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1.
J Cardiothorac Surg ; 19(1): 441, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003445

RESUMO

BACKGROUND: Deep venous thrombosis (DVT) is a serious public health issue that threatens human health and economic development. Presently, differences in the prevalence of DVT among individuals from different nationalities, residents of high-altitude areas, and those consuming any special diet are unknown. Therefore, we aimed to elucidate the prevalence of and the associated risk factors for DVT in hospitalized patients in the plateau areas. METHODS: The subjects were hospitalized patients in three grade III-a hospitals in the Qinghai Province, China, during January-October 2020. The demographic, clinical, and laboratory data were collected at admission, and ultrasonography of the bilateral lower extremities was performed. The hospital stay-duration was recorded at the time of discharge. RESULTS: A total of 3432 patients were enrolled, of which 159 (4.60%) were diagnosed with DVT. The age of > 50 years (OR = 2.434, 95% CI: 1.521-3.894252, P < 0.001), residence altitude of ≥ 3000 m (OR = 2.346, 95% CI: 1.239-4.440, P = 0.009), D-dimer level of ≥ 0.5 mg/L (OR = 2.211, 95% CI: 1.547-3.161, P < 0.001), presence of comorbidities (OR = 1.904, 95% CI: 1.386-2.705, P < 0.001), a history of varicose veins (OR = 1.990, 95% CI: 0.959-4.128, P = 0.045), and current medications (OR = 2.484, 95% CI: 1.778-3.471, P < 0.001) were identified as risk factors for DVT in these plateau areas. CONCLUSION: The prevalence of DVT in the hospitalized patients of the studied plateau areas was 4.60%. We recommend considering individualized risk stratification (age > 50 years, residence altitude ≥ 3000 m, a history of varicose veins, D-dimer level ≥ 0.5 mg/L, current medications, and comorbidities) for patients at the time of admission.


Assuntos
Hospitalização , Trombose Venosa , Humanos , Trombose Venosa/epidemiologia , Fatores de Risco , Feminino , Pessoa de Meia-Idade , Masculino , Prevalência , China/epidemiologia , Estudos Transversais , Hospitalização/estatística & dados numéricos , Idoso , Adulto , Altitude
2.
Arch Gynecol Obstet ; 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38852111

RESUMO

BACKGROUND: Left-right laterality disorders are a heterogeneous group of disorders caused by an altered position or orientation of the thoracic and intra-abdominal organs and vasculature across the left-right axis. They mainly include situs inversus and heterotaxy. Those disorders are complicated by cardiovascular abnormalities significantly more frequently than situs solitus. METHODS: In this study, 16 patients with a fetal diagnosis of laterality disorder with congenital heart defects (CHD) were evaluated with a single nucleotide polymorphism array (SNP-arry) combined with whole-exome sequencing (WES). RESULTS: Although the diagnostic rate of copy number variations was 0 and the diagnostic rate of WES was 6.3% (1/16), the likely pathogenic gene DNAH11 and the candidate gene OFD1 were ultimately identified. In addition, novel compound heterozygous mutations in the DNAH11 gene and novel hemizygous variants in the OFD1 gene were found. Among the combined CHD, a single atrium/single ventricle had the highest incidence (50%, 8/16), followed by atrioventricular septal defects (37.5%, 6/16). Notably, two rare cases of common pulmonary vein atresia (CPVA) were also found on autopsy. CONCLUSION: This study identified the types of CHD with a high incidence in patients with laterality disorders. It is clear that WES is an effective tool for diagnosing laterality disorders and can play an important role in future research.

3.
BMC Pregnancy Childbirth ; 24(1): 420, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858685

RESUMO

BACKGROUND: Frontonasal dysplasia (FND) is a rare congenital anomaly resulting from the underdevelopment of the frontonasal process, and it can be syndromic or nonsyndromic. The typical features of FND include a deformed nose and ocular hypertelorism, which are sometimes associated with cleft lip and/or palate. Only approximately 10 cases of prenatally diagnosed nonsyndromic FND have been reported in the past 30 years. CASE PRESENTATION: A 33-year-old woman (G2P1) was referred to our center at 20 gestational weeks for bilateral hydrocephaly. We detected typical features of FND, including severe hypertelorism, median nasal bifidity, a minor cleft lip, and multiple limb anomalies using three-dimensional (3D) ultrasound. A hypoplastic corpus callosum, unilateral microtia, and a ventricular septal defect were also detected. Genetic testing, including karyotype analysis, copy number variation (CNV) analysis, trio-whole exome sequencing (trio-WES), and trio-whole-gene sequencing (trio-WGS), was performed; however, we did not find any de novo gene variants in the fetus as compared to the parents. Postmortem examination confirmed the prenatal diagnosis of FND. CONCLUSION: The present case expands the wide phenotypic spectrum of prenatal FND patients. 3D ultrasound is a useful tool for detecting facial and limb deformities.


Assuntos
Agenesia do Corpo Caloso , Anormalidades Craniofaciais , Face , Hidrocefalia , Imageamento Tridimensional , Deformidades Congênitas dos Membros , Ultrassonografia Pré-Natal , Humanos , Feminino , Adulto , Gravidez , Anormalidades Craniofaciais/diagnóstico por imagem , Agenesia do Corpo Caloso/diagnóstico por imagem , Agenesia do Corpo Caloso/genética , Deformidades Congênitas dos Membros/diagnóstico por imagem , Deformidades Congênitas dos Membros/genética , Face/anormalidades , Face/diagnóstico por imagem , Hidrocefalia/diagnóstico por imagem , Comunicação Interventricular/diagnóstico por imagem , Comunicação Interventricular/genética , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/genética
4.
Sci Rep ; 14(1): 11656, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778127

RESUMO

Conventional binding materials, such as silicate cement and lime, present high energy consumption, pollution, and carbon emissions. Therefore, we utilize crushed stone as a stabilization material. Magnesium oxychloride cement (MOC) is modified and used as an inorganic admixture owing to its eco-friendly nature and low carbon content. We analysed the control indicators of an integrated design of MOC-stabilized crushed stone by conducting unconfined compressive strength and water-resistance tests. The optimum mixing composition of the MOC-stabilized crushed stone was determined through the response surface methodology. We determined the best approach and dosage for improving the water resistance of MOC-stabilized crushed stone by comparing the effects of four modification methods: fly ash, citric acid + silica fume, phosphoric acid + waterborne polyurethane, and dihydrogen phosphate potassium salt. We also perform a comparison with 5% ordinary silicate cement-stabilized crushed stone. The results indicate that the MOC-stabilized crushed stone exhibits a rapid increase in strength in the early stage, but this rate reduces after 28 days. The mixing design employs the 4-day unconfined compressive strength and 1-day water resistance coefficient as the technical indicators. The best mixing composition includes a 4.27% MOC dosage and a molar ratio of MgO/MgCl2 of 5.85. We use 1% citric acid + 10% silica fume in equal amounts to replace the MOC dopant method for composite modification of the MOC stabilized crushed stone. Consequently, the 1-day water resistance coefficient before water immersion is significantly increased from 0.78 to 0.91 and its 4-day unconfined compressive strength is only reduced by 0.10 MPa. This significantly improves the water resistance of the MOC-stabilized crushed stone and ensures that its strength remains unaffected, which is the optimal modification method. However, this method must ensure that a small amount of citric acid and silica fume are uniformly distributed in the MOC-stabilized crushed stone, which increases the construction difficulty of the road base.

5.
Cell Prolif ; : e13663, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38803043

RESUMO

Macrophage pyroptosis is of key importance to host defence against pathogen infections and may participate in the progression and recovery of periodontitis. However, the role of pyroptotic macrophages in regulating periodontal ligament stem cells (PDLSCs), the main cell source for periodontium renewal, remains unclear. First, we found that macrophage pyroptosis were enriched in gingiva tissues from periodontitis patients compared with those of healthy people through immunofluorescence. Then the effects of pyroptotic macrophages on the PDLSC osteogenic differentiation were investigated in a conditioned medium (CM)-based coculture system in vitro. CM derived from pyroptotic macrophages inhibited the osteogenic differentiation-related gene and protein levels, ALP activity and mineralized nodule formation of PDLSCs. The osteogenic inhibition of CM was alleviated when pyroptosis was inhibited by VX765. Further, untargeted metabolomics showed that glutamate limitation may be the underlying mechanism. However, exogenous glutamate supplementation aggravated the CM-inhibited osteogenic differentiation of PDLSCs. Moreover, CM increased extracellular glutamate and decreased intracellular glutamate levels of PDLSCs, and enhanced the gene and protein expression levels of system xc - (a cystine/glutamate antiporter). After adding cystine to CM-based incubation, the compromised osteogenic potency of PDLSCs was rescued. Our data suggest that macrophage pyroptosis is related to the inflammatory lesions of periodontitis. Either pharmacological inhibition of macrophage pyroptosis or nutritional supplements to PDLSCs, can rescue the compromised osteogenic potency caused by pyroptotic macrophages.

6.
J Environ Manage ; 361: 121197, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38820791

RESUMO

Heavy metal pollution of agricultural soil is a major global concern, prompting the establishment of maximum allowable limits (MALs) to ensure food safety and protect human health. This study collected and compared MALs for six heavy metals (As, Cd, Hg, Pb, Zn, and Cu) in agricultural soils from representative countries and organizations (EU and WHO/FAO). The research evaluated the critical health risks and efficacy of these MALs under the hypothetical scenario of metals concentrations reaching the maximum allowable level. Safe thresholds for heavy metals were then derived based on maximum acceptable health risk levels. The comparative analysis revealed significant variations in the specific limit values and terms of MALs across countries and organizations, even for the same metal. This suggests that there is no consensus among countries and organizations regarding the level of metal-related health risks. Furthermore, the risk analysis of metal concentrations reaching the maximum level accentuated heightened risks associated with As, suggesting that the current risk of soil As exposure was underestimated, particularly for children. However, soil Cu, Cd, and Zn limits generally resulted in low health risks, implying that the current limits may overestimate their hazard. Overall, the results highlight that the current MALs for soil heavy metals may not fully safeguard human health. There is a critical need to optimize current soil MALs based on localized risks and the actual impact of these metals on human health. It is suggested to appropriately lower the limits of metals (such as As) whose impact on health risks is underestimated, and cautiously increase the limits of metals (such as Cu, Cd, and Zn) that currently pose minor health risks. This approach aims to reduce both over and insufficient protection problems of soil heavy metal MALs, emphasizing the importance of considering the locality in setting these limits.


Assuntos
Metais Pesados , Poluentes do Solo , Solo , Metais Pesados/análise , Medição de Risco , Poluentes do Solo/análise , Humanos , Solo/química , Monitoramento Ambiental
7.
Ultrasound Med Biol ; 50(8): 1280-1286, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38806338

RESUMO

OBJECTIVE: This study utilized real-time shear wave elasticity imaging (SWE) and ultrafast pulse wave velocity (ufPWV) to assess carotid arterial stiffness, aiming to predict atherosclerosis risk in patients with metabolic syndrome (MS). METHODS: In this study, 181 patients with metabolic syndrome (MS group) were compared with 73 healthy adults. The MS group was divided into three groups: MS I group: CIMT was normal (CIMT < 1.0 mm, no plaque, n = 61); MS II group: CIMT thickening (1.0 mm ≤ CIMT<1.5 mm, no plaque, n = 39); MS III group: plaque group (CIMT ≥ 1.5 mm, plaque, n = 81). Concurrently, the group of 73 healthy individuals was designated as the control set (NC). Parameters assessed include carotid intima-media thickness (CIMT), elastic modulus values of the carotid artery's anterior and posterior walls (Mean, Max, Min), pulse wave velocity at systole's commencement (PWV-BS), and pulse wave velocity at systole's termination (PWV-ES). Differences, distribution characteristics, and correlations across these groups were analyzed. RESULTS: A significant association was found between PWV-BS, PWV-ES, and arteriosclerosis severity, with these factors gaining importance as arteriosclerosis progressed. Notably, PWV-ES differences were significant across the four groups (p < 0.05). Both MS III and MS II groups exhibited higher PWV-ES values compared to the MS I group and controls. Statistically significant differences were observed between MS III, MS II, and MS I groups relative to the control group (p < 0.05). Additionally, the Mean, Max, and Min values of the anterior and posterior carotid walls in the MS III group surpassed those of the other groups. CONCLUSION: Real-time shear wave elasticity imaging and ultrafast pulse wave velocity are valuable tools for assessing atherosclerosis risk in MS patients. These non-invasive, safe, and reproducible imaging techniques can quantitatively evaluate the stiffness of the common carotid artery's wall, offering important insights into cardiovascular risk assessment.


Assuntos
Artérias Carótidas , Técnicas de Imagem por Elasticidade , Síndrome Metabólica , Análise de Onda de Pulso , Rigidez Vascular , Humanos , Masculino , Feminino , Síndrome Metabólica/fisiopatologia , Síndrome Metabólica/diagnóstico por imagem , Síndrome Metabólica/complicações , Técnicas de Imagem por Elasticidade/métodos , Pessoa de Meia-Idade , Rigidez Vascular/fisiologia , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/fisiopatologia , Adulto , Espessura Intima-Media Carotídea , Reprodutibilidade dos Testes , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/fisiopatologia , Doenças das Artérias Carótidas/complicações , Sistemas Computacionais , Módulo de Elasticidade
8.
Artigo em Inglês | MEDLINE | ID: mdl-38598394

RESUMO

Interactive semantic segmentation pursues high-quality segmentation results at the cost of a small number of user clicks. It is attracting more and more research attention for its convenience in labeling semantic pixel-level data. Existing interactive segmentation methods often pursue higher interaction efficiency by mining the latent information of user clicks or exploring efficient interaction manners. However, these works neglect to explicitly exploit the semantic correlations between user corrections and model mispredictions, thus suffering from two flaws. First, similar prediction errors frequently occur in actual use, causing users to repeatedly correct them. Second, the interaction difficulty of different semantic classes varies across images, but existing models use monotonic parameters for all images which lack semantic pertinence. Therefore, in this article, we explore the semantic correlations existing in corrections and mispredictions by proposing a simple yet effective online learning solution to the above problems, named correction-misprediction correlation mining ( CM2 ). Specifically, we leverage the correction-misprediction similarities to design a confusion memory module (CMM) for automatic correction when similar prediction errors reappear. Furthermore, we measure the semantic interaction difficulty by counting the correction-misprediction pairs and design a challenge adaptive convolutional layer (CACL), which can adaptively switch different parameters according to interaction difficulties to better segment the challenging classes. Our method requires no extra training besides the online learning process and can effectively improve interaction efficiency. Our proposed CM2 achieves state-of-the-art results on three public semantic segmentation benchmarks.

9.
Insects ; 15(4)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38667344

RESUMO

To explore the feasibility of adjusting the photoperiod to regulate the life parameters and predation ability of Harmonia axyridis Pallas in greenhouses during the winter, life tables were constructed for H. axyridis under the three following photoperiods: 9L:15D (light/dark), 12L:12D, and 16L:8D at 15 °C, an average greenhouse temperature during the winter when aphids severely damage vegetables. The effects of photoperiods on predation by this ladybird were tested in both laboratory and greenhouse settings. The results showed that increased illumination promoted the development and reproduction of H. axyridis; under medium and long photoperiods, the pre-adult periods were 3.61 days and 4.34 days shorter than that under the short photoperiod, respectively, and the fecundity increased by 1.78 and 2.41 times. Population parameters r, λ, and R0 increased as illumination time increased, whereas T decreased. Increased illumination also increased the predation by third- and fourth-instar larvae and adults. The amounts of predation by fourth-instar larvae and adults increased by 22.16% and 75.09% under the medium photoperiod, and those under the long photoperiod increased by 71.96% and 89.64%, respectively. The numbers of Myzus persicae Sulzer predated by H. axyridis under the long photoperiod were higher than those under the short photoperiod in a greenhouse, and the predation parameters were influenced.

10.
Mol Nutr Food Res ; 68(8): e2300909, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38602246

RESUMO

SCOPE: In cases where breast milk is unavailable or inadequate, hydrolyzed infant formula is recommended as the primary alternative. The aim of this study is to assess and compare the allergenicity of two partially hydrolyzed whey-based formulas (PHF-Ws) using serum samples from patients with cow's milk allergy (CMA). METHODS AND RESULTS: LC-MS/MS technology is used to investigate the peptide distribution in both samples. The immunoreactivity of two PHF-Ws in 27 serum samples from 50 Chinese infants (02 years) with CMA is analyzed. The results demonstrate that even with a similar a degree of hydrolysis (DH), primary protein sources, peptides with molecular weights <5 kDa, and differences in the number of residual allergenic epitopes in the hydrolyzed peptide segments can lead to varying immune responses. CONCLUSION: The two PHF-Ws have notably high intolerance rates, exceeding 10% among infants with CMA. Therefore, suggesting that PHF-Ws may not be suitable for infants and children with CMA in China.


Assuntos
Alérgenos , Fórmulas Infantis , Hipersensibilidade a Leite , Proteínas do Soro do Leite , Humanos , Hipersensibilidade a Leite/imunologia , Lactente , China , Feminino , Alérgenos/imunologia , Masculino , Hidrólise , Espectrometria de Massas em Tandem , Soro do Leite/química , Animais
11.
BMJ Open ; 14(4): e079635, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594184

RESUMO

OBJECTIVES: Little study has reported the association of maternal weight gain in early pregnancy with fetal congenital heart disease (CHD). We aimed to explore the potential relationship based on a China birth cohort while adjusting by multiple factors. DESIGN: Cohort study. SETTING: China birth cohort study conducted from 2017 to 2021. PARTICIPANTS: The study finally included 114 672 singleton pregnancies in the 6-14 weeks of gestation, without missing data or outliers, loss to follow-up or abnormal conditions other than CHD. The proportion of CHD was 0.65% (749 cases). PRIMARY AND SECONDARY OUTCOME MEASURES: Association between maternal pre-pregnancy weight gain and CHD in the offspring were analysed by multivariate logistic regression, with the unadjusted, minimally adjusted and maximally adjusted methods, respectively. RESULTS: The first-trimester weight gain showed similar discrimination of fetal CHD to that period of maternal body mass index (BMI) change (DeLong tests: p=0.091). Compared with weight gain in the lowest quartile (the weight gain less than 0.0 kg), the highest quartile (over 2.0 kg) was associated with a higher risk of fetal CHD in unadjusted (OR 1.36, 95% CI: 1.08 to 1.72), minimally adjusted (adjusted OR (aOR) 1.29, 95% CI: 1.02 to 1.62) and maximally adjusted (aOR 1.29, 95% CI: 1.02 to 1.63) models. The association remains robust in pregnant women with morning sickness, normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with folic acid (FA) and/or multivitamin supplementation. CONCLUSIONS AND RELEVANCE: Although the association of maternal pre-pregnancy weight gain on fetal CHD is weak, the excessive weight gain may be a potential predictor of CHD in the offspring, especially in those with morning sickness and other conditions that are routine in the cohort, such as normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with FA and/or multivitamin supplementation.


Assuntos
Ganho de Peso na Gestação , Cardiopatias Congênitas , Êmese Gravídica , Gravidez , Feminino , Humanos , Estudos de Coortes , Aumento de Peso , Índice de Massa Corporal , Cardiopatias Congênitas/epidemiologia , Peso ao Nascer
12.
ChemSusChem ; : e202400575, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38651621

RESUMO

Simultaneous utilization of photogenerated electrons and holes to achieve overall redox reactions is attractive but still far from practical application. The emerging step (S)-scheme mechanism has proven to be an ideal approach to inhibit charge recombination and supply photoinduced charges with highest redox potentials. Herein, a hierarchical phosphotungstic acid (H3PW12O40, HPW)@Znln2S4 (ZISW) heterojunction was prepared through one-pot hydrothermal method for simultaneous hydrogen (H2) evolution and benzyl alcohol upgrading. The fabricated HPW-based heterojunctions indicated much enhanced visible-light absorption, promoted photogenerated charge transfer and inhibited charge recombination, owing to hierarchical architecture based on visible-light responsive Znln2S4 microspheres, and S-scheme charge transfer pathway. The S-scheme mechanism was further verified by free-radical trapping electron spin resonance (ESR) spectra. Moreover, the wettability of composite heterojunction was improved by the modification of hydrophilic HPW, contributing to gaining active hydrogen (H+) from water sustainably. The optimal ZISW-30 heterojunction photocatalyst indicated an enhanced hydrogen evolution rate of 27.59 mmol g-1 h-1 in benzyl alcohol (10 vol. %) solution under full-spectrum irradiation, along with highest benzaldehyde production rate is 8.32 mmol g-1 h-1. This work provides a promising guideline for incorporating HPW into S-scheme heterojunctions to achieve efficient overall redox reactions.

13.
Front Plant Sci ; 15: 1344717, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38533402

RESUMO

With global climate change and rising temperatures, rainfall will change. The impact of global rainfall changes on ecosystems has prompted people to delve deeper into how changes in rainfall affect plant growth; Plant biomass, nutrient element content, and non-structural carbohydrate content are very sensitive to changes in precipitation. Therefore, understanding the impact of rainfall changes on seedlings is crucial. However, it is currently unclear how the seedlings of Fraxinus malacophylla Hemsl in rocky desertification areas respond to changes in rainfall. In this study, the response of biomass, nutrient accumulation, and NSC content of Fraxinus malacophylla Hemsl seedlings to different rainfall intervals and rainfall during the dry and rainy seasons was studied. Use natural rainfall duration of 5 days (T) and extended rainfall duration of 10 days(T+) as rainfall intervals; average monthly rainfall was used as the control (W), with a corresponding 40% increase in rainfall (W+) and a 40% decrease in rainfall (W-) as rainfall treatments. The research results indicate that the biomass of roots, stems, and leaves, as well as the accumulation of C, N, and P in Fraxinus malacophylla Hemsl seedlings increase with the increase of rainfall, while the soluble sugar and starch content show a pattern of first increasing and then decreasing. The biomass and nutrient accumulation of each organ showed root>leaf>stem. Except for the beginning of the dry season, prolonging the duration of rainfall in other periods inhibits the biomass accumulation of Fraxinus malacophylla Hemsl seedlings, and promotes the accumulation of C, N, and P nutrients and an increase in soluble sugar and starch content. There was a significant positive correlation (P<0.05) between the nutrient contents of C, N, and P in various organs, as well as between soluble sugar and starch content; And N: P>16, plant growth is limited by P element. These results indicate that changes in rainfall can affect the growth and development of Fraxinus malacophylla Hemsl seedlings, increasing rainfall can promote biomass and nutrient accumulation of Fraxinus malacophylla Hemsl seedlings, and prolonging rainfall intervals and reducing rainfall have inhibitory effects on them. The exploration of the adaptation of Fraxinus malacophylla Hemsl seedlings to rainfall patterns has promoted a basic understanding of the impact of rainfall changes on the growth of Fraxinus malacophylla Hemsl. This provides a theoretical basis for understanding how Fraxinus malacophylla Hemsl can grow better under rainfall changes and for future management of Fraxinus malacophylla Hemsl artificial forests in rocky desertification areas.

14.
Cancer Cell ; 42(3): 474-486.e12, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38402610

RESUMO

Chronic stress is associated with increased risk of metastasis and poor survival in cancer patients, yet the reasons are unclear. We show that chronic stress increases lung metastasis from disseminated cancer cells 2- to 4-fold in mice. Chronic stress significantly alters the lung microenvironment, with fibronectin accumulation, reduced T cell infiltration, and increased neutrophil infiltration. Depleting neutrophils abolishes stress-induced metastasis. Chronic stress shifts normal circadian rhythm of neutrophils and causes increased neutrophil extracellular trap (NET) formation via glucocorticoid release. In mice with neutrophil-specific glucocorticoid receptor deletion, chronic stress fails to increase NETs and metastasis. Furthermore, digesting NETs with DNase I prevents chronic stress-induced metastasis. Together, our data show that glucocorticoids released during chronic stress cause NET formation and establish a metastasis-promoting microenvironment. Therefore, NETs could be targets for preventing metastatic recurrence in cancer patients, many of whom will experience chronic stress due to their disease.


Assuntos
Armadilhas Extracelulares , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Neutrófilos/patologia , Neoplasias Pulmonares/patologia , Pulmão/patologia , Microambiente Tumoral
15.
Org Biomol Chem ; 22(11): 2182-2186, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38390690

RESUMO

Three novel phragmalin-type limonoids, swieteliacates S-U (1-3), were isolated from Swietenia macrophylla leaves, alongside four previously identified limonoids (4-7). The structures, encompassing absolute configurations, were delineated through 1D and 2D NMR analyses, high-resolution mass spectrometry (HR-MS), and NMR and ECD calculations. Swieteliacate S (1) is a distinctive cryptate comprising a tricyclo[4.2.110,30.11,4]decane fragment and an additional five-membered oxygen ring. Compounds 3 and 5 exhibited inhibition rates of 26.08 ± 2.26% and 15.42 ± 3.66%, respectively, on triglyceride (TG) production in Hep G2 cells at 40 µM.


Assuntos
Limoninas , Meliaceae , Limoninas/química , Limoninas/farmacologia , Estrutura Molecular , Espectroscopia de Ressonância Magnética , Meliaceae/química
18.
Eur Radiol ; 34(2): 1324-1333, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37615763

RESUMO

OBJECTIVES: Artificial intelligence (AI) systems can diagnose thyroid nodules with similar or better performance than radiologists. Little is known about how this performance compares with that achieved through fine needle aspiration (FNA). This study aims to compare the diagnostic yields of FNA cytopathology alone and combined with BRAFV600E mutation analysis and an AI diagnostic system. METHODS: The ultrasound images of 637 thyroid nodules were collected in three hospitals. The diagnostic efficacies of an AI diagnostic system, FNA-based cytopathology, and BRAFV600E mutation analysis were evaluated in terms of sensitivity, specificity, accuracy, and the κ coefficient with respect to the gold standard, defined by postsurgical pathology and consistent benign outcomes from two combined FNA and mutation analysis examinations performed with a half-year interval. RESULTS: The malignancy threshold for the AI system was selected according to the Youden index from a retrospective cohort of 346 nodules and then applied to a prospective cohort of 291 nodules. The combination of FNA cytopathology according to the Bethesda criteria and BRAFV600E mutation analysis showed no significant difference from the AI system in terms of accuracy for either cohort in our multicenter study. In addition, for 45 included indeterminate Bethesda category III and IV nodules, the accuracy, sensitivity, and specificity of the AI system were 84.44%, 95.45%, and 73.91%, respectively. CONCLUSIONS: The AI diagnostic system showed similar diagnostic performance to FNA cytopathology combined with BRAFV600E mutation analysis. Given its advantages in terms of operability, time efficiency, non-invasiveness, and the wide availability of ultrasonography, it provides a new alternative for thyroid nodule diagnosis. CLINICAL RELEVANCE STATEMENT: Thyroid ultrasonic artificial intelligence shows statistically equivalent performance for thyroid nodule diagnosis to FNA cytopathology combined with BRAFV600E mutation analysis. It can be widely applied in hospitals and clinics to assist radiologists in thyroid nodule screening and is expected to reduce the need for relatively invasive FNA biopsies. KEY POINTS: • In a retrospective cohort of 346 nodules, the evaluated artificial intelligence (AI) system did not significantly differ from fine needle aspiration (FNA) cytopathology alone and combined with gene mutation analysis in accuracy. • In a prospective multicenter cohort of 291 nodules, the accuracy of the AI diagnostic system was not significantly different from that of FNA cytopathology either alone or combined with gene mutation analysis. • For 45 indeterminate Bethesda category III and IV nodules, the AI system did not perform significantly differently from BRAFV600E mutation analysis.


Assuntos
Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/genética , Biópsia por Agulha Fina/métodos , Neoplasias da Glândula Tireoide/patologia , Estudos Retrospectivos , Estudos Prospectivos , Inteligência Artificial
19.
Protein Cell ; 15(2): 83-97, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37470727

RESUMO

The exposure to either medical sources or accidental radiation can cause varying degrees of radiation injury (RI). RI is a common disease involving multiple human body parts and organs, yet effective treatments are currently limited. Accumulating evidence suggests gut microbiota are closely associated with the development and prevention of various RI. This article summarizes 10 common types of RI and their possible mechanisms. It also highlights the changes and potential microbiota-based treatments for RI, including probiotics, metabolites, and microbiota transplantation. Additionally, a 5P-Framework is proposed to provide a comprehensive strategy for managing RI.


Assuntos
Microbioma Gastrointestinal , Microbiota , Probióticos , Lesões por Radiação , Humanos , Probióticos/uso terapêutico , Transplante de Microbiota Fecal , Lesões por Radiação/terapia
20.
Chembiochem ; 25(3): e202300678, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38015421

RESUMO

Using myoglobin (Mb) as a model protein, we herein developed a facial approach to modifying the heme active site. A cavity was first generated in the heme distal site by F46 C mutation, and the thiol group of Cys46 was then used for covalently linked to exogenous ligands, 1H-1,2,4-triazole-3-thiol and 1-(4-hydroxyphenyl)-1H-pyrrole-2,5-dione. The engineered proteins, termed F46C-triazole Mb and F46C-phenol Mb, respectively, were characterized by X-ray crystallography, spectroscopic and stopped-flow kinetic studies. The results showed that both the heme coordination state and the protein function such as H2 O2 activation and peroxidase activity could be efficiently regulated, which suggests that this approach might be generally applied to the design of functional heme proteins.


Assuntos
Heme , Mioglobina , Mioglobina/química , Mioglobina/genética , Mioglobina/metabolismo , Domínio Catalítico , Heme/química , Cinética , Conformação Proteica , Compostos de Sulfidrila
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