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1.
Aging Clin Exp Res ; 36(1): 189, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259235

RESUMEN

The prevalence of frailty is increasing, and it is associated with increased risk of diseases and adverse outcomes. Although substantial research has focused on post-stroke frailty, understanding of pre-stroke frailty remains limited. Our aim was to synthesize literature on pre-stroke frailty and stroke risk to explore their relationship and impact on prognosis. A systematic search of multiple databases was conducted to identify cohort studies published until October 28, 2023. Meta-analysis was conducted using a random effects model. Heterogeneity was assessed with the I² statistic, and publication bias was evaluated using Begg's test. Finally, we included 11 studies (n = 1,660,328 participants). The pooled hazard ratios (HRs) for stroke risk associated with pre-stroke frailty compared to non-frail individuals was 1.72 (95% confidence interval, CI: 1.46-2.02, p = 0.002, I2 = 69.2%, Begg's test: p = 0.536). The pooled HRs for mortality and the pooled relative risk (RRs) modified Rankin Scale (mRs) associated with pre-stroke frailty were 1.68 (95% CI: 1.10-2.56, p = 0.136, I2 = 49.9%, Begg's test: p = 0.296) and 3.11 (95% CI: 1.77-5.46, p = 0.192, I2 = 39.4%, Begg's test: p = 1.000), respectively. In conclusion, pre-stroke frailty is strongly associated with stroke risk and impacts its prognosis, irrespective of the measurement method. Future research should focus on prospective studies to assess the effects of early intervention for frailty. This has significant implications for primary healthcare services and frailty management.


Asunto(s)
Fragilidad , Accidente Cerebrovascular , Anciano , Humanos , Anciano Frágil/estadística & datos numéricos , Fragilidad/complicaciones , Fragilidad/epidemiología , Pronóstico , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/complicaciones
2.
Phys Chem Chem Phys ; 26(37): 24689-24698, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39282755

RESUMEN

Mixed ionic-electronic conductors are widely used as electroactive materials in energy applications. The contact of a mixed conductor with another phase plays a crucial role in charge storage and transport in energy devices. However, the interfacial chemistry at the heterojunctions comprising mixed conductors and its interplay with the bulk chemistry remains imperative yet inadequately understood. This study addresses the fundamentals of space charge effects by exploring the equilibrium situations for contacts consisting of mixed conductors. From the perspective of defect chemistry, and by unifying the bulk and interfacial conditions with the electrochemical potential, our treatment allows for predicting the built-in potential at heterojunctions, profiling the space charge distributions, and evaluating the resulting interfacial charge storage and transport. The treatment can be related to experimental characterization, including coulometric titration, conductivity, and capacitance measurements at electrochemical interfaces in all-solid-state batteries. Besides, our treatment also highlights the significance of size and doping effects in nanocrystalline electrodes. This work provides a comprehensive framework for understanding and engineering the heterojunctions in electrochemical devices.

3.
Med Acupunct ; 36(4): 173-177, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39309623

RESUMEN

Pediatric tuina is a traditional Chinese medicine (TCM) modality that is well-accepted and applied in China currently. As a traditional medicine, it is based on TCM theories and clinical experience. In the TCM area, the "self-healing" system of the human body includes two aspects: self-regulation and adaptation, through which pediatric tuina could rectify dysfunctional states and guide the transition back to homeostasis. Pediatric tuina manipulations sufficiently, specifically, and accurately simulate certain sensory receptors in the skin, which in turn activates the internal self-healing function of the human body. We summarized the main opinions on pediatric tuina mechanism in ancient literature into three minor perspectives and demonstrated them by combining them with modern medical knowledge. First, children at a young age are more responsive to stimulations on the skin surface; second, the sensory receptors and pediatric tuina acupoints on the skin surface have a similar distribution pattern; third, the specific manipulations of pediatric tuina provide multiple stimuli that are detected by a variety of surface sensory receptors for information collection. Each point could be tested via clinical trials with appropriate-designed comparisons.

4.
Front Med (Lausanne) ; 11: 1453609, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39301491

RESUMEN

Objective: To determine the comparative effects and safety of traditional Chinese medicine (TCM) interventions based on meridian theory for pain relief in patients with primary dysmenorrhea (PD). Methods: This is a systematic review with network meta-analysis. Randomized controlled trials (RCTs) comparing meridian-based TCM interventions with waitlist, placebo, western medicine, and conventional therapies for PD pain. A SUCRA was used to estimate the probability ranking for the effects of interventions. Results: 57 RCTs involving 3,903 participants and 15interventions were included. Thirty-two RCTs were rated as low risk of bias. A network diagram was drawn with 105 pairs of comparisons. Compared with NSAIDs and waitlist, significantly better effects were found in acupressure [SMD = -1.51, 95%CI (-2.91, -0.12)/SMD = -2.31, 95%CI (-4.61, -0.02)], warm needling [SMD = -1.43, 95%CI (-2.68, -0.18)/SMD = -2.23, 95%CI (-4.43, -0.03)], moxibustion [SMD = -1.21, 95%CI (-1.85, -0.57)/SMD = -2.10, 95%CI (-3.95, -0.07)], and acupuncture [SMD = -1.09, 95%CI (-1.62, -0.55)/SMD = -1.89, 95%CI (-3.67, -0.11)]. No adverse events were detected. Conclusion: For PD pain, the effects of acupressure, acupuncture, warm needling, and moxibustion were superior to those of NSAIDs and waitlist. Oral contraceptive pill, electro-acupuncture, acupressure, and warm needling demonstrated higher probabilities of being better interventions. More high-quality clinical trials are needed to provide more robust evidence of this network. Systematic review registration: PROSPERO CRD42022373312.

5.
Front Plant Sci ; 15: 1416886, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39323534

RESUMEN

This study establishes the first core collection (CC) for Taiwanese Phalaenopsis orchids to preserve genetic diversity and key traits essential for breeding and research, thereby enhancing breeding efficiency without the need for a large maintained parent population. We examined 207 commercial orchid cultivars from ten nurseries, characterized by two phenotypes and genotypic data from eight simple sequence repeat markers. Multiple imputation was applied to estimate missing phenotypes, minimizing potential uncertainties and ensuring the reliability of population structure analysis. Weighted k-means clustering identified seven distinct clusters, highlighting substantial genetic diversity. We proposed a two-step phenotype and genotype strategy and modified genetic distance algorithms to effectively preserve both phenotypic and genetic diversity while retaining key features. Consequently, 22 core accessions were selected, distributed across seven clusters, and representing the orchid germplasm collection. Our evaluation revealed significant diversity preservation, particularly in distinct characteristics and rare features, outperforming other methodologies. Pedigree background analysis further confirmed the representativeness of the CC in maintaining diverse genetic materials. We emphasized the importance of evaluating the CC by detailing the criteria and statistical analyses used to ensure the quality, representativeness, and effectiveness of the selected accessions. This study contributes to orchid breeding, conservation efforts, and sustainable agricultural practices by providing a valuable and comprehensive resource. In conclusion, our research establishes a groundbreaking CC, offering insights into the genetic landscape of Taiwanese Phalaenopsis orchids and highlighting potential advancements in breeding commercially desirable varieties.

6.
Artículo en Inglés | MEDLINE | ID: mdl-39324336

RESUMEN

Hybrid organic-inorganic molecular ferroelectrics (HOIMFs) have garnered significant attention owing to their potential applications in optoelectronic and spintronic devices. However, HOIMFs with high Curie temperature (Tc), narrow bandgap (Eg), excellent stability, and high breakdown voltage are still very rare. Herein, we present a novel lead-halide molecular ferroelectric, (1,4-butanediammonium)PbI4 (1), synthesized hydrothermally. 1 exhibits a ferroelectric-to-paraelectric phase transition with a high Curie temperature of 485 K, a room temperature ferroelectric hysteresis loop with a robust saturation polarization of 3.9 µC/cm2 and strong coercivity of 33 kV/cm, and a typical semiconductor behavior with a direct bandgap of 2.28 eV. Switchable photovoltaic effect was observed in 1-based device with a fast response time of ∼2 ms and high breakdown electric field of 80 kV/cm. Dramatically enhanced photovoltaic performance has been achieved by manipulating the ferroelectric polarization, resulting in a maximum photovoltage of Voc ∼ 0.84 V and a photocurrent of Jsc ∼ 33.31 nA/cm2 under standard AM 1.5 G illumination. This study offers a bright avenue for advancing high-Tc lead-halide molecular ferroelectrics with promising potentials in photodetectors, data storage, and logical switching devices.

7.
Front Plant Sci ; 15: 1439972, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39263419

RESUMEN

Autophagy is a highly conserved process in eukaryotes that is used to recycle the cellular components from the cytoplasm. It plays a crucial function in responding to both biotic and abiotic stress, as well as in the growth and development of plants. Autophagy-related genes (ATG) and their functions have been identified in numerous crop species. However, their specific tasks in potatoes (Solanum tuberosum L.), are still not well understood. This work is the first to identify and characterize the potato StATG18 subfamily gene at the whole-genome level, resulting in a total of 6 potential StATG18 subfamily genes. We analyzed the phylogenetic relationships, chromosome distribution and gene replication, conserved motifs and gene structure, interspecific collinearity relationship, and cis-regulatory elements of the ATG18 subfamily members using bioinformatics approaches. Furthermore, the quantitative real-time polymerase chain reaction (qRT-PCR) analysis suggested that StATG18 subfamily genes exhibit differential expression in various tissues and organs of potato plants. When exposed to heat stress, their expression pattern was observed in the root, stem, and leaf. Based on a higher expression profile, the StATG18a gene was further analyzed under heat stress in potatoes. The subcellular localization analysis of StATG18a revealed its presence in both the cytoplasm and nucleus. In addition, StATG18a altered the growth indicators, physiological characteristics, and photosynthesis of potato plants under heat stresses. In conclusion, this work offers a thorough assessment of StATG18 subfamily genes and provides essential recommendations for additional functional investigation of autophagy-associated genes in potato plants. Moreover, these results also contribute to our understanding of the potential mechanism and functional validation of the StATG18a gene's persistent tolerance to heat stress in potato plants.

8.
J Inflamm Res ; 17: 5633-5643, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39219813

RESUMEN

Purpose: Visceral adiposity is a significant risk factor for severe COVID-19. However, the impact of the Chinese visceral adiposity index (CVAI) on the efficacy of SARS-CoV-2 vaccines remains poorly understood. This study aims to explore the impact of CVAI on the production of neutralizing antibodies (NAb) in inactivated SARS-CoV-2 vaccines and the potential mechanism, thereby optimizing vaccination guidance. Methods: In this cross-sectional study, 206 health workers (completed two SARS-CoV-2 vaccination on February 8th and March 10th, 2021, respectively) were recruited. All baseline anthropometric parameters of the participants were collected, and venous blood samples were obtained 6 weeks later to measure peripheral innate immune cells, inflammatory cytokines, and NAb titers against SARS-CoV-2. CVAI were calculated according to the formula and divided participants into two groups depending on CVAI median. Results: The median NAb titer among healthcare workers was 12.94 AU/mL, with an efficacy of 87.86% for the SARS-CoV-2 vaccine. NAb titers were lower in the CVAI dysfunction group than in the CVAI reference group (median: 11.40 AU/mL vs 15.57 AU/mL), the hsCRP levels (median: 0.50 mg/L vs 0.30 mg/L) and peripheral monocyte count (mean: 0.47 × 109/L vs 0.42 × 109/L) in the CVAI dysfunction group were higher than in the CVAI reference group. Additionally, CVAI showed positive correlations with hsCRP, monocytes, lymphocytes, and B-lymphocytes, and a negative correlation with NAb titers. Conclusion: CVAI may inhibit SARS-CoV-2 neutralizing antibody expression through inducing immune dysfunction and chronic inflammation. Thus, more attention should be paid to the vaccination for high CVAI population to improve the effectiveness of vaccination, which could provide more robust support for COVID-19 epidemic prevention and control.

9.
ACS Omega ; 9(34): 36518-36530, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39220516

RESUMEN

When Fourier transform (FT) spectrum peaks are overlapped, primary maxima of odd-order derivatives can be used to evaluate their independent intensities. We studied the feasibility of higher odd-order derivatives on Lorentzian peak shape and magnitude peak shape. Simulation studies for FT nuclear magnetic resonance (NMR) spectroscopy demonstrated good results toward quantitative deconvolution of overlapping FT spectrum peaks. Although it is not so desirable to deconvolute special line shapes such as Gaussian, Voigt, and Tsallis profiles, the odd-order derivatives exhibit a bright future compared to even-order derivatives. An application example of practical NMR spectroscopy with ethylbenzene isomers is presented. White Gaussian noises were added to the simulated spectra at two different signal-to-noise ratios (20 and 40). Kauppinen's denoising and smoothing algorithms can effectively remove interference of the noise and help to have good deconvoluting results using the odd-order derivatives. We compared features of our approach with popular deconvolution sharpening algorithms and conducted a comparison study with Kauppinen's Fourier self-deconvolution. Our approach has a better dynamic range of peak intensities and is not sensitive to the sampling rates. Other common deconvolution methods are also discussed briefly.

10.
Heliyon ; 10(16): e35468, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39220951

RESUMEN

This study investigates the rampant spread of offensive and derogatory language during the COVID-19 pandemic and aims to mitigate it through machine learning. Employing advanced Large Language Models (LLMs), the research develops a sophisticated framework adept at detecting and transforming abusive and hateful speech. The project begins by meticulously compiling a dataset, focusing specifically on Chinese language abuse and hate speech. It incorporates an extensive list of 30 pandemic-related terms, significantly enriching the resources available for this type of research. A two-tier detection model is then introduced, achieving a remarkable accuracy of 94.42 % in its first phase and an impressive 81.48 % in the second. Furthermore, the study enhances paraphrasing efficiency by integrating generative AI techniques, primarily Large Language Models, with a Latent Dirichlet Allocation (LDA) topic model. This combination allows for a thorough analysis of language before and after modification. The results highlight the transformative power of these methods. They show that the rephrased statements not only reduce the initial hostility but also preserve the essential themes and meanings. This breakthrough offers users effective rephrasing suggestions to prevent the spread of hate speech, contributing to more positive and constructive public discourse.

12.
BMC Med ; 22(1): 357, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39227839

RESUMEN

BACKGROUND: Our previous genome­wide association studies (GWAS) have suggested rs912304 in 14q12 as a suggestive risk variant for type 1 diabetes (T1D). However, the association between this risk region and T1D subgroups and related clinical risk features, the underlying causal functional variant(s), putative candidate gene(s), and related mechanisms are yet to be elucidated. METHODS: We assessed the association between variant rs912304 and T1D, as well as islet autoimmunity and islet function, stratified by the diagnosed age of 12. We used epigenome bioinformatics analyses, dual luciferase reporter assays, and expression quantitative trait loci (eQTL) analyses to prioritize the most likely functional variant and potential causal gene. We also performed functional experiments to evaluate the role of the causal gene on islet function and its related mechanisms. RESULTS: We identified rs912304 as a risk variant for T1D subgroups with diagnosed age ≥ 12 but not < 12. This variant is associated with residual islet function but not islet-specific autoantibody positivity in T1D individuals. Bioinformatics analysis indicated that rs912304 is a functional variant exhibiting spatial overlaps with enhancer active histone marks (H3K27ac and H3K4me1) and open chromatin status (ATAC-seq) in the human pancreas and islet tissues. Luciferase reporter gene assays and eQTL analyses demonstrated that the biallelic sites of rs912304 had differential allele-specific enhancer activity in beta cell lines and regulated STXBP6 expression, which was defined as the most putative causal gene based on Open Targets Genetics, GTEx v8 and Tiger database. Moreover, Stxbp6 was upregulated by T1D-related proinflammatory cytokines but not high glucose/fat. Notably, Stxbp6 over-expressed INS-1E cells exhibited decreasing insulin secretion and increasing cell apoptosis through Glut1 and Gadd45ß, respectively. CONCLUSIONS: This study expanded the genomic landscape regarding late-onset T1D risk and supported islet function mechanistically connected to T1D pathogenesis.


Asunto(s)
Diabetes Mellitus Tipo 1 , Islotes Pancreáticos , Humanos , Diabetes Mellitus Tipo 1/genética , Islotes Pancreáticos/metabolismo , Femenino , Masculino , Polimorfismo de Nucleótido Simple/genética , Predisposición Genética a la Enfermedad , Citocinas/genética , Citocinas/metabolismo , Niño , Adolescente , Sitios de Carácter Cuantitativo , Animales , Edad de Inicio , Regulación de la Expresión Génica , Estudio de Asociación del Genoma Completo
13.
Biomaterials ; 314: 122835, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39276409

RESUMEN

Induction of reactive oxygen species (ROS) production in cancer cells plays a critical role for cancer treatment. However, therapeutic efficiency remains challenging due to insufficient ROS production of current ROS inducers. We designed a novel platinum (Pt)-based drug named "carrier-platin" that integrates ultrasmall Pt-based nanoparticles uniformly confined within a poly(amino acids) carrier. Carrier-platin dramatically triggered a burst of ROS in cancer cells, leading to cancer cell death as quick as 30 min. Unlike traditional Pt-based drugs which induce cell apoptosis through DNA intercalation, carrier-platin with superior ROS catalytic activities induces a unique pattern of cancer cell death that is neither apoptosis nor ferroptosis and operates independently of DNA damage. Importantly, carrier-platin demonstrates superior anti-tumor efficacy against a broad spectrum of cancers, particularly those with multidrug resistance, while maintaining minimal systemic toxicity. Our findings reveal a distinct mechanism of action of Pt in cancer cell eradication, positioning carrier-platin as a novel category of anti-cancer chemotherapeutics.

14.
Biomacromolecules ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39289809

RESUMEN

Silica encapsulation under ambient conditions is commonly used to shield protein-based nanosystems from chemical stress. However, encapsulation-induced photo- and structural instabilities at elevated temperatures have been overlooked. Using bovine serum albumin-capped fluorescent gold nanoclusters (BSA-AuNCs) as a model, we demonstrated that chaperone/polymer layer-by-layer complexation can stabilize the template to resist encapsulation-induced fragmentation/reorganization and emission increases at 37 °C or higher temperatures. We first wrapped BSA-AuNCs with α-crystallin chaperones (α-Crys) to gain the highest thermal stability at a 1:50 molar ratio and then enfolded BSA-AuNC/α-Crys with thermoresponsive poly-N-isopropylacrylamide (PNIPAM) at 60 °C to shield silica interaction and increase the chaperone-client protein accessibility. The resulting BSA-AuNC/α-Crys/PNIPAM (BαP) was encapsulated by a sol-gel process to yield BαP-Si (∼80 ± 4.5 nm), which exhibited excellent structural integrity and photostability against chemical and thermal stresses. Moreover, targeted BαP-Si demonstrated prolonged fluorescence stability for cancer cell imaging. This template stabilization strategy for silica encapsulation is biocompatible and applicable to other protein-based nanosystems.

15.
Cell Death Differ ; 31(9): 1184-1201, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39103535

RESUMEN

Ferroptosis holds significant potential for application in cancer therapy. However, ferroptosis inducers are not cell-specific and can cause phospholipid peroxidation in both tumor and non-tumor cells. This limitation greatly restricts the use of ferroptosis therapy as a safe and effective anticancer strategy. Our previous study demonstrated that macrophages can engulf ferroptotic cells through Toll-like receptor 2 (TLR2). Despite this advancement, the precise mechanism by which phospholipid peroxidation in macrophages affects their phagocytotic capability during treatment of tumors with ferroptotic agents is still unknown. Here, we utilized flow sorting combined with redox phospholipidomics to determine that phospholipid peroxidation in tumor microenvironment (TME) macrophages impaired the macrophages ability to eliminate ferroptotic tumor cells by phagocytosis, ultimately fostering tumor resistance to ferroptosis therapy. Mechanistically, the accumulation of phospholipid peroxidation in the macrophage endoplasmic reticulum (ER) repressed TLR2 trafficking to the plasma membrane and caused its retention in the ER by disrupting the interaction between TLR2 and its chaperone CNPY3. Subsequently, this ER-retained TLR2 recruited E3 ligase MARCH6 and initiated the proteasome-dependent degradation. Using redox phospholipidomics, we identified 1-steaoryl-2-15-HpETE-sn-glycero-3-phosphatidylethanolamine (SAPE-OOH) as the crucial mediator of these effects. Conclusively, our discovery elucidates a novel molecular mechanism underlying macrophage phospholipid peroxidation-induced tumor resistance to ferroptosis therapy and highlights the TLR2-MARCH6 axis as a potential therapeutic target for cancer therapy.


Asunto(s)
Ferroptosis , Peroxidación de Lípido , Macrófagos , Fagocitosis , Fosfolípidos , Fosfolípidos/metabolismo , Macrófagos/metabolismo , Animales , Ratones , Humanos , Receptor Toll-Like 2/metabolismo , Microambiente Tumoral , Línea Celular Tumoral , Ratones Endogámicos C57BL , Neoplasias/metabolismo , Neoplasias/patología , Células RAW 264.7
16.
Environ Monit Assess ; 196(9): 856, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39196401

RESUMEN

Rapid socio-economic development has led to many water environmental issues in small watersheds such as non-compliance with water quality standards, complex pollution sources, and difficulties in water environment management. To achieve a quantitative evaluation of water quality, identify pollution sources, and implement refined management in small watersheds, this study collected monthly seven water quality indexes of four monitoring points from 2010 to 2023, and ten water quality indexes of 23 sampling points in the Shiting River and Mianyuan River which are tributaries of the Tuojiang River Basin. Then, water quality evaluation and pollution source analysis were conducted from both temporal and spatial perspectives using the Water Quality Index (WQI) method, the Absolute Principal Component Scores/Multiple Linear Regression (APCS-MLR) method, and the Positive Matrix Factorization (PMF) receptor modeling technique. The results indicated that except for total nitrogen (TN), the concentrations of other water quality indexes exhibited a decreasing trend, and all were divided into two obvious stages before and after 2016. Furthermore, the proportion of water quality grade of Good and above increased from 73.96 to 84.94% from 2010-2015 to 2016-2023, and the water quality grade of Good and above from upstream to downstream dropped from 100 to 23.33%. From the temporal scale, four and five pollution sources were identified in the first and second stages, respectively. The distinct TN pollutant is mainly affected by agricultural non-point sources (NPS), whose impact is enhanced from 17.76 to 78.31%. Total phosphorus (TP) was affected by the phosphorus chemical industry, whose contribution gradually weakened from 50.8 to 24.9%. From a spatial perspective, four and five pollution sources were identified in the upstream and downstream, respectively. Therefore, even though there are some limitations due to the data availability of water monitory and hydrology data, the proposed research framework of this study can be applied to the water environmental management of other similar watersheds.


Asunto(s)
Monitoreo del Ambiente , Fósforo , Ríos , Contaminantes Químicos del Agua , Calidad del Agua , China , Monitoreo del Ambiente/métodos , Contaminantes Químicos del Agua/análisis , Ríos/química , Fósforo/análisis , Nitrógeno/análisis , Contaminación Química del Agua/estadística & datos numéricos
17.
Transl Oncol ; 49: 102103, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39181117

RESUMEN

OBJECTIVE: Mitomycin C (MMC), a DNA-damaging chemotherapeutic, is commonly used clinically for recurrent cervical carcinoma (CC), either alone or in combination. MMC generates DNA damage resulting in CC cell death yet also induces increased AKT-BAD phosphorylation associated with drug resistance and reduced clinical benefit. The present study evaluates the efficacy of combined MMC and a BAD phosphorylation inhibitor in CC. METHODS: The association and function of phosphorylation of BAD on serine 99 (pBADS99) for cell survival of both MMC-resistant or sensitive-CC cells was explored. BAD was mutated to BADS99A to examine the requirement of BADS99 for CC cell survival and a novel small-molecule inhibitor of pBADS99 was utilized. Cell proliferation, survival, foci formation, and patient-derived organoids (PDOs) assays were utilized to determine efficacy, synergy and related mechanisms. RESULTS: MMC IC50 was positively correlated to the cell line pBADS99/BAD ratio. Increased BADS99 phosphorylation was observed in both MMC-sensitive or -resistant CC cells after MMC treatment. Inhibition of pBADS99 in CC cell lines produced synergistic apoptosis through BAD-mediated apoptotic pathways and enhanced DNA damage in response to MMC. The concurrent use of pharmacological inhibition of pBADS99 and MMC was synergistic, resulting in diminished cell viability and inducing apoptotic cell death in MMC-sensitive and -resistant CC cell lines or patient-derived organoids. CONCLUSION: A combination of MMC with inhibition of BAD phosphorylation potentiated efficacy compared to single agent treatment. The potential further development of such strategies may provide outcome benefits to patients with CC.

18.
Phys Med Biol ; 69(18)2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39191289

RESUMEN

Objective.The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is challenging due to nonspecific early symptoms, complex diagnostic processes, and small lesion sizes. This study aims to develop an automatic diagnosis method for CTEPH using non-contrasted computed tomography (NCCT) scans, enabling automated diagnosis without precise lesion annotation.Approach.A novel cascade network (CN) with multiple instance learning (CNMIL) framework was developed to improve the diagnosis of CTEPH. This method uses a CN architecture combining two Resnet-18 CNN networks to progressively distinguish between normal and CTEPH cases. Multiple instance learning (MIL) is employed to treat each 3D CT case as a 'bag' of image slices, using attention scoring to identify the most important slices. An attention module helps the model focus on diagnostically relevant regions within each slice. The dataset comprised NCCT scans from 300 subjects, including 117 males and 183 females, with an average age of 52.5 ± 20.9 years, consisting of 132 normal cases and 168 cases of lung diseases, including 88 cases of CTEPH. The CNMIL framework was evaluated using sensitivity, specificity, and the area under the curve (AUC) metrics, and compared with common 3D supervised classification networks and existing CTEPH automatic diagnosis networks.Main results. The CNMIL framework demonstrated high diagnostic performance, achieving an AUC of 0.807, accuracy of 0.833, sensitivity of 0.795, and specificity of 0.849 in distinguishing CTEPH cases. Ablation studies revealed that integrating MIL and the CN significantly enhanced performance, with the model achieving an AUC of 0.978 and perfect sensitivity (1.000) in normal classification. Comparisons with other 3D network architectures confirmed that the integrated model outperformed others, achieving the highest AUC of 0.8419.Significance. The CNMIL network requires no additional scans or annotations, relying solely on NCCT. This approach can improve timely and accurate CTEPH detection, resulting in better patient outcomes.


Asunto(s)
Automatización , Hipertensión Pulmonar , Embolia Pulmonar , Tomografía Computarizada por Rayos X , Humanos , Hipertensión Pulmonar/diagnóstico por imagen , Femenino , Persona de Mediana Edad , Masculino , Enfermedad Crónica , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/complicaciones , Aprendizaje Automático , Procesamiento de Imagen Asistido por Computador/métodos , Adulto , Redes Neurales de la Computación , Anciano
19.
Environ Monit Assess ; 196(9): 803, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39120619

RESUMEN

High-quality development of water resources supports high-quality socio-economic development. High-quality development connects high-quality life, and clarifying the key management contents of small watersheds plays an important role in building ecologically clean small watersheds and promoting regional production and life. Previous research on pollution loads has focused on examining the impact of various external drivers on pollution loads but still lacks research on the impact of changes in pollution sources themselves on pollution loads. In this study, sensitivity analysis was used to determine the impact of changes from different sources on the total pollution loads, which can recognize the critical pollution sources. We first employed the pollutant discharge coefficient method to quantify non-point source pollution loads in the small watershed in the upstream Tuojiang River basin from 2010 to 2021. Then, combination sensitivity analysis with Getis-Ord Gi* was used to identify the critical sources and their crucial areas at the global, districts (counties), and towns (streets) scales, respectively. The results indicate: (1) The pollution loads of COD, NH3-N, TN, and TP all show a decreasing trend, reducing by 18.3%, 16.2%, 18.6%, and 28.1% from 2010 to 2021, respectively; (2) Livestock and poultry breeding pollution source is the most critical source for majority areas across watershed; (3) High-risk areas are mainly concentrated in Jingyang district and its subordinate towns (streets). There is a trend of low-pollution risk areas transitioning to high-pollution risk areas, with high-risk areas predominantly concentrated in the southeast and exhibiting a noticeable phenomenon of pollution load spilling around. This study can promote other similar small watersheds, holding significant importance for non-point source pollution control in small watersheds.


Asunto(s)
Monitoreo del Ambiente , Ríos , Contaminantes Químicos del Agua , China , Ríos/química , Monitoreo del Ambiente/métodos , Contaminantes Químicos del Agua/análisis , Medición de Riesgo , Contaminación Química del Agua/estadística & datos numéricos , Nitrógeno/análisis , Fósforo/análisis , Análisis Espacio-Temporal
20.
J Pediatr Nurs ; 78: e417-e423, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39122579

RESUMEN

PURPOSE: Parenting resilience is essential for the well-being and development of children with chronic illnesses. Given the importance of parenting resilience in this context, this study explored the nature of parenting resilience among mothers caring for adolescents with congenital heart disease (CHD). DESIGN AND METHODS: We adopted Husserl's phenomenological approach and conducted semistructured in-depth interviews. In addition, we conducted purposive sampling at the pediatric cardiology outpatient departments of 2 medical centers in Taiwan to recruit 11 mothers of adolescents with CHD; all of these adolescents had received open-heart surgery. Furthermore, we analyzed data by using Colaizzi's approach, and we adhered to the COnsolidated criteria for REporting Qualitative research checklist. RESULTS: Mothers caring for adolescents with CHD was a dynamic process involving problem solving. The 11 mothers in this study employed resilience to remain strong, provided a sense of normalcy for their children, and approached challenges calmly and bravely. We uncovered three major themes among these mothers: "providing support for the child, "facing challenges with equanimity," and "overcoming adversity through positivity and gratitude." CONCLUSIONS: The present results provide a deeper understanding of how mothers caring for adolescents with CHD can cultivate resilience. PRACTICE IMPLICATIONS: The study's findings can inform transitional programs for adolescents with CHD and their families, with nursing professionals supporting mothers' resilience.


Asunto(s)
Cardiopatías Congénitas , Relaciones Madre-Hijo , Madres , Investigación Cualitativa , Resiliencia Psicológica , Humanos , Femenino , Cardiopatías Congénitas/enfermería , Cardiopatías Congénitas/psicología , Adolescente , Madres/psicología , Adulto , Taiwán , Masculino , Adaptación Psicológica , Responsabilidad Parental/psicología
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