SnoRNA U50A mediates everolimus resistance in breast cancer through mTOR downregulation.

Breast cancer remains the most prevalent cancer in women globally, posing significant challenges in treatment due to the inevitable development of resistance to targeted therapies like everolimus, an mTOR inhibitor. While several mechanisms of resistance have been proposed, the role of snoRNAs in this context remains inadequately explored. Our study unveils a novel connection between snoRNAs and everolimus resistance, focusing on the snoRNA U50A. We discovered that U50A negatively regulates mTOR signaling by transcriptionally downregulating mTOR gene expression, which consequently leads to decreased sensitivity to everolimus treatment. Through RNA sequencing, gene set enrichment analyses, and experimental validations, we established that U50A overexpression in breast cancer cells results in mTOR downregulation and subsequently, everolimus desensitization. Clinical results further supported our findings, showing a higher prevalence of everolimus resistance in tumors with elevated U50A expression. Moreover, our results suggest that U50A's effect on mTOR is mediated through the suppression of the transcription factors c-Myc, with a notable impact on cancer cell viability under everolimus treatment. This study not only highlights the complex role of snoRNAs in cancer drug resistance but also proposes U50A as a potential biomarker for predicting everolimus efficacy in breast cancer treatment.

Identification of a cancer driver gene-associated lncRNA signature for prognostic prediction and immune response evaluation in clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) predominates among kidney cancer cases and is influenced by mutations in cancer driver genes (CDGs). However, significant obstacles persist in the early diagnosis and treatment of ccRCC. While various genetic models offer new hopes for improving ccRCC management, the relationship between CDG-related long non-coding RNAs (CDG-RlncRNAs) and ccRCC remains poorly understood. Therefore, this study aims to construct prognostic molecular features based on CDG-RlncRNAs to predict the prognosis of ccRCC patients, and aims to provide a new strategy to enhance clinical management of ccRCC patients. Methods: This study employed Cox and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses to comprehensively investigate the association between lncRNAs and CDGs in ccRCC. Leveraging The Cancer Genome Atlas (TCGA) dataset, we identified 97 prognostically significant CDG-RlncRNAs and developed a robust prognostic model based on these CDG-RlncRNAs. The performance of the model was rigorously validated using the TCGA dataset for training and the International Cancer Genome Consortium (ICGC) dataset for validation. Functional enrichment analysis elucidated the biological relevance of CDG-RlncRNA features in the model, particularly in tumor immunity. Experimental validation further confirmed the functional role of representative CDG-RlncRNA SNHG3 in ccRCC progression. Results: Our analysis revealed that 97 CDG-RlncRNAs are significantly associated with ccRCC prognosis, enabling patient stratification into different risk groups. Development of a prognostic model incorporating key lncRNAs such as HOXA11-AS, AP002807.1, APCDD1L-DT, AC124067.2, and SNHG3 demonstrated robust predictive accuracy in both training and validation datasets. Importantly, risk stratification based on the model revealed distinct immune-related gene expression patterns. Notably, SNHG3 emerged as a key regulator of the ccRCC cell cycle, highlighting its potential as a therapeutic target. Conclusions: Our study established a concise CDG-RlncRNA signature and underscored the pivotal role of SNHG3 in ccRCC progression. It emphasizes the clinical relevance of CDG-RlncRNAs in prognostic prediction and targeted therapy, offering potential avenues for personalized intervention in ccRCC.

Vitamin D receptor attenuates carbon tetrachloride-induced liver fibrosis via downregulation of YAP.

Liver fibrosis is characterized by the excessive accumulation of extracellular matrix proteins, which can lead to cirrhosis and liver cancer. Metabolic dysfunction-associated steatosis liver diseases are common causes of liver fibrosis, sharing a similar pathogenesis with carbon tetrachloride (CCl4) exposure. This process involves the activation of hepatic stellate cells (HSCs) into myofibroblasts. However, the detailed mechanism and effective treatment strategies require further investigation. In this study, we uncovered a negative correlation between VDR expression and YAP within HSCs. Subsequently, we demonstrated that VDR exerted a downregulatory influence on YAP transcriptional activity in HSCs. Intriguingly, activation VDR effectively inhibited the culture induced activation of primary HSCs by suppressing the transcriptional activity of early YAP. Furthermore, in vivo results manifested that hepatic-specific deletion of YAP/TAZ ameliorates CCl4-induced liver fibrosis, and nullified the antifibrotic efficacy of VDR. Importantly, a YAP inhibitor rescued the exacerbation of liver fibrosis induced by hepatic-specific VDR knockout. Moreover, the combined pharmacological of VDR agonist and YAP inhibitor demonstrated a synergistic effect in diminishing CCl4-induced liver fibrosis, primary HSCs activation and hepatic injury in vivo. These effects were underpinned by their collective ability to inhibit HSC activation through AMPK activation, consequently curbing ATP synthesis and HSCs proliferation. In conclusion, our results not only revealed the inhibition of VDR on YAP-activated liver stellate cells but also identified a synergistic effect of VDR agonist and YAP inhibitor in an AMPKα-dependent manner, providing a practical foundation for integration of multi-targeted drugs in the therapy of CCl4-induced hepatic fibrosis.

Revolutionizing early Alzheimer's disease and mild cognitive impairment diagnosis: a deep learning MRI meta-analysis.

BACKGROUND: The early diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains a significant challenge in neurology, with conventional methods often limited by subjectivity and variability in interpretation. Integrating deep learning with artificial intelligence (AI) in magnetic resonance imaging (MRI) analysis emerges as a transformative approach, offering the potential for unbiased, highly accurate diagnostic insights. OBJECTIVE: A meta-analysis was designed to analyze the diagnostic accuracy of deep learning of MRI images on AD and MCI models. METHODS: A meta-analysis was performed across PubMed, Embase, and Cochrane library databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on the diagnostic accuracy of deep learning. Subsequently, methodological quality was assessed using the QUADAS-2 checklist. Diagnostic measures, including sensitivity, specificity, likelihood ratios, diagnostic odds ratio, and area under the receiver operating characteristic curve (AUROC) were analyzed, alongside subgroup analyses for T1-weighted and non-T1-weighted MRI. RESULTS: A total of 18 eligible studies were identified. The Spearman correlation coefficient was -0.6506. Meta-analysis showed that the combined sensitivity and specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.84, 0.86, 6.0, 0.19, and 32, respectively. The AUROC was 0.92. The quiescent point of hierarchical summary of receiver operating characteristic (HSROC) was 3.463. Notably, the images of 12 studies were acquired by T1-weighted MRI alone, and those of the other 6 were gathered by non-T1-weighted MRI alone. CONCLUSION: Overall, deep learning of MRI for the diagnosis of AD and MCI showed good sensitivity and specificity and contributed to improving diagnostic accuracy.

ANTECEDENTES: O diagnóstico precoce da doença de Alzheimer (DA) e do comprometimento cognitivo leve (CCL) continua sendo um desafio significativo na neurologia, com métodos convencionais frequentemente limitados pela subjetividade e variabilidade na interpretação. A integração da aprendizagem profunda com a inteligência artificial (IA) na análise de imagens de ressonância magnética surge como uma abordagem transformadora, oferecendo o potencial para insights diagnósticos imparciais e altamente precisos. OBJETIVO: Uma metanálise foi projetada para analisar a precisão diagnóstica do aprendizado profundo de imagens de ressonância magnética em modelos de DA e CCL. MéTODOS: Uma metanálise foi realizada nos bancos de dados das bibliotecas PubMed, Embase e Cochrane seguindo as diretrizes Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), com foco na precisão diagnóstica do aprendizado profundo. Posteriormente, a qualidade metodológica foi avaliada por meio do checklist QUADAS-2. Medidas diagnósticas, incluindo sensibilidade, especificidade, razões de verossimilhança, razão de chances diagnósticas e área sob a curva característica de operação do receptor (area under the receiver operating characteristic curve [AUROC]) foram analisadas, juntamente com análises de subgrupo para ressonância magnética ponderada em T1 e não ponderada em T1. RESULTADOS: Um total de 18 estudos elegíveis foram identificados. O coeficiente de correlação de Spearman foi de -0,6506. A metanálise mostrou que a sensibilidade e a especificidade combinadas, a razão de verossimilhança positiva, a razão de verossimilhança negativa e a razão de chances de diagnóstico foram 0,84, 0,86, 6,0, 0,19 e 32, respectivamente. A AUROC foi de 0,92. O ponto quiescente do resumo hierárquico da característica de operação do receptor (hierarchical summary of receiver operating characteristic [HSROC]) foi 3,463. Notavelmente, as imagens de 12 estudos foram adquiridas apenas por ressonância magnética ponderada em T1, e as dos outros 6 foram obtidas apenas por ressonância magnética não ponderada em T1. CONCLUSãO: Em geral, a aprendizagem profunda da ressonância magnética para o diagnóstico de DA e CCL mostrou boa sensibilidade e especificidade e contribuiu para melhorar a precisão diagnóstica.

Formation mechanism of blue pigment in boiled lotus rhizome discs: Insight into the chelation of polyphenols and iron.

Boiled lotus rhizome discs (BLRDs), as common processed products of lotus rhizome, have gained increasing attention from consumers and food manufacturers. However, the blue pigment formed during boiling affects its appearance and reduces the appetite of BLRDs. In this study, the effects of polyphenols and iron contents on blue pigment formation in BLRDs in different regions and months were investigated. Results revealed that blue variation was more serious in March and April of the second year in Wuhan, and polyphenols and iron contents in these two months were significantly higher than those in other months. Then, UPLC and UV-Vis analysis showed that polyphenols causing the formation of blue pigment in BLRDs were L-dopa, gallocatechin, catechin, epigallocatechin, chlorogenic acid and epicatechin, among which L-dopa (52.450 mg/100 g in fresh lotus rhizome (FLR)) and gallocatechin (36.210 mg/100 g in FLR) possessed the greatest effect. Moreover, the ESI-Q-TOF-MS analysis of L-dopa-iron chelate and gallocatechin-iron chelate suggested that the blue pigment of BLRDs was mainly in the form of bis-complexes under boiling conditions. The study on formation mechanism of blue pigment in BLRDs can provide a reference for lotus rhizome processing.

Internal mechanism of correlation between angiotensin II gene and serum adiponectin level in patients with cerebrovascular complications of H-type hypertension.

Background: The study aimed to explore the correlation between the angiotensin II (Ang II) gene and serum adiponectin expression in patients with cerebrovascular complications of H-type hypertension (HH) and its mechanism. Methods: A total of 50 cases of outpatient patients in Tianjin Fourth Central Hospital were recruited from January 2022 to June 2023 and rolled into three groups according to their blood pressure and basic information, namely the HH cerebrovascular complications group, the non-H-type hypertension (NHH) group, and the healthy control (HC) group. Peripheral blood samples were taken; one sample was utilized to test for the Ang II gene and the methylation of Ang II, and the other sample was utilized to measure serum adiponectin levels to analyze the relationship between serum adiponectin level and Ang II in patients with cerebrovascular complications of HH. Results: The ratio of male to female was 8:7 in the group of cerebrovascular complications of HH, and mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 167.34 mm Hg and 112.56 mm Hg, respectively. In the NHH group, the mean SBP was 165.89 mm Hg, and the mean DBP was 113.47 mm Hg. The blood pressure of the HC group was in the normal range. The Ang II content was the highest in the group with cerebrovascular complications of HH, followed by the group with NHH, and the lowest in the HC group. Conclusions: Pyrosequencing chart of patients with cerebrovascular complications of HH showed that the content of deoxyphosphate ribose G was the highest, while the content of A was the highest in NHH patients. Moreover, the serum adiponectin level of patients with HH and NHH was superior to that of the HC group, and the adiponectin level between the former two groups and the HC group differed considerably. Ang II levels were high in patients with cerebrovascular complications of HH and were positively correlated with adiponectin levels. The incidence of cerebrovascular complications of HH may be related to Ang II levels in patients.

Prevalence and Prognostic Significance of Malnutrition in Patients with Type B Aortic Dissection Undergoing Endovascular Repair.

Background: Malnutrition is a poor prognostic factor in a wide range of diseases. Nevertheless, there is a lack of data investigating the association between malnutrition and outcomes of patients with type B aortic dissection (TBAD) undergoing thoracic endovascular aortic repair (TEVAR). Therefore, the aim of the present study was to report the prevalence and clinical impact of malnutrition assessed by the controlling nutritional status (CONUT) score in TBAD patients undergoing TEVAR. Methods: The retrospective study indicated that a total of 881 patients diagnosed with TBAD and treated with TEVAR from January 2010 to December 2017 were categorized into subgroups based on their CONUT score (low ≤ 5 vs. high > 5). To assess the correlation between malnutrition and early and follow-up outcomes of TBAD patients, logistic and Cox regression analysis were utilized, incorporating inverse probability weighting. Results: Malnutrition was present in 20.3% of patients according to the CONUT score. Multivariate logistic regression analysis revealed that pre-operative CONUT score modeled as a continuous variable was an independent risk factor for prolonged intensive care unit stay (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.02-1.17; p = 0.015), 30-day death (OR, 1.43; 95% CI, 1.19-1.72; p < 0.001), delirium (OR, 1.11; 95% CI, 1.01-1.23; p = 0.035) and acute kidney injury (OR, 1.09; 95% CI, 1.01-1.16; p = 0.027). During a median follow-up of 70.8 (46.1-90.8) months, 102 (11.8%) patients died (high CONUT group: 21.8% vs. low CONUT group: 9.0%; p < 0.001). Multivariable Cox proportional-hazards models showed that malnutrition was an independent predictor for follow-up mortality (hazard ratio, 1.68; 95% CI, 1.11-2.53; p = 0.014). Results remained consistent across various sensitivity analyses. Conclusions: Malnutrition assessed by the CONUT score could profoundly affect the early and follow-up prognosis in patients undergoing TEVAR. Routine pre-intervention nutritional evaluation might provide valuable prognostic information.

Endoplasmic Reticulum Membrane Protein Complex Regulates Cancer Stem Cells and is Associated with Sorafenib Resistance in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, underscoring the need for novel therapeutic targets. This study aimed to elucidate the role of endoplasmic reticulum membrane protein complex subunit 1 (EMC1) in HCC progression and its therapeutic potential. Methods: Publicly available sequencing data and biopsy specimens were analyzed to assess EMC's clinical value and functions in HCC. In vitro experiments validated EMC functions, and multiplex immunofluorescence analysis examined EMC-associated sorafenib resistance mechanisms. EMC1 expression was knocked down in HCC cell lines, followed by cell viability, wound healing, and transwell migration assays. Tumor growth and response to sorafenib treatment were evaluated in mouse models. Metabolomic analysis assessed changes in the TCA cycle. Results: EMC genes were aberrantly expressed in HCC, and high EMC1 expression correlated with poorer survival rates. EMC1 disruption enhanced HCC cells' sensitivity to sorafenib, reducing cell viability, increasing apoptosis, and decreasing tumor size and weight. EMC1 maintained cancer cell stemness and promoted M2 macrophage infiltration. Metabolomic analysis revealed significant changes in the TCA cycle, indicating EMC1's role in HCC metabolic reprogramming. Importantly, EMC1 is highly associated with sorafenib resistance, potentially linked to CTNNB1 mutation or activation. Conclusion: EMC1 plays a critical role in regulating the sorafenib resistance in HCC. Targeting EMC1 may improve HCC treatment efficacy.

Preparation of Single-cell Suspension of Mouse Thymic Epithelial Cells and Staining of Intracellular Molecules for Flow Cytometric Analysis.

Thymic epithelial cells (TECs) play an essential role in promoting the development and repertoire selection of T cells. Cortical TECs (cTECs) in the thymic cortex induce early T cell development and positive selection of cortical thymocytes. In contrast, medullary TECs (mTECs) in the thymic medulla attract positively selected thymocytes from the cortex and establish self-tolerance in T cells. A variety of molecules, including DLL4 and beta5t expressed in cTECs, as well as Aire and CCL21 expressed in mTECs, contribute to thymus function supporting T cell development and selection. Flow cytometric analysis of functionally relevant molecules in cTECs and mTECs is useful to improve our understanding of the biology of TECs, even though current methods for the preparation of single-cell suspensions of TECs can retrieve only a small fraction of TECs (approximately 1% for cTECs and approximately 10% for mTECs) from young adult mouse thymus. Because many of these functionally relevant molecules in TECs are localized within the cells, we describe our protocols for the preparation of single-cell suspension of mouse TECs and the staining of intracellular molecules for flow cytometric analysis.

Differential toxic effects of nano-titanium dioxide on clams (Meretrix meretrix) with various individuality.

Nano-TiO2 is inevitably released into aquatic environment with increasing of nanotechnology industries. Study pointed that different individuality showed divergent behavioral and physiological response when facing environmental stress. However, the effects of nano-TiO2 on tolerance of bivalves with different individualities remain unknown. In the study, clams were divided into two types of individuality - proactive and reactive by post-stress recovery method. It turned out that proactive individuals had quicker shell opening level, stronger burrowing behavior, faster feeding recovery, higher standard metabolic rate and more rapid ammonia excretion ability than reactive individuals after exposed to air. Then, the survival rate, hemocytes response and oxidase activity of classified clams were evaluated after nano-TiO2 exposure. Results showed that after 30 d exposure, proactive individuals accelerated burrowing behavior with higher survival rate. Moreover, proactive clams had better adaptability and less hemocytes response and oxidative damage than reactive clams. The study highlights the individualities of marine shell fish determine individual capacity to adapt to environmental changes, play important roles in aquaculture and coastal ecosystem health.

Large-scale analysis of the PAC domain structure of arogenate dehydratases reveals their evolutionary patterns in angiosperms.

Arogenate dehydratase (ADT) is the key limiting enzyme of plant phenylalanine biosynthesis, but some ADTs display a prephenate decarboxylase/dehydratase activity-conferring (PAC) domain. The genome resources of 70 species were employed to identify genes and outline their characteristics, especially the number and type of PAC domain structures. We obtained 522 ADTs, and their size, exon number, amino acid number and putative protein isoelectric point greatly varied from 306 to 2520 bp, 1 to 15, 101 to 839 and 4.37 to 11.18, respectively. We classified the ADTs into Class α (without a PAC domain) (115, 22.0 %), ß (with a type I PAC domain) (244, 46.7 %) and γ (with a type II PAC domain) (163, 31.2 %), and their distribution frequencies exhibited large differences among various branches of angiosperms. We found that Class γ members are more conserved than Class ß members, although they commonly experienced multiple duplication events and strong purifying selection, which resulted in a small number, and the putative origin order was from Class α to ß and then to γ. In addition, the co-occurrence of both Class ß and γ members could ensure the survival of angiosperms, while their optimized composition and strategically intertwined regulation may facilitate core eudicot success.

Prediction of Proximal Junctional Kyphosis and Failure After Corrective Surgery for Adult Spine Deformity: An MRI-Based Model Combining Bone and Paraspinal Muscle Quality Metrics.

BACKGROUND: Proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) are common complications observed after adult spinal deformity (ASD) surgery and major cause for unplanned reoperations. In addition to spinal alignment, osteoporosis and paraspinal muscle (PSM) degeneration are reportedly indispensable factors that account for PJK/PJF. PURPOSE: To investigate the utility of the preoperative risk assessment model using MRI-based skeletomuscular metrics in predicting PJK and/or PJF(PJK/PJF) after ASD correction. STUDY DESIGN: Retrospective Case-Control study. PATIENT SAMPLE: Consecutive series of 149 patients at a single academic institution. OUTCOME MEASURES: MRI based measurements of vertebral bone quality at upper instrumented vertebra (VBQ-U) score and fat infiltration rate (FI%) of paraspinal muscle (PSM). METHODS: We performed a retrospective analysis of patients with ASD who underwent ≥5-segment fusion. The vertebral bone quality (VBQ) scoring system was used to assess the bone quality. The PSM quality including FI% and cross-sectional area (CSA) were evaluated. Multivariate logistic regression was performed to determine potential risk factors of PJK/PJF. RESULTS: Of 149 patients who underwent ASD surgery, PJK/PJF was found in 45(30.2%). Mean VBQ-U scores were 3.45 ± 0.64 and 3.00 ± 0.56 for patients with and without PJK/PJF (P<0.001). Mean FI% of PSM(L3/L4) was 27.9 ± 12.8 and 20.7 ± 13.3 for patients with and without PJK/PJF (P<0.001). On multivariate analysis, the VBQ-U score and FI% of PSM were significant independent predictors of PJK/PJF. The AUC for the novel risk assessment model is 0.806, with a predictive accuracy of 86.7%. CONCLUSION: In patients undergoing ASD correction, paraspinal muscle and vertebral bone quality significantly outweigh radiographic alignment parameters in predicting PJK/PJF. The MRI-based risk assessment model offers a valuable tool for early assessing individualized risk information for PJK/PJF.

1α,25-hydroxyvitamin D/VDR suppresses stem-like properties of ovarian cancer cells by restraining nuclear translocation of ß-catenin.

Several studies have indicated that 1α,25-hydroxyvitamin D [1α,25(OH)2D3] inhibits the proliferation and metastasis of cancer cells through suppressing epithelial-mesenchymal transition. However, its influence on the translocation of ß-catenin remains unclear. In the present study, ovarian cancer stem-like cells (CSCs), including side population (SP) and CD44+/CD117+, were isolated from mouse ovarian surface epithelial (MOSE) cells with malignant transformation. The findings revealed that 1α,25(OH)2D3 obviously reduced the sphere-forming ability, as well as Notch1 and Klf levels. Moreover, the limiting dilution assay demonstrated that 1α,25(OH)2D3 effectively hindered the tumorigenesis of ovarian CSCs in vitro. Notably, treatment with 1α,25(OH)2D3 led to a substantial increase in the cell population of CD44+/CD117+ forming one tumor from ≤ 100 to 445 in orthotopic transplanted model, indicating a pronounced suppression of stemness of ovarian CSCs. Additionally, 1α,25(OH)2D3 robustly promoted the translocation of ß-catenin from the nuclear to the cytoplasm through directly binding to VDR, which resulted in decreased levels of c-Myc and CyclinD1 within late MOSE cells. Taken together, these results strongly supported the role of 1α,25(OH)2D3 in inhibiting stem-like properties in ovarian cancer cells by restraining nuclear translocation of ß-catenin, thereby offering a promising target for cancer therapeutics.

The Evaluation Value of the Modified Lund-Kennedy Nasal Endoscopy Score on the Efficacy of Sublingual Immunotherapy for Allergic Rhinitis.

OBJECTIVE: Allergic rhinitis (AR) is a growing public health problem worldwide. Respecting the significance of the modified Lund-Kennedy (MLK) score in rhinitis assessment, we delved into its evaluation value on the sublingual immunotherapy (SLIT) efficacy in AR patients. METHODS: Totally 100 AR patients were enrolled, with pre- and post-SLIT MLK score, total nasal symptoms score (TNSS), total medication score (TMS), visual analogue scale (VAS), inflammatory cytokines, and immune function-related parameters compared. The correlations of MLK score with TNSS/TMS/VAS, as well as with IL-4/INF-γ/eosinophil (EOS)/percentage/specific immunoglobulin (sIgE)/sIgG were assessed by Spearman correlation analysis. The value of MLK score on assessing SLIT efficacy in AR patients was analyzed. RESULTS: SLIT treatment reduced MLK/TNSS/TMS/VAS scores, abated IL-4 level/EOS percentage/sIgE, and elevated INF-γ/sIgG levels. MLK score was positively correlated with pre- and post-SLIT TNSS score (rpre-treatment = 0.592, rpost-treatment = 0.756), TMS score (rpre-treatment = 0.385, rpost-treatment = 0.718), VAS score (rpre-treatment = 0.369, rpost-treatment = 0.704), IL-4 (rpre-treatment = 0.553, rpost-treatment = 0.639), EOS percentage (rpre-treatment = 0.511, rpost-treatment = 0.632), and sIgE (rpre-treatment = 0.472, rpost-treatment = 0.524), and negatively with INF-γ (rpre-treatment = -0.418, rpost-treatment = -0.578) and sIgG4 (rpre-treatment = -0.460, rpost-treatment = -0.613). The MLK score had an area under curve of 0.846 (77.01% sensitivity, 76.92% specificity, 4 cut-off value) and 0.944 (91.67% sensitivity, 92.11% specificity, 2 cut-off value) for assessing SLIT treatment as effective and markedly effective for the patients, respectively. CONCLUSION: The MLK score had good evaluation value on the efficacy of SLIT treatment in AR patients.

New insight into the CNC-bZIP member, NFE2L3, in human diseases.

Nuclear factor erythroid 2 (NF-E2)-related factor 3 (NFE2L3), a member of the CNC-bZIP subfamily and widely found in a variety of tissues, is an endoplasmic reticulum (ER) membrane-anchored transcription factor that can be released from the ER and moved into the nucleus to bind the promoter region to regulate a series of target genes involved in antioxidant, inflammatory responses, and cell cycle regulation in response to extracellular or intracellular stress. Recent research, particularly in the past 5 years, has shed light on NFE2L3's participation in diverse biological processes, including cell differentiation, inflammatory responses, lipid homeostasis, immune responses, and tumor growth. Notably, NFE2L3 has been identified as a key player in the development and prognosis of multiple cancers including colorectal cancer, thyroid cancer, breast cancer, hepatocellular carcinoma, gastric cancer, renal cancer, bladder cancer, esophageal squamous cell carcinoma, T cell lymphoblastic lymphoma, pancreatic cancer, and squamous cell carcinoma. Furthermore, research has linked NFE2L3 to other cancers such as lung adenocarcinoma, malignant pleural mesothelioma, ovarian cancer, glioblastoma multiforme, and laryngeal carcinoma, indicating its potential as a target for innovative cancer treatment approaches. Therefore, to gain a better understanding of the role of NFE2L3 in disease, this review offers insights into the discovery, structure, function, and recent advancements in the study of NFE2L3 to lay the groundwork for the development of NFE2L3-targeted cancer therapies.

Electroencephalography microstate alterations reflect potential double-edged cognitive adaptation in Ménière's disease.

PURPOSE: To explore the microstate characteristics and underlying brain network activity of Ménière's disease (MD) patients based on high-density electroencephalography (EEG), elucidate the association between microstate dynamics and clinical manifestation, and explore the potential of EEG microstate features as future neurobiomarkers for MD. METHODS: Thirty-two patients diagnosed with MD and 29 healthy controls (HC) matched for demographic characteristics were included in the study. Dysfunction and subjective symptom severity were assessed by neuropsychological questionnaires, pure tone audiometry, and vestibular function tests. Resting-state EEG recordings were obtained using a 256-channel EEG system, and the electric field topographies were clustered into four dominant microstate classes (A, B, C, and D). The dynamic parameters of each microstate were analyzed and utilized as input for a support vector machine (SVM) classifier to identify significant microstate signatures associated with MD. The clinical significance was further explored through Spearman correlation analysis. RESULTS: MD patients exhibited an increased presence of microstate class C and a decreased frequency of transitions between microstate class A and B, as well as between class A and D. The transitions from microstate class A to C were also elevated. Further analysis revealed a positive correlation between equilibrium scores and the transitions from microstate class A to C under somatosensory challenging conditions. Conversely, transitions between class A and B were negatively correlated with vertigo symptoms. No significant correlations were detected between these characteristics and auditory test results or emotional scores. Utilizing the microstate features identified via sequential backward selection, the linear SVM classifier achieved a sensitivity of 86.21% and a specificity of 90.61% in distinguishing MD patients from HC. CONCLUSIONS: We identified several EEG microstate characteristics in MD patients that facilitate postural control yet exacerbate subjective symptoms, and effectively discriminate MD from HC. The microstate features may offer a new approach for optimizing cognitive compensation strategies and exploring potential neurobiological markers in MD.

Role of sex steroids in colorectal cancer: pathomechanisms and medical applications.

Given that the colon represents the most extensive hormone-responsive tissue in the human body, it prompts a compelling inquiry into whether the progression of its cancer is intimately linked to hormonal dynamics. Consequently, the interplay between sex steroids - a pivotal constituent of hormones - and colorectal cancer has increasingly captivated scientific interest. Upon a comprehensive review of pertinent literature both domestically and internationally, this study delineates the present landscape of three pivotal steroids - estrogen, progestin, and androgen - in the context of colorectal cancer. More specifically, this investigation probes into the potential utility of these steroids in providing therapeutic interventions, diagnostic insights, and prognostic indicators. Furthermore, this study also delves into the mechanistic pathways through which sex steroid interventions exert influence on colorectal cancer. It was discovered that the trio of sex steroid hormones partakes in an array of biological processes, thereby influencing the onset and progression of colorectal cancer. In conclusion, this study posits that a profound interconnection exists between colorectal cancer and sex steroids, suggesting that elucidating the targets of their action mechanisms could unveil novel avenues for the diagnosis and prevention of colorectal cancer.

Green fabrication of modified lignin/zeolite/chitosan-based composite membranes for preservation of perishable foods.

Chitosan, as a kind of naturally occurring green and degradable material for the preservation of perishable foods, was investigated in this study with the objective of enhancing its preservation performances. Herein, lignin was modified using the solvent fractionation method (modified lignin, ML, including ML1-ML3), while natural clinoptilolite zeolite was modified using the alkali modification method (modified clinoptilolite zeolite, MCZ, including MCZ1-MCZ5). After optimizing the conditions, it was discovered that incorporating both ML3 and MCZ3 into pure chitosan-based membranes might be conducive to fabricate chitosan-based composite membranes for the preservation of perishable foods. As-prepared composite membranes possessed better visible light transmittance, antioxidant activity, and carbon dioxide/oxygen selectivity, resulting in improved preservation effects on the model perishable foods such as bananas, cherry tomatoes, and cheeses. These findings might indicate promising applications for chitosan-based composite membranes with modified lignin and zeolite in the field of eco-friendly degradable materials for the preservation of perishable foods.

The Influence of Rumination and Dyadic Coping on Parenting Sense of Competence in Chinese Postpartum Women: A cross-sectional study.

PURPOSE: This study aimed to explore the potential categories of parenting sense of competence and to analyze the influence of rumination and dyadic coping on the potential categories of parenting sense of competence. METHODS: A total of 199 postpartum women who met the criteria were surveyed from a tertiary grade-A hospital in XX (China) from May 2023 to August 2023. The instruments included the general demographic characteristics, Chinese version of parenting sense of competence scale, Chinese event related rumination inventory, and Chinese version of dyadic coping inventory. Latent profile analysis (LPA) was used to classify the parenting sense of competence in postpartum women, and logistic regression analysis was used to identify the influencing factors. RESULTS: The characteristics of parenting sense of competence in postpartum women can be divided into two potential categories, namely, easy-to-satisfy group (39.3%) and strict-demand group (60.7%). Logistic regression analysis showed that years of marriage, place of residence, deliberate rumination and dyadic coping were the influencing factors of the potential categories of parenting sense of competence in postpartum women (p< .05). CONCLUSIONS: Through latent profile analysis, it was found that postpartum women's parenting sense of competence exhibits different characteristics. Clinical workers should identify the characteristics and influencing factors of different categories of women and adopt targeted intervention strategies to promote the level of parenting sense of competence.