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Rationale: Extrachromosomal circular DNA is a hallmark of cancer, but its role in shaping the genome heterogeneity of urothelial bladder carcinoma (UBC) remains poorly understood. Here, we comprehensively analyzed the features of extrachromosomal circular DNA in 80 UBC patients. Methods: We performed whole-genome/exome sequencing (WGS/WES), Circle-Seq, single-molecule real-time (SMRT) long-read sequencing of circular DNA, and RNA sequencing (RNA-Seq) on 80 pairs of tumor and AT samples. We used our newly developed circular DNA analysis software, Circle-Map++ to detect small extrachromosomal circular DNA from Circle-Seq data. Results: We observed a high load and significant heterogeneity of extrachromosomal circular DNAs in UBC, including numerous single-locus and complex chimeric circular DNAs originating from different chromosomes. This includes highly chimeric circular DNAs carrying seven oncogenes and circles from nine chromosomes. We also found that large tumor-specific extrachromosomal circular DNAs could influence genome-wide gene expression, and are detectable in time-matched urinary sediments. Additionally, we found that the extrachromosomal circular DNA correlates with hypermutation, copy number variation, oncogene amplification, and clinical outcome. Conclusions: Overall, our study provides a comprehensive extrachromosomal circular DNA map of UBC, along with valuable data resources and bioinformatics tools for future cancer and extrachromosomal circular DNA research.

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Variaciones en el Número de Copia de ADN , ADN Circular , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética , Humanos , ADN Circular/genética , Variaciones en el Número de Copia de ADN/genética , Secuenciación Completa del Genoma/métodos , Heterogeneidad Genética , Masculino , Femenino , Secuenciación del Exoma/métodos , Anciano , Mutación/genética

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Purpose: To develop a combined diagnostic model integrating the subclassification of the 2022 version of the American College of Radiology (ACR) Ovarian-Adnexal Reporting and Data System (O-RADS) with carbohydrate antigen 125 (CA125) and to validate whether the combined model can offer superior diagnostic efficacy than O-RADS alone in assessing adnexal malignancy risk. Methods: A retrospective analysis was performed on 593 patients with adnexal masses (AMs), and the pathological and clinical data were included. According to the large differences in malignancy risk indices for different image features in O-RADS category 4, the lesions were categorized into groups A and B. A new diagnostic criterion was developed. Lesions identified as category 1, 2, 3, or 4A with a CA125 level below 35 U/ml were classified as benign. Lesions identified as category 4A with a CA125 level more than or equal to 35 U/ml and lesions with a category of 4B and 5 were classified as malignant. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC) of O-RADS (v2022), CA125, and the combined model in the diagnosis of AMs were calculated and compared. Results: The sensitivity, specificity, PPV, NPV, accuracy, and AUCs of the combined model were 92.4%, 96.5%, 80.2%, 98.8%, 94.1%, and 0.945, respectively. The specificity, PPV, accuracy, and AUC of the combined model were significantly higher than those of O-RADS alone (all P < 0.01). In addition, both models had acceptable sensitivity and NPV, but there were no significant differences among them (P > 0.05). Conclusion: The combined model integrating O-RADS subclassification with CA125 could improve the specificity and PPV in diagnosing malignant AMs. It could be a valuable tool in the clinical application of risk stratification of AMs.

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Objectives: This study aimed to explore the performance of a model based on Chinese Thyroid Imaging Reporting and Data Systems (C-TIRADS), clinical characteristics, and shear wave elastography (SWE) for the prediction of Bethesda I thyroid nodules before fine needle aspiration (FNA). Materials and methods: A total of 267 thyroid nodules from 267 patients were enrolled. Ultrasound and SWE were performed for all nodules before FNA. The nodules were scored according to the 2020 C-TIRADS, and the ultrasound and SWE characteristics of Bethesda I and non-I thyroid nodules were compared. The independent predictors were determined by univariate analysis and multivariate logistic regression analysis. A predictive model was established based on independent predictors, and the sensitivity, specificity, and area under the curve (AUC) of the independent predictors were compared with that of the model. Results: Our study found that the maximum diameter of nodules that ranged from 15 to 20 mm, the C-TIRADS category <4C, and E max <52.5 kPa were independent predictors for Bethesda I thyroid nodules. Based on multiple logistic regression, a predictive model was established: Logit (p) = -3.491 + 1.630 × maximum diameter + 1.719 × C-TIRADS category + 1.046 × E max (kPa). The AUC of the model was 0.769 (95% CI: 0.700-0.838), which was significantly higher than that of the independent predictors alone. Conclusion: We developed a predictive model for predicting Bethesda I thyroid nodules. It might be beneficial to the clinical optimization of FNA strategy in advance and to improve the accurate diagnostic rate of the first FNA, reducing repeated FNA.

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Highly circularly polarized (CP) infrared thermal radiation is greatly in demand because of its significant potential in mid-infrared (mid-IR) applications. To exploit the magnitude and quality factor of circular dichroism (CD) simultaneously, a lithography-free platform consisting of a Weyl semimetal (WSM)/dielectric (Ge)/WSM stack sitting on a metallic substrate (Mo) is proposed. A chiral response and varying CD values from -1 to 0.957 have been demonstrated. The numerical results from a generalized 4 × 4 transfer matrix algorithm verify that the chiral structure manifests a remarkably high quality factor (Q-factor) of 605. The effect of the thickness of each layer in the stack on the CD value is investigated. Moreover, it is identified that the design results in an angle-independent performance. A dual-channel chiral absorber operating in the 18-21 µm wavelength range has also been achieved. Our simple yet powerful paradigm could offer a new way of manipulating the Q-factor and resonance wavelength of a chiral absorber while maintaining near-unity CD, offering a new approach for the advancement of more efficient and tunable chiral optical devices. The approach is generally applicable to other planar configurations with different WSMs and can be extended to other wavelengths.

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Osteoarthritis (OA) is a common age-related degenerative disease characterized by changes in the local tissue environment as inflammation progresses. Inspired by the wind-dispersal mechanism of dandelion seeds, this study develops responsive biomimetic microsphere-drug conjugate for OA therapy and protection. The conjugate integrates dibenzaldehyde polyethylene glycol (DFPEG) with chitosan and polyethylene glycol diacrylate (PEGDA) through dynamic covalent bonds to form a dual-network hydrogel microsphere. Based on the progression of OA, the conjugate with the surface-anchored cyclic peptide cortistatin-14 (CST-14) achieves targeted drug therapy and a self-regulating hydrogel network. In cases of progressing inflammation (pH < 5), CST-14 dissociates from the microsphere surface (viz. the drug release rate increased) and inhibits TNF-α signaling to suppress OA. Concurrently, the monomer DFPEG responsively detaches from the hydrogel network and scavenges reactive oxygen species (ROS) to protect the cartilage tissue. The ROS scavenging of DFPEG is comparable to that of coenzyme Q10 and vitamin C. The degraded PEGDA microspheres provide tissue lubrication through reused conjugates. The rat OA model successfully achieved a synergistic therapeutic effect greater than the additive effect (1 + 1 > 2). This strategy offers an approach for anchoring amine-containing drugs and has marked potential for OA treatment and protection.

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There is increasing evidence that the activation of glucagon-like peptide-1 receptor (GLP-1R) can be used as a therapeutic intervention for cognitive disorders. Here, we have screened GLP-1R targeted compounds from Scutellaria baicalensis, which revealed baicalein is a potential GLP-1R small-molecule agonist. Mitophagy, a selective autophagy pathway for mitochondrial quality control, plays a neuroprotective role in multiple cognitive impairment diseases. We noticed that Glp1r knock-out (KO) mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze (MWM) test than their wide-type (WT) counterparts. Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice. Finally, we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1R-dependent manner. Our findings shed light on the importance of GLP-1R for cognitive function maintenance, and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis. Furthermore, we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.

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Ketolides (3-keto) such as TE-802 and acylides (3-O-acyl) like TEA0929 are ineffective against constitutively resistant pathogens harboring erythromycin ribosomal methylation (erm) genes. Following our previous work on alkylides (3-O-alkyl), we explored the structure-activity relationships of hybrids combining (R/S) 3-descladinosyl erythromycin with 6/7-quinolone motifs, featuring extended ether-linked spacers, with a focus on their efficacy against pathogens bearing constitutive erm gene resistance. Optimized compounds 17a and 31f not only reinstated efficacy against inducibly resistant pathogens but also demonstrated significantly augmented activities against constitutively resistant strains of Streptococcus pneumoniae and Streptococcus pyogenes, which are typically refractory to existing C-3 modified macrolides. Notably, hybrid 31f (coded ZN-51) represented a pioneering class of agents distinguished by its dual modes of action, with ribosomes as the primary target and topoisomerases as the secondary target. As a novel chemotype of macrolide-quinolone hybrids, alkylide 31f is a valuable addition to our armamentarium against macrolide-resistant bacteria.

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Antibacterianos , Macrólidos , Pruebas de Sensibilidad Microbiana , Quinolonas , Streptococcus pneumoniae , Relación Estructura-Actividad , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Quinolonas/química , Quinolonas/farmacología , Quinolonas/síntesis química , Macrólidos/química , Macrólidos/farmacología , Streptococcus pneumoniae/efectos de los fármacos , Estructura Molecular , Diseño de Fármacos , Streptococcus pyogenes/efectos de los fármacos , Streptococcus pyogenes/enzimología , Relación Dosis-Respuesta a Droga , Éteres/química , Éteres/farmacología , Éteres/síntesis química

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The manifestation of benign hematological infiltration in the liver is a challenge due to their rare occurrence and therefore, limited awareness and the general need for biopsy and histological confirmation. Owing to the rarity of these lesions, there are limited data concerning their appearance on ultrasound and, specifically, contrast-enhanced ultrasound. In a series of papers, we have compiled the US and CEUS characteristics of rare FLL, where there are few reports and images available, in order to build up a library of these cases. This paper describes the US and CEUS features of benign hematological FLL which include hepatic extramedullary hematopoiesis (EMH), hemophagocytic lymphohistiocytosis (HLH) and reactive lymphoid hyperplasia (RLH). Although these lesions occur rarely in the liver, their correct identification is imperative for appropriate patient`s management.

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The risk of chronic inflammatory diseases has been linked to exposure to polycyclic aromatic hydrocarbons (PAHs). However, limited data are available regarding their impact on periodontitis. This study aims to explore the association between PAHs and periodontitis while also evaluating the potential modifying effects of healthy lifestyles. We included 17,031 participants from the US National Health and Nutrition Examination Survey (NHANES, 2001-2004 and 2009-2014). A meta-analysis-based environment-wide association study (EWAS) was adopted to identify environmental chemicals for the mean probing pocket depth (PPD) and the mean attachment loss (AL). PAHs were further evaluated concerning the cross-sectional association with Mod/Sev periodontitis using multivariable logistic regression models. Moreover, healthy lifestyle scores were estimated to assess their modifying effect on the PAH-periodontitis association. EWAS analysis identified several urinary PAH metabolites as significant risk factors for the mean PPD and AL (false discovery rate <0.05, Q > 0.05). Periodontitis severity was positively associated with eight individual and total PAH concentrations. Stratifying the participants in terms of healthy lifestyle scores did not reveal any association in the healthy group. Moreover, the association weakened in never-smokers and individuals with sufficient physical activity and normal weight. PAH exposure was a risk factor for periodontitis. A healthier lifestyle was observed to offset the risk potentials of PAHs for periodontitis. Smoking cessation, physical activity, and weight loss might be recommended as a healthy lifestyle strategy for ameliorating PAH-related periodontitis.

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To investigate the application of low temperature plasma ablation combined with fullly degradable sinus stent system in the treatment of congenital choanal atresia mainly menbranous atresia. A child with membranous bilateral choanal atresia admitted in April 2023 was analyzed. This case underwent endoscopic ablative posterior nostriplasty and placed a fully degradable drug stent in bilateral operative cavities. The case's nasal ventilation was effectively improved after operation and the profile of postnaris was well formed. No restenosis oratresia was found under electronic nasopharyngoscope and the drug stent was completely degraded after 8 months follow-up. Low temperature plasma ablation has the advantages of reducing surgical trauma, protecting normal tissue and avoiding complications in the treatment of congenital choanal atresia. At the same time, combined with the application of the fully degradable sinus drug stent, it can achieve remarkable efficacy by alleviating mucosal edema, reducing granulation tissue hyperplasia, accelerating wound mucosification, and effectively reducing the incidence of nasal adhesion, restenosis or even atresia.

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Atresia de las Coanas , Humanos , Atresia de las Coanas/cirugía , Masculino , Endoscopía/métodos , Stents , Resultado del Tratamiento

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Tuning immune-cold tumor hot has largely attracted attention to improve cancer treatment, including immunotherapy and antibody-drug conjugates (ADCs). Utilizing multiomic analyses and experimental validation, this work identifies a pivotal role for the USP10/B7-H4 proteolytic axis in mediating the interplay between tumor immune responses and ADC efficacy, particularly for sacituzumab govitecan (SG) in treating triple negative breast cancers (TNBCs). Mechanistically, the inhibition of autocrine motility factor receptor (AMFR)-mediated ubiquitylation of B7-H4 by the deubiquitinase USP10 leads to the stabilization of B7-H4, which suppresses tumor immune activity and reduces SG treatment effectiveness. Pharmacological inhibition of USP10 promotes the degradation of B7-H4, enhancing tumor immunogenicity and consequently improving the tumor-killing efficacy of SG. In preclinical TNBC models, suppression of USP10/B7-H4 proteolytic axis is effective in increasing SG killing efficacy and reducing tumor growth, especially for the tumors with the USP10high/B7-H7high signature. Collectively, these findings uncover a novel strategy for targeting the immunosuppressive molecule B7-H4 for cancer therapy.

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OBJECTIVES: This study analyzed the basic condition and the influencing factors of hospitalization costs of patients with gastric cancer in Shanghai from 2014 to 2021, so as to provide a scientific reference for promoting the reform of the medical and healthcare system. METHODS: The study data were obtained from the electronic medical record system of Shanghai Hospital. The grey relational analysis was applied to analyze the correlation strength of various expenses with hospitalization costs. The structural equation modeling was constructed to analyze the influences of factors on the hospitalization expenses, as well as the relationship between each factor. RESULTS: A total of 23 335 study subjects were included. The results of grey relational analysis showed that the total cost of drugs had the strongest correlation with hospitalization expenses, followed by material expenses and surgery cost, whereas those of others were lower. The results of the structural equation modeling showed that age had the greatest influence on hospitalization expenses with a path coefficient of 0.618. Other influencing factors included surgery history, length of stay, hospital level, gender, and medical insurance. CONCLUSIONS: The total cost of drugs had the strongest correlation with hospitalization expenses. Factors such as gender, age, and hospital level all affect the hospitalization expenses. In the future, it is necessary to take further measures to control the cost of drugs and constantly optimize the structure of hospitalization costs. Meanwhile, the reform of the medical and healthcare system should be deepened to reasonably regulate the medical behaviors and reduce the financial burden of patients.

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BACKGROUND: As the global consumption of sugary and non-sugar sweetened beverages continues to rise, there is growing concern about their health impacts, particularly among pregnant women and their offspring. OBJECTIVE: This study aimed to investigate the consumption patterns of various beverages among pregnant women in Shanghai and their potential health impacts on both mothers and offspring. METHOD: We applied a multi-stage random sampling method to select participants from 16 districts in Shanghai. Each district was categorised into five zones. Two towns were randomly selected from each zone, and from each town, 30 pregnant women were randomly selected. Data were collected through face-to-face questionnaires. Follow-up data on births within a year after the survey were also obtained. RESULT: The consumption rates of total beverages (TB), sugar-sweetened beverages (SSB), and non-sugar sweetened beverages (NSS) were 73.2%, 72.8%, and 13.5%, respectively. Logistic regression analysis showed that compared to non-consumers, pregnant women consuming TB three times or less per week had a 38.4% increased risk of gestational diabetes mellitus (GDM) (OR = 1.384; 95% CI: 1.129-1.696) and a 64.2% increased risk of gestational hypertension (GH) (OR = 1.642; 95% CI: 1.129-2.389). Those consuming TB four or more times per week faced a 154.3% higher risk of GDM (OR = 2.543; 95% CI: 2.064-3.314) and a 169.3% increased risk of GH (OR = 2.693; 95% CI: 1.773-4.091). Similar results were observed in the analysis of SSB. Regarding offspring health, compared to non-consumers, TB consumption four or more times per week was associated with a substantial increase in the risk of macrosomia (OR = 2.143; 95% CI: 1.304-3.522) and large for gestational age (LGA) (OR = 1.695; 95% CI: 1.219-2.356). In the analysis of NSS, with a significantly increased risk of macrosomia (OR = 6.581; 95% CI:2.796-13.824) and LGA (OR = 7.554; 95% CI: 3.372-16.921). CONCLUSION: The high level of beverage consumption among pregnant women in Shanghai needs attention. Excessive consumption of beverages increases the risk of GDM and GH, while excessive consumption of NSS possibly has a greater impact on offspring macrosomia and LGA.

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Bebidas , Diabetes Gestacional , Bebidas Azucaradas , Humanos , Femenino , Embarazo , Adulto , China/epidemiología , Bebidas/estadística & datos numéricos , Bebidas/efectos adversos , Diabetes Gestacional/epidemiología , Diabetes Gestacional/etiología , Bebidas Azucaradas/efectos adversos , Bebidas Azucaradas/estadística & datos numéricos , Hipertensión Inducida en el Embarazo/epidemiología , Hipertensión Inducida en el Embarazo/etiología , Adulto Joven , Resultado del Embarazo/epidemiología , Factores de Riesgo

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Objective: To validate the feasibility of ultrasound in assessing the curative effect of botulinum toxin type A (BTXA) in treating hypertrophic scar (HS). Methods: Eight healthy New Zealand long-eared rabbits were utilized in the study. Four wounds, each measuring 1.0 cm in diameter, were created on both ears of each rabbit. Immediately after surgery, each of these wounds received an injection containing a distinct concentration of BTXA. On postoperative week 6, scar thickness, vascularity, and hardness were assessed based on high frequency ultrasound (HFUS), superb microvascular imaging (SMI), shear wave elastography (SWE), Masson staining, and immunohistochemical staining for CD31. Results: All wounds healed well, and HSs formed after 6 weeks post-surgery. Scar thickness based on HFUS presented a significant decrease with increasing BTXA concentration (p < 0.05), aligning with the gross morphology. Simultaneously, scar stiffness, evaluated using SWE, showed a significant decrease in accordance with the variation of the collagen volume fraction, which refers to the ratio of the collagen positive area to the total area (p < 0.05). Although the vascularity index obtained by SMI did not exhibit a statistically significant change across different BTXA concentrations, this technique effectively illustrated the microvascular perfusion in HS. Immunohistochemical staining for CD31 revealed that BTXA inhibited angiogenesis. Conclusion: HFUS and SWE displayed excellent performance in evaluating HS thickness and stiffness. SMI showed a good performance in reflecting microvascular signals in HS. These ultrasound techniques have great potential in assessing the therapeutic effect of BTXA in HS.

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Introduction: This study aimed to investigate the cognitive profile and prospective cognitive changes in non-demented adults with elevated Modified Dementia Risk Scores (MDRS), while also exploring the potential relationship between these associations and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathology and neuroinflammation. Methods: Within the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database, 994 participants without dementia were assessed on MDRS, CSF biomarkers and cognition. We examined the associations of the MDRS with CSF biomarkers and cognitive scores using linear regressions. Causal mediation analyses were conducted to analyze the associations among MDRS, brain pathologies, and cognition. The Alzheimer's Disease Neuroimaging Initiative (ADNI) study was used to validate the mediation effects and to investigate the longitudinal association between MDRS and cognitive decline. Results: The results revealed that higher MDRS were linked to poorer cognitive performance (Model 1: PFDR < 0.001; Model 2: PFDR < 0.001) and increases in CSF levels of phosphorylated tau (P-tau, Model 1: PFDR < 0.001; Model 2: PFDR < 0.001), total tau (T-tau, Model 1: PFDR < 0.001; Model 2: PFDR < 0.001), P-tau/Aß42 ratio (Model 1: PFDR = 0.023; Model 2: PFDR = 0.028), T-tau/Aß42 ratio (Model 1: PFDR < 0.001; Model 2: PFDR < 0.001) and soluble triggering receptor expressed on myeloid cells 2 (sTrem2, Model 1: PFDR < 0.001; Model 2: PFDR < 0.001) in the CABLE study. The impact of MDRS on cognition was partially mediated by neuroinflammation and tau pathology. These mediation effects were replicated in the ADNI study. Baseline MDRS were significantly associated with future cognitive decline, as indicated by lower scores on the Mini-Mental State Examination (MMSE, Model 1: PFDR = 0.045; Model 2: PFDR < 0.001), ADNI composite memory score (ADNI-MEM, Model 1: PFDR = 0.005; Model 2: PFDR < 0.001), ADNI composite executive function score (ADNI-EF, Model 1: PFDR = 0.045; Model 2: PFDR < 0.001), and higher score on the Alzheimer's Disease Assessment Scale (ADAS13, Model 1: PFDR = 0.045; Model 2: PFDR < 0.001). Discussion: The findings of this study revealed significant associations between MDRS and cognitive decline, suggesting a potential role of tau pathology and neuroinflammation in the link between MDRS and poorer cognitive performance in individuals without dementia. Consequently, the MDRS holds promise as a tool for targeted preventive interventions in individuals at high risk of cognitive impairment.

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Objective: To assess the effects of comprehensive nursing intervention on quality of life, self-efficacy, gastrointestinal reaction and immune function of patients with breast cancer undergoing chemotherapy. Methods: This was a retrospective study. One hundred and twenty patients receiving chemotherapy after breast cancer surgery were randomly divided into the experimental group and the control group(n=60) from January 2021 to January 2023. Patients in the perioperative period, the experimental group were given comprehensive nursing intervention, while those in the control group were given conventional specialist nursing intervention. The differences in quality of life, self-efficacy, gastrointestinal reaction, immune function and patient satisfaction between the two groups were compared and analyzed. Results: After the intervention, the SF-36 scores in the experimental group were significantly higher than those in the control group (P=0.00), the efficacy indicators were significantly improved compared to the control group(P=0.00); the scores of gastrointestinal symptoms in the experimental group were significantly lower than those in the control group after the intervention(P<0.05). The indexes of CD3+, CD4+ and CD4+/CD8+ in the experimental group after the intervention were significantly higher than those in the control group(P=0.00); The patient satisfaction in the experimental group was 100%, which was significantly higher than 92% in the control group, with statistically significant differences(P=0.02). Conclusion: Comprehensive nursing intervention leads to a variety of benefits in the treatment of patients with breast cancer during postoperative chemotherapy, such as relieving patients' gastrointestinal reactions, improving their immune function and quality of life, besides effectively improving their self-efficacy, which is worthy of clinical application.

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The construction of novel structured Prussian blue analogs (PBAs) by chemical etching has attracted the most attention to PBA derivatives with outstanding performance. In this work, the unprecedented PBA orthogonal frustums are first prepared from nanocubes through a selective chemical etching approach using trisodium citrate as an etchant. The citrate ions can chelate with nickel species from the edges/corners of NiCo-PBA nanocubes and then disintegrate NiCo-PBAs resulting in the generation of NiCo-PBA orthogonal frustums. The derived CoNi2S4/Co0.91S composites still inherit the original orthogonal frustum structure and possess outstanding supercapacitor performance. This study develops a popularized method to construct novel structured PBAs and brings inspiration for designing PBA-based electrodes with advanced electrochemical performance.

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Renal cell carcinoma (RCC) is considered a "metabolic disease" characterized by elevated glycolysis in patients with advanced RCC. Tyrosine kinase inhibitor (TKI) therapy is currently an important treatment option for advanced RCC, but drug resistance may develop in some patients. Combining TKI with targeted metabolic therapy may provide a more effective approach for patients with advanced RCC. An analysis of 14 RCC patients (including three needle biopsy samples with TKI resistance) revealed by sing-cell RNA sequencing (scRNA-seq) that glycolysis played a crucial role in poor prognosis and drug resistance in RCC. TCGA-KIRC and glycolysis gene set analysis identified DEPDC1 as a target associated with malignant progression and drug resistance in KIRC. Subsequent experiments demonstrated that DEPDC1 promoted malignant progression and glycolysis of RCC, and knockdown DEPDC1 could reverse TKI resistance in RCC cell lines. Bulk RNA sequencing (RNA-seq) and non-targeted metabolomics sequencing suggested that DEPDC1 may regulate RCC glycolysis via AKT/mTOR/HIF1α pathway, a finding supported by protein-level analysis. Clinical tissue samples from 98 RCC patients demonstrated that DEPDC1 was associated with poor prognosis and predicted RCC metastasis. In conclusion, this multi-omics analysis suggests that DEPDC1 could serve as a novel target for TKI combined with targeted metabolic therapy in advanced RCC patients with TKI resistance.

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Carcinoma de Células Renales , Glucólisis , Subunidad alfa del Factor 1 Inducible por Hipoxia , Neoplasias Renales , Proteínas Proto-Oncogénicas c-akt , Serina-Treonina Quinasas TOR , Animales , Femenino , Humanos , Masculino , Ratones , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/tratamiento farmacológico , Línea Celular Tumoral , Resistencia a Antineoplásicos/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica , Glucólisis/efectos de los fármacos , Proteínas Activadoras de GTPasa/metabolismo , Proteínas Activadoras de GTPasa/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Ratones Desnudos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo

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Background: Compliance to sublingual immunotherapy (SLIT) is generally low, resulting in reduced short- and long-term clinical efficacy. Compliance is a critical factor determining the success of allergic rhinitis (AR) treatment. Objective: To analyze the compliance of patients with house dust mite (HDM)-induced AR to SLIT and the impact of coronavirus disease 2019 (COVID-19) on compliance. Methods: The clinical data of 3117 patients with HDM-induced AR who started SLIT between July 2018 and April 2022 were retrospectively reviewed. We assessed the reasons for non-compliance and the changes in non-compliance during the COVID-19 pandemic compared to the pre-pandemic period. Results: Of 3117 patients, 507 (16.27%) patients (ages, 5-67 years) were identified as non-compliant. The most common reason for non-compliance was poor efficacy (27.22%). The non-compliance rate was highest during 24-36 months of SLIT (28.13%, 153/544), followed by 12-24 months (7.02%, 91/1296). Non-compliance was significantly higher in adolescents/adults than in children (P = 0.000). Although the generalized linear model analysis indicated that compliance was affected by the COVID-19 pandemic during 3-6 months of SLIT, the overall compliance to SLIT was not significantly affected by the pandemic, according to the Kaplan-Meier survival analysis. Conclusions: The non-compliance rate of SLIT in this study was low, and poor efficacy was the most common reason for non-compliance. The compliance of adolescents/adults was lower than that of children. The COVID-19 pandemic did not significantly impact compliance to SLIT, which is an appropriate strategy for the home treatment of AR patients during major public health events.

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Hydrolytic nanozyme-based visual colorimetry has emerged as a promising strategy for the detection of aluminum ions. However, most studies focus on simulating the structure of natural enzymes while neglecting to regulate the rate of hydrolysis-related steps, leading to low enzyme-like activity for hydrolytic nanozymes. Herein, we constructed a ruthenium dioxide (RuO2) in situ embedded cerium oxide (CeO2) nanozyme (RuO2/CeO2) with a Lewis acid-base pair (Ce-O-Ru-OH), which can simulate the catalytic behavior of phosphatase (PPase) and can be quantitatively quenched by Al3+ to achieve accurate and sensitive Al3+ colorimetric sensing detection. The incorporation of Ru into CeO2 nanorods accelerates the dissociation of H2O, followed by subsequent combination of hydroxide species to Lewis acidic Ce-O sites. This synergistic effect facilitates substrate activation and significantly enhances the hydrolysis activity of the nanozyme. The results show that the RuO2/CeO2 nanozyme exhibits a limit of detection as low as 0.5 ng/mL. We also demonstrate their efficacy in detecting Al3+ in various practical food samples. This study offers novel insights into the advancement of highly sensitive hydrolytic nanozyme engineering for sensing applications.