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1.
Mol Cell ; 84(18): 3438-3454.e8, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39232583

ABSTRACT

Spreading of H3K27me3 is crucial for the maintenance of mitotically inheritable Polycomb-mediated chromatin silencing in animals and plants. However, how Polycomb repressive complex 2 (PRC2) accesses unmodified nucleosomes in spreading regions for spreading H3K27me3 remains unclear. Here, we show in Arabidopsis thaliana that the chromatin remodeler PICKLE (PKL) plays a specialized role in H3K27me3 spreading to safeguard cell identity during differentiation. PKL specifically localizes to H3K27me3 spreading regions but not to nucleation sites and physically associates with PRC2. Loss of PKL disrupts the occupancy of the PRC2 catalytic subunit CLF in spreading regions and leads to aberrant dedifferentiation. Nucleosome density increase endowed by the ATPase function of PKL ensures that unmodified nucleosomes are accessible to PRC2 catalytic activity for H3K27me3 spreading. Our findings demonstrate that PKL-dependent nucleosome compaction is critical for PRC2-mediated H3K27me3 read-and-write function in H3K27me3 spreading, thus revealing a mechanism by which repressive chromatin domains are established and propagated.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Cell Differentiation , Chromatin Assembly and Disassembly , Histones , Nucleosomes , Polycomb Repressive Complex 2 , Nucleosomes/metabolism , Nucleosomes/genetics , Arabidopsis/genetics , Arabidopsis/metabolism , Histones/metabolism , Histones/genetics , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Polycomb Repressive Complex 2/metabolism , Polycomb Repressive Complex 2/genetics , Gene Expression Regulation, Plant , Chromatin/metabolism , Chromatin/genetics
2.
Lasers Med Sci ; 39(1): 234, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39240409

ABSTRACT

Although the technologies for auricular reconstruction in microtia have improved, issues such as low hairlines or excessive hair growth can still pose aesthetic problems for the reconstructed ear. Laser depilation has been reported as a solution for hair problems. However, few studies have discussed the appropriate region for hair removal. A retrospective analysis was performed on 276 patients with unilateral microtia who underwent the Nagata two-stage ear reconstruction. The gender ratio of male to female was 2.5 (198 males/78 females). Intense pulsed light depilation was used to remove hair. To determine the proper hair removal area, we measured the extent of hair removal. Before the first stage, the average vertical distance between the upper point (after localization) and hairline was 3.42 ± 4.75 mm (-10-20 mm). After the first stage, the average vertical distance between the upper point of the reconstructed ear and the hairline was 1.27 ± 2.41 mm (-10-15 mm). By using chi-square test to assess differences in hair removal success rates among various regions, we aimed to identify the suitable depilation region. Before the first stage, a depilation vertical distance ≥ 10 mm led to a 92.1% success rate. After the first stage surgery, among the patients needing additional hair removal, a vertical depilation distance ≥ 4 mm resulted in an 81.3% success rate. Based on our observation, we suggested that a depilation region of ≥ 10 mm (before the first surgery) or ≥ 4 mm (after the first surgery) would be the ideal range for laser hair removal.


Subject(s)
Congenital Microtia , Hair Removal , Plastic Surgery Procedures , Humans , Female , Male , Retrospective Studies , Congenital Microtia/surgery , Hair Removal/methods , Plastic Surgery Procedures/methods , Adolescent , Young Adult , Adult , Child , Laser Therapy/methods , Laser Therapy/instrumentation
3.
Exp Cell Res ; 442(1): 114199, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39103070

ABSTRACT

Brain metastases account for more than 50 % of intracranial central nervous system tumors. The blood-brain barrier (BBB) is mainly composed of endothelial cells, which exhibit low endocytosis and high efflux pumps. Although they are connected by continuous tight junctions and serve as a protective insulation, the BBB does not prevent the development of brain metastases from non-small cell lung cancer (NSCLC). Improving understanding on the mechanisms underlying the development of brain metastasis and the differential molecular characteristics relative to the primary tumor are therefore key in the treatment of brain metastases. This study evaluated the differential expression of miR-522-3p in NSCLC and brain metastases using the Gene Expression Omnibus database. NSCLC brain metastasis model was constructed to screen for cell lines that demonstrated high potential for brain metastasis; We also observed differential expression of miRNA-522-3p in the paraffin-embedded specimens of non-small cell lung cancer and brain metastases from our hospital. The molecular biological functions of miRNA-522-3p were verified using 5-ethynyl-2'-deoxyuridine (EdU) proliferation assay and Transwell invasion assays. RNA-seq was employed to identify downstream target proteins, and the dual-luciferase reporter assay confirmed Tensin 1 (TNS1), a protein that links the actin cytoskeleton to the extracellular matrix, as the downstream regulatory target protein. In vitro blood-brain barrier models and co-culture models were constructed to further identify the role of miRNA-522-3p and TNS1; the expression of BBB-related proteins (ZO-1 and OLCN) was also identified. In vivo experiments were performed to verify the effects of miRNA-522-3p on the time and incidence of NSCLC brain metastasis. The results showed significantly high expression in GSE51666; consistent results were obtained in brain metastasis cells and paraffin samples. RNA-seq combined with miRNA target protein prediction demonstrated TNS1 to be directly downstream of miR-522-3p and to be associated with cell proliferation and invasion. By regulating ZO-1 and OCLN expression, mi-522-3p/TNS1 may increase tumor cell penetration through the BBB while decreasing its permeability. In vivo, miR-522-3p was further demonstrated to significantly promote the formation of brain metastases. miR-522-3p/TNS1 can affect BBB permeability and encourage the growth of brain metastases by modifying the BBB TJ proteins. This axis offers new therapeutic targets for the prevention of brain metastasis.


Subject(s)
Blood-Brain Barrier , Brain Neoplasms , Carcinoma, Non-Small-Cell Lung , Gene Expression Regulation, Neoplastic , Lung Neoplasms , MicroRNAs , Tensins , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/pathology , MicroRNAs/genetics , MicroRNAs/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Humans , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Lung Neoplasms/secondary , Lung Neoplasms/metabolism , Brain Neoplasms/secondary , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Animals , Gene Expression Regulation, Neoplastic/genetics , Mice , Tensins/metabolism , Tensins/genetics , Cell Proliferation/genetics , Mice, Nude , Cell Line, Tumor , Permeability , Mice, Inbred BALB C , Cell Movement/genetics
4.
Environ Res ; 258: 119411, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38876423

ABSTRACT

Epidemiological evidence on the impact of airborne organic pollutants on lung function among the elderly is limited, and their underlying biological mechanisms remain largely unexplored. Herein, a longitudinal panel study was conducted in Jinan, Shandong Province, China, involving 76 healthy older adults monitored over a span of five months repetitively. We systematically evaluated personal exposure to a diverse range of airborne organic pollutants using a wearable passive sampler and their effects on lung function. Participants' pulmonary function indicators were assessed, complemented by comprehensive multi-omics analyses of blood and urine samples. Leveraging the power of interaction analysis, causal inference test (CIT), and integrative pathway analysis (IPA), we explored intricate relationships between specific organic pollutants, biomolecules, and lung function deterioration, elucidating the biological mechanisms underpinning the adverse impacts of these pollutants. We observed that bis (2-chloro-1-methylethyl) ether (BCIE) was significantly associated with negative changes in the forced vital capacity (FVC), with glycerolipids mitigating this adverse effect. Additionally, 31 canonical pathways [e.g., high mobility group box 1 (HMGB1) signaling, phosphatidylinositol 3-kinase (PI3K)/AKT pathway, epithelial mesenchymal transition, and heme and nicotinamide adenine dinucleotide (NAD) biosynthesis] were identified as potential mechanisms. These findings may hold significant implications for developing effective strategies to prevent and mitigate respiratory health risks arising from exposure to such airborne pollutants. However, due to certain limitations of the study, our results should be interpreted with caution.


Subject(s)
Air Pollutants , Humans , Aged , Air Pollutants/analysis , Air Pollutants/toxicity , Male , Female , China , Longitudinal Studies , Middle Aged , Lung/drug effects , Environmental Exposure/adverse effects , Respiratory Function Tests , Vital Capacity/drug effects
5.
J Org Chem ; 89(13): 9381-9388, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38885147

ABSTRACT

A Pd(II)/N,N'-disulfonyl bisimidazoline-catalyzed asymmetric 1,4-conjugate addition reaction of low-cost arylboronic acids with readily available ß-substituted cyclic enones is described, providing a straightforward way of constructing cyclic all-carbon quaternary stereocenters with high enantioselectivity, in which ≥96% ee was obtained in most cases. The reaction proceeded without the protection of inert gas, making the operation process simple. Theoretical calculations have been applied to understand the origins of enantioselectivity.

6.
Tissue Eng Regen Med ; 21(5): 791-807, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38771465

ABSTRACT

BACKGROUND: Tissue engineering is increasingly viewed as a promising avenue for functional cartilage reconstruction. However, chondrocyte dedifferentiation during in vitro culture remains an obstacle for clinical translation of tissue engineered cartilage. Re-differentiated induction have been employed to induce dedifferentiated chondrocytes back to their original phenotype. Regrettably, these strategies have been proven to be only moderately effective. METHODS: To explore underlying mechanism, RNA transcriptome sequencing was conducted on primary chondrocytes (P0), dedifferentiated chondrocytes (P5), and redifferentiated chondrocytes (redifferentiation-induction of P5, P5.R). Based on multiple bioinformatics analysis, LGR5 was identified as a target gene. Subsequently, stable cell lines with LGR5 knocking-down and overexpression were established using P0 chondrocytes. The phenotypic changes in P1 and P5 chondrocytes with either LGR5 knockdown or overexpression were assessed to ascertain the potential influence of LGR5 dysregulation on chondrocyte phenotypes. Regulatory mechanism was then investigated using bioinformatic analysis, protein-protein docking, immunofluorescence co-localization and immunoprecipitation. RESULTS: The current study found that dysregulation of LGR5 can significantly impact the dedifferentiated phenotypes of chondrocytes (P5). Upregulation of LGR5 appears to activate the PI3K/AKT signal via increasing the phosphorylation levels of AKT (p-AKT1). Moreover, the increase of p-AKT1 may stabilize ß-catenin and enhance the intensity of Wnt/ß-catenin signal, and help to restore the dedifferentated phenotype of chondrocytes. CONCLUSION: LGR5 can modulate the phenotypes of chondrocytes in P5 passage through PI3K/AKT signaling pathway.


Subject(s)
Cell Differentiation , Chondrocytes , Phenotype , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Receptors, G-Protein-Coupled , Signal Transduction , Chondrocytes/metabolism , Chondrocytes/cytology , Proto-Oncogene Proteins c-akt/metabolism , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/genetics , Phosphatidylinositol 3-Kinases/metabolism , Animals , Humans , Cell Dedifferentiation , Cells, Cultured
7.
Anal Methods ; 16(22): 3522-3529, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38775028

ABSTRACT

To develop a sensitive and simple ampicillin (AMP) sensor for trace antibiotic residue detection, the influencing factors of the modification effect of nanogold-functionalized nucleic acid sequences (Adenine: A, Thymine: T) were comprehensively analyzed in this study, including the modification method, base length and type. It was found that under the same base concentration, longer chains are more likely to reach saturation than shorter chains; and when the base concentration and length are both the same, A exhibits a higher saturation modification level compared to T. Based on these research findings, a highly sensitive fluorescence aptamer sensor for detecting ampicillin was constructed using the optimized functionalized sequence (ployA6-aptamer) and experimental conditions (6 hours binding time between nucleic acid aptamer and complementary strand, pH 7 working solution, 20 minutes detection time) based on the principle of fluorescence resonance energy transfer. The sensor has a detection range of 0.18 ng ml-1 to 3.11 ng ml-1 for ampicillin, with a detection limit of 0.04 ng ml-1. It exhibits significant selectivity and achieves an average recovery rate of 98.71% in tap water and 91.83% in milk. This method can be used not only for residual ampicillin detection, but also for highly sensitive detection of various antibiotics and small biological molecules by replacing the aptamer type. It provides a research basis for the design of highly sensitive fluorescence aptamer sensors and further applications of nanogold@DNA composite structures.


Subject(s)
Ampicillin , Anti-Bacterial Agents , Aptamers, Nucleotide , Biosensing Techniques , Limit of Detection , Milk , Aptamers, Nucleotide/chemistry , Ampicillin/analysis , Ampicillin/chemistry , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/chemistry , Milk/chemistry , Biosensing Techniques/methods , Animals , Fluorescence Resonance Energy Transfer/methods , Metal Nanoparticles/chemistry , Gold/chemistry
8.
Mol Genet Genomic Med ; 12(4): e2426, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38562046

ABSTRACT

BACKGROUND: Mandibulofacial dysostosis with microcephaly (MFDM, OMIM# 610536) is a rare monogenic disease that is caused by a mutation in the elongation factor Tu GTP binding domain containing 2 gene (EFTUD2, OMIM* 603892). It is characterized by mandibulofacial dysplasia, microcephaly, malformed ears, cleft palate, growth and intellectual disability. MFDM can be easily misdiagnosed due to its phenotypic overlap with other craniofacial dysostosis syndromes. The clinical presentation of MFDM is highly variable among patients. METHODS: A patient with craniofacial anomalies was enrolled and evaluated by a multidisciplinary team. To make a definitive diagnosis, whole-exome sequencing was performed, followed by validation by Sanger sequencing. RESULTS: The patient presented with extensive facial bone dysostosis, upward slanting palpebral fissures, outer and middle ear malformation, a previously unreported orbit anomaly, and spina bifida occulta. A novel, pathogenic insertion mutation (c.215_216insT: p.Tyr73Valfs*4) in EFTUD2 was identified as the likely cause of the disease. CONCLUSIONS: We diagnosed this atypical case of MFDM by the detection of a novel pathogenetic mutation in EFTUD2. We also observed previously unreported features. These findings enrich both the genotypic and phenotypic spectrum of MFDM.


Subject(s)
Intellectual Disability , Mandibulofacial Dysostosis , Microcephaly , Humans , Microcephaly/pathology , Mandibulofacial Dysostosis/genetics , Mandibulofacial Dysostosis/pathology , Phenotype , Mutation , Intellectual Disability/genetics , Peptide Elongation Factors/genetics , Peptide Elongation Factors/metabolism , Ribonucleoprotein, U5 Small Nuclear/genetics , Ribonucleoprotein, U5 Small Nuclear/metabolism
10.
Sci Rep ; 14(1): 9543, 2024 04 25.
Article in English | MEDLINE | ID: mdl-38664511

ABSTRACT

Depression, a pervasive global mental disorder, profoundly impacts daily lives. Despite numerous deep learning studies focused on depression detection through speech analysis, the shortage of annotated bulk samples hampers the development of effective models. In response to this challenge, our research introduces a transfer learning approach for detecting depression in speech, aiming to overcome constraints imposed by limited resources. In the context of feature representation, we obtain depression-related features by fine-tuning wav2vec 2.0. By integrating 1D-CNN and attention pooling structures, we generate advanced features at the segment level, thereby enhancing the model's capability to capture temporal relationships within audio frames. In the realm of prediction results, we integrate LSTM and self-attention mechanisms. This incorporation assigns greater weights to segments associated with depression, thereby augmenting the model's discernment of depression-related information. The experimental results indicate that our model has achieved impressive F1 scores, reaching 79% on the DAIC-WOZ dataset and 90.53% on the CMDC dataset. It outperforms recent baseline models in the field of speech-based depression detection. This provides a promising solution for effective depression detection in low-resource environments.


Subject(s)
Deep Learning , Depression , Speech , Humans , Depression/diagnosis , Neural Networks, Computer
11.
Int J Pediatr Otorhinolaryngol ; 179: 111905, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38493660

ABSTRACT

OBJECTIVES: The primary problem in simultaneous bilateral auricle reconstruction is the fragility of the reconstructed ear structure. Postoperative pressure is strictly prohibited to ensure the operation's effectiveness. The study aimed to summarize the experience of perioperative postural management in simultaneous bilateral auricular reconstruction. METHOD: This study summarizes the experience of perioperative postural management, providing preoperative sleeping posture adaptability training, neck movement training, standardization of the head position angles and the head suspension time in surgery, using protective headrests, paying attention to the transfer and handover procedures, and using specially designed pillows. RESULTS: The comprehensive nursing approach in simultaneous bilateral auricular reconstruction significantly reduced complications, improved patient comfort, and optimized postoperative adaptation. Preoperative posture training, standardized intraoperative head positions, and vigilant postoperative care played pivotal roles, demonstrating positive outcomes in 46 cases. DISCUSSION: Perioperative position management can reduce the risk of complications and pressure injuries, improving patients' postoperative comfort, emotional state, tolerance, and adaptability. CONCLUSION: All ears were viable and in good shape after long-term follow-up. The experiences discussed in this study can be broadly applied to technically mature ear reconstruction teams.


Subject(s)
Congenital Microtia , Ear Auricle , Plastic Surgery Procedures , Humans , Plastic Surgery Procedures/adverse effects , Ear, External/surgery , Postoperative Care , Postoperative Period , Ear Auricle/surgery , Congenital Microtia/surgery
12.
Genet Test Mol Biomarkers ; 28(2): 50-58, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38416666

ABSTRACT

Introduction: Microtia is the second most common maxillofacial birth defect worldwide. However, the involvement of long non-coding RNAs (lncRNAs) in isolated microtia is not well understood. This study aimed at identifying lncRNAs that regulate the expression of genes associated with isolated microtia. Methods: We used our microarray data to analyze the expression pattern of lncRNA in the auricular cartilage tissues from 10 patients diagnosed with isolated microtia, alongside 15 control subjects. Five lncRNAs were chosen for validation using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results: We identified 4651 differentially expressed lncRNAs in the auricular cartilage from patients with isolated microtia. By Gene Ontology/Kyoto Encyclopedia of Genes and Genomes pathway (GO/KEGG) analysis, we identified 27 differentially expressed genes enriched in pathways associated with microtia. In addition, we predicted 9 differentially expressed genes as potential cis-acting targets of 12 differentially expressed lncRNAs. Our findings by qRT-PCR demonstrate significantly elevated expression levels of ZFAS1 and DAB1-AS1, whereas ADIRF-AS1, HOTAIRM1, and EPB41L4A-AS1 exhibited significantly reduced expression levels in the auricular cartilage tissues of patients with isolated microtia. Conclusions: Our study sheds light on the potential involvement of lncRNAs in microtia and provides a basis for further investigation into their functional roles and underlying mechanisms.


Subject(s)
Congenital Microtia , RNA, Long Noncoding , Humans , Gene Expression Profiling , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Congenital Microtia/genetics , Ear Cartilage/metabolism , Microarray Analysis , Gene Regulatory Networks
13.
Dev Cell ; 59(7): 924-939.e6, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38359831

ABSTRACT

Brassinosteroid (BR) signaling leads to the nuclear accumulation of the BRASSINAZOLE-RESISTANT 1 (BZR1) transcription factor, which plays dual roles in activating or repressing the expression of thousands of genes. BZR1 represses gene expression by recruiting histone deacetylases, but how it activates transcription of BR-induced genes remains unclear. Here, we show that BR reshapes the genome-wide chromatin accessibility landscape, increasing the accessibility of BR-induced genes and reducing the accessibility of BR-repressed genes in Arabidopsis. BZR1 physically interacts with the BRAHMA-associated SWI/SNF (BAS)-chromatin-remodeling complex on the genome and selectively recruits the BAS complex to BR-activated genes. Depletion of BAS abrogates the capacities of BZR1 to increase chromatin accessibility, activate gene expression, and promote cell elongation without affecting BZR1's ability to reduce chromatin accessibility and expression of BR-repressed genes. Together, these data identify that BZR1 recruits the BAS complex to open chromatin and to mediate BR-induced transcriptional activation of growth-promoting genes.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Brassinosteroids/metabolism , Chromatin/genetics , Chromatin/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Transcriptional Activation , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Gene Expression Regulation, Plant
14.
Sci Data ; 11(1): 13, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38167545

ABSTRACT

Early and accurate diagnosis of ear deformities in newborns is crucial for an effective non-surgical correction treatment, since this commonly seen ear anomalies would affect aesthetics and cause mental problems if untreated. It is not easy even for experienced physicians to diagnose the auricular deformities of newborns and the classification of the sub-types, because of the rich bio-metric features embedded in the ear shape. Machine learning has already been introduced to analyze the auricular shape. However, there is little publicly available datasets of ear images from newborns. We released a dataset that contains quality-controlled photos of 3,852 ears from 1,926 newborns. The dataset also contains medical diagnosis of the ear shape, and the health data of each newborn and its mother. Our aim is to provide a freely accessible dataset, which would facilitate researches related with ear anatomies, such as the AI-aided detection and classification of auricular deformities and medical risk analysis.


Subject(s)
Ear, External , Machine Learning , Humans , Infant, Newborn , Ear, External/abnormalities , Ear, External/surgery , Physicians , Risk Assessment
15.
Nat Commun ; 15(1): 935, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38296999

ABSTRACT

Switch defective/sucrose non-fermentable (SWI/SNF) chromatin remodeling complexes are multi-subunit machineries that establish and maintain chromatin accessibility and gene expression by regulating chromatin structure. However, how the remodeling activities of SWI/SNF complexes are regulated in eukaryotes remains elusive. B-cell lymphoma/leukemia protein 7 A/B/C (BCL7A/B/C) have been reported as subunits of SWI/SNF complexes for decades in animals and recently in plants; however, the role of BCL7 subunits in SWI/SNF function remains undefined. Here, we identify a unique role for plant BCL7A and BCL7B homologous subunits in potentiating the genome-wide chromatin remodeling activities of SWI/SNF complexes in plants. BCL7A/B require the catalytic ATPase BRAHMA (BRM) to assemble with the signature subunits of the BRM-Associated SWI/SNF complexes (BAS) and for genomic binding at a subset of target genes. Loss of BCL7A and BCL7B diminishes BAS-mediated genome-wide chromatin accessibility without changing the stability and genomic targeting of the BAS complex, highlighting the specialized role of BCL7A/B in regulating remodeling activity. We further show that BCL7A/B fine-tune the remodeling activity of BAS complexes to generate accessible chromatin at the juvenility resetting region (JRR) of the microRNAs MIR156A/C for plant juvenile identity maintenance. In summary, our work uncovers the function of previously elusive SWI/SNF subunits in multicellular eukaryotes and provides insights into the mechanisms whereby plants memorize the juvenile identity through SWI/SNF-mediated control of chromatin accessibility.


Subject(s)
Chromatin , Transcription Factors , Animals , Chromatin/genetics , Transcription Factors/metabolism , Adenosine Triphosphatases/genetics , Adenosine Triphosphatases/metabolism , Chromatin Assembly and Disassembly , Gene Expression
16.
Clin Neurol Neurosurg ; 236: 108103, 2024 01.
Article in English | MEDLINE | ID: mdl-38199118

ABSTRACT

BACKGROUND: Isocitrate dehydrogenase-wildtype (IDHwt) glioblastoma (GBM) is one of the most aggressive primary brain tumors. The recurrence of GBM is almost inevitable. As an adjuvant option to surgery, intraoperative radiotherapy (IORT) is gaining increasing attention in the treatment of glioma. This study is aimed to evaluate the therapeutic efficacy of IORT on recurrent IDHwt GBM. METHODS: In total, 34 recurrent IDHwt GBM patients who received a second surgery were included in the analysis (17 in the surgery group and 17 in the surgery + IORT group). RESULTS: The progression-free survival and overall survival after the second surgery were defined as PFS2 and OS2, respectively. The median PFS2 was 7.3 months (95% CI: 6.3-10.5) and 10.6 months (95% CI: 9.3-14.6) for those patients who received surgery and surgery + IORT, respectively. Patients in the surgery + IORT group also had a longer OS2 (12.8 months, 95% CI: 11.4-17.2) than those in the surgery group (9.3 months, 95% CI: 8.9-12.9). The Kaplan-Meier survival curves, analyzed by log-rank test, revealed a statistically significant difference in PFS2 and OS2 between both groups, suggesting that IORT plays an active role in the observed benefits for PFS2 and OS2. The effects of IORT on PFS2 and OS2 were further confirmed by multivariate Cox hazards regression analysis. Two patients in the surgery group developed distant glioma metastases, and no radiation-related complications were observed in the IORT group. CONCLUSIONS: This study suggests that low-dose IORT may improve the prognosis of recurrent IDHwt GBM patients. Future prospective large-scale studies are needed to validate the efficacy and safety of IORT.


Subject(s)
Glioblastoma , Humans , Glioblastoma/genetics , Glioblastoma/radiotherapy , Glioblastoma/surgery , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/radiotherapy , Neoplasm Recurrence, Local/surgery , Prognosis , Retrospective Studies
17.
Plast Reconstr Surg ; 153(4): 905-913, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-37184475

ABSTRACT

BACKGROUND: The EarWell System offers a correction opportunity for infants born with ear anomalies. However, the long-term effectiveness of ear molding remains unclear. This study aimed to explore the long-term effectiveness of this novel technique and to determine the risk factors for recurrence. METHODS: This retrospective, population-based cohort study was performed from 2017 through 2021. Infants who completed ear molding therapy and were followed up for longer than 6 months were enrolled. The main outcomes were immediate and long-term efficacy, which were graded by two blinded plastic surgeons. RESULTS: A total of 226 infants (334 ears) were recruited. The most common anomalies were helical deformities [113 ears (33.8%)], and the rarest were cryptotia [five ears (1.5%)] and conchal crus [five ears (1.5%)]. The age at initiation of treatment was a factor affecting both immediate ( P = 0.004) and long-term effectiveness ( P = 0.009). The type of anomaly also influenced long-term molding outcomes. For cup ears, the success rate of long-term outcomes (76.0%) was significantly lower than that of immediate outcomes (98.7%) ( P < 0.001). Prominent ear, cup ear, and microtia were found to be the most likely to relapse during long-term follow-up. The results of logistic regression also demonstrated age, duration time, and the type of anomaly to be risk factors of ear molding effects. CONCLUSIONS: The EarWell System was shown to be a secure and effective method for treatment of congenital ear anomalies. Some infants' ear anomalies recurred after successful immediate results. The age at initiation of treatment and the type of anomaly were predictors of long-term outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.


Subject(s)
Ear Auricle , Plastic Surgery Procedures , Infant , Humans , Ear, External/surgery , Ear, External/abnormalities , Retrospective Studies , Cohort Studies , Ear Auricle/surgery , Ear Auricle/abnormalities , Treatment Outcome
18.
Laryngoscope ; 134(1): 148-153, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37243347

ABSTRACT

Hearing improvement is another basic requirement for microtia patients in addition to aesthetic needs. This quantitative framework fabrication method can reduce the learning curve, obtain satisfactory aesthetic results with few complications, and reserve a certain space for future canalplasty. Laryngoscope, 134:148-153, 2024.


Subject(s)
Congenital Microtia , Costal Cartilage , Plastic Surgery Procedures , Humans , Costal Cartilage/transplantation , Ear, External/surgery , Congenital Microtia/surgery , Cartilage/transplantation
19.
Cell Signal ; 115: 111017, 2024 03.
Article in English | MEDLINE | ID: mdl-38123043

ABSTRACT

Microtia is one of the most common craniofacial birth defects worldwide, and its primary clinical manifestation is auricle deformity. Epigenetic factors are known to contribute to the etiology of microtia, yet the involvement of circular RNAs (circRNAs) in human auricle development and their association with microtia remains poorly understood. In this study, we aimed to analyze differentially expressed circRNAs and explore their functional implications in isolated microtia. By employing circRNA microarray analysis and bioinformatics approaches, we identified 340 differentially expressed circRNAs in auricle cartilage of patients with isolated microtia, comprising 152 upregulated and 188 downregulated circRNAs. A circRNA-mRNA co-expression network was constructed, followed by gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Subsequently, we selected four significantly upregulated circRNAs from the co-expression network based on their association with cartilage development and validated their expressions in 30 isolated microtia and 30 control clinical auricle cartilage samples. Among these circRNAs, circCOL1A2, the most significantly upregulated circRNA, was selected as a representative circRNA for investigating its role in isolated microtia. Overexpression of circCOL1A2 significantly inhibited chondrocyte proliferation and chondrogenic differentiation of human mesenchymal stem cells. Additionally, circCOL1A2 upregulated Dermatan Sulfate Epimerase Like (DSEL) expression by sponging miR-637 through the competing endogenous RNA (ceRNA) mechanism. Notably, the downregulation of DSEL attenuated the inhibitory effect of circCOL1A2 overexpression on cell proliferation and chondrogenic differentiation. Collectively, these findings highlight the involvement of circCOL1A2 in the pathogenesis of isolated microtia and emphasize the potential significance of dysregulated circRNAs in disease development.


Subject(s)
Congenital Microtia , MicroRNAs , Humans , RNA, Circular/genetics , RNA, Circular/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Congenital Microtia/genetics , Gene Expression Profiling , Cartilage/metabolism
20.
Aging (Albany NY) ; 15(23): 13799-13821, 2023 Dec 05.
Article in English | MEDLINE | ID: mdl-38054820

ABSTRACT

Colorectal cancer (CRC) is a malignancy that is both highly lethal and heterogeneous. Although the correlation between intra-tumoral genetic and functional heterogeneity and cancer clinical prognosis is well-established, the underlying mechanism in CRC remains inadequately understood. Utilizing scRNA-seq data from GEO database, we re-isolated distinct subsets of cells, constructed a CRC tumor-related cell differentiation trajectory, and conducted cell-cell communication analysis to investigate potential interactions across cell clusters. A prognostic model was built by integrating scRNA-seq results with TCGA bulk RNA-seq data through univariate, LASSO, and multivariate Cox regression analyses. Eleven distinct cell types were identified, with Epithelial cells, Fibroblasts, and Mast cells exhibiting significant differences between CRC and healthy controls. T cells were observed to engage in extensive interactions with other cell types. Utilizing the 741 signature genes, prognostic risk score model was constructed. Patients with high-risk scores exhibited a significant correlation with unfavorable survival outcomes, high-stage tumors, metastasis, and low responsiveness to chemotherapy. The model demonstrated a strong predictive performance across five validation cohorts. Our investigation involved an analysis of the cellular composition and interactions of infiltrates within the microenvironment, and we developed a prognostic model. This model provides valuable insights into the prognosis and therapeutic evaluation of CRC.


Subject(s)
Colorectal Neoplasms , Single-Cell Gene Expression Analysis , Humans , RNA-Seq , Tumor Microenvironment/genetics , Cell Communication , Colorectal Neoplasms/genetics , Prognosis
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