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1.
Arch Endocrinol Metab ; 68: e230097, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38739522

RESUMO

Objective: This study sought to investigate the regulation of long noncoding RNA (lncRNA) XIST on the microRNA (miR)-101-3p/vascular endothelial growth factor A (VEGFA) axis in neovascularization in diabetic retinopathy (DR). Materials and methods: Serum of patients with DR was extracted for the analysis of XIST, miR-101-3p, and VEGFA expression levels. High glucose (HG)-insulted HRMECs and DR model rats were treated with lentiviral vectors. MTT, transwell, and tube formation assays were performed to evaluate cell viability, migration, and angiogenesis, and ELISA was conducted to detect the levels of inflammatory cytokines. Dual-luciferase reporter, RIP, and RNA pull-down experiments were used to validate the relationships among XIST, miR-101-3p, and VEGFA. Results: XIST and VEGFA were upregulated and miR-101-3p was downregulated in serum from patients with DR. XIST knockdown inhibited proliferation, migration, vessel tube formation, and inflammatory responsein HG-treated HRMECs, whereas the above effects were nullified by miR-101-3p inhibition or VEGFA overexpression. miR-101-3p could bind to XIST and VEGFA. XIST promoted DR development in rats by regulating the miR-101-3p/VEGFA axis. Conclusion: LncRNA XIST promotes VEGFA expression by downregulating miR-101-3p, thereby stimulating angiogenesis and inflammatory response in DR.


Assuntos
Retinopatia Diabética , MicroRNAs , Neovascularização Patológica , RNA Longo não Codificante , Fator A de Crescimento do Endotélio Vascular , RNA Longo não Codificante/genética , Retinopatia Diabética/genética , Retinopatia Diabética/sangue , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Ratos , Humanos , Masculino , Neovascularização Patológica/genética , Ratos Sprague-Dawley , Feminino , Movimento Celular/genética , Proliferação de Células/genética , Pessoa de Meia-Idade , Diabetes Mellitus Experimental
2.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(2): 159-174, 2024 Feb 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38755712

RESUMO

OBJECTIVES: Melanoma is highly malignant and heterogeneous. It is essential to develop a specific prognostic model for improving the patients' survival and treatment strategies. Recent studies have shown that ferroptosis results from the overproduction of lipid peroxidation and is an iron-dependent form of programmed cell death. Despite this, ferroptosis-related genes (FRGs) and their clinical significances remain unknown in malignant melanoma. This study aims to assess the role of FRGs in melanoma, with the goal of developing a novel prognostic model that provides new insights into personalized treatment and improvement of therapeutic outcomes for melanoma. METHODS: We systematically characterized the genetic alterations and mRNA expression of 73 FRGs in The Cancer Genome Atlas (TCGA)-skin cutaneous melanoma (SKCM) dataset in this study. The results were validated with real-time RT-PCR and Western blotting. Subsequently, a multi-gene feature model was constructed using the TCGA-SKCM cohort. Melanoma patients were classified into a high-risk group and a low-risk group based on the feature model. As a final step, correlations between ferroptosis-related signatures and immune features, immunotherapy efficacy, or drug response were analyzed. RESULTS: By analyzing melanoma samples from TCGA-SKCM dataset, FRGs exhibited a high frequency of genetic mutations and copy number variations (CNVs), significantly impacting gene expression. Additionally, compared with normal skin tissue, 30 genes with significantly differential expression were identified in melanoma tissues. A prognostic model related to FRGs, constructed using the LASSO Cox regression method, identified 13 FRGs associated with overall survival prognosis in patients and was validated with external datasets. Finally, functional enrichment and immune response analysis further indicated significant differences in immune cell infiltration, mutation burden, and hypoxia status between the high-risk group and the low-risk group, and the model was effective in predicting responses to immunotherapy and drug sensitivity. CONCLUSIONS: This study develops a strong ferroptosis-related prognostic signature model which could put forward new insights into target therapy and immunotherapy for patients with melanoma.


Assuntos
Ferroptose , Melanoma , Neoplasias Cutâneas , Ferroptose/genética , Humanos , Melanoma/genética , Prognóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Mutação , Melanoma Maligno Cutâneo , Variações do Número de Cópias de DNA , Regulação Neoplásica da Expressão Gênica , Multiômica
3.
Clin Exp Rheumatol ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38757282

RESUMO

OBJECTIVES: To investigate whether the interplay of anti-galectin-3 antibodies (anti-Gal3 Abs) with neutrophils contributes to the development of lupus cutaneous vasculitis. METHODS: Enzyme-linked immunosorbent assay was used to determine the serum level of anti-Gal3 Abs in lupus patients. Flow cytometry, quantitative PCR and western blot were performed to investigate the expression of cell surface receptors, proinflammatory cytokines and signalling molecules in neutrophils stimulated by serum from lupus patients or healthy controls (HCs) or anti-Gal3 Ab, respectively. Immunofluorescence was performed to visualise the formation of neutrophil extracellular traps (NETs). Human umbilical vein endothelial cells were co-cultured with the supernatants from neutrophils stimulated by anti-Gal3 Ab, and cytokine production was measured at mRNA and protein levels. Immunohistochemistry was adopted to reveal the distribution of Gal3, cytokines and myeloperoxidase within lupus skin lesions. REULTS: Serum levels of anti-Gal3 Abs were negatively correlated with peripheral counts of neutrophils. Anti-Gal3 Abs positive sera from SLE patients accelerated neutrophil death, altered cell phenotype and promoted formation of NETs with the involvement of p38 MAPK pathway. Supernatants collected from neutrophils co-cultured with anti-Gal3 Ab provoked endothelial cells to produce cytokines such as IL-1, ICAM-1, SELE and particularly IL-6. Consistently, IL-6 was higher in SLE patients with anti-Gal3 Ab positive sera and enriched in the area of vascular inflammation together with enhanced expression of Gal3 protein and infiltration of neutrophils. CONCLUSIONS: Overall, these findings suggested that neutrophils were crucial mediators in anti-Gal3 Ab induced lupus cutaneous vasculitis.

4.
Food Sci Biotechnol ; 33(8): 1909-1919, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38752119

RESUMO

Mechanized, automated and intelligent brewing is an important trend of innovation and transition in Jiang-flavor baijiu industry. In this study, physicochemical parameters, microbial community composition and flavor substances during 3rd round heap fermentation between mechanical and traditional workshop were investigated and compared based on traditional culturable methods, high-throughput sequencing technology and gas chromatography analysis. The dominant bacterial and fungal genera were consistent between the two workshops, but mechanized brewing had a significant impact on the composition of fungal communities. Rhodococcus and Monascus were special genera in mechanical workshop. The interaction relationship between physicochemical parameters and dominant microorganisms in mechanized workshop was different from traditional workshop as well. This study provided a scientific basis for further analyzing the mechanism of mechanized brewing of Jiang-flavor baijiu. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01483-y.

5.
Heliyon ; 10(7): e28374, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38590880

RESUMO

1 Background: In lung cancer, the use of small-molecule inhibitors, chemotherapy and immunotherapy has led to unprecedented survival benefits in selected patients. Considering most patients will experience a relapse within a short period of time due to single drug resistance, combination therapy is also particularly important to improve patient prognosis. Therefore, more robust biomarkers to predict responses to immunotherapy, targeted therapy, chemotherapy and rationally drug combination therapies may be helpful in clinical treatment choices. 2 Methods: We defined tumor-specific T cells (TSTs) and their features (TSTGs) by single-cell RNA sequencing. We applied LASSO regression to filter out the most survival-relevant TSTGs to form the Tumor-specific T cell score (TSTS). Immunological characteristics, enriched pathways, and mutation were evaluated in high- and low TSTS groups. 3 Results: We identified six clusters of T cells as TSTs in lung cancer, and four most robust genes from 9 feature genes expressed only on tumor-specific T cells were screened to construct a tumor-specific T cells score (TSTS). TSTS was positively correlated with immune infiltration and angiogenesis and negatively correlated with malignant cell proliferation. Moreover, potential vascular-immune crosstalk in lung cancer provides the theoretical basis for combined anti-angiogenic and immunotherapy. Noticeable, patients in high TSTS had better response to ICB and targeted therapy and patients in the low TSTS group often benefit from chemotherapy. 4 Conclusion: The proposed TSTS is a promising indicator to predict immunotherapy, targeted therapy and chemotherapy responses in lung cancer patients for helping clinical treatment choices.

6.
Asian J Surg ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38604849

RESUMO

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly heterogeneous liver tumor. The associations between histopathological feature and prognosis of ICC are limited. The present study aimed to investigate the prognostic significance of glandular structure and tumor budding in ICC. METHODS: Patients received radical hepatectomy for ICC were included. Glandular structure and tumor budding were detected by Hematoxylin-eosin staining. The Kaplan-Meier method and the Cox proportional hazards regression model were used to calculate the survival and hazard ratio. Based on the results of multivariate analysis, nomograms of OS and DFS were constructed. C-index and Akaike information criterion (AIC) were used to assess accuracy of models. RESULTS: A total of 323 ICC patients who underwent surgery were included in our study. Glandular structure was associated with worse overall survival (OS) [hazard ratio (HR): 2.033, 95% confidence interval (CI): 1.047 to 3.945] and disease-free survival (DFS) [HR: 1.854, 95% CI: 1.082 to 3.176]. High tumor budding was associated with worse DFS [HR: 1.636, 95%CI: 1.060 to 2.525]. Multivariate analysis suggested that glandular structure, tumor number, lymph node metastasis, and CA19-9 were independent risk factors for OS. Independent predictor factors for DFS were tumor budding, glandular structure, tumor number, and lymph node metastasis. The c-index (0.641 and 0.642) and AIC (957.69 and 1188.52) showed that nomograms of OS and DFS have good accuracy. CONCLUSION: High tumor budding and glandular structure are two important histopathological features that serve as prognostic factors for ICC patients undergoing hepatectomy.

7.
Nat Commun ; 15(1): 2858, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570522

RESUMO

Nutrient enrichment is a major global change component that often disrupts the relationship between aboveground biodiversity and ecosystem functions by promoting species dominance, altering trophic interactions, and reducing ecosystem stability. Emerging evidence indicates that nutrient enrichment also reduces soil biodiversity and weakens the relationship between belowground biodiversity and ecosystem functions, but the underlying mechanisms remain largely unclear. Here, we explore the effects of nutrient enrichment on soil properties, soil biodiversity, and multiple ecosystem functions through a 13-year field experiment. We show that soil acidification induced by nutrient enrichment, rather than changes in mineral nutrient and carbon (C) availability, is the primary factor negatively affecting the relationship between soil diversity and ecosystem multifunctionality. Nitrogen and phosphorus additions significantly reduce soil pH, diversity of bacteria, fungi and nematodes, as well as an array of ecosystem functions related to C and nutrient cycling. Effects of nutrient enrichment on microbial diversity also have negative consequences at higher trophic levels on the diversity of microbivorous nematodes. These results indicate that nutrient-induced acidification can cascade up its impacts along the soil food webs and influence ecosystem functioning, providing novel insight into the mechanisms through which nutrient enrichment influences soil community and ecosystem properties.


Assuntos
Ecossistema , Solo , Solo/química , Biodiversidade , Microbiologia do Solo , Nutrientes , Concentração de Íons de Hidrogênio
8.
Heliyon ; 10(7): e28523, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38601660

RESUMO

Background: The associations of body fat parameters with arterial stiffness measured by brachial-ankle pulse wave velocity in hypertensive patients were scarce. Methods: This cross-sectional study analyzed 4322 hypertensive adults. The correlations between the anthropometric indexes (body mass index [BMI], waist circumference, waist-tohip ratio [WHR], waist-to-height ratio [WHtR], a body shape index [ABSI], body round index [BRI]) and ba-PWV values were analyzed using multivariable linear regression model. Results: In both sex categories, linear regression models showed that BMI levels were inversely related to baPWV (adjusted-ß per SD increase in male: -0.51, 95% CI -0.66 to -0.36, P < 0.001; female: -0.50, 95% CI -0.63 to -0.37, P < 0.001). Waist circumference positively correlated with baPWV only in male hypertensive individuals. BaPWV positively correlated to WHR or WHtR levels (adjusted-ß per SD increase: 0.32, 95% CI 0.21 to 0.43, P < 0.001; 0.64, 95% CI 0.47 to 0.82, P < 0.001; respectively), ABSI (adjusted-ß per SD increase for ABSI × 100: 0.27, 95% CI 0.18 to 0.36, P < 0.001) and BRI (adjusted-ß per SD increase: 0.64, 95% CI 0.46 to 0.81, P < 0.001) levels. The relationship between anthropometric indices and arterial stiffness based on baPWV values were also consistent. ABSI had the highest predictive power of arterial stiffness (area under the curve, 0.594; P < 0.001). Conclusion: In Chinese adults with hypertension, BMI was inversely related to baPWV, while WHR, WHtR, ABSI and BRI were positively related. Waist circumference positively correlated with baPWV only in male hypertensive individuals.

9.
BMC Public Health ; 24(1): 1129, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654172

RESUMO

BACKGROUND: In China, enhancing the pooling levels of basic health insurance has consistently been regarded as a pivotal measure to promote the refinement of the healthcare insurance system. From 2020 to 2022, the widespread outbreak of COVID-19 posed new challenges to China's basic health insurance. METHODS: The research utilizes Data Envelopment Analysis (DEA), Malmquist index assessment, and fixed-effects panel Tobit models to analyze panel data from 2020 to 2022, assessing the efficiency of basic health insurance in Gansu Province. RESULTS: From 2020 to 2022, the average overall efficiency of the municipal pooling of Basic Medical Insurance for Urban and Rural Residents was 0.941, demonstrating a stable trend with a modest increase. The efficiency frontier regions have expanded from 5 (35.71%) to 7 (50%). Operational efficiency exhibited a negative correlation with per capita hospitalization expenses and per capita fund balance but a positive correlation with per capita accumulated fund balance and reimbursement rates for hospitalized patients. In 2021, compared to 2020, the county-pooling Basic Medical Insurance for Urban Employees saw a decline of 0.126 in overall efficiency, reducing the efficiency frontier regions from 8 to 3. However, from 2021 to 2022, the municipal-coordinated Basic Medical Insurance for Urban Employees experienced a 0.069 increase in overall efficiency, with the efficiency frontier regions expanding from 3 to 5. Throughout 2020 to 2022, the operational efficiency of the Urban Employee Basic Medical Insurance showed a consistent negative correlation with per capita fund balance. CONCLUSION: From 2020 to 2022, the overall operational performance of basic health insurance in Gansu Province was satisfactory, and enhancing the pooling level is beneficial in addressing the impact of unforeseen events on the health insurance system.


Assuntos
COVID-19 , Seguro Saúde , China , Humanos , Seguro Saúde/estatística & dados numéricos , COVID-19/epidemiologia , Eficiência Organizacional , População Rural/estatística & dados numéricos
10.
Ecotoxicol Environ Saf ; 276: 116315, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38614001

RESUMO

This study explores the role of endogenous indole-3-acetic acid (IAA) in modulating plant responses to pollution stress and its effect on pollutant accumulation, with a focus on fluoranthene (Flu) in ryegrass. To elucidate the mechanism, we employed an IAA promoter (α-aminobutyric acid [α-AB]) and an IAA inhibitor (naphthylphthalamic acid [NPA]) to regulate IAA levels and analyze Flu uptake characteristics. The experimental setup included a Flu treatment group (ryegrass with Flu addition) and a control group (ryegrass without Flu). Our findings demonstrate that Flu treatment enhanced IAA content and plant growth in ryegrass compared to the control. The Flu+AB treatment further enhanced these effects, while the Flu+NPA treatment exhibited a contrasting trend. Moreover, Flu+AB treatment led to increased Flu accumulation, in contrast to the inhibitory effect observed with Flu+NPA treatment. Flu treatment also enhanced the activities of key antioxidant enzymes (SOD, POD, CAT) and increased soluble sugar and protein levels, indicative of enzymatic and nonenzymatic defense responses, respectively. The Flu+AB treatment amplified these responses, whereas the Flu+NPA treatment attenuated them. Significantly, Flu treatment raised H+-ATPase activity compared to the control, an effect further elevated by Flu+AB treatment and diminished by Flu+NPA treatment. A random forest analysis suggested that Flu accumulation dependency varied under different treatments: it relied more on H+-ATPase activity under Flu+AB treatment and more on SOD activity under Flu+NPA treatment. Additionally, Flu+AB treatment boosted the transpiration rate in ryegrass, thereby increasing the Flu translocation factor, a trend reversed by Flu+NPA treatment. This research highlights crucial factors influencing Flu accumulation in ryegrass, offering potential new avenues for controlling the gathering of contaminants within plant systems.


Assuntos
Fluorenos , Ácidos Indolacéticos , Lolium , Superóxido Dismutase , Fluorenos/toxicidade , Lolium/efeitos dos fármacos , Lolium/crescimento & desenvolvimento , Ácidos Indolacéticos/metabolismo , Superóxido Dismutase/metabolismo , Poluentes do Solo/toxicidade , Reguladores de Crescimento de Plantas , Antioxidantes/metabolismo
12.
ACS Appl Mater Interfaces ; 16(17): 21463-21471, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38650081

RESUMO

The storage of dynamic information in hydrogels has aroused considerable interest regarding the multiple responsiveness of soft matter. Herein, we propose an electrical writing methodology to prepare dopamine (DA)-modified chitosan hydrogels with a dynamic information storage ability. A pH-responsive chitosan hydrogel medium was patterned by cathodic writing to in situ generate OH- in the writing area, at which dopamine underwent an auto-oxidation reaction in the locally alkaline environment to generate a dark color. The patterned information on the hydrogel can be encoded simply by electrical signals. The speed of information retrieval is positively correlated with the charge transfer during the electrical writing process, and the hiding of information is negatively correlated with the environmental stimulus (i.e., dopamine concentration, pH value, etc.). To showcase the versatility of this medium for information storage and the precision of the pattern, a quick response (QR) code is electronically written on dopamine-modified chitosan hydrogel and can be recognized programmably by a standard mobile phone. The results show that electrical regulation is a novel means to program the information storage process of hydrogels, which inspires future research on structural and functional information storage using stimulus-responsive hydrogels.

13.
Nature ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589574

RESUMO

RAS oncogenes (collectively NRAS, HRAS and especially KRAS) are among the most frequently mutated genes in cancer, with common driver mutations occurring at codons 12, 13 and 611. Small molecule inhibitors of the KRAS(G12C) oncoprotein have demonstrated clinical efficacy in patients with multiple cancer types and have led to regulatory approvals for the treatment of non-small cell lung cancer2,3. Nevertheless, KRASG12C mutations account for only around 15% of KRAS-mutated cancers4,5, and there are no approved KRAS inhibitors for the majority of patients with tumours containing other common KRAS mutations. Here we describe RMC-7977, a reversible, tri-complex RAS inhibitor with broad-spectrum activity for the active state of both mutant and wild-type KRAS, NRAS and HRAS variants (a RAS(ON) multi-selective inhibitor). Preclinically, RMC-7977 demonstrated potent activity against RAS-addicted tumours carrying various RAS genotypes, particularly against cancer models with KRAS codon 12 mutations (KRASG12X). Treatment with RMC-7977 led to tumour regression and was well tolerated in diverse RAS-addicted preclinical cancer models. Additionally, RMC-7977 inhibited the growth of KRASG12C cancer models that are resistant to KRAS(G12C) inhibitors owing to restoration of RAS pathway signalling. Thus, RAS(ON) multi-selective inhibitors can target multiple oncogenic and wild-type RAS isoforms and have the potential to treat a wide range of RAS-addicted cancers with high unmet clinical need. A related RAS(ON) multi-selective inhibitor, RMC-6236, is currently under clinical evaluation in patients with KRAS-mutant solid tumours (ClinicalTrials.gov identifier: NCT05379985).

14.
J Environ Manage ; 356: 120664, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38508006

RESUMO

Continuous discharge of wastewater, emissions, and solid wastes from steelworks poses environmental risks to ecosystems. However, the role of keystone taxa in maintaining multifunctional stability during environmental disturbances remains poorly understood. To address this, we investigated the community diversity, assembly mechanisms, and soil multifunctionality of soils collected from within the steelworks (I), within 2.5 km radius from the steelworks (E), and from an undisturbed area (CK) in Jiangsu Province, China, via 16 S rRNA sequencing. Significant differences were found in the Chao1 and the richness indexes of the total taxa (p < 0.05), while the diversity of keystone taxa was not significant at each site (p > 0.05). The deterministic processes for total taxa were 42.9%, 61.9% and 47.7% in CK, E, and I, respectively. Steelworks stress increased the deterministicity of keystone taxa from 52.3% in CK to 61.9% in E and I soils. The average multifunctionality indices were 0.518, 0.506 and 0.513 for CK, E and I, respectively. Although the soil multifunctionality was positive correlated with α diversity of both the total and keystone taxa, the average degree of keystone taxa in functional network increased significantly (79.96 and 65.58, respectively), while the average degree of total taxa decreased (44.59 and 51.25, respectively) in the E and I. This suggests keystone taxa contribute to promoting the stability of ecosystems. With increasing disturbance, keystone taxa shift their function from basic metabolism (ribosome biogenesis) to detoxification (xenobiotics biodegradation, metabolism, and benzoate degradation). Here we show that keystone taxa are the most important factor in maintaining stable microbial communities and functions, providing new insights for mitigating pollution stress and soil health protection.


Assuntos
Microbiota , Solo , Microbiologia do Solo , Bactérias/genética , Poluição Ambiental
15.
Nat Commun ; 15(1): 2728, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553434

RESUMO

Establishing appropriate metal-support interactions is imperative for acquiring efficient and corrosion-resistant catalysts for water splitting. Herein, the interaction mechanism between Ru nanoparticles and a series of titanium oxides, including TiO, Ti4O7 and TiO2, designed via facile non-stoichiometric engineering is systematically studied. Ti4O7, with the unique band structure, high conductivity and chemical stability, endows with ingenious metal-support interaction through interfacial Ti-O-Ru units, which stabilizes Ru species during OER and triggers hydrogen spillover to accelerate HER kinetics. As expected, Ru/Ti4O7 displays ultralow overpotentials of 8 mV and 150 mV for HER and OER with a long operation of 500 h at 10 mA cm-2 in acidic media, which is expanded in pH-universal environments. Benefitting from the excellent bifunctional performance, the proton exchange membrane and anion exchange membrane electrolyzer assembled with Ru/Ti4O7 achieves superior performance and robust operation. The work paves the way for efficient energy conversion devices.

16.
Aging (Albany NY) ; 16(7): 6008-6034, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38536014

RESUMO

Thyroid eye disease (TED) has brought great physical and mental trauma to patients worldwide. Although a few potential signaling pathways have been reported, knowledge of TED remains limited. Our objective is to explore the fundamental mechanism of TED and identify potential therapeutic targets using diverse approaches. To perform a range of bioinformatic analyses, such as identifying differentially expressed genes (DEGs), conducting enrichment analysis, establishing nomograms, analyzing weighted gene correlation network analysis (WGCNA), and studying immune infiltration, the datasets GSE58331, GSE105149, and GSE9340 were integrated. Further validation was conducted using qPCR, western blot, and immunohistochemistry techniques. Eleven ferroptosis-related DEGs derived from the lacrimal gland were originally screened. Their high diagnostic value was proven, and diagnostic prediction nomogram models with high accuracy and robustness were established by using machine learning. A total of 15 hub gene-related DEGs were identified by WGCNA. Through CIBERSORTx, we uncovered five immune cells highly correlated with TED and found several special associations between these immune cells and the above DEGs. Furthermore, EGR2 from the thyroid sample was revealed to be closely negatively correlated with most DEGs from the lacrimal gland. High expression of APOD, COPB2, MYH11, and MYCN, as well as CD4/CD8 T cells and B cells, was verified in the periorbital adipose tissues of TED patients. To summarize, we discovered a new gene signature associated with ferroptosis that has a critical impact on the development of TED and provides valuable insights into immune infiltration. These findings might highlight the new direction and therapeutic strategies of TED.


Assuntos
Ferroptose , Oftalmopatia de Graves , Ferroptose/genética , Humanos , Oftalmopatia de Graves/genética , Oftalmopatia de Graves/imunologia , Oftalmopatia de Graves/patologia , Redes Reguladoras de Genes , Perfilação da Expressão Gênica , Biologia Computacional , Glândula Tireoide/imunologia , Glândula Tireoide/patologia , Glândula Tireoide/metabolismo , Transcriptoma , Aparelho Lacrimal/imunologia , Aparelho Lacrimal/patologia , Aparelho Lacrimal/metabolismo , Bases de Dados Genéticas , Nomogramas
17.
IEEE Trans Cybern ; PP2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38546997

RESUMO

This article develops the adaptive neural cooperative control scheme for a group of mobile robots with a limited sensing range in presence of input quantization by a dynamic surface control technique. First, to make the controller design feasible, the original robotic system is transformed into a new fully actuated system using a transverse function. Then, taking into consideration the effects of a hysteresis quantizer, an adaptive neural cooperative controller is developed based on the universal approximation property of the radial basis function neural networks and the connectivity preservation strategy. Furthermore, the proposed control scheme can guarantee that all closed-loop signals are semi-globally uniformly ultimately bounded. Meanwhile, desired constraints are not breached and tracking errors are within the predefined domains. Finally, several simulation results are carried out to testify the feasibility and efficiency of the theoretical findings revealed in this article.

18.
Cancer Cell ; 42(3): 330-332, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38471455

RESUMO

The histologic transformation of adenocarcinoma (ADC) to squamous cell carcinoma (SCC), known as adeno-squamous transition or AST, is frequently observed in patients with lung cancer undergoing cancer therapy. In this issue, Tong and colleagues investigate genetic and epigenetic mechanisms that drive AST to confer resistance to KRAS inhibitors in preclinical models and patients.


Assuntos
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Proteínas Proto-Oncogênicas p21(ras) , Neoplasias Pulmonares/genética , Adenocarcinoma/patologia , Carcinoma de Células Escamosas/tratamento farmacológico
19.
Front Microbiol ; 15: 1295184, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38351916

RESUMO

Background: The aim of this study is to compare the diagnostic value of metagenomic next-generation sequencing (mNGS) vs. conventional culture methods (CM) in chronic infection and acute infection. Methods: We retrospectively analyzed the bronchoalveolar lavage fluid (BALF) of 88 patients with acute infection and 105 patients with chronic infection admitted to three hospitals from 2017 to 2022. Results: The results showed that the sensitivity and specificity of mNGS were higher than those of CM. The number of patients who changed the antibiotic treatment in the mNGS positive group was larger than that of patients in the mNGS negative group in both the acute infection group (60.5 vs. 28.0%, P = 0.0022) and chronic infection group (46.2 vs. 22.6%, P = 0.01112). High levels of temperature (OR: 2.02, 95% CI: 1.18-3.70, P: 0.015), C-reactive protein (CRP) (OR: 15, 95% CI: 2.74-280.69, P: 0.011), neutrophil count (OR: 3.09, 95% CI: 1.19-8.43, P: 0.023), and low levels of lymphocyte count (OR: 3.43, 95% CI:1.26-10.21, P: 0.020) may lead to positive mNGS results in the acute infection group while no significant factor was identified to predict positive results in the chronic infection group. Conclusion: mNGS could provide useful guidance on antibiotic strategies in infectious diseases and may be more valuable for the diagnosis and treatment of acute infection vs. chronic infection.

20.
Nat Commun ; 15(1): 1838, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418810

RESUMO

Plastic crystals as barocaloric materials exhibit the large entropy change rivalling freon, however, the limited pressure-sensitivity and large hysteresis of phase transition hinder the colossal barocaloric effect accomplished reversibly at low pressure. Here we report reversible colossal barocaloric effect at low pressure in two-dimensional van-der-Waals alkylammonium halides. Via introducing long carbon chains in ammonium halide plastic crystals, two-dimensional structure forms in (CH3-(CH2)n-1)2NH2X (X: halogen element) with weak interlayer van-der-Waals force, which dictates interlayer expansion as large as 13% and consequently volume change as much as 12% during phase transition. Such anisotropic expansion provides sufficient space for carbon chains to undergo dramatic conformation disordering, which induces colossal entropy change with large pressure-sensitivity and small hysteresis. The record reversible colossal barocaloric effect with entropy change ΔSr ~ 400 J kg-1 K-1 at 0.08 GPa and adiabatic temperature change ΔTr ~ 11 K at 0.1 GPa highlights the design of novel barocaloric materials by engineering the dimensionality of plastic crystals.

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