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Tissue engineering scaffolds can mediate the maneuverability of neural stem cell (NSC) niche to influence NSC behavior, such as cell self-renewal, proliferation, and differentiation direction, showing the promising application in spinal cord injury (SCI) repair. Here, dual-network porous collagen fibers (PCFS) are developed as neurogenesis scaffolds by employing biomimetic plasma ammonia oxidase catalysis and conventional amidation cross-linking. Following optimizing the mechanical parameters of PCFS, the well-matched Young's modulus and physiological dynamic adaptability of PCFS (4.0 wt%) have been identified as a neurogenetic exciter after SCI. Remarkably, porous topographies and curving wall-like protrusions are generated on the surface of PCFS by simple and non-toxic CO2 bubble-water replacement. As expected, PCFS with porous and matched mechanical properties can considerably activate the cadherin receptor of NSCs and induce a series of serine-threonine kinase/yes-associated protein mechanotransduction signal pathways, encouraging cellular orientation, neuron differentiation, and adhesion. In SCI rats, implanted PCFS with matched mechanical properties further integrated into the injured spinal cords, inhibited the inflammatory progression and decreased glial and fibrous scar formation. Wall-like protrusions of PCFS drive multiple neuron subtypes formation and even functional neural circuits, suggesting a viable therapeutic strategy for nerve regeneration and functional recovery after SCI.
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Colágeno , Mecanotransdução Celular , Células-Tronco Neurais , Proteínas Proto-Oncogênicas c-akt , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/terapia , Animais , Porosidade , Células-Tronco Neurais/metabolismo , Colágeno/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Nicho de Células-Tronco , Biomimética , Diferenciação Celular , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Alicerces Teciduais/química , Materiais Biomiméticos/química , Proteínas de Sinalização YAPRESUMO
We report intriguing continuous-wave quasi-single-mode random lasing in methylammonium lead bromide (CH3NH3PbBr3) perovskite films synthesized on a patterned sapphire substrate (PSS) under excitation of a 532-nm laser diode. The random laser emission evolves from a typical multi-mode to a quasi-single-mode with increasing pump fluences. The full width at half-maximum of the lasing peak is as narrow as 0.06â nm at â¼547.8â nm, corresponding to a high Q-factor of â¼9000. Such excellent random lasing performance is plausibly ascribed to the exciton resonance in optical absorption at 532â nm and the enhanced optical resonance due to the increased likelihood for randomly scattered light to re-enter the optical loops formed among the perovskite grains by multi-reflection at the perovskite/PSS interfaces. This work demonstrates the promise of single-mode perovskite random lasers by introducing the exciton resonance effect and ingeniously designed periodic nano/micro optical structure.
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The combination of high-capacitance MXenes and wide-electrochemical-window ionic liquids (ILs) has exhibited bright prospects in supercapacitors. Several strategies, such as surficial functionalization and interlayer spacing tuning, have been used to enhance the electrochemical performance of supercapacitors. However, the lack of theoretical guidance on these strategies, including the effects of the microenvironment in the interlayer of confined ILs, hindered the further exploration of such devices. Herein, we performed molecular dynamics simulations to comprehensively investigate the effects of the interlayer space and surface terminations of MXene electrodes on capacity. The results show that the electrical double layer (EDL) structure was found to form on the interface between the MXene electrode and ILs electrolyte by analyzing the ion number density and charge density in the nanometer confined spaces. Under the same potential, the -OH terminations significantly impact the ion orientation in the EDL, particularly near the electrode surface, where cations tend to align vertically, allowing the retention of more cations at the electrode surfaces. Interestingly, such an orientation distribution was decisively from the hydrogen bonds expressed by O-H···O between the -OH termination of MXene and -OH groups of ILs. The differential capacitances of the supercapacitors were calculated by the surficial electron density, and it showed that the capacitance is a nearly one-quarter increase in the 14 Å interlayer spacing compared with that of 10 Å under an applied potential of 2 V. At the same time, the Ti3C2(OH)2 electrode had a higher differential capacitance than the Ti3C2O2 electrode, which possibly originates from the stronger hydrogen bonds to contribute to the vertical aggregation of the cations. Our results highlighted the roles of the interlayer spacing distance and surface terminations of the MXene on the performance of the type of supercapacitor.
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PURPOSE: Complications such as explosive choroidal hemorrhage, residual cortex, and capsule rupture often occur during intraocular surgery combined with penetrating keratoplasty (PKP) due to poor maintenance of the anterior chamber. To address these challenges, we have innovatively utilized a sterile polyethylene instrument cover to temporarily reconstruct the anterior chamber. METHODS: In this report, we describe a technique where a 'temporary corneal patch' was created from a sterile instrument cover, using a trephine to ensure a diameter approximately 1-2 mm wider than the corneal bed or perforation. This patch was then sutured into the host corneal bed or the perforation with 10-0 nylon sutures during intraocular surgery combined with PKP. Each case was evaluated for surgical efficacy and complications. RESULTS: We successfully applied this technique in three cases of combined corneal transplantation surgery. In two cases, PKP, phacoemulsification, and intraocular lens implantation were successfully performed. In the third case, PKP, vitrectomy, and other intraocular procedures were performed. No intraoperative or postoperative complications were observed. CONCLUSION: The use of a sterile polyethylene material as a temporary corneal patch for anterior chamber reconstruction represents a safe, effective, and cost-efficient approach for intraocular surgery combined with PKP or posterior segment surgery as a keratoprosthesis.
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INTRODUCTION: Migraine, as a complex neurological disease, brings heavy burden to patients and society. Despite the availability of established therapies, existing medications have limited efficacy. Thus, we aimed to find the drug targets that improve the prognosis of migraine. METHOD: We used Mendelian Randomization (MR) and Summary-data-based MR (SMR) analyses to study possible drug targets of migraine by summary statistics from FinnGen cohorts (nCase = 44,616, nControl = 367,565), with further replication in UK Biobank (nCase = 26,052, nControl = 487,214). Genetic instruments were obtained from eQTLGen and UKB-PPP to verify the drug targets at the gene expression and protein levels. The additional analyses including Bayesian co-localization, the heterogeneity in dependent instruments(HEIDI), Linkage Disequilibrium Score(LDSC), bidirectional MR, multivariate MR(MVMR), heterogeneity test, horizontal pleiotropy test, and Steiger filtering were implemented to consolidate the findings further. Lastly, drug prediction analysis and phenome-wide association study(PheWAS) were employed to imply the possibility of drug targets for future clinical applications. RESULT: The MR analysis of eQTL data showed that four drug targets (PROCR, GSTM4, SLC4A1, and TNFRSF10A) were significantly associated with migraine risk in both the FinnGen and UK Biobank cohorts. However, only GSTM4 exhibited consistent effect directions across the two outcomes(Discovery cohort: OR(95%CI) = 0.94(0.93-0.96); p = 2.70e - 10; Replication cohort: OR(95%CI) = 0.93(0.91-0.94); p = 4.21e - 17). Furthermore, GSTM4 passed the SMR at p < 0.05 and HEIDI test at p > 0.05 at both the gene expression and protein levels. The protein-level MR analysis revealed a strong correlation between genetically predicted GSTM4 with a lower incidence of migraine and its subtypes(Overall migraine: OR(95%CI) = 0.91(0.87-0.95); p = 6.98e-05; Migraine with aura(MA): OR(95%CI) = 0.90(0.85-0.96); p = 2.54e-03; Migraine without aura(MO): OR(95%CI) = 0.90(0.83-0.96); p = 2.87e-03), indicating a strong co-localization relationship (PPH4 = 0.86). Further analyses provided additional validation for the possibility of GSTM4 as a migraine treatment target. CONCLUSION: This study identifies GSTM4 as a potential druggable gene and promising therapeutic target for migraine.
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Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Transtornos de Enxaqueca , Humanos , Transtornos de Enxaqueca/genética , Transtornos de Enxaqueca/tratamento farmacológico , Análise da Randomização Mendeliana/métodos , Locos de Características Quantitativas/genética , Polimorfismo de Nucleotídeo Único/genética , Glutationa Transferase/genética , Predisposição Genética para Doença/genética , MultiômicaRESUMO
The amyloid-ß (Aß) peptide, produced from amyloid precursor protein (APP) by ß and γ-secretases, has been implicated in the etiology of Alzheimer's disease (AD). However, the precise intracellular trafficking pathway of APP and its subcellular locations to produce Aß have remained unclear. To address these issues, we established fly AD models that recapitulated multiple AD-like symptoms by expressing human APP in the Drosophila nerve system. The ESCRT (endosomal sorting complexes required for transport) machinery regulates the sorting and trafficking of endocytosed proteins, yet its role in AD pathogenesis has not been explored in vivo. We found that knockdown of distinct ESCRT components ameliorated APP-induced morphological and behavioral defects, including impaired wing expansion, eye degeneration, dopamine neuron loss, locomotor disability, lifespan shortening, and cognitive deficits. Mechanistically, we showed that impaired ESCRT impeded APP's intracellular transportation from early endosomes to late endosomes, resulting in reduced Aß production and amyloid deposit load. These data suggest that APP undergoes ESCRT-mediated endocytic trafficking, and Aß is generated mainly in late endosomes. Our data provide the first in vivo evidence to support a physiological role of ESCRT in AD pathogenesis, suggesting that interfering with ESCRT machinery might be an alternative therapeutic strategy for AD.
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Doença de Alzheimer , Precursor de Proteína beta-Amiloide , Complexos Endossomais de Distribuição Requeridos para Transporte , Animais , Humanos , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Drosophila/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Transporte Proteico/fisiologiaRESUMO
OBJECTIVE: To evaluate electroencephalography (EEG) microstate differences between patients with migraine with aura (MWA), patients with migraine without aura (MWoA), and healthy controls (HC). BACKGROUND: Previous research employing microstate analysis found unique microstate alterations in patients with MWoA; however, it is uncertain how microstates appear in patients with MWA. METHODS: This study was conducted at the Headache Clinic of the First Affiliated Hospital of Xi'an Jiaotong University. In total, 30 patients with MWA, 30 with MWoA, and 30 HC were enrolled in this cross-sectional study. An EEG was recorded for all participants under resting state. The microstate parameters of four widely recognized microstate classes A-D were calculated and compared across the three groups. RESULTS: The occurrence of microstate B (MsB) in the MWoA group was significantly higher than in the HC (p = 0.006, Cohen's d = 0.72) and MWA (p = 0.016, Cohen's d = 0.57) groups, while the contribution of MsB was significantly increased in the MWoA group compared to the HC group (p = 0.016, Cohen's d = 0.64). Microstate A (MsA) displayed a longer duration in the MWA group compared to the MWoA group (p = 0.007, Cohen's d = 0.69). Furthermore, the transition probability between MsB and microstate D was significantly increased in the MWoA group compared to the HC group (p = 0.009, Cohen's d = 0.68 for B to D; p = 0.007, Cohen's d = 0.71 for D to B). Finally, the occurrence and contribution of MsB were positively related to headache characteristics in the MWoA group but negatively in the MWA group, whereas the duration of MsA was positively related to the visual analog scale in the MWA group (all p < 0.05). CONCLUSIONS: Patients with MWA and MWoA have altered microstate dynamics, indicating that resting-state brain network disorders may play a role in migraine pathogenesis. Microstate parameters may have the potential to aid clinical management, which needs to be investigated further.
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Encefalopatias , Epilepsia , Enxaqueca com Aura , Enxaqueca sem Aura , Humanos , Projetos Piloto , Estudos Transversais , Enxaqueca com Aura/diagnóstico por imagem , Enxaqueca sem Aura/diagnóstico por imagem , Cefaleia , EletroencefalografiaRESUMO
BACKGROUND: Pneumocephalus is rare in vaginal deliveries. Pneumocephalus may be asymptomatic or present with signs of increased intracranial pressure. However, parturients who received epidural anesthesia with air in their brains may experience low intracranial pressure headaches after giving birth, causing the diagnosis of pneumocephalus to be delayed. We report a case of a parturient who developed post-dural puncture headache combined with pneumocephalus secondary to vaginal delivery following epidural anesthesia. CASE PRESENTATION: A 24-year-old G1P0 Chinese woman at 38 weeks gestation was in labor and received epidural anesthesia using the loss of resistance to air technique and had a negative prior medical history. She presented with postural headache, neck stiffness and auditory changes 2 h after vaginal delivery. The head non-contrast computed tomography revealed distributed gas density shadows in the brain, indicating pneumocephalus. Her headache was relieved by bed rest, rehydration, analgesia, and oxygen therapy and completely disappeared after 2 weeks of postpartum bed rest. CONCLUSIONS: This is the first report that positional headaches after epidural anesthesia may not indicate low intracranial pressure alone; it may combine with pneumocephalus, particularly when using the loss of resistance to air technique. At this moment, head computed tomography is essential to discover other conditions like pneumocephalus.
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Anestesia Epidural , Pneumocefalia , Cefaleia Pós-Punção Dural , Feminino , Gravidez , Humanos , Adulto Jovem , Adulto , Cefaleia Pós-Punção Dural/terapia , Cefaleia Pós-Punção Dural/complicações , Pneumocefalia/etiologia , Pneumocefalia/complicações , Anestesia Epidural/efeitos adversos , Cefaleia/etiologia , Parto Obstétrico/efeitos adversosRESUMO
Lycorine (Lyc) and its hydrochloride (LycâHCl) as effective drugs can fight against many diseases including novel coronavirus (COVID-19) based on their antiviral and antitumor mechanism. Beta-cyclodextrin (ß-CD) is considered a promising carrier in improving its efficacy while minimizing cytotoxicity due to the good spatial compatibility with Lyc. However, the detailed mechanism of inclusion interaction still remains to be further evaluated. In this paper, six inclusion complexes based on ß-CDs, Lyc and LycâHCl were processed through ultrasound in the mixed solvent of ethanol and water, and their inclusion behavior was characterized after lyophilization. It was found that the inclusion complexes based on sulfobutyl-beta-cyclodextrin (SBE-ß-CD) and LycâHCl had the best encapsulation effect among prepared inclusion complexes, which may be attributed to the electrostatic interaction between sulfonic group of SBE-ß-CD and quaternary amino group of LycâHCl. Moreover, the complexes based on SBE-ß-CD displayed pH-sensitive drug release property, good solubilization, stability and blood compatibility, indicating their potential as suitable drug carriers for Lyc and LycâHCl.
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A copper-catalyzed regiodivergent hydrosilylation of a wide range of simple allenes is reported. Linear and branched allylsilanes were formed by judicious choice of solvents. Furthermore, branched allylsilanes were obtained with high enantioselectivity (up to 97% enantiomeric excess) with the aid of a C2-symmetric bisphosphine ligand in the unprecedented asymmetric allene hydrosilylation.
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Alcadienos , Cobre , Catálise , EstereoisomerismoRESUMO
By introducing Brønsted acidic ionic liquids (ILs), two dual-emitting lanthanide metal-organic complexes (Ln-MOCs) of {[Ln(imdc)(CH3OH)(H2O)3]Cl2}n (LnIMDC, Ln = Eu and Tb, imdc = 1,3-bis(carboxymethyl)imidazolium ion) were first prepared under solvothermal conditions. The crystal structures of LnIMDC were measured by single-crystal X-ray diffraction, and the crystal growth process of LnIMDC was carefully studied. It is found that the crystals are three-dimensional supramolecular structures built up by Ln-O coordination bonds and supramolecular forces. In the temperature range of 303-403 K, LnIMDC show good temperature-dependent emission properties with maximum relative thermal sensitivities of 3.29% K-1 at 375 K and 2.08% K-1 at 303 K for EuIMDC and TbIMDC, respectively. It is worth mentioning that both EuIMDC and TbIMDC exhibit good linear ratiometric emission-temperature response in temperature ranges of 353-403 and 323-373 K, respectively, which render EuIMDC and TbIMDC good ratiometric thermometers in high temperature range. Computational studies on the energy level of ILs [H2imdc]Cl and [imdc]- ion were performed, which validated the high energy transfer efficiency between the [imdc]- and Ln3+ ions and the unique solution concentration- and wavelength-dependent fluorescence properties of [H2imdc]Cl. The high fluorescence performance opens up new opportunities for practical applications of ILs in optical sensing.
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A base-promoted (4 + 2) cyclization of aza-o-quinone methides (aza-o-QMs) in situ generated from N-(o-chloromethyl)aryl amides was established. In this approach, azlactones were utilized as competent two-atom reaction partners to undergo (4 + 2) cyclization with aza-o-QMs, which afforded a series of dihydroquinolinone derivatives in overall good yields (up to 98%). This protocol has not only advanced the development of aza-o-QM-involved reactions, but also offered a useful method for constructing biologically important dihydroquinolinone frameworks.
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Amidas/química , Iminas/química , Lactonas/química , Quinolonas/síntese química , CiclizaçãoRESUMO
The unique physical structure and chemical and electrical properties of graphene make it an ideal choice for sensor materials. The sensing platform of biomolecule functionalized graphene has received extensive attention due to its high sensitivity and selectivity, especially the biosensors constructed by combining antibodies, nucleic acids and enzymes that efficiently recognize specific targets with graphene having a large specific surface area and a fast electron transfer rate, which has become a significant research direction. In this paper, electrochemical biosensors based on graphene materials developed in recent years are summarized. The methods of functional modification of graphene, graphene oxide and reduced graphene oxide with antibodies, nucleic acids and enzymes are briefly described. In addition, the advantages and disadvantages of the constructed electrochemical biosensors in detecting pathogens and disease markers are also reviewed. Finally, we are optimistic about this prospect for the development direction and application prospects of such electrochemical biosensors.
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Anticorpos/química , Biomarcadores/análise , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Enzimas/química , Grafite/química , Ácidos Nucleicos/química , Doença/classificação , HumanosRESUMO
The liver is considered unique in its enormous capacity for regeneration and self-repair. In contrast to other regenerative organs (i.e., skin, skeletal muscle, and intestine), whether the adult liver contains a defined department of stem cells is still controversial. In order to compensate for the massive loss of hepatocytes following liver injury, the liver processes a precisely controlled transcriptional reprogram that can trigger cell proliferation and cell-fate switch. Epigenetic events are thought to regulate the organization of chromatin architecture and gene transcription during the liver regenerative process. In this review, we will summarize how changes to the chromatin by epigenetic modifiers are translated into cell fate transitions to restore liver homeostasis during liver regeneration.
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BACKGROUND: The primary health care (PHC) system plays an important role in China's health care system, but there are challenges such as irrational allocation of health resources and inefficient operation, which need to be improved. The purpose of this study was to explore the impact of resource allocation on the efficiency of the PHC system in China. METHODS: The data in 31 provinces were collected from the China Statistical Yearbook 2017-2021 and the China Health Statistical Yearbook 2017-2021. The comprehensive health resource density index (CHRDI) was constructed based on the entropy method and the health resource density index (HRDI), which was used to analyze the allocation of primary health resources in each province. The adjusted efficiency of the PHC system in each province was calculated by the bootstrap data envelopment analysis (DEA). Finally, the spatial Dubin model was used to explore the effect of the CHRDI on efficiency. RESULTS: From 2016 to 2020, the allocation of primary health resources in 31 provinces showed an increasing trend, and the average efficiency after correction showed a decreasing state year by year. The spatial direct effect and spatial spillover effect coefficients of CHRDI were 0.820 and 1.471, which positively affect the efficiency. Per capita Gross Domestic Product (GDP), urbanization rate, and the proportion of the elderly were the factors affecting the efficiency of the PHC system. CONCLUSIONS: The allocation of primary health resources in all provinces in China has improved each year, but there are still great differences, and efficiency must be further improved. Pay attention to the spatial spillover effect of the level of resource allocation and formulate differentiated measures for different regions. Attention should also be paid to the impact of population aging and economic development on the utilization of primary health resources by increasing health needs and choices.
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Equidade em Saúde , Humanos , Idoso , Recursos em Saúde , Eficiência , Atenção à Saúde , ChinaRESUMO
BACKGROUND: Major depressive disorder (MDD) and interstitial cystitis (IC) are two highly debilitating conditions that often coexist with reciprocal effect, significantly exacerbating patients' suffering. However, the molecular underpinnings linking these disorders remain poorly understood. METHODS: Transcriptomic data from GEO datasets including those of MDD and IC patients was systematically analyzed to develop and validate our model. Following removal of batch effect, differentially expressed genes (DEGs) between respective disease and control groups were identified. Shared DEGs of the conditions then underwent functional enrichment analyses. Additionally, immune infiltration analysis was quantified through ssGSEA. A diagnostic model for MDD was constructed by exploring 113 combinations of 12 machine learning algorithms with 10-fold cross-validation on the training sets following by external validation on test sets. Finally, the "Enrichr" platform was utilized to identify potential drugs for MDD. RESULTS: Totally, 21 key genes closely associated with both MDD and IC were identified, predominantly involved in immune processes based on enrichment analyses. Immune infiltration analysis revealed distinct profiles of immune cell infiltration in MDD and IC compared to healthy controls. From these genes, a robust 11-gene (ABCD2, ATP8B4, TNNT1, AKR1C3, SLC26A8, S100A12, PTX3, FAM3B, ITGA2B, OLFM4, BCL7A) diagnostic signature was constructed, which exhibited superior performance over existing MDD diagnostic models both in training and testing cohorts. Additionally, epigallocatechin gallate and 10 other drugs emerged as potential targets for MDD. CONCLUSION: Our work developed a diagnostic model for MDD employing a combination of bioinformatic techniques and machine learning methods, focusing on shared genes between MDD and IC.
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Cistite Intersticial , Transtorno Depressivo Maior , Aprendizado de Máquina , Humanos , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/diagnóstico , Cistite Intersticial/genética , Cistite Intersticial/diagnóstico , Transcriptoma/genética , Perfilação da Expressão GênicaRESUMO
PURPOSE: To investigate the preparedness, perceived stress, risk of depression, and quality of life of family caregivers of patients receiving a temporary enterostomy, to provide a reference for improving the long-term care and quality of life of patients receiving a temporary enterostomy. METHODS: We enrolled 181 family caregivers of patients in a hospital in China from 2021 to 2023. Responses to the General Information Questionnaire, the Chinese Caregiver Preparedness Scale, the Chinese Perceived Stress Scale, the Chinese bilingual version of the Patient Health Questionnaire-2, and the 12-item Short Form Survey were collected online. RESULTS: Pearson's correlation analysis revealed that family caregivers' risk of depression was negatively correlated with their preparedness, the physical component summary score, and the mental component summary score but was positively correlated with perceived stress. Multiple linear regression analysis identified factors influencing caregiver preparedness. CONCLUSIONS: These findings help healthcare personnel to identify high-risk individuals among family caregivers of patients receiving a temporary enterostomy. This provides a basis for formulating well-planned, dynamic health education programs that meet patients' needs for disease-related knowledge and care.
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Cuidadores , Enterostomia , Qualidade de Vida , Estresse Psicológico , Humanos , Masculino , Feminino , Cuidadores/psicologia , Pessoa de Meia-Idade , Adulto , China , Enterostomia/psicologia , Inquéritos e Questionários , Idoso , Depressão/epidemiologia , Adaptação Psicológica , Estudos TransversaisRESUMO
Recent research has discovered disulfidptosis as a form of programmed cell death characterized by disulfide stress. However, its significance in clear cell renal cell carcinoma (ccRCC) remains unclear. To investigate this, data from The Cancer Genome Atlas were collected and used to identify ccRCC subgroups. Unsupervised clustering was employed to determine ccRCC heterogeneity. The mutation landscape and immune microenvironment of the subgroups were analyzed. The Disulfidptosis-Related Score was calculated using the LASSO-penalized Cox regression algorithm. The E-MATB-1980 cohort was used to validate the signature. The role of SLC7A11 in ccRCC metastasis was explored using western blotting and Transwell assays. Disulfidptosis-related genes are commonly downregulated in cancers and are linked to hypermethylation and copy number variation. The study revealed that ccRCC is divided into two sub-clusters: the disulfidptosis-desert sub-cluster, which is associated with a poor prognosis, a higher mutation frequency, and an immunosuppressive microenvironment. A 14-gene prognostic model was developed using differentially expressed genes and was validated in the E-MATB-1980 cohort. The low-risk group demonstrated longer overall and disease-free survival and responded better to targeted immunotherapy. Results from in vitro experiments identified SLC7A11 as a key participant in ccRCC metastasis.
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Carcinoma de Células Renais , Neoplasias Renais , Microambiente Tumoral , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/mortalidade , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/imunologia , Neoplasias Renais/mortalidade , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Prognóstico , Regulação Neoplásica da Expressão Gênica , Mutação , Linhagem Celular Tumoral , Apoptose/genética , Feminino , Biomarcadores Tumorais/genética , Masculino , Metilação de DNARESUMO
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a common and lethal urological malignancy for which there are no effective personalized therapeutic strategies. Programmed cell death (PCD) patterns have emerged as critical determinants of clinical prognosis and immunotherapy responses. However, the actual clinical relevance of PCD processes in ccRCC is still poorly understood. METHODS: We screened for PCD-related gene pairs through single-sample gene set enrichment analysis (ssGSEA), consensus cluster analysis, and univariate Cox regression analysis. A novel machine learning framework incorporating 12 algorithms and 113 unique combinations were used to develop the cell death-related gene pair score (CDRGPS). Additionally, a radiomic score (Rad_Score) derived from computed tomography (CT) image features was used to classify the CDRGPS status as high or low. Finally, we conclusively verified the function of PRSS23 in ccRCC. RESULTS: The CDRGPS was developed through an integrated machine learning approach that leveraged 113 algorithm combinations. CDRGPS represents an independent prognostic biomarker for overall survival and demonstrated consistent performance between training and external validation cohorts. Moreover, CDRGPS showed better prognostic accuracy compared to seven previously published cell death-related signatures. In addition, patients classified as high-risk by CDRGPS exhibited increased responsiveness to tyrosine kinase inhibitors (TKIs), mammalian Target of Rapamycin (mTOR) inhibitors, and immunotherapy. The Rad_Score demonstrated excellent discrimination for predicting high versus low CDRGPS status, with an area under the curve (AUC) value of 0.813 in the Cancer Imaging Archive (TCIA) database. PRSS23 was identified as a significant factor in the metastasis and immune response of ccRCC, thereby validating experimental in vitro results. CONCLUSIONS: CDRGPS is a robust and non-invasive tool that has the potential to improve clinical outcomes and enable personalized medicine in ccRCC patients.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Prognóstico , Apoptose , Aprendizado de Máquina , Neoplasias Renais/genética , BiomarcadoresRESUMO
Bone marrow lesion (BML) volume is a potential biomarker of knee osteoarthritis (KOA) as it is associated with cartilage degeneration and pain. However, segmenting and quantifying the BML volume is challenging due to the small size, low contrast, and various positions where the BML may occur. It is also time-consuming to delineate BMLs manually. In this paper, we proposed a fully automatic segmentation method for BMLs without requiring human intervention. The model takes intermediate weighted fat-suppressed (IWFS) magnetic resonance (MR) images as input, and the output BML masks are evaluated using both regular 2D Dice similarity coefficient (DSC) of the slice-level area metric and 3D DSC of the subject-level volume metric. On a dataset with 300 subjects, each subject has a sequence of 36 IWFS MR images approximately. We randomly separated the dataset into training, validation, and testing sets with a 70%/15%/15% split at the subject level. Since not every subject or image has a BML, we excluded the images without a BML in each subset. The ground truth of the BML was labeled by trained medical staff using a semi-automatic tool. Compared with the ground truth, the proposed segmentation method achieved a Pearson's correlation coefficient of 0.98 between the manually measured volumes and automatically segmented volumes, a 2D DSC of 0.68, and a 3D DSC of 0.60 on the testing set. Although the DSC result is not high, the high correlation of 0.98 indicates that the automatically measured BML volume is strongly correlated with the manually measured BML volume, which shows the potential to use the proposed method as an automatic measurement tool for the BML biomarker to facilitate the assessment of knee OA progression.