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1.
Front Pediatr ; 12: 1282408, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966493

RESUMO

Purpose: This study aimed to explore the clinical characteristics and evaluate the different types of thyroid dysfunction in babies with neonatal hyperthyroidism. Methods: The clinical data of 19 neonates with hyperthyroidism admitted to the Children's Hospital of Chongqing Medical University between January 2012 and April 2021 were retrospectively analyzed. Results: Fifteen (78.9%) infants were born to mothers with Graves' disease. Eleven (57.9%) infants were premature; two babies were born at small for gestational age. The age at diagnosis ranged from 3 to 34 days, with a mean of 18.53 ± 6.85 days. The majority of the babies presented with goiter (84.2%) and tachycardia (94.7%) after birth. Nine (47.4%) of them presented with abnormal weight gain, seven (36.8%) presented with stare or ocular protrusion, six (31.6%) presented with hyperexcitability, four (21.1%) presented with jaundice and liver dysfunction, two (10.5%) presented with sweating, one (5.3%) presented with fever, and one case presented without any symptoms. Transient hyperthyroidism was the main thyroid dysfunction in our study. Overt hyperthyroidism was diagnosed in 13 (68.4%) neonates. Another three babies (15.8%) presented with hyperthyroidism with slightly elevated free triiodothyronine levels, normal thyroxine (T4) levels, and low thyroid-stimulating hormone (TSH) levels. Normal thyroid hormone levels with low TSH levels were observed in three (15.8%) neonates. Ten children were treated with antithyroid drugs. Eighteen children recovered normal thyroid function at 1-3 months of age; one baby in the study group required further levothyroxine supplementation due to primary hypothyroidism (HT). One child was found to have developmental delay at 2 years of age during follow-up. Conclusions: Our study highlights the need for prolonged monitoring of thyroid function in suspected patients. A single normal screening for hyperthyroidism or the absence of a maternal history of hyperthyroidism cannot exclude this disease.

2.
J Affect Disord ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38960335

RESUMO

BACKGROUND: Depression is a leading cause of disability and poor health worldwide and is expected to rank first worldwide by 2030. The aim of this study is to analyze the transition and trend of depression burden in China and various income-level countries by utilizing the Global Burden of Disease (GBD) database and the Joinpoint regression model. This analysis seeks to comprehend the variations in the burden of depression across different income regions and evaluate their developmental patterns. METHODS: Based on the GBD 2019 open dataset, this study extracted data on YLD (Years Lived with Disability), DALY (Disability-Adjusted Life Years), and incidence related to depression. The analysis focused on the period between 1990 and 2019, covering global data and distinguishing between high-income, upper-middle-income, lower-middle-income, low-income countries, and China. We utilized the Joinpoint regression model to fit the spatiotemporal trend changes among different income-level countries. Pairwise comparisons were conducted to examine the parallelism and to determine if the differences in trend changes among various regions were statistically significant. RESULTS: From 1990 to 2019, the age-standardized YLD and DALY for depression female were higher than that in male. The YLD total change rate of depression men was higher than that of women. China exhibited the largest disparity in total YLD change rates between genders, reaching 0.08. During 1990 to 2019, the incidence of depression in 2005-2019 increased among females in middle to high-income countries, low-income countries, and China as compare to that of 1990-2005. Notably, China shown the most increase the incidence rate of females (from -0.4 % to 0.84 %). China experienced the most significant change in the YLD of depression during this period (AAPC = 0.45, 95 % CI = 0.41, 0.48, P < 0.01). China's YLD/Incidence rate was higher compared to the global, HICs, UMCs, LMCs, and LICs. In China, the YLD/incidence rate of depression began to rise in 1994, peaking around 2010, and then gradually declining. Since 2010, the growth rate of depression DALYs in China has been higher than the global average, high-income countries, upper-middle-income countries, lower-middle-income countries, and low-income countries. The DALY's AAPC value for the HLCs was the highest (AAPC = 0.24, 95 % CI = 0.22, 0.25, P < 0.01). The UMCs, in comparison to other regions, incidence rate had the highest AAPC value (AAPC = 0.48, 95 % CI = 0.46, 0.50, P < 0.01). CONCLUSIONS: Given the significant variations in the burden of depression across countries with different income levels, future strategies aimed at reducing the burden of depression should adopt tailored and differentiated approaches according to each country's specific needs and developmental stages.

4.
Biochem Pharmacol ; 226: 116408, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38969297

RESUMO

Metastatic recurrence is still a major challenge in breast cancer treatment. Patients with triple negative breast cancer (TNBC) develop early recurrence and relapse more frequently. Due to the lack of specific therapeutic targets, new targeted therapies for TNBC are urgently needed. Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway is one of the active pathways involved in chemoresistance and survival of TNBC, being considered as a potential target for TNBC treatment. Our present study identified ticagrelor, an anti-platelet drug, as a pan-PI3K inhibitor with potent inhibitory activity against four isoforms of class I PI3K. At doses normally used in clinic, ticagrelor showed weak cytotoxicity against a panel of breast cancer cells, but significantly inhibited the migration, invasion and the actin cytoskeleton organization of human TNBC MDA-MB-231 and SUM-159PT cells. Mechanistically, ticagrelor effectively inhibited PI3K downstream mTOR complex 1 (mTORC1) and mTORC2 signaling by targeting PI3K and decreased the protein expression of epithelial-mesenchymal transition (EMT) markers. In vivo, ticagrelor significantly suppressed tumor cells lung metastasis in 4T1 tumor bearing BALB/c mice model and experimental lung metastasis model which was established by tail vein injection of GFP-labeled MDA-MB-231 cells. The above data demonstrated that ticagrelor can inhibit the migration and invasion of TNBC both in vitro and in vivo by targeting PI3K, suggesting that ticagrelor, a pan-PI3K inhibitor, might represent a promising therapeutic agent for the treatment of metastatic TNBC.

5.
J Am Chem Soc ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980287

RESUMO

Hybrid halide perovskites are good candidates for a range of functional materials such as optical electronic and photovoltaic devices due to their tunable band gaps, long carrier diffusion lengths, and solution processability. However, the instability in moisture/air, the toxicity of lead, and rigorous reaction setup or complex postprocessing have long been the bottlenecks for practical application. Herein, we present a simultaneous configurational entropy design at A-sites, B-sites, and X-sites in the typical (CHA)2PbBr4 two-dimensional (2D) hybrid perovskite. Our results demonstrate that the high-entropy effect favors the stabilization of the hybrid perovskite phase and facilitates a simple crystallization process without precise control of the cooling rate to prepare regular crystals. Moreover, high-entropy 2D perovskite crystals exhibit tunable energy band gaps, broadband emission, and a long carrier lifetime. Meanwhile, the high-entropy composition almost maintains the initial crystal structure in deionized water for 18 h while the original (CHA)2PbBr4 crystal mostly decomposes, suggesting obviously improved humidity stability. This work offers a facile approach to synthesize humidity-stable hybrid perovskites under mild conditions, accelerating relevant preparation of optoelectronics and light-emitting devices and facilitating the ultimate commercialization of halide perovskite.

6.
Artigo em Chinês | MEDLINE | ID: mdl-38973042

RESUMO

Objective:To explore the effect of prenatal glucocorticoids therapy on hearing screening in premature infants Methods:Data of 693 preterm infants with gestational age of 24-34+6weeks admitted to theJiangxi Maternal and Child Health Hospital within 24 h after birth from June 2022 to June 2023 were retrospectively analyzed. The infants were divided into the DXM group (544 cases) and the non-DXM group (149 cases) based on whether dexamethasone (DXM) was administered prenatally. General data of preterm infants and parturients in two groups were compared, and the effects of different doses and timing of DXM on hearing screening were analyzed. Results:In the terms of preliminary hearing screening. the pass rate of initial hearing screening in DXM group was significantly higher than that in non-DXM group(53.9% vs 35.6%), with statistical significance(P<0.05). Further subgroup analysis showed that the passing rate of preliminary hearing screening in adequate prenatal dose(=4 doses) DXM group(58.1%) was significantly higher than that in insufficient group(48.0%) and excessive group(42.4%), with statistical significance(P<0.05). Administering DXM 48 hours to 7 days before birth resulted in a higher pass rate for initial hearing screening compared to administration <48 hours or >7 days before birth (56.4% vs. 48.6%), with a statistically significant difference (P < 0.05). In terms of re-hearing screening, the pass rate of secondary hearing screening was not significantly correlated with DXM treatment(P>0.05), but was significantly correlated with gestational age, birth weight, hospital stays, invasive mechanical ventilation, and common neonatal diseases(bronchopulmonary dysplasia, respiratory distress syndrome)(P<0.05). Among them, bronchopulmonary dysplasia was an independent risk factor forsecondary hearing screening referral(P<0.05). Conclusion:A single course of adequate dexamethasone use within 48 h-7 d of prenatal has a positive effect on the preliminary hearing screening of preterm infants.


Assuntos
Dexametasona , Glucocorticoides , Testes Auditivos , Recém-Nascido Prematuro , Humanos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Recém-Nascido , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Estudos Retrospectivos , Gravidez , Masculino , Idade Gestacional , Triagem Neonatal/métodos , Cuidado Pré-Natal/métodos
7.
Macromol Rapid Commun ; : e2400300, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38950172

RESUMO

Antibacterial materials with high hydrophobicity have drawbacks such as protein adsorption, bacterial contamination, and biofilm formation, which are responsible for some serious adverse health events. Therefore, antibacterial materials with high hydrophilicity are highly desired. In this paper, UV-curable antibacterial materials are prepared from silicone-containing Choline chloride (ChCl) functionalized hyperbranched quaternary ammonium salts (QAS) and tri-hydroxylethyl acrylate phosphate (TAEP). The materials show high hydrophilic performance because their water contact angle is as low as 19.3°. The materials also exhibit quite high antibacterial efficiency against S. aureus over 95.6%, fairly high transmittance over 90%, and good mechanical performance with tensile strength as high as 6.5 MPa. It reveals that it is a feasible strategy to develop antibacterial materials with low hydrophobicity from silicone-modified ChCl-functionalized hyperbranched QAS.

8.
World J Clin Cases ; 12(18): 3453-3460, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38983421

RESUMO

BACKGROUND: This study adopts a descriptive phenomenological approach to investigate the facilitators and barriers of community nurses' abilities in managing critical and emergency conditions. With the transition of healthcare systems to the community, the evolution of nursing practices, and the attention from policies and practices, community nurses play a crucial role in the management of critical and emergency conditions. However, there is still a lack of comprehensive understanding regarding the factors that promote or hinder their capabilities in this area. AIM: To understand the facilitators and barriers of community nurses in managing critical and emergency conditions, exploring the fundamental reasons and driving forces influencing their treatment capabilities. METHODS: This study utilized the destination sampling method between May 2023 and July 2023. It employed a descriptive phenomenological approach within qualitative research methodologies. Through objective sampling, 17 community nurses from 7 communities in Changning District, Shanghai, were selected as the study subjects. Semi-structured interviews were conducted to gather data, which were subsequently organized and analyzed using Colaizzi's seven-step analysis method, leading to the extraction of final themes. RESULTS: The barrier factors identified from the interviews encompassed three topics: resource allocation, professional factors, and personal literacy. The facilitators comprised three themes: professionalism, management attention, and training and continuing education. We identified that the root causes of the barriers included the lack of practical treatment experience among community nurses, insufficient awareness of self-directed learning, and limited knowledge and technical proficiency. The professional quality of community nurses and management attention serve as motivation for them to enhance their treatment abilities. CONCLUSION: To enhance the capability of community nurses in treating acute and critical patients, it is recommended to bolster training specifically tailored to acute and critical care, raise awareness of first aid practices, and elevate knowledge and skill levels.

9.
BMC Pulm Med ; 24(1): 303, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937809

RESUMO

BACKGROUND: This study investigated the current status of the quality of life (QOL) of drug-resistant tuberculosis (DR-TB) patients in Nanjing, China, and analyzed the influencing factors. METHODS: The survey was conducted among patients with DR-TB who were hospitalized in the tuberculosis department of the Second Hospital of Nanjing (Nanjing Public Health Medical Center) from July 2022 to May 2023. The Chinese version of the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire was used to investigate the QOL levels of patients with DR-TB, and a multiple linear regression model was used to analyze the QOL influencing factors. RESULTS: A total of 135 patients participated in the study; 69.6% were male, the average age was 46.30 ± 17.98 years, 13.33% had an education level of elementary school or below, and 75.56% were married. The QOL scores were 51.35 ± 17.24, 47.04 ± 20.28, 43.89 ± 17.96, and 35.00 ± 11.57 in the physiological, psychological, social, and environmental domains, respectively. The differences between the four domain scores and the Chinese normative results were statistically significant (P < 0.05). The results of multiple linear regression analysis showed that the factors related to the physiological domain included residence, family per-capita monthly income, payment method, adverse drug reactions (ADRs), and comorbidities; psychological domain correlates included educational level, family per-capita monthly income, course of the disease, and caregivers; social domain correlates included age and comorbidities; and factors related to the environmental domain included age, education level, and comorbidities. CONCLUSIONS: In Nanjing, China, patients with younger age, higher education level, living in urban areas, high family per-capita monthly income, no adverse drug reactions, no comorbidities, and having caregivers have better quality of life. Future interventions to improve the quality of life of patients with drug-resistant tuberculosis could be tailored to a specific factor.


Assuntos
Qualidade de Vida , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Masculino , Feminino , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/psicologia , Pessoa de Meia-Idade , Estudos Transversais , Adulto , China , Inquéritos e Questionários , Modelos Lineares , Idoso
10.
Cell Chem Biol ; 31(6): 1101-1117, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38876100

RESUMO

RNA-targeting small molecules (rSMs) have become an attractive modality to tackle traditionally undruggable proteins and expand the druggable space. Among many innovative concepts, RNA-targeting chimeras (RNATACs) represent a new class of multispecific, induced proximity small molecules that act by chemically bringing RNA targets into proximity with an endogenous RNA effector, such as a ribonuclease (RNase). Depending on the RNA effector, RNATACs can alter the stability, localization, translation, or splicing of the target RNA. Although still in its infancy, this new modality has the potential for broad applications in the future to treat diseases with high unmet need. In this review, we discuss potential advantages of RNATACs, recent progress in the field, and challenges to this cutting-edge technology.


Assuntos
RNA , Bibliotecas de Moléculas Pequenas , Humanos , RNA/metabolismo , RNA/química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Ribonucleases/metabolismo
11.
RSC Med Chem ; 15(6): 2114-2126, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38911165

RESUMO

Inflammation is the body's response to defence against infection or injury, and is associated with the progression of many diseases, such as inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). LCA, a dibenzylbutane lignan extracted from the roots of traditional medicinal plant Litsea cubeba (Lour.) Pers., has demonstrated promising anti-inflammatory activity. In this study, a series of novel LCA derivatives were designed, synthesized, and evaluated for anti-inflammatory activity. Lipopolysaccharide (LPS)-induced RAW 264.7 cell model experiments showed that compound 10h (at 20 µM of concentration) had the strongest inhibitory effect on NO release, and inhibited the secretion and gene expression levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in vitro. In addition, western blot, immunofluorescence, and molecular docking showed that the anti-inflammatory mechanism of compound 10h may be related to the nuclear factor (NF)-κB signalling pathway. In vivo studies based on a carrageenan-induced mouse paw edema model have shown significant anti-inflammatory activity of compound 10h at 20 mg kg-1. Preliminary in vitro and in vivo studies indicate that compound 10h has the potential to be developed as a novel anti-inflammatory agent.

12.
Food Chem Toxicol ; 190: 114832, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38908816

RESUMO

Rare Earth Elements (REEs) have been implicated in potential health effects. However, the health risk of REE exposure among tea drinkers in China remains poorly understood. This study aimed to characterize the concentration of REEs in different tea categories and evaluate the associated health risks for tea consumers in China. By analyzing the content of 16 REEs in 4326 tea samples from China, the exposure level of REEs to the general population was estimated. The content of these 16 REEs was similar across six types of tea, with oolong tea exhibiting the highest levels. The concentration of light rare earth elements (LREEs) in six types of tea was higher than that of heavy rare earth elements (HREEs). The daily mean and 95th percentile (P95) exposure to REEs from tea for the general population in China were 0.0328 µg/kg BW and 0.1283 µg/kg BW, respectively, which are significantly lower than the temporary acceptable daily dose (tADI). Our findings suggest that REEs from tea do not pose a known health risk to Chinese consumers.

13.
Mikrochim Acta ; 191(7): 389, 2024 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-38871997

RESUMO

A novel photoelectrochemical sensor, employing an S-scheme heterojunction of phthalocyanine and TiO2 nanoparticles, has been developed to enable highly sensitive determination of glutathione. By integrating the favorable stability, environmental benignity, and electronic properties of the TiO2 matrix with the unique photoactivity of phthalocyanine species, the designed sensor presents a substantial linear dynamic range and a low detection limit for the quantification of glutathione. The sensitivity is attributed to efficient charge transfer and separation across the staggered heterojunction energy levels, which generates measurable photocurrent signals. Systematic variation of phthalocyanine content reveals an optimal composition that balances light harvesting capacity and electron-hole recombination rates. The incorporation of phosphotungstic acid (PTA) in sample preparation effectively minimizes interference from compounds like L-cysteine and others. Consequently, this leads to an improvement in accuracy through the reduction of impurity levels. Appreciable photocurrent enhancements are observed upon introduction of both oxidized and reduced glutathione at the optimized composite photoanode. Coupled with advantageous features of photoelectrochemical transduction such as simplicity, cost-effectiveness, and resistance to fouling, this sensor holds great promise for practical applications in complex biological media.


Assuntos
Técnicas Eletroquímicas , Glutationa , Indóis , Isoindóis , Titânio , Titânio/química , Glutationa/química , Glutationa/análise , Indóis/química , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Limite de Detecção , Processos Fotoquímicos , Eletrodos
14.
Opt Express ; 32(10): 18293-18300, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38858989

RESUMO

Accurate measurement of the dielectric functions of emerging optical materials is of great importance for advancements in solid-state physics. However, it is rather challenging since most materials are highly active in ambient conditions, which makes in-situ measurements tough. Here, we report an analytical ellipsometry method (AEM) accessible in ambient conditions for measuring the dielectric functions of chemically reactive materials under bulk encapsulation. Taking the highly pursued low-loss plasmonic materials, such as sodium films, as an example, the effectiveness and measuring errors of the proposed AEM have been systematically demonstrated. This verifies AEM's superiority in overcoming the limitations of traditional spectroscopic ellipsometry methodologies, which include complex multi-parameter fitting procedures and the issue of potentially unphysical results, especially in newly developed low-loss materials. Our results will provide a generalized and convenient ellipsometric measurement strategy for sensitive materials under bulk encapsulation.

15.
Opt Express ; 32(9): 16333-16350, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38859263

RESUMO

Compressed ultrafast photography (CUP) is a computational imaging technology capable of capturing transient scenes in picosecond scale with a sequence depth of hundreds of frames. Since the inverse problem of CUP is an ill-posed problem, it is challenging to further improve the reconstruction quality under the condition of high noise level and compression ratio. In addition, there are many articles adding an external charge-coupled device (CCD) camera to the CUP system to form the time-unsheared view because the added constraint can improve the reconstruction quality of images. However, since the images are collected by different cameras, slight affine transformation may have great impacts on the reconstruction quality. Here, we propose an algorithm that combines the time-unsheared image constraint CUP system with unsupervised neural networks. Image registration network is also introduced into the network framework to learn the affine transformation parameters of input images. The proposed algorithm effectively utilizes the implicit image prior in the neural network as well as the extra hardware prior information brought by the time-unsheared view. Combined with image registration network, this joint learning model enables our proposed algorithm to further improve the quality of reconstructed images without training datasets. The simulation and experiment results demonstrate the application prospect of our algorithm in ultrafast event capture.

16.
Transl Cancer Res ; 13(5): 2475-2496, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38881933

RESUMO

Background: Tumors emerge by acquiring a number of mutations over time. The first mutation provides a selective growth advantage compared to adjacent epithelial cells, allowing the cell to create a clone that can outgrow the cells that surround it. Subsequent mutations determine the risk of the tumor progressing to metastatic cancer. Some secondary mutations may inhibit the aggressiveness of the tumor while still increasing the survival of the clone. Meaningful mutations in genes may provide a strong molecular foundation for developing novel therapeutic strategies for cancer. Methods: The somatic mutation and prognosis in colon adenocarcinoma (COAD) were analyzed. The copy number variation (CNV) and differentially expressed genes (DEGs) between the collagen type VI alpha 6 chain (COL6A6) mutation (COL6A6-MUT) and the COL6A6 wild-type (COL6A6-WT) subgroups were evaluated. The independent prognostic signatures based on COL6A6-allelic state were determined to construct a Cox model. The biological characteristics and the immune microenvironment between the two risk groups were compared. Results: COL6A6 was found to be highly mutated in COAD at a frequency of 9%. Patients with COL6A6-MUT had a good overall survival (OS) compared to those with COL6A6-WT, who had a different CNV pattern. Significant differences in gene expression were established for 593 genes between the COL6A6-MUT and COL6A6-WT samples. Among them, MUC16, ASNSP1, PRR18, PEG10, and RPL26P8 were determined to be independent prognostic factors. The internally validated prognostic risk model, constructed using these five genes, demonstrated its value by revealing a significant difference in patient prognosis between the high-risk and low-risk groups. Specifically, patients in the high-risk group exhibited a considerably worse prognosis than did those in the low-risk group. The high-risk group had a significantly higher proportion of patients over 60 years of age and patients in stage III. Moreover, the tumor immune dysfunction and exclusion (TIDE) score and the expression of human leukocyte antigen (HLA) family genes were all higher in the high-risk group than that in the low-risk group. Conclusions: The allelic state of COL6A6 and the five associated DEGs were identified as novel biomarkers for the diagnosis and prognosis of COAD and may be therapeutic targets in COAD.

17.
Cell Death Dis ; 15(6): 431, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898028

RESUMO

Non-small cell lung cancer (NSCLC) presents a global health challenge due to its low five-year survival rates, underscoring the need for novel therapeutic strategies. Our research explored the synergistic mechanisms of syrosingopine and UK-5099 in treating NSCLC. In vitro experiments showed that the combination of syrosingopine and UK-5099 significantly synergized to suppress NSCLC proliferation. Further experiments revealed that this combination induced cell cycle arrest and promoted apoptosis in NSCLC cells. In vivo experiments demonstrated that the combination of syrosingopine and UK-5099 markedly inhibited tumor growth. Mechanistic studies revealed that this drug combination promoted mitochondrial damage by inducing lactate accumulation and oxidative stress. Additionally, the combination triggered an integrated stress response (ISR) through the activation of heme-regulated inhibitor kinase (HRI). Importantly, our findings suggested that the synergistic suppression of NSCLC by syrosingopine and UK-5099 was dependent on ISR activation. In summary, our study proposed a promising therapeutic approach that involved the combination of Syrosingopine and UK-5099 to activate ISR, significantly hindering NSCLC growth and proliferation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Sinergismo Farmacológico , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Camundongos , Camundongos Nus , Linhagem Celular Tumoral , Estresse Oxidativo/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB C , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
18.
Medicine (Baltimore) ; 103(23): e38457, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847684

RESUMO

To investigate the utility of serum bile acid profiling for the diagnosis of inflammatory bowel disease (IBD). We analyzed 15 specific bile acids in the serum of 269 IBD patients, 200 healthy controls (HC), and 174 patients with other intestinal diseases (OID) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Serum bile acid levels were compared between IBD group, HC group, and OID group. Binary logistic regression-based models were developed to model the bile acids and diagnose IBD. Furthermore, receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic accuracy of each bile acid and the model. Compared to HC group, IBD group exhibited significantly lower levels of chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), glycodeoxycholic acid (GDCA), taurodeoxycholic acid (TDCA), lithocholic acid (LCA), glycolithocholic acid (GLCA), taurolithocholic acid (TLCA), and an elevated primary-to-secondary bile acid ratio. DCA had an area under the curve (AUC) of 0.860 for diagnosing IBD, with a sensitivity of 80.67% and a specificity of 82.50%. A model Y0 combining DCA and CDCA to distinguish between IBD group and HC group further improved accuracy (AUC = 0.866, sensitivity = 76.28%, specificity = 89.37%). Compared to non-IBD group (which combined healthy controls and those with other intestinal diseases), IBD group had significantly lower levels of DCA, GDCA, TDCA, LCA, GLCA, and TLCA, and elevated levels of glycocholic acid (GCA) and glycochenodeoxycholic acid (GCDCA). A model Y1 incorporating GCDCA, DCA and TLCA to distinguish between IBD group and non-IBD group yielded an AUC of 0.792, with a sensitivity of 77.67% and specificity of 71.91%. IBD patients exhibit decreased serum secondary bile acid levels and an elevated primary-to-secondary bile acid ratio. Serum bile acid alterations are associated with the onset of IBD. A model consisting of CDCA and DCA has potential for distinguishing between IBD group and HC group, while a model incorporating GCDCA, DCA and TLCA may be suitable for distinguishing between IBD group and non-IBD group.


Assuntos
Ácidos e Sais Biliares , Doenças Inflamatórias Intestinais , Humanos , Ácidos e Sais Biliares/sangue , Masculino , Feminino , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/sangue , Adulto , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Curva ROC , Estudos de Casos e Controles , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida , Biomarcadores/sangue , Adulto Jovem
19.
Magn Reson Med ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725197

RESUMO

PURPOSE: This study aims to assess ultrashort-TE magnetization transfer (UTE-MT) imaging of collagen degradation using an in vitro model of rotator cuff tendinopathy. METHODS: Thirty-six supraspinatus tendon specimens were divided into three groups and treated with 600 U collagenase (Group 1), 150 U collagenase (Group 2), and phosphate buffer saline (Group 3). UTE-MT imaging was performed to assess changes in macromolecular fraction (MMF), macromolecule transverse relaxation time (T2m), water longitudinal relaxation rate constant (R1m), the magnetization exchange rate from the macromolecular to water pool (Rm0 w) and from water to the macromolecular pool (Rm0 m), and magnetization transfer ratio (MTR) at baseline and following digestion and their differences between groups. Biochemical and histological studies were conducted to determine the extent of collagen degradation. Correlation analyses were performed with MMF, T2m, R1m, Rm0 w, Rm0 m, and MTR, respectively. Univariate and multivariate linear regression analyses were performed to evaluate combinations of UTE-MT parameters to predict collagen degradation. RESULTS: MMF, T2m, R1m, Rm0 m, and MTR decreased after digestion. MMF (r = -0.842, p < 0.001), MTR (r = -0.78, p < 0.001), and Rm0 m (r = -0.662, p < 0.001) were strongly negatively correlated with collagen degradation. The linear regression model of differences in MMF and Rm0 m before and after digestion explained 68.9% of collagen degradation variation in the tendon. The model of postdigestion in MMF and T2m and the model of MTR explained 54.2% and 52.3% of collagen degradation variation, respectively. CONCLUSION: This study highlighted the potential of UTE-MT parameters for evaluation of supraspinatus tendinopathy.

20.
Nano Lett ; 24(19): 5673-5682, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38703077

RESUMO

Water, covering over two-thirds of the Earth's surface, holds immense potential for generating clean water, sustainable energy, and metal resources, which are the cornerstones of modern society and future development. It is highly desired to produce these crucial elements through eco-friendly processes with minimal carbon footprints. Interfacial solar evaporation, which utilizes solar energy at the air-liquid interface to facilitate water vaporization and solute separation, offers a promising solution. In this review, we systematically report the recent progress of the cogeneration of clean water and energy/resources including electricity, hydrogen, and metal resources via interfacial solar evaporation. We first gain insight into the energy and mass transport for a typical interfacial solar evaporation system and reveal the residual energy and resources for achieving the cogeneration goal. Then, we summarize the recent advances in materials/device designs for efficient cogeneration. Finally, we discuss the existing challenges and potential opportunities for the further development of this field.

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