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1.
Nutr Metab (Lond) ; 21(1): 40, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956564

RESUMEN

BACKGROUND: Obstructive sleep apnoea (OSA) is commonly associated with insulin resistance (IR) and dyslipidaemia. Apolipoprotein E (APOE) plays important roles in lipid metabolism. The study aimed to disentangle the multifactorial relationships between IR and APOE based on a large-scale population with OSA. METHODS: A total of 5,591 participants who underwent polysomnography for OSA diagnosis were finally enrolled. We collected anthropometric, fasting biochemical and polysomnographic data for each participant. Linear regression analysis was performed to evaluate the relationships between APOE, IR, and sleep breathing-related parameters. Logistic regression, restricted cubic spline (RCS) and mediation analyses were used to explore relationships between APOE and IR in patients with OSA. RESULTS: Increasing OSA severity was associated with greater obesity, more obvious dyslipidaemia, and higher levels of APOE and IR. APOE was positively correlated with the apnoea-hypopnoea index (AHI), oxygen desaturation index (ODI) and microarousal index (MAI) even after adjusting for age, sex, body mass index, and smoking and drinking levels (ß = 0.107, ß = 0.102, ß = 0.075, respectively, all P < 0.001). The risks of IR increased from the first to fourth quartiles of APOE (odds ratio (OR) = 1.695, 95% CI: 1.425-2.017; OR = 2.371, 95% confidence interval (CI): 2.009-2.816; OR = 3.392, 95% CI: 2.853-4.032, all P < 0.001) after adjustments. RCS analysis indicated non-linear and dose response relationships between APOE, AHI, ODI, MAI and insulin resistance. Mediation analyses showed that HOMA-IR explained 9.1% and 10% of the association between AHI, ODI and APOE. The same trends were observed in men, but not in women. CONCLUSIONS: This study showed that APOE is a risk factor for IR; moreover, IR acts as a mediator between OSA and APOE in men. APOE, IR, and OSA showed non-linear and multistage relationships. Taken together, these observations revealed the complex relationships of metabolic disorders in patients with OSA, which could lead to the development of new treatment modalities and a deeper understanding of the systemic impact of OSA.

2.
ACS Nano ; 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39001855

RESUMEN

Solution-based processes have received considerable attention in the fabrication of electronics and sensors owing to their merits of being low-cost, vacuum-free, and simple in equipment. However, the current solution-based processes either lack patterning capability or have low resolution (tens of micrometers) and low pattern fidelity in terms of line edge roughness (LER, several micrometers). Here, we present a surface energy-directed assembly (SEDA) process to fabricate metal oxide patterns with up to 2 orders of magnitude improvement in resolution (800 nm) and LER (16 nm). Experiment results show that high pattern fidelity can be achieved only at low relative humidities of below 30%. The reason for this phenomenon lies in negligible water condensation on the solution droplet. Employing the SEDA process, all-solution-processed metal oxide thin film transistors (TFTs) are fabricated by using indium oxide as channel layers, indium tin oxide as source/drain electrodes and gate electrodes, and aluminum oxide as gate dielectrics. TFT-based logic gate circuits, including NOT, NOR, NAND, and AND are fabricated as well, demonstrating the applicability of the SEDA process in fabricating large area functional electronics.

3.
Hypertension ; 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39005213

RESUMEN

BACKGROUND: The blood pressure (BP) etiologic study is complex due to multifactorial influences, including genetic, environmental, lifestyle, and their intricate interplays. We used a metabolomics approach to capture internal pathways and external exposures and to study BP regulation mechanisms after well-controlled dietary interventions. METHODS: In the ProBP trail (Protein and Blood Pressure), a double-blinded crossover randomized controlled trial, participants underwent dietary interventions of carbohydrate, soy protein, and milk protein, receiving 40 g daily for 8 weeks, with 3-week washout periods. We measured plasma samples collected at baseline and at the end of each dietary intervention. Multivariate linear models were used to evaluate the association between metabolites and systolic/diastolic BP. Nominally significant metabolites were examined for enriching biological pathways. Significant ProBP findings were evaluated for replication among 1311 participants of the BHS (Bogalusa Heart Study), a population-based study conducted in the same area as ProBP. RESULTS: After Bonferroni correction for 77 independent metabolite clusters (α=6.49×10-4), 18 metabolites were significantly associated with BP at baseline or the end of a dietary intervention, of which 11 were replicated in BHS. Seven emerged as novel discoveries, which are as follows: 1-linoleoyl-GPE (18:2), 1-oleoyl-GPE (18:1), 1-stearoyl-2-linoleoyl-GPC (18:0/18:2), 1-palmitoyl-2-oleoyl-GPE (16:0/18:1), maltose, N-stearoyl-sphinganine (d18:0/18:0), and N6-carbamoylthreonyladenosine. Pathway enrichment analyses suggested dietary protein intervention might reduce BP through pathways related to G protein-coupled receptors, incretin function, selenium micronutrient network, and mitochondrial biogenesis. CONCLUSIONS: Seven novel metabolites were identified to be associated with BP at the end of different dietary interventions. The beneficial effects of protein interventions might be mediated through specific metabolic pathways.

4.
Neural Netw ; 179: 106516, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-39003981

RESUMEN

Temporal Knowledge Graphs (TKGs) enable effective modeling of knowledge dynamics and event evolution, facilitating deeper insights and analysis into temporal information. Recently, extrapolation of TKG reasoning has attracted great significance due to its remarkable ability to capture historical correlations and predict future events. Existing studies of extrapolation aim mainly at encoding the structural and temporal semantics based on snapshot sequences, which contain graph aggregators for the association within snapshots and recurrent units for the evolution. However, these methods are limited to modeling long-distance history, as they primarily focus on capturing temporal correlations over shorter periods. Besides, a few approaches rely on compiling historical repetitive statistics of TKGs for predicting future facts. But they often overlook explicit interactions in the graph structure among concurrent events. To address these issues, we propose a PotentiaL concurrEnt Aggregation and contraStive learnING (PLEASING) method for TKG extrapolation. PLEASING is a two-step reasoning framework that effectively leverages the historical and potential features of TKGs. It includes two encoders for historical and global events with an adaptive gated mechanism, acquiring predictions with appropriate weight of the two aspects. Specifically, PLEASING constructs two auxiliary graphs to capture temporal interaction among timestamps and correlations among potential concurrent events, respectively, enabling a holistic investigation of temporal characteristics and future potential possibilities in TKGs. Furthermore, PLEASING incorporates contrastive learning to strengthen its capacity to identify whether queries are related to history. Extensive experiments on seven benchmark datasets demonstrate the state-of-the-art performances of PLEASING and its comprehensive ability to model TKG semantics.

5.
Artículo en Inglés | MEDLINE | ID: mdl-38836730

RESUMEN

Context: Elevated uric-acid levels in the blood are closely associated with hypertension, metabolic syndrome, diabetic nephropathy, cardiovascular diseases, and chronic kidney disease (CKD). A high-glucose diet promotes the accumulation of uric acid. Fibrosis commonly occurs in patients with late-stage type 1 or 2 diabetes and can lead to organ dysfunction. Objective: The study intended to investigate whether high uric acid under high glucose conditions can promote the fibrotic progression of diabetic nephropathy by activating the reactive oxygen species (ROS)/ "nod-like receptor (NLR) family pyrin domain containing 3" (NLRP3)/ "Src homology 2 (SH2) domain-containing protein tyrosine phosphatase-2" (SHP2) pathway, which can promote epithelial-mesenchymal transition (EMT) in renal tubular epithelial cells. Design: The research team conducted an animal study. Setting: The study took place at the Affiliated Hospital of Hebei University in Baoding, Hebei Province, China. Animals: The animals were 14 healthy, male, C57BL/6J mice. Outcome Measures: The research team: (1) using Masson's trichrome staining, examined the fibrosis of renal, tubular epithelial cells in the streptozotocin (STZ) modeling and the STZ modeling + uric-acid groups; (2) used Western Blot analysis to detect the protein expression of NLRP3, "nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase 2" (NOX2), NOX4, alpha-smooth muscle actin (α-SMA), fibronectin 1 (FN-1), collagen-I, and mothers against decapentaplegic homolog 2/3 (SMAD2/3); (3) conducted in-vitro experiments by dividing transformed C3H mouse kidney-1 (TCMK-1) cells into different groups: STZ modeling group, STZ modeling + high-glucose group, STZ modeling + high-glucose + advanced glycation end (AGE) product group, STZ modeling+ high-glucose + AGE + uric-acid group, STZ modeling+ high glucose + SHP2 small interfering RNA (SiRNA) group, STZ modeling + high glucose + SHP2 SiRNA + AGE group, and STZ modeling+ high-glucose + SHP2 SiRNA + AGE + uric-acid group for Western Blot experiments; and (4) performed immunofluorescence, CCK-8, and transwell experiments on the seven groups of TCMK-1 cells with different treatments. Results: The STZ modeling + uric acid group's levels of fibrosis was significantly higher than that of the STZ modeling group (P < .01). Additionally, the STZ modeling + uric acid groups' expression of α-SMA, FN-1, collagen-I, P-SMAD2, P-SMAD3, NLRP3, and reactive oxygen species (ROS), EMT, and SMAD-related proteins were significantly higher than those of the STZ modeling group (P < .01). The protein expression of SHP2, P-SMAD2, α-SMA, and FN-1 for the STZ modeling + high glucose + SHP2 SiRNA, the STZ modeling + high glucose + SHP2 SiRNA + AGE, and the STZ modeling + high glucose + SHP2 SiRNA + AGE + uric acid groups were significantly lower than those of the STZ modeling + high glucose, STZ modeling + high glucose + AGE, and the STZ modeling + high glucose + AGE + uric acid groups, respectively. Immunofluorescence indicated that the STZ modeling+ high glucose + AGE + uric acid group had the highest relative fluorescence intensity, while the three groups treated with SHP2 SiRNA showed the least expression. The cell counting kit-8 (CCK-8) assay showed that STZ modeling group had less cell proliferation, STZ modeling + high sugar group had less cell proliferation than STZ modeling + high sugar +AGE group, STZ modeling + high sugar +AGE+ uric acid group had the highest cell proliferation, STZ modeling + high sugar +SHP2 SiRNA group and STZ modeling + high sugar +SHP2 SiRNA+AGE group and STZ modeling + high sugar +SHP2 SiRNA+AGE+ uric acid group showed the least number of cell proliferation. The results of the transwell cell migration assay were consistent with the CCK-8 assay. Conclusions: In a high-glucose environment, high uric acid can promote the fibrotic progression of diabetic nephropathy by activating the ROS/NLRP3/SHP2 pathway, leading to mesenchymal transition between renal tubular epithelial cells.

6.
bioRxiv ; 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38915487

RESUMEN

Patients with cutaneous T cell lymphoma (CTCL) experience high morbidity and mortality due to S. aureus skin infections and sepsis, but the causative immune defect is unclear. We previously identified high levels of LAIR2, a decoy protein for the inhibitory receptor LAIR1, in advanced CTCL. Mice do not have a LAIR2 homolog, so we used Lair1 knock-out (KO) mice to model LAIR2 overexpression. In a model of subcutaneous S. aureus skin infection, Lair1 KO mice had significantly larger abscesses and areas of dermonecrosis compared to WT. Lair1 KO exhibited a pattern of increased inflammatory responses in infection and sterile immune stimulation, including increased production of proinflammatory cytokines and myeloid chemokines, neutrophil ROS, and collagen/ECM remodeling pathways. Notably, Lair1 KO infected skin had a similar bacterial burden and neutrophils and monocytes had equivalent S. aureus phagocytosis compared to WT. These findings support a model in which lack of LAIR1 signaling causes an excessive inflammatory response that does not improve infection control. CTCL skin lesions harbored similar patterns of increased expression in cytokine and collagen/ECM remodeling pathways, suggesting that high levels of LAIR2 in CTCL recapitulates Lair1 KO, causing inflammatory tissue damage and compromising host defense against S. aureus infection.

7.
Neural Netw ; 178: 106459, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38901098

RESUMEN

Deep neural network security is a persistent concern, with considerable research on visible light physical attacks but limited exploration in the infrared domain. Existing approaches, like white-box infrared attacks using bulb boards and QR suits, lack realism and stealthiness. Meanwhile, black-box methods with cold and hot patches often struggle to ensure robustness. To bridge these gaps, we propose Adversarial Infrared Curves (AdvIC). Using Particle Swarm Optimization, we optimize two Bezier curves and employ cold patches in the physical realm to introduce perturbations, creating infrared curve patterns for physical sample generation. Our extensive experiments confirm AdvIC's effectiveness, achieving 94.8% and 67.2% attack success rates for digital and physical attacks, respectively. Stealthiness is demonstrated through a comparative analysis, and robustness assessments reveal AdvIC's superiority over baseline methods. When deployed against diverse advanced detectors, AdvIC achieves an average attack success rate of 76.2%, emphasizing its robust nature. We conduct thorough experimental analyses, including ablation experiments, transfer attacks, adversarial defense investigations, etc. Given AdvIC's substantial security implications for real-world vision-based applications, urgent attention and mitigation efforts are warranted.

8.
Heliyon ; 10(10): e31346, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38807872

RESUMEN

Pancreatic cancer is one of the most lethal cancers with significant radioresistance and tumor repopulation after radiotherapy. As a type of short non-coding RNA that regulate various biological and pathological processes, miRNAs might play vital role in radioresistance. We found by miRNA sequencing that microRNA-26a (miR-26a) was upregulated in pancreatic cancer cells after radiation, and returned to normal state after a certain time. miR-26a was defined as a tumor suppressive miRNA by conventional tumor biology experiments. However, transient upregulation of miR-26a after radiation significantly promoted radioresistance, while stable overexpression inhibited radioresistance, highlighting the importance of molecular dynamic changes after treatment. Mechanically, transient upregulation of miR-26a promoted cell cycle arrest and DNA damage repair to promote radioresistance. Further experiments confirmed HMGA2 as the direct functional target, which is an oncogene but enhances radiosensitivity. Moreover, PTGS2 was also the target of miR-26a, which might potentiate tumor repopulation via delaying the synthesis of PGE2. Overall, this study revealed that transient upregulation of miR-26a after radiation promoted radioresistance and potentiated tumor repopulation, highlighting the importance of dynamic changes of molecules upon radiotherapy.

9.
Front Oncol ; 14: 1382496, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38812782

RESUMEN

Scope: The present investigation seeks to illuminate the current state and disparities in the knowledge, attitudes, and practices (KAP) among healthcare professionals regarding the management of lung cancer palliative care (LCPC) in China, while simultaneously assessing the prevalence and context of patient-controlled analgesia (PCA) usage in the management of cancer-related pain. Methods: A total of 2093 healthcare practitioners from 706 hospitals across China completed a structured questionnaire that probed various facets of LCPC management. The questionnaire consisted of seven thematic sections, incorporating chi-square tests and Fisher's exact probabilities to statistically assess the discrepancies in KAP among healthcare professionals across different hospital grades. Ordered data distributions among hospital grades were compared using non-parametric Kruskal-Wallis H and Mann-Whitney U tests. Multiple-choice items were subjected to multiple-response cross-tabulation analysis, while the Spearman rank-order correlation coefficient was employed to gauge potential associations among variables. Results: Around 84.2% of the respondents perceived anti-tumor therapy to be of equal importance to palliative care. Statistically significant differences (χ² = 27.402, P = 0.002) in satisfaction levels were observed, with participants from Tertiary hospitals demonstrating higher satisfaction compared to those from Secondary and Primary hospitals. Pain emerged as the most prevalent symptom necessitating LCPC. Major impediments to LCPC adoption included patients' and families' concerns about the safety of long-term palliative care-related drug use. 31.1% of the respondents cited the most frequent rationale for PCA use as cases involving patients who required systemic administration of large opioid doses or exhibited intolerable adverse reactions to opioids. The principal deterrents against the use of PCA for cancer pain management were (1): apprehension about adverse drug reactions due to overdose (2), concern about the potential for opioid addiction, and (3) the anticipated increase in patients' economic burdens. Over the preceding 24-month period, 33.9% of the surveyed healthcare practitioners reported no engagement in either online or offline LCPC-related training initiatives. Conclusion: This study emphasizes the pressing need for comprehensive training in LCPC among Chinese health personnels, particularly focusing on the effective management of cancer pain symptoms.

11.
Biochem Biophys Res Commun ; 721: 149972, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38772213

RESUMEN

Endoplasmic reticulum stress (ERS) plays a crucial role in the pathogenesis of diabetic nephropathy (DN), and it is often accompanied by an increase in reactive oxygen species (ROS) production. However, the precise relationship between NFE2-related factor-2 (Nrf2), a key regulator of ROS balance, and ERS in DN remains elusive. This study aimed to investigate the impact of Nrf2 on ERS and its therapeutic potential in DN. Herein, ERS-related changes, including increased activating transcription factor-6 (ATF6), glucose-regulated protein 78 (GRP78), and transcription factor C/EBP homologous protein (CHOP) expression, were observed in the renal tissues of streptozotocin-induced DN mice and high glucose cultured human renal proximal tubular (HK-2) cells. Nrf2 knockdown increased the sensitivity of HK-2 cells to ERS under high glucose conditions, underscoring the regulatory role of Nrf2 in ERS modulation. Notably, upregulating Nrf2 in ezetimibe-treated diabetic mice restored ERS markers and ameliorated albuminuria, glomerular hypertrophy, mesangial expansion, and tubulointerstitial fibrosis. Furthermore, the inhibition of ERS in HK-2 cells by the ROS scavenger, N-acetylcysteine, highlights the interplay between ROS and ERS. This study, for the first time, elucidates that the upregulation of Nrf2 may alleviate the negative influence of ROS-mediated ERS, presenting a promising therapeutic avenue for delaying the progression of DN. These findings suggest a potential strategy for targeting Nrf2 and ERS in developing novel therapeutic interventions for DN.


Asunto(s)
Diabetes Mellitus Experimental , Nefropatías Diabéticas , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2 , Especies Reactivas de Oxígeno , Regulación hacia Arriba , Animales , Humanos , Masculino , Ratones , Línea Celular , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/tratamiento farmacológico , Chaperón BiP del Retículo Endoplásmico/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Regulación hacia Arriba/efectos de los fármacos
12.
Artículo en Inglés | MEDLINE | ID: mdl-38683903

RESUMEN

Graphene is a promising material for thermoacoustic sources due to its extremely low heat capacity per unit area and high thermal conductivity. However, current graphene thermoacoustic devices have limited device area and relatively high cost, which limit their applications of daily use. Here, we adopt a dip-coating method to fabricate a large-scale and cost-effective graphene sound source. This sound source has the three-dimensional (3D) porous structure that can increase the contact area between graphene and air, thus assisting heat to release into the air. In this method, polyurethane (PU) is used as a support, and graphene nanoplates are attached onto the PU skeleton so that a highly flexible graphene foam (GrF) device is obtained. At a measuring distance of 1 mm, it can emit sound at up to 70 dB under the normalized input power of 1 W. Considering its unique porous structure, we establish a thermoacoustic analysis model to simulate the acoustic performance of GrF. Furthermore, the obtained GrF can be made up to 44 in. (100 cm × 50 cm) in size, and it has good flexibility and processability, which broadens the application fields of GrF loudspeakers. It can be attached to the surfaces of objects with different shapes, making it suitable to be used as a large-area speaker in automobiles, houses, and other application scenarios, such as neck mounted speaker. In addition, it can also be widely used as a fully flexible in-ear earphone.

13.
Neural Netw ; 175: 106310, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38663301

RESUMEN

Thermal infrared detectors have a vast array of potential applications in pedestrian detection and autonomous driving, and their safety performance is of great concern. Recent works use bulb plate, "QR" suit, and infrared patches as physical perturbations to perform white-box attacks on thermal infrared detectors, which are effective but not practical for real-world scenarios. Some researchers have tried to utilize hot and cold blocks as physical perturbations for black-box attacks on thermal infrared detectors. However, this attempts has not yielded robust and multi-view physical attacks, indicating limitations in the approach. To overcome the limitations of existing approaches, we introduce a novel black-box physical attack method, called adversarial infrared blocks (AdvIB). By optimizing the physical parameters of the infrared blocks and deploying them to pedestrians from multiple views, including the front, side, and back, AdvIB can execute robust and multi-view attacks on thermal infrared detectors. Our physical tests show that the proposed method achieves a success rate of over 80% under most distance and view conditions, validating its effectiveness. For stealthiness, our method involves attaching the adversarial infrared block to the inside of clothing, enhancing its stealthiness. Additionally, we perform comprehensive experiments and compare the experimental results with baseline to verify the robustness of our method. In summary, AdvIB allows for potent multi-view black-box attacks, profoundly influencing ethical considerations in today's society. Potential consequences, including disasters from technology misuse and attackers' legal liability, highlight crucial ethical and security issues associated with AdvIB. Considering these concerns, we urge heightened attention to the proposed AdvIB. Our code can be accessed from the following link: https://github.com/ChengYinHu/AdvIB.git.


Asunto(s)
Rayos Infrarrojos , Humanos , Seguridad Computacional , Algoritmos , Peatones , Redes Neurales de la Computación , Conducción de Automóvil
14.
J Nutr Biochem ; 128: 109626, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38527560

RESUMEN

Along with the increasing prevalence of obesity worldwide, the deleterious effects of high-calorie diet are gradually recognized through more and more epidemiological studies. However, the concealed and chronic causality whitewashes its unhealthy character. Given an ingenious mechanism orchestrates the metabolic adaptation to high-fat high-fructose (HFF) diet and connive its lipotoxicity, in this study, an experimental rat/mouse model of obesity was induced and a comparative transcriptomic analysis was performed to probe the mystery. Our results demonstrated that HFF diet consumption altered the transcriptomic pattern as well as different high-calorie diet fed rat/mouse manifested distinct hepatic transcriptome. Validation with RT-qPCR and Western blotting confirmed that SREBP1-FASN involved in de novo lipogenesis partly mediated metabolic self-adaption. Moreover, hepatic ACSL1-CPT1A-CPT2 pathway involved in fatty acids ß-oxidation, played a key role in the metabolic adaption to HFF. Collectively, our findings enrich the knowledge of the chronic adaptation mechanisms and also shed light on future investigations. Meanwhile, our results also suggest that efforts to restore the fatty acids metabolic fate could be a promising avenue to fight against obesity and associated steatosis and insulin resistance challenged by HFF diet.


Asunto(s)
Dieta Alta en Grasa , Acido Graso Sintasa Tipo I , Fructosa , Hígado , Obesidad , Proteína 1 de Unión a los Elementos Reguladores de Esteroles , Transcriptoma , Animales , Fructosa/efectos adversos , Dieta Alta en Grasa/efectos adversos , Masculino , Hígado/metabolismo , Obesidad/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Lipogénesis , Ratones Endogámicos C57BL , Ratas , Ratones , Ratas Sprague-Dawley , Ácidos Grasos/metabolismo
15.
PLoS One ; 19(3): e0296695, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38483859

RESUMEN

Based on the unbalanced panel data of Chinese professional health insurance companies from 2011 to 2021, the paper constructs "PW+PCSE" model to empirically investigate the main factors affecting the commercial health insurance surrender in China from the company level. The results show that asset-liability ratio has a significant positive effect on health insurance surrender rate. The value preservation and appreciation rate of capital and R&D expenditure rate both have significant negative effects on health insurance surrender rate. These studies bring important enlightenment for domestic health insurance companies to avoid surrender risk.


Asunto(s)
Seguro de Salud , Seguro de Responsabilidad Civil , Gastos en Salud , China
16.
Int J Mol Sci ; 25(4)2024 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-38396845

RESUMEN

Hepatocellular carcinoma (HCC), the main pathological type of liver cancer, is related to risk factors such as viral hepatitis, alcohol intake, and non-alcoholic fatty liver disease (NAFLD). The constitutive activation of the PI3K/AKT signaling pathway is common in HCC and has essential involvement in tumor progression. The serine/threonine kinase AKT has several downstream substrates, which have been implicated in the regulation of cellular metabolism. However, the contribution of each of the three AKT isoforms, i.e., AKT1, AKT2 and AKT3, to HCC metabolism has not been comprehensively investigated. In this study, we analyzed the functional role of AKT1, AKT2 and AKT3 in HCC metabolism. The overexpression of activated AKT1, AKT2 and AKT3 isoforms in the human HCC cell lines Hep3B and Huh7 resulted in higher oxygen consumption rate (OCR), ATP production, maximal respiration and spare respiratory capacity in comparison to vector-transduced cells. Vice versa, lentiviral vector-mediated knockdowns of each AKT isoform reduced OCR in both cell lines. Reduced OCR rates observed in the three AKT isoform knockdowns were associated with reduced extracellular acidification rates (ECAR) and reduced lactate production in both analyzed cell lines. Mechanistically, the downregulation of OCR by AKT isoform knockdowns correlated with an increased phosphorylation of the pyruvate dehydrogenase on Ser232, which negatively regulates the activity of this crucial gatekeeper of mitochondrial respiration. In summary, our data indicate that each of the three AKT isoforms is able to upregulate OCR, ECAR and lactate production independently of each other in human HCC cells through the regulation of the pyruvate dehydrogenase.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas Proto-Oncogénicas c-akt , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Ácido Láctico/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Oxidorreductasas , Oxígeno/metabolismo , Fosfatidilinositol 3-Quinasas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Piruvatos
17.
ACS Appl Mater Interfaces ; 16(8): 10380-10388, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38356188

RESUMEN

Skin-like flexible pressure sensors with good sensing performance have great application potential, but their development is limited owing to the need for multistep, high-cost, and low-efficiency preparation processes. Herein, a simple, low-cost, and efficient laser-induced forming process is proposed for the first time to prepare a skin-like flexible piezoresistive sensor. In the laser-induced forming process, based on the photothermal effect of graphene and the foaming effect of glucose, a skin-like polydimethylsiloxanes (PDMS) film with porous structures and surface protrusions is obtained by using infrared laser irradiation of the glucose/graphene/PDMS prepolymer film. Further, based on the skin-like PDMS film with a graphene conductive layer, a new skin-like flexible piezoresistive sensor is obtained. Due to the stress concentration caused by the surface protrusions and the low stiffness caused by the porous structures, the flexible piezoresistive sensor realizes an ultrahigh sensitivity of 1348 kPa-1 at 0-2 kPa, a wide range of 200 kPa, a fast response/recovery time of 52 ms/35 ms, and good stability over 5000 cycles. The application of the sensor to the detection of human pulses and robot clamping force indicates its potential for health monitoring and soft robots. Furthermore, in combination with the neural network (CNN) algorithm in artificial intelligence technology, the sensor achieves 95% accuracy in speech recognition, which demonstrates its great potential for intelligent wearable electronics. Especially, the laser-induced forming process is expected to facilitate the efficient, large-scale preparation of flexible devices with multilevel structures.


Asunto(s)
Grafito , Percepción del Habla , Humanos , Inteligencia Artificial , Rayos Infrarrojos , Dimetilpolisiloxanos , Glucosa
18.
Waste Manag ; 177: 252-265, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38354633

RESUMEN

The larvae of black soldier fly (BSFL) convert organic waste into insect proteins used as feedstuff for livestock and aquaculture. BSFL production performance is considerably reduced during winter season. Herein, the intraspecific diversity of ten commercial BSF colonies collected in China was evaluated. The Bioforte colony was subjected to selective breeding at 12 °C and 16 °C to develop cold-tolerant BSF with improved production performance. After breeding for nine generations, the weight of larvae, survival rate, and the dry matter conversion rate significantly increased. Subsequently, intestinal microbiota in the cold-tolerant strain showed that bacteria belonging to Morganella, Dysgonomonas, Salmonella, Pseudochrobactrum, and Klebsiella genera were highly represented in the 12 °C bred, while those of Acinetobacter, Pseudochrobactrum, Enterococcus, Comamonas, and Leucobacter genera were significantly represented in the 16 °C bred group. Metagenomic revealed that several animal probiotics of the Enterococcus and Vagococcus genera were greatly enriched in the gut of larvae bred at 16 °C. Moreover, bacterial metabolic pathways including carbohydrate, lipid, amino acids, and cofactors and vitamins, were significantly increased, while organismal systems and human diseases was decreased in the 16 °C bred group. Transcriptomic analysis revealed that the upregulated differentially expressed genes in the 16 °C bred groups mainly participated in Autophagy-animal, AMPK signaling pathway, mTOR signaling pathway, Wnt signaling pathway, FoxO signaling pathway, Hippo signaling pathway at day 34 under 16 °C conditions, suggesting their significant role in the survival of BSFL. Taken together, these results shed lights on the role of intestinal microflora and gene pathways in the adaptation of BSF larvae to cold stress.


Asunto(s)
Dípteros , Microbioma Gastrointestinal , Animales , Humanos , Larva/genética , Selección Artificial , Aminoácidos , Dípteros/genética
19.
Sci Rep ; 14(1): 4477, 2024 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-38396063

RESUMEN

We conducted a systematic search across medical databases, including PubMed, Web of Science, EMBASE, and Cochrane Library, up to March 2023. A total of 1944 subjects or individuals from 17 studies were included in our final analysis. The correlation coefficient (r) between sKlotho and calcium was [0.14, (0.02, 0.26)], and a moderate heterogeneity was observed (I2 = 66%, P < 0.05). The correlation coefficient (r) between Klotho and serum phosphate was [- 0.21, (- 0.37, - 0.04)], with apparent heterogeneity (I2 = 84%, P < 0.05). The correlation coefficient (r) between sKlotho and parathyroid hormone and vascular calcification was [- 0.23,(- 0.29, - 0.17); - 0.15, (- 0.23, - 0.08)], with no significant heterogeneity among the studies. (I2 = 40%, P < 0.05; I2 = 30%, P < 0.05). A significant correlation exists between low sKlotho levels and an increased risk of CKD-MBD in patients with CKD. According to the findings, sKlotho may play a role in alleviating CKD-MBD by lowering phosphorus and parathyroid hormone levels, regulating calcium levels, and suppressing vascular calcification. As analysis showed that sKlotho has an important impact on the pathogenesis and progression of CKD-MBD in CKD patients. Nonetheless, further comprehensive and high-quality studies are needed to validate our conclusions.


Asunto(s)
Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica , Insuficiencia Renal Crónica , Calcificación Vascular , Humanos , Calcio , Hormona Paratiroidea , Insuficiencia Renal Crónica/complicaciones
20.
Nanomicro Lett ; 16(1): 119, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38363512

RESUMEN

Due to the constraints imposed by physical effects and performance degradation, silicon-based chip technology is facing certain limitations in sustaining the advancement of Moore's law. Two-dimensional (2D) materials have emerged as highly promising candidates for the post-Moore era, offering significant potential in domains such as integrated circuits and next-generation computing. Here, in this review, the progress of 2D semiconductors in process engineering and various electronic applications are summarized. A careful introduction of material synthesis, transistor engineering focused on device configuration, dielectric engineering, contact engineering, and material integration are given first. Then 2D transistors for certain electronic applications including digital and analog circuits, heterogeneous integration chips, and sensing circuits are discussed. Moreover, several promising applications (artificial intelligence chips and quantum chips) based on specific mechanism devices are introduced. Finally, the challenges for 2D materials encountered in achieving circuit-level or system-level applications are analyzed, and potential development pathways or roadmaps are further speculated and outlooked.

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