p in CD19+ B cells was capable of raising the expression levels of NFAT5, thereby promoting B cells to differentiate into mBregs. In addition, the observed enhancement of differentiation and immunosuppressive function of mBregs upon miR-29a-3p inhibition was abolished by the knockdown of NFAT5 in B cells. CONCLUSIONS: miR-29a-3p was found to be a crucial regulator for mBregs differentiation and immunosuppressive function. Silencing miR-29a-3p could be a potentially effective therapeutic strategy for inducing immune tolerance after liver transplantation.
Subject(s)
Antigens, CD19 , B-Lymphocytes, Regulatory , CD24 Antigen , Cell Differentiation , Liver Transplantation , MicroRNAs , Humans , MicroRNAs/metabolism , MicroRNAs/genetics , B-Lymphocytes, Regulatory/immunology , B-Lymphocytes, Regulatory/metabolism , Antigens, CD19/metabolism , Antigens, CD19/genetics , Male , CD24 Antigen/metabolism , CD24 Antigen/genetics , Signal Transduction , Graft Rejection/immunology , Graft Rejection/genetics , Female , Transcription Factors/genetics , Transcription Factors/metabolism , Middle Aged , Immune Tolerance , Cells, Cultured , Adult , Phenotype , Immunologic MemoryABSTRACT
OBJECTIVE: To investigate whether simethicone expediates the remission of abdominal distension after laparoscopic cholecystectomy (LC). METHODS: This retrospective study involved LC patients who either received perioperative simethicone treatment or not. Propensity score matching (PSM) was employed to minimize bias. The primary endpoint was the remission rate of abdominal distension within 24 h after LC. Univariable and multivariable logistic regression analyses were conducted to identify independent risk factors affecting the early remission of abdominal distension after LC. Subsequently, a prediction model was established and validated. RESULTS: A total of 1,286 patients were divided into simethicone (n = 811) and non-simethicone groups (n = 475) as 2:1 PSM. The patients receiving simethicone had better remission rates of abdominal distension at both 24 h and 48 h after LC (49.2% vs. 34.7%, 83.9% vs. 74.8%, respectively), along with shorter time to the first flatus (14.6 ± 11.1 h vs. 17.2 ± 9.1 h, P < 0.001) compared to those without. Multiple logistic regression identified gallstone (OR = 0.33, P = 0.001), cholecystic polyp (OR = 0.53, P = 0.050), preoperative abdominal distention (OR = 0.63, P = 0.002) and simethicone use (OR = 1.89, P < 0.001) as independent factors contributing to the early remission of abdominal distension following LC. The prognosis model developed for predicting remission rates of abdominal distension within 24 h after LC yielded an area under the curve of 0.643 and internal validation a value of 0.644. CONCLUSIONS: Simethicone administration significantly enhanced the early remission of post-LC abdominal distension, particularly for patients who had gallstones, cholecystic polyp, prolonged anesthesia or preoperative abdominal distention. TRIAL REGISTRATION: ChiCTR2200064964 (24/10/2022).
Subject(s)
Cholecystectomy, Laparoscopic , Postoperative Complications , Propensity Score , Simethicone , Humans , Retrospective Studies , Female , Male , Middle Aged , Simethicone/therapeutic use , Simethicone/administration & dosage , Postoperative Complications/prevention & control , Adult , Treatment Outcome , Aged , Abdomen/surgeryABSTRACT
Liposomes serve as promising and versatile vehicles for drug delivery. Tracking these nanosized vesicles, particularly in vivo, is crucial for understanding their pharmacokinetics. This study introduces the design and synthesis of three new conjugated electrolyte (CE) molecules, which emit in the second near-infrared window (NIR-II), facilitating deeper tissue penetration. Additionally, these CEs, acting as biomimetics of lipid bilayers, demonstrate superior compatibility with lipid membranes compared to commonly used carbocyanine dyes like DiR. To counteract the aggregation-caused quenching effect, CEs employ a twisted backbone, as such their fluorescence intensities can effectively enhance after a fluorophore multimerization strategy. Notably, a "passive" method was employed to integrate CEs into liposomes during the liposome formation, and membrane incorporation efficiency was significantly promoted to nearly 100%. To validate the in vivo tracking capability, the CE-containing liposomes were functionalized with cyclic arginine-glycine-aspartic acid (cRGD) peptides, serving as tumor-targeting ligands. Clear fluorescent images visualizing tumor site in living mice were captured by collecting the NIR-II emission. Uniquely, these CEs exhibit additional emission peak in visible region, enabling in vitro subcellular analysis using routine confocal microscopy. These results underscore the potential of CEs as a new-generation of membrane-targeting probes to facilitate the liposome-based medicine research.
Subject(s)
Liposomes , Neoplasms , Mice , Animals , Liposomes/chemistry , Lipid Bilayers/chemistry , Biomimetics , Drug Delivery Systems , Fluorescent Dyes/chemistryABSTRACT
Starch accounts for up to 90% of the dry weight of rice endosperm and is a key determinant of grain quality. Although starch biosynthesis enzymes have been comprehensively studied, transcriptional regulation of starch-synthesis enzyme-coding genes (SECGs) is largely unknown. In this study, we explored the role of a NAC transcription factor, OsNAC24, in regulating starch biosynthesis in rice. OsNAC24 is highly expressed in developing endosperm. The endosperm of osnac24 mutants is normal in appearance as is starch granule morphology, while total starch content, amylose content, chain length distribution of amylopectin and the physicochemical properties of the starch are changed. In addition, the expression of several SECGs was altered in osnac24 mutant plants. OsNAC24 is a transcriptional activator that targets the promoters of six SECGs; OsGBSSI, OsSBEI, OsAGPS2, OsSSI, OsSSIIIa and OsSSIVb. Since both the mRNA and protein abundances of OsGBSSI and OsSBEI were decreased in the mutants, OsNAC24 functions to regulate starch synthesis mainly through OsGBSSI and OsSBEI. Furthermore, OsNAC24 binds to the newly identified motifs TTGACAA, AGAAGA and ACAAGA as well as the core NAC-binding motif CACG. Another NAC family member, OsNAP, interacts with OsNAC24 and coactivates target gene expression. Loss-of-function of OsNAP led to altered expression in all tested SECGs and reduced the starch content. These results demonstrate that the OsNAC24-OsNAP complex plays key roles in fine-tuning starch synthesis in rice endosperm and further suggest that manipulating the OsNAC24-OsNAP complex regulatory network could be a potential strategy for breeding rice cultivars with improved cooking and eating quality.
Subject(s)
Endosperm , Oryza , Endosperm/genetics , Endosperm/metabolism , Oryza/metabolism , Plant Breeding , Starch/metabolism , Amylopectin/metabolism , Amylose/metabolism , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
KEY MESSAGE: Mapping of QTLs for dorsal aleurone thickness (DAT) was performed using chromosome segment substitution lines in rice. Three QTLs, qDAT3.1, qDAT3.2, and qDAT7.1, were detected in multiple environments. As a specified endosperm cell type, the aleurone has an abundance of various nutrients. Increasing the number of aleurone layers is a practicable way of developing highly nutritious cereals. Identifying genes that can increase aleurone thickness is useful for the breeding of aleurone traits to improve the nutritional and health values of rice. Here, we found that iodine staining could efficiently distinguish the aleurone layers, which revealed great variation of the aleurone thickness in rice, especially at the dorsal side of the seed. Therefore, we used a population of chromosome segmental substitution lines (CSSLs) derived from Koshihikari and Nona Bokra for quantitative trait locus (QTL) analysis of the dorsal aleurone thickness (DAT). Three QTLs, qDAT3.1, qDAT3.2, and qDAT7.1, were detected in multiple seasons. Among these, qDAT3.2 colocalizes with Hd6 and Hd16, two QTLs previously identified to regulate the heading date of Koshihikari, explaining the negative correlation between the DAT and days to heading (DTH) in rice. We also provide evidence that early-heading ensures the filling of rice seed under a relatively high temperature to promote aleurone thickening. qDAT7.1, the most stable QTL expressed in different environments, functions independently from heading date. Although Nona Bokra has a lower DAT, its qDAT7.1 allele significantly increased DAT in rice, which was further validated using two near-isogenic lines (NILs). These findings pave the way for further gene cloning of aleurone-related QTLs and may aid the development of highly nutritious rice.
Subject(s)
Oryza , Quantitative Trait Loci , Oryza/genetics , Chromosomes, Plant , Plant BreedingABSTRACT
OBJECTIVE: To investigate the diagnostic value of computed tomography (CT) and magnetic resonance imaging (MRI) in ovarian malignant mesothelioma (OMM). METHODS: The clinical and imaging data of 10 pathologically-confirmed OMM patients were analyzed retrospectively. RESULT: (1) The patients were 27 years to 70 years old, with an average age of 57.2 ± 15.4 years. Seven patients reported abdominal distension and pain, 1 reported lower abdominal discomfort and decreased appetite, and 2 patients had no symptoms. (2) Two cases of localized OMM with incomplete semi-annular "capsule" observed around the localized OMM tumors were reported while 8 cases had diffuse OMM in which the tumor parenchyma showed isointense or slightly hypointense on T1WI, inhomogeneous hyperintense on T2WI, and obviously hyperintense on DWI, with obvious inhomogeneous enhancement after enhancement. Diffuse OMM was not mainly composed of ovarian masses and was mainly characterized by mild ovarian enlargement, nodular and irregular thickening of the peritoneum, cloudy omentum, unclear fat gap, and reticular or irregular thickening, which can fuse into a "cake-shape". (3) All 10 patients underwent surgery, while 9 patients underwent systemic chemotherapy or immunotherapy after surgery. All patients with localized OMM survived. Out of the 8 diffuse-type patients, 5 died, 1 was lost to follow-up, and 2 survived. CONCLUSION: OMM has certain clinical and imaging characteristics. There is no liquefaction, calcification, or partition in the tumor. The ovarian enlargement in the diffuse lesion is not significant. The diffuse thickening of the peritoneum and omentum with early appearance of mural nodules and ascites in the upper abdomen, help the diagnosis of OMM.
Subject(s)
Mesothelioma, Malignant , Ovarian Neoplasms , Female , Humans , Adult , Middle Aged , Aged , Mesothelioma, Malignant/diagnostic imaging , Retrospective Studies , Magnetic Resonance Imaging/methods , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/surgery , Tomography, X-Ray Computed/methodsABSTRACT
BACKGROUND: Patients' pain beliefs are the main obstacle to effective pain management. Assessing and correcting negative perceptions is important for improving pain intensity and quality of life of patients with cancer pain. AIMS: To explore pain beliefs among oral cancer patients using the Common-Sense Model of Self-Regulation as a theoretical framework. The primary components of the model, cognitive representations, emotional representations, and coping responses, were examined. DESIGN: A qualitative method was used. SETTINGS: PARTICIPANTS/SUBJECTS: ⯠METHODS: Semi-structured, qualitative, in-depth interviews were conducted with patients newly diagnosed with oral cancer in a tertiary care hospital. The interviews were analyzed using thematic analysis. RESULTS: Interviews with 15 patients revealed that the pain beliefs of patients with oral cancer included three themes: pain cognitive representations of oral cancer, pain emotional representations of oral cancer, and pain coping responses. CONCLUSIONS: Negative pain beliefs are common among oral cancer patients. This novel application of the self-regulatory model demonstrates that it can be used to capture the key pain beliefs (i.e., cognitions, emotions, and coping responses) of oral cancer patients within a single, unifying framework.
Subject(s)
Mouth Neoplasms , Pain Management , Pain , Quality of Life , Humans , Adaptation, Psychological , East Asian People , Emotions , Mouth Neoplasms/complications , Mouth Neoplasms/ethnology , Mouth Neoplasms/psychology , Pain/ethnology , Pain/etiology , Pain/psychology , Qualitative Research , Quality of Life/psychology , Pain Management/psychology , Health Knowledge, Attitudes, PracticeABSTRACT
BACKGROUND: The aim of this retrospective study was to compare the clinical outcomes of total endoscopic transaxillary (TET) breast augmentation with those of non-TET (NTET) breast augmentation. For the purposes of this study, the term NTET refers to the combination of blunt dissection and endoscopic techniques, whereas TET did not involve blunt dissection. METHODS: We conducted a retrospective review of 119 consecutive cases of primary breast augmentation from May 1, 2020, to August 31, 2020. The primary outcomes were the number of drainage days and pain scores as assessed using the visual analog scale on the first postoperative day. The secondary outcomes were the daily drainage volume recorded during the postoperative drainage days, the presence of postoperative daily pain that required the administration of tramadol for relief, reoperation rate, and operative time. RESULTS: The number of drainage days was significantly lower in the TET group than in the NTET group (TET vs NTET: 2.56 ± 0.57 vs 3.78 ± 1.30 days, P = 0.000). The visual analog scale score on the first postoperative day was significantly lower in the TET group than in the NTET group (TET vs NTET: 4.96 ± 0.63 vs 5.93 ± 0.93, P = 0.000). CONCLUSIONS: We observed that the major outcomes of the TET group were more favorable than those of the NTET group. Based on our results, we recommend the avoidance of blunt dissection during endoscopic transaxillary breast augmentation. LEVEL OF EVIDENCE: III.
Subject(s)
Breast Implantation , Humans , Breast Implantation/methods , Breast Implants , Endoscopy/methods , Mammaplasty , Pain, Postoperative/etiology , Retrospective StudiesABSTRACT
BACKGROUND: Acceptance-based pain management interventions have been receiving growing attention in cancer pain care. This study aimed to develop a cancer pain management program based on belief modification to improve the cancer pain experience of Chinese oral cancer survivors and to explore the acceptability and preliminary outcomes of the Cancer Pain Belief Modification Program (CPBMP). METHODS: A mixed-methods approach was applied to develop and revise the program. The CPBMP was developed and revised using the Delphi technique, and its further improvement was explored with a one-group pre- and post-trial designed with a sample of 16 Chinese oral cancer survivors, and semi-structured interviews. Research instruments included Numeric Rating Scale (NRS), Chinese version of Illness Perception Questionnaire-Revised for Cancer Pain (IPQ-CaCP), and the University of Washington Quality of Life assessment scale (UW-QOL). Descriptive statistics, t-test, and Mann-Whitney U test were used to analyse the data. The semi-structured questions were analysed using content analysis. RESULTS: The six-module CPBMP was endorsed by most experts and patients. The expert authority coefficient value was 0.75 in the first round of the Delphi survey and 0.78 in the second round. The "pain intense", "negative pain beliefs" scores of pre- and post-testing decreased from 5.63 ± 0.48 to 0.81 ± 0.54 (t = -3.746, p < 0.001); from 140.63 ± 9.02 to 52.75 ± 7.27 (Z = 12.406, p < 0.001); and the "positive pain beliefs", "quality of life" scores increased from 55.13 ± 4.54 to 66.00 ± 4.70 (Z = -6.983, p < 0.001); from 66.97 ± 15.01 to 86.69 ± 8.42 (Z = 7.283, p < 0.001). The qualitative data also indicated that CPBMP was well acceptable. CONCLUSION: Our study showed the acceptability and preliminary outcomes of CPBMP patients. CPBMP improves the pain experience of Chinese oral cancer patients and provides a reference for cancer pain management in the future. TRIAL REGISTRATION: The feasibility study has already been registered on the Chinese Clinical Trial Registry (ChiCTR) ( www.chictr.org.cn ) in 11/09/2021. (ChiCTR2100051065).
ABSTRACT
Background and Objectives: The modification of histone acetylation plays a vital role in regulating tumor occurrence and development, but the interaction between histone acetylation modulator genes and the liver hepatocellular carcinoma (LIHC) microenvironment, as well as immunotherapy, has not been investigated. Materials and Methods: Analysis of all statistical data was carried out using R software (Version 4.2.0) and the online tool Sangerbox. Comprehensive bioinformatics analysis, including signature construction and validation, functional analyses, immune and genomic features analyses, and immunotherapy prediction analyses, were performed to explore the prognostic and therapeutic role of histone acetylation modulator genes in LIHC development and progression. Results: The LIHC cohort from The Cancer Genome Atlas (TCGA) database was selected as the training cohort; the GSE76427 cohort from the Gene Expression Omnibus (GEO) database and the LIRI-JP cohort from the International Cancer Genome Consortium (ICGC) database were selected as the validation cohorts. The histone acetylation modulator gene-based prognostic signature was constructed and validated successfully. Immune infiltration analysis showed that most immune cells and immune functions were enriched in patients with high histone acetylation risk scores (HARS). Additionally, high levels of checkpoint inhibitors (ICIs) and human leukocyte antigens (HLAs) were also observed in high HARS patients. Meanwhile, TIDE algorithm analysis was conducted to explore the relationship between HARS and immunotherapy response, and submap algorithm analysis was used for the verification of the results, from which we found that high HAPS patients were more likely to respond to immunotherapy. Conclusions: Our findings revealed that the histone acetylation modulator genes, particularly for KAT21, SIRT6, and HAT1, may have the potential to function as a new prognostic marker and therapeutic target for LIHC.