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BACKGROUND: This study aimed to synthesize and quantitatively examine Health State Utility Values (HSUVs) for Type 2 Diabetes Mellitus (T2DM) and its complications, providing a robust meta-regression framework for selecting appropriate HSUV estimates. METHOD: We conducted a systematic review to extract HSUVs for T2DM and its complications, encompassing various influencing factors. Relevant literature was sourced from a review spanning 2000-2020, supplemented by literature from PubMed, Embase, and the Web of Science (up to March 2024). Multivariate meta-regression was performed to evaluate the impact of measurement tools, tariffs, health status, and clinical and demographic variables on HSUVs. RESULTS: Our search yielded 118 studies, contributing 1044 HSUVs. The HSUVs for T2DM with complications varied, from 0.65 for cerebrovascular disease to 0.77 for neuropathy. The EQ-5D-3L emerged as the most frequently employed valuation method. HSUV differences across instruments were observed; 15-D had the highest (0.89), while HUI-3 had the lowest (0.70) values. Regression analysis elucidated the significant effects of instrument and tariff choice on HSUVs. Complication-related utility decrement, especially in diabetic foot, was quantified. Age <70 was linked to increased HSUVs, while longer illness duration, hypertension, overweight and obesity correlated with reduced HSUVs. CONCLUSION: Accurate HSUVs are vital for the optimization of T2DM management strategies. This study provided a comprehensive data pool for HSUVs selection, and quantified the influence of various factors on HSUVs, informing analysts and policymakers in understanding the utility variations associated with T2DM and its complications.

Asunto(s)

Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/psicología , Diabetes Mellitus Tipo 2/complicaciones , Estado de Salud , Calidad de Vida , Complicaciones de la Diabetes/psicología , Años de Vida Ajustados por Calidad de Vida , Análisis de Regresión

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The real-time and room-temperature detection of nitrogen dioxide (NO2) holds significant importance for environmental monitoring. However, the performance of NO2 sensors has been hampered by the trade-off between the high sensitivity and stability of conventional sensitive materials. Here, we present a novel fully flexible paper-based gas sensing structure by combining a homogeneous screen-printed titanium carbide (Ti3C2Tx) MXene-based nonmetallic electrode with a MoS2 quantum dots/Ti3C2Tx (MoS2 QDs/Ti3C2Tx) gas-sensing film. These precisely designed gas sensors demonstrate an improved response value (16.3% at 5 ppm) and a low theoretical detection limit of 12.1 ppb toward NO2, which exhibit a remarkable 3.5-fold increase in sensitivity compared to conventional Au interdigital electrodes. The outstanding performance can be attributed to the integration of the quantum confinement effect of MoS2 QDs and the conductivity of Ti3C2Tx, establishing the main active adsorption sites and enhanced charge transport pathways. Furthermore, an end-sealing effect strategy was applied to decorate the defect sites with naturally oxygen-rich tannic acid and conductive polymer, and the formed hydrogen bonding network at the interface effectively mitigated the oxidative degradation of the Ti3C2Tx-based gas sensors. The exceptional stability has been achieved with only a 1.8% decrease in response over 4 weeks. This work highlights the innovative design of high-performance gas sensing materials and homogeneous gas sensor techniques.

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A speech intelligibility (SI) prediction model is proposed that includes an auditory preprocessing component based on the physiological anatomy and activity of the human ear, a hierarchical spiking neural network, and a decision back-end processing based on correlation analysis. The auditory preprocessing component effectively captures advanced physiological details of the auditory system, such as retrograde traveling waves, longitudinal coupling, and cochlear nonlinearity. The ability of the model to predict data from normal-hearing listeners under various additive noise conditions was considered. The predictions closely matched the experimental test data under all conditions. Furthermore, we developed a lumped mass model of a McGee stainless-steel piston with the middle-ear to study the recovery of individuals with otosclerosis. We show that the proposed SI model accurately simulates the effect of middle-ear intervention on SI. Consequently, the model establishes a model-based relationship between objective measures of human ear damage, like distortion product otoacoustic emissions, and speech perception. Moreover, the SI model can serve as a robust tool for optimizing parameters and for preoperative assessment of artificial stimuli, providing a valuable reference for clinical treatments of conductive hearing loss.

Asunto(s)

Redes Neurales de la Computación , Inteligibilidad del Habla , Percepción del Habla , Humanos , Percepción del Habla/fisiología , Estimulación Acústica , Oído Medio/fisiología , Ruido/efectos adversos , Emisiones Otoacústicas Espontáneas , Otosclerosis/fisiopatología , Otosclerosis/cirugía , Simulación por Computador , Vías Auditivas/fisiología , Cóclea/fisiología

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Ultra-low-frequency vibration is prevalent in many critical research fields. Nevertheless, for ultra-low-frequency vibration signals below 1 Hz, there is currently a lack of a cost-effective and efficient measurement method. A new ultra-low-frequency vibration signal testing method based on the passive radio frequency tag phase is proposed using the Radio Frequency Identification (RFID) sensing method. By employing vibration detection on ultra-low-frequency vibration signals, the effectiveness of the proposed approach across different frequencies is validated while thoroughly considering factors such as measurement range, precision, distance, and occlusion effects. The results indicate that this method can accurately measure ultra-low frequency vibration signals as low as 0.01 Hz, with an average relative error of only less than 1.5% for all measurement results, and the error decreases with increasing detection frequency. For the measurement of a 1 Hz vibration signal, the average relative error is less than 1%. In addition, the measurement accuracy remains unaffected by distance or occlusion. Sensitivity and stability tests are also conducted. Continuous monitoring for 8 hours demonstrates the excellent measurement stability of the proposed method. Finally, a performance comparison has been made with laser displacement sensors commonly used in non-contact ultra-low-frequency measurement methods. The results show that the RFID sensing method can detect lower vibration frequencies and has a larger amplitude measurement range and better environmental adaptability. Overall, for ultra-low-frequency vibration, this method offers advantages such as high precision, passive non-contact operation, non-line-of-sight path monitoring, affordability, and convenience. These attributes render it suitable for extensive application in various engineering scenarios requiring ultra-low-frequency vibration testing.

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Aims: This study investigated vancomycin-microbubbles (Vm-MBs) and meropenem (Mp)-MBs with ultrasound-targeted microbubble destruction (UTMD) to disrupt biofilms and improve bactericidal efficiency, providing a new and promising strategy for the treatment of device-related infections (DRIs). Methods: A film hydration method was used to prepare Vm-MBs and Mp-MBs and examine their characterization. Biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli were treated with different groups. Biofilm biomass differences were determined by staining. Thickness and bacterial viability were observed with confocal laser scanning microscope (CLSM). Colony counts were determined by plate-counting. Scanning electron microscopy (SEM) observed bacterial morphology. Results: The Vm-MBs and Mp-MBs met the experimental requirements. The biofilm biomass in the Vm, Vm-MBs, UTMD, and Vm-MBs + UTMD groups was significantly lower than in the control group. MRSA and E. coli biofilms were most notably damaged in the Vm-MBs + UTMD group and Mp-MBs + UTMD group, respectively, with mean 21.55% (SD 0.08) and 19.73% (SD 1.25) remaining in the biofilm biomass. Vm-MBs + UTMD significantly reduced biofilm thickness and bacterial viability (p = 0.005 and p < 0.0001, respectively). Mp-MBs + UTMD could significantly decrease biofilm thickness and bacterial viability (allp < 0.001). Plate-counting method showed that the numbers of MRSA and E. coli bacterial colonies were significantly lower in the Vm-MBs + UTMD group and the Mp, Mp-MBs, UTMD, Mp-MBs + UTMD groups compared to the control group (p = 0.031). SEM showed that the morphology and structure of MRSA and E. coli were significantly damaged in the Vm-MBs + UTMD and Mp-MBs + UTMD groups. Conclusion: Vm-MBs or Mp-MBs combined with UTMD can effectively disrupt biofilms and protectively release antibiotics under ultrasound mediation, significantly reducing bacterial viability and improving the bactericidal effect of antibiotics.

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Sepsis is a life-threatening condition caused by an excessive inflammatory response to an infection. However, the precise regulatory mechanism of sepsis remains unclear. Using a strand-specific RNA-sequencing, we identified 115 hub differentially expressed long noncoding RNAs (lncRNAs) and 443 mRNAs in septic patients, primarily participated in crucial pathways including neutrophil extracellular trap (NET) formation and toll-like receptor signaling. Notably, NETs related gene aquaporin-9 (AQP9) and its associated lncRNAs exhibited significant upregulation in septic neutrophils. Functional experiments revealed AQP9 interacts with its lncRNAs to augment the formation of neutrophil NETs. In murine sepsis models, AQP9 inhibition with phloretin reduced proinflammatory cytokine production and lung damage. These findings provide crucial insights into the regulatory role of AQP9 in sepsis, unraveling its interaction with associated lncRNAs in transmitting downstream signals, holding promise in informing the development of novel therapeutic strategies aimed at ameliorating the debilitating effects of sepsis.

Asunto(s)

Acuaporinas , Trampas Extracelulares , Neutrófilos , ARN Largo no Codificante , ARN Mensajero , Sepsis , Sepsis/inmunología , Sepsis/genética , Sepsis/metabolismo , Trampas Extracelulares/metabolismo , Trampas Extracelulares/inmunología , Humanos , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Mensajero/metabolismo , ARN Mensajero/genética , Neutrófilos/inmunología , Ratones , Masculino , Acuaporinas/genética , Acuaporinas/metabolismo , Ratones Endogámicos C57BL , Citocinas/metabolismo , Inflamación/genética , Inflamación/inmunología , Inflamación/metabolismo , Transducción de Señal

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Cistanche deserticola Y. C. Ma (CD), is mainly distributed in the regions of China (Xinjiang, Inner Mongolia, Gansu), Mongolia, Iran and India. Cistanche deserticola polysaccharide (CDPs), as one of the main components and a crucial bioactive substance of CD, has a variety of pharmacological activities, including immunomodulatory, anti-aging, anti-oxidant, hepatoprotective, anti-osteoporotic, anti-inflammatory, intestinal flora regulatory effects. Many polysaccharides have been successfully obtained in the last three decades from CD. However, there is currently no comprehensive review available concerning CDPs. Considering the importance of CDPs for biological study and drug discovery, the present review aims to systematically summarize the recent major studies on extraction and purification methods of polysaccharides from CD, as well as the characterization of their chemical structure, biological activity, structure-activity relationship, and the application of CDPs in pharmaceutical field. Meanwhile, the shortcomings of CDPs research are further discussed in detail, and new valuable insights for future CDPs research as therapeutic agents and functional foods are proposed.

Asunto(s)

Cistanche , Polisacáridos , Polisacáridos/química , Polisacáridos/farmacología , Polisacáridos/aislamiento & purificación , Cistanche/química , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Humanos , Relación Estructura-Actividad , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación

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With the rapid development of emerging information technologies such as artificial intelligence, cloud computing, and the Internet of Things, the world has entered the era of big data. In the face of growing medical big data, research on the privacy protection of personal information has attracted more and more attention, but few studies have analyzed and forecasted the research hotspots and future development trends on the privacy protection. Presently, to systematically and comprehensively summarize the relevant privacy protection literature in the context of big healthcare data, a bibliometric analysis was conducted to clarify the spatial and temporal distribution and research hotspots of privacy protection using the information visualization software CiteSpace. The literature papers related to privacy protection in the Web of Science were collected from 2012 to 2023. Through analysis of the time, author and countries distribution of relevant publications, we found that after 2013, research on the privacy protection has received increasing attention and the core institution of privacy protection research is the university, but the countries show weak cooperation. Additionally, keywords like privacy, big data, internet, challenge, care, and information have high centralities and frequency, indicating the research hotspots and research trends in the field of the privacy protection. All the findings will provide a comprehensive privacy protection research knowledge structure for scholars in the field of privacy protection research under the background of health big data, which can help them quickly grasp the research hotspots and choose future research projects.

Asunto(s)

Macrodatos , Seguridad Computacional , Confidencialidad , Privacidad , Humanos , Bibliometría

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Significant challenges are posed by the limitations of gas sensing mechanisms for trace-level detection of ammonia (NH3). In this study, we propose to exploit single-atom catalytic activation and targeted adsorption properties to achieve highly sensitive and selective NH3 gas detection. Specifically, Ni single-atom active sites based on N, C coordination (Ni-N-C) were interfacially confined on the surface of two-dimensional (2D) MXene nanosheets (Ni-N-C/Ti3C2Tx), and a fully flexible gas sensor (MNPE-Ni-N-C/Ti3C2Tx) was integrated. The sensor demonstrates a remarkable response value to 5 ppm NH3 (27.3%), excellent selectivity for NH3, and a low theoretical detection limit of 12.1 ppb. Simulation analysis by density functional calculation reveals that the Ni single-atom center with N, C coordination exhibits specific targeted adsorption properties for NH3. Additionally, its catalytic activation effect effectively reduces the Gibbs free energy of the sensing elemental reaction, while its electronic structure promotes the spill-over effect of reactive oxygen species at the gas-solid interface. The sensor has a dual-channel sensing mechanism of both chemical and electronic sensitization, which facilitates efficient electron transfer to the 2D MXene conductive network, resulting in the formation of the NH3 gas molecule sensing signal. Furthermore, the passivation of MXene edge defects by a conjugated hydrogen bond network enhances the long-term stability of MXene-based electrodes under high humidity conditions. This work achieves highly sensitive room-temperature NH3 gas detection based on the catalytic mechanism of Ni single-atom active center with N, C coordination, which provides a novel gas sensing mechanism for room-temperature trace gas detection research.

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In order to improve the prediction accuracy of the sound quality of vehicle interior noise, a novel sound quality prediction model was proposed based on the physiological response predicted metrics, i.e., loudness, sharpness, and roughness. First, a human-ear sound transmission model was constructed by combining the outer and middle ear finite element model with the cochlear transmission line model. This model converted external input noise into cochlear basilar membrane response. Second, the physiological perception models of loudness, sharpness, and roughness were constructed by transforming the basilar membrane response into sound perception related to neuronal firing. Finally, taking the calculated loudness, sharpness, and roughness of the physiological model and the subjective evaluation values of vehicle interior noise as the parameters, a sound quality prediction model was constructed by TabNet model. The results demonstrate that the loudness, sharpness, and roughness computed by the human-ear physiological model exhibit a stronger correlation with the subjective evaluation of sound quality annoyance compared to traditional psychoacoustic parameters. Furthermore, the average error percentage of sound quality prediction based on the physiological model is only 3.81%, which is lower than that based on traditional psychoacoustic parameters.

Asunto(s)

Percepción Sonora , Ruido del Transporte , Psicoacústica , Humanos , Percepción Sonora/fisiología , Estimulación Acústica/métodos , Análisis de Elementos Finitos , Modelos Biológicos , Automóviles , Membrana Basilar/fisiología , Cóclea/fisiología , Percepción Auditiva/fisiología , Ruido , Oído Medio/fisiología , Simulación por Computador

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BACKGROUND: Albendazole (ABZ) and atovaquone (ATO) achieve killing efficacy on Echinococcus granulosus (Egs) by inhibiting energy metabolism, but their utilization rate is low. This study aims to analyze the killing efficacy of ABZ-ATO loading nanoparticles (ABZ-ATO NPs) on Egs. METHODS: Physicochemical properties of NPs were evaluated by ultraviolet spectroscopy and nanoparticle size potentiometer. In vitro experiments exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on protoscolex activity, drug toxicity on liver cell LO2, ROS production, and energy metabolism indexes (lactic dehydrogenase, lactic acid, pyruvic acid, and ATP). In vivo of Egs-infected mouse model exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on vesicle growth and organ toxicity. RESULTS: Drug NPs are characterized by uniform particle size, stability, high drug loading, and - 21.6mV of zeta potential. ABZ or ATO NPs are more potent than free drugs in inhibiting protoscolex activity. The protoscolex-killing effect of ATO-ABZ NPs was stronger than that of free drugs. In vivo Egs-infected mice experiment showed that ATO-ABZ NPs reduced vesicle size and could protect various organs. The results of energy metabolism showed that ATO-ABZ NPs significantly increased the ROS level and pyruvic acid content, and decreased lactate dehydrogenase, lactic acid content, and ATP production in the larvae. In addition, ATO-ABZ NPs promoted a decrease in DHODH protein expression in protoscolexes. CONCLUSION: ATO-ABZ NPs exhibits anti-CE in vitro and in vivo, possibly by inhibiting energy production and promoting pyruvic acid aggregation.

Asunto(s)

Albendazol , Atovacuona , Equinococosis , Echinococcus granulosus , Metabolismo Energético , Nanopartículas , Animales , Albendazol/farmacología , Albendazol/química , Albendazol/administración & dosificación , Ratones , Metabolismo Energético/efectos de los fármacos , Echinococcus granulosus/efectos de los fármacos , Nanopartículas/química , Equinococosis/tratamiento farmacológico , Equinococosis/parasitología , Atovacuona/farmacología , Antihelmínticos/farmacología , Antihelmínticos/administración & dosificación , Humanos , Tamaño de la Partícula , Modelos Animales de Enfermedad , Femenino

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Real-time and accurate biomarker detection is highly desired in point-of-care diagnosis, food freshness monitoring, and hazardous leakage warning. However, achieving such an objective with existing technologies is still challenging. Herein, we demonstrate a wireless inductor-capacitor (LC) chemical sensor based on platinum-doped partially deprotonated-polypyrrole (Pt-PPy+ and PPy0) for real-time and accurate ammonia (NH3) detection. With the chemically wide-range tunability of PPy in conductivity to modulate the impedance, the LC sensor exhibits an up-to-180% improvement in return loss (S11). The Pt-PPy+ and PPy0 shows the p-type semiconductor nature with greatly-manifested adsorption-charge transfer dynamics toward NH3, leading to an unprecedented NH3 sensing range. The S11 and frequency of the Pt-PPy+ and PPy0-based sensor exhibit discriminative response behaviors to humidity and NH3, enabling the without-external-calibration compensation and accurate NH3 detection. A portable system combining the proposed wireless chemical sensor and a handheld instrument is validated, which aids in rationalizing strategies for individuals toward various scenarios.

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Objective: The current study aimed to investigate the potential therapeutic impact of allantoin on diabetes produced by a high-fat diet (HFD) and streptozotocin (STZ) in rats. Subjects and methods: Male Sprague-Dawley rats were fed a high-fat diet to induce insulin resistance, followed by streptozotocin injection to induce diabetes. The effect of oral treatment of allantoin (200, 400 and 800 mg/kg/day) for 8 weeks was evaluated by calculating the alteration in metabolic parameters, biochemical indicators, the oral glucose tolerance tests (OGTT) and hyperinsulinemic-euglycemic clamp tests were performed. Histopathological studies were performed in the liver, kidney and pancreas. Next, the expressions of the MAPK and insulin signaling pathway were measured by Western blot analysis to elucidate the potential mechanism underlying these antidiabetic activities. Results: The administration of allantoin resulted in a significant decrease in fasting blood glucose (FBG) levels, glycogen levels, and glycosylated hemoglobin levels in diabetic rats. Additionally, allantoin therapy led to a dose-dependent increase in body weight growth and serum insulin levels. In addition, the administration of allantoin resulted in a considerable reduction in lipid profile levels and amelioration of histological alterations in rats with diabetes. The administration of allantoin to diabetic rats resulted in a notable decrease in Malondialdehyde (MDA) levels, accompanied by an increase in the activity of antioxidant enzymes in the serum, liver, and kidney. The findings of oral glucose tolerance and hyperinsulinemic-euglycemic clamp tests demonstrated a significant rise in insulin resistance following the administration of allantoin. The upregulation of IRS-2/PI3K/p-Akt/GLUT expression by allantoin suggests a mechanistic relationship between the PI3K/Akt signaling pathway and the antihyperglycemic activity of allantoin. Furthermore, it resulted in a reduction in the levels of TGF-ß1/p38MAPK/Caspase-3 expression in the aforementioned rat tissues affected by diabetes. Conclusions: This study implies that allantoin treats type 2 diabetes by activating PI3K. Additionally, it reduces liver, kidney, and pancreatic apoptosis and inflammation-induced insulin resistance.re.

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BACKGROUND: Ovarian cancer is insidious and usually detected in advanced stages of the disease. As the ovaries are pelvic organs, changes in their pelvic fluid metabolites may be associated with ovarian cancer. METHODS: Metabolomic changes in the pelvic fluid were detected using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in patients with ovarian cancer, ovarian cysts and uterine fibroids. Area under the curve (AUC) analysis was used to assess the diagnostic performance of lipid metabolites and blood tumor indices. The Pearson correlation algorithm was used to analyze the correlation between clinical characteristics and lipid metabolites in ovarian cancer patients. RESULTS: There were 24 lipid metabolites significantly changed in the pelvic fluid of ovarian cancer patients (p < 0.05). Palmitoylcarnitine, lipoamide, lipid metabolites, and blood tumor indices (CA15-3 and CA125) showed AUC > 0.8, with palmitoylcarnitine reaching a high of 0.942. In addition, we found that some lipid metabolites were significantly associated with the clinical stage, abdominal water volume, lymphatic metastasis, and recurrence (p < 0.05, r > 0.5). CONCLUSION: Levels of specific lipid metabolites are potential biomarkers of ovarian cancer and may play a key role in the early diagnosis and prognostic assessment of ovarian cancer. SIGNIFICANCE: Our results showed that pelvic metabolites, especially some lipid metabolites, play an important role in the diagnosis of ovarian cancer. Meanwhile, partial lipid metabolites were closely associated with the clinical presentation and prognosis of patients with ovarian cancer. We believe that our study makes a significant contribution to the literature because it provides a potential approach that is more effective for ovarian cancer detection.

Asunto(s)

Biomarcadores de Tumor , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/diagnóstico , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/análisis , Persona de Mediana Edad , Estudios de Casos y Controles , Adulto , Lípidos/análisis , Lípidos/sangre , Metabolismo de los Lípidos , Líquidos Corporales/metabolismo , Líquidos Corporales/química , Pelvis , Espectrometría de Masas en Tándem , Anciano

RESUMEN

Background: Ovarian cancer (OC) ranks as the fifth most prevalent neoplasm in women and exhibits an unfavorable prognosis. To improve the OC patient's prognosis, a pioneering risk signature was formulated by amalgamating disulfidptosis-related genes. Methods: A comparative analysis of OC tissues and normal tissues was carried out, and differentially expressed disulfidptosis-related genes (DRGs) were found using the criteria of |log2 (fold change) | > 0.585 and adjusted P-value <0.05. Subsequently, the TCGA training set was utilized to create a prognostic risk signature, which was validated by employing both the TCGA testing set and the GEO dataset. Moreover, the immune cell infiltration, mutational load, response to chemotherapy, and response to immunotherapy were analyzed. To further validate these findings, QRT-PCR analysis was conducted on ovarian tumor cell lines. Results: A risk signature was created using fourteen differentially expressed genes (DEGs) associated with disulfidptosis, enabling the classification of ovarian cancer (OC) patients into high-risk group (HRG) and low-risk group (LRG). The HRG exhibited a lower overall survival (OS) compared to the LRG. In addition, the risk score remained an independent predictor even after incorporating clinical factors. Furthermore, the LRG displayed lower stromal, immune, and estimated scores compared to the HRG, suggesting a possible connection between the risk signature, immune cell infiltration, and mutational load. Finally, the QRT-PCR experiments revealed that eight genes were upregulated in the human OC cell line SKOV3 compared with the human normal OC line IOSE80, while six genes were down-regulated. Conclusions: A fourteen-biomarker signature composed of disulfidptosis-related genes could serve as a valuable risk stratification tool in OC, facilitating the identification of patients who may benefit from individualized treatment and follow-up management.

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Prussian blue analogs (PBAs) have been widely recognized as superior cathode materials for sodium-ion batteries (SIBs) owing to numerous merits. However, originating from the rapid crystal growth, PBAs still suffer from considerable vacancy defects and interstitial water, making the preparation of long-cycle-life PBAs the greatest challenge for its practical application. Herein, a novel equilibrium chelation strategy is first proposed to synthesize a high crystallinity (94.7%) PBAs, which is realized by modulating the chelating potency of strong chelating agents via "acid effect" to achieve a moderate chelating effect, forcefully breaking through the bottleneck of poor cyclic stability for PBAs cathodes. Impressively, the as-prepared highly crystalline PBAs represent an unprecedented level of electrochemical performance including ultra-long lifespan (10000 cycles with 86.32% capacity maintenance at 6 A g-1), excellent rate capability (82.0 mAh g-1 at 6 A g-1). Meanwhile, by pairing with commercial hard carbon, the as-prepared PBAs-based SIBs exhibit high energy density (350 Wh kg-1) and excellent capacity retention (82.4% after 1500 cycles), highlighting its promising potential for large-scale energy storage applications.

RESUMEN

Flexible ammonia (NH3) gas sensors have gained increasing attention for their potential in medical diagnostics and health monitoring, as they serve as a biomarker for kidney disease. Utilizing the pre-designable and porous properties of covalent organic frameworks (COFs) is an innovative way to address the demand for high-performance NH3 sensing. However, COF particles frequently encounter aggregation, low conductivity, and mechanical rigidity, reducing the effectiveness of portable NH3 detection. To overcome these challenges, we propose a practical approach using polyvinyl alcohol-carrageenan (κPVA) as a template for in the situ growth of two-dimensional COF film and particles to produce a flexible hydrogel gas sensor (COF/κPVA). The synergistic effect of COF and κPVA enhances the gas sensing, water retention, and mechanical properties. The COF/κPVA hydrogel shows a 54.4% response to 1 ppm NH3 with a root mean square error of less than 5% and full recovery compared to the low response and no recovery of bare κPVA. Owing to the dual effects of the COF film and the particles anchoring the water molecules, the COF/κPVA hydrogel remained stable after 70 h in atmospheric conditions, in contrast, the bare κPVA hydrogel was completely dehydrated. Our work might pave the way for highly sensitive hydrogel gas sensors, which have intriguing applications in flexible electronic devices for gas sensing.

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BACKGROUND: To identify key genes associated with cisplatin resistance in ovarian cancer, a comprehensive analysis was conducted on three datasets from the GEO database and through experimental validation. METHODS: Gene expression profiles were retrieved from the GEO database. DEGs were identified by comparing gene expression profiles between cisplatin-sensitive and resistant ovarian cancer cell lines. The identified genes were further subjected to GO, KEGG, and PPI network analysis. Potential inhibitors of key genes were identified through methods such as LibDock nuclear molecular docking. In vitro assays and RT-qPCR were performed to assess the expression levels of key genes in ovarian cancer cell lines. The sensitivity of cells to chemotherapy and proliferation of key gene knockout cells were evaluated through CCK8 and Clonogenic assays. RESULTS: Results showed that 12 genes influenced the chemosensitivity of the ovarian cancer cell line SKOV3, and 9 genes were associated with the prognosis and survival outcomes of ovarian cancer patients. RT-qPCR results revealed NDRG1, CYBRD1, MT2A, CNIH3, DPYSL3, and CARMIL1 were upregulated, whereas ERBB4, ANK3, B2M, LRRTM4, EYA4, and SLIT2 were downregulated in cisplatin-resistant cell lines. NDRG1, CYBRD1, and DPYSL3 knock-down significantly inhibited the proliferation of cisplatin-resistant cell line SKOV3. Finally, photofrin, a small-molecule compound targeting CYBRD1, was identified. CONCLUSION: This study reveals changes in the expression level of some genes associated with cisplatin-resistant ovarian cancer. In addition, a new small molecule compound was identified for the treatment of cisplatin-resistant ovarian cancer.

Asunto(s)

Antineoplásicos , Cisplatino , Biología Computacional , Resistencia a Antineoplásicos , Neoplasias Ováricas , Cisplatino/farmacología , Cisplatino/uso terapéutico , Femenino , Humanos , Neoplasias Ováricas/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Resistencia a Antineoplásicos/genética , Biología Computacional/métodos , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Perfilación de la Expresión Génica/métodos , Mapas de Interacción de Proteínas , Proliferación Celular/efectos de los fármacos

RESUMEN

We aimed to investigate the dysregulation of the microRNAs(miRNAs) in cholangiocarcinoma (CCA), including its impact on the homeostasis of the transcriptome and cellular behavior. MiRNAs serve as potent epigenetic regulators of transcriptional output, targeting various signaling pathways. This study aimed to investigate the expression level, epigenetic mechanism and function of miR-125a-3 in CCA. The study data showed that the expression level of miR125a-3p was decreased in CCA tissue samples and cell lines, and it was closely related to lymph node metastasis, tissue differentiation and TNM stage. The data demonstrate a strong association between decreased miR-125a-3p expression and poorer prognosis in cholangiocarcinoma patients. miR-125a-3p acts as a tumor suppressor by inhibiting the viability, migration and invasion of CCA cells. There are CpG islands in the promoter region of miR-125a-3p gene, and the methylation of the promoter region of miR-125a-3p gene leads to the transcriptional repression of miR-125a-3p. In addition, miR125a-3p can target and regulate CAC1 mRNA and protein expression in the downstream mechanism, and the high expression of CAC1 can promote the proliferation, migration and invasion of cholangiocarcinoma cells. These data demonstrate that miR-125a-3p promoter methylation leads to silencing of its expression. Mechanically, miR-125a-3p acts as a tumor suppressor and participates in the occurrence and development of CCA through targeting CAC1 gene expression. Therefore, miR-125a-3p may serve as a new target for the diagnosis, prognostic assessment or molecular therapy of CCA.