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1.
Eur Heart J ; 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36721994

RESUMO

AIMS: Proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of pulmonary hypertension (PH). Proliferative cells utilize purine bases from the de novo purine synthesis (DNPS) pathways for nucleotide synthesis; however, it is unclear whether DNPS plays a critical role in VSMC proliferation during development of PH. The last two steps of DNPS are catalysed by the enzyme 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (ATIC). This study investigated whether ATIC-driven DNPS affects the proliferation of pulmonary artery smooth muscle cells (PASMCs) and the development of PH. METHODS AND RESULTS: Metabolites of DNPS in proliferative PASMCs were measured by liquid chromatography-tandem mass spectrometry. ATIC expression was assessed in platelet-derived growth factor-treated PASMCs and in the lungs of PH rodents and patients with pulmonary arterial hypertension. Mice with global and VSMC-specific knockout of Atic were utilized to investigate the role of ATIC in both hypoxia- and lung interleukin-6/hypoxia-induced murine PH. ATIC-mediated DNPS at the mRNA, protein, and enzymatic activity levels were increased in platelet-derived growth factor-treated PASMCs or PASMCs from PH rodents and patients with pulmonary arterial hypertension. In cultured PASMCs, ATIC knockdown decreased DNPS and nucleic acid DNA/RNA synthesis, and reduced cell proliferation. Global or VSMC-specific knockout of Atic attenuated vascular remodelling and inhibited the development and progression of both hypoxia- and lung IL-6/hypoxia-induced PH in mice. CONCLUSION: Targeting ATIC-mediated DNPS compromises the availability of purine nucleotides for incorporation into DNA/RNA, reducing PASMC proliferation and pulmonary vascular remodelling and ameliorating the development and progression of PH.

2.
Sci Total Environ ; 866: 161444, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36621470

RESUMO

Excessive nitrate has been a critical issue in the water environment, originating from the burning of fossil fuels, inefficient use of nitrogen fertilizers, and discharge of domestic and industrial wastewater. Among the effective treatments for nitrate reduction, electrocatalysis has become an advanced technique because it uses electrons as green reducing agents and can achieve high selectivity through cathode potential control. The effectiveness of electrocatalytic nitrate reduction (NO3RR) mainly lies in the electrocatalyst. Iron-based catalysts have the advantages of high activity and low cost, which are well-used in the field of electrocatalytic nitrates. A comprehensive overview of the electrocatalytic mechanism and the iron-based materials for NO3RR are given in terms of monometallic iron-based materials as well as bimetallic and oxide iron-based materials. A detailed introduction to NO3RR on zero valent iron, single-atom iron catalysts, and Cu/Fe-based bimetallic electrocatalysts are provided, as they are essential for the improvement of NO3RR performance. Finally, the advantages of iron-based materials for NO3RR and the problems in current applications are summarized, and the development prospects of efficient iron-based catalysts are proposed.

3.
Food Res Int ; 163: 112181, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36596120

RESUMO

In this study, from the perspective of simulating the milk fat globule (MFG) emulsion, the interaction between soybean lecithin (SL) and the main protein in milk, whey protein (WP), and its effect on physical characteristics and lipid digestion were investigated through multiple spectroscopic techniques and in vitro digestion. The mechanism of SL and WP was static quenching, indicating that a complex formed between WP and SL through hydrophobic interaction and hydrogen bonding. The addition of SL changed the secondary structure of WP. When the ratio of SL to WP was 1:3, the obtained SL-WP emulsion that simulated milk fat globule exhibited the smallest particle size distribution and the highest absolute value of zeta potential. In addition, the emulsion exhibited high encapsulation efficiency (91.67 ± 1.24 %) and good stability. Compared with commercially available infant formula (IF), the final free fatty acid release of prepared SL-WP emulsion was close to that of human milk (HM). The addition of lecithin increased the digestibility of fat and the release of free fatty acids, and the digestive characteristic and particle size change also were closer to that of HM from results of kinetics of free fatty acid release and microstructure analysis.


Assuntos
Ácidos Graxos não Esterificados , Lecitinas , Lactente , Humanos , Proteínas do Soro do Leite/química , Lecitinas/química , Emulsões/química , Leite Humano
4.
Nat Biotechnol ; 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624150

RESUMO

Here we developed an adenine transversion base editor, AYBE, for A-to-C and A-to-T transversion editing in mammalian cells by fusing an adenine base editor (ABE) with hypoxanthine excision protein N-methylpurine DNA glycosylase (MPG). We also engineered AYBE variants enabling targeted editing at genomic loci with higher transversion editing activity (up to 72% for A-to-C or A-to-T editing).

5.
J Pharmacol Exp Ther ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635085

RESUMO

Metabolic flux augmentation via glucose transport activation may be desirable in Glucose transporter 1 (Glut1) deficiency (G1D) and dementia, whereas suppression might prove useful in cancer. Using lung adenocarcinoma cells that predominantly express Glut1 relative to other glucose transporters, we screened 11,613 compounds for effects on the accumulation of an extracellularly-applied fluorescent glucose analog. 5 drugs currently prescribed for unrelated indications or preclinically-characterized robustly enhanced intracellular fluorescence. Additionally identified were 37 novel activating and 9 inhibitory compounds lacking previous biological characterization. Because few glucose-related mechanistic or pharmacological studies were available for these compounds, we developed a method to quantify G1D mouse behavior to infer potential therapeutic value. To this end, we designed a 5-track apparatus to record and evaluate spontaneous locomotion videos. We applied this to a G1D mouse model that replicates the ataxia and other manifestations cardinal to the human disorder. Because the first two drugs that we examined in this manner (baclofen and acetazolamide) exerted various impacts on several gait aspects, we used deep learning neural networks to more comprehensively assess drug effects. Using this method, 49 locomotor parameters differentiated G1D from control mice. Thus, we used parameter modifiability to quantify efficacy on gait. We tested this by measuring the effects of saline as control and glucose as G1D therapy. The results indicate that this in vivo approach can estimate preclinical suitability from the perspective of G1D locomotion. This justifies the use of this method to evaluate our drugs or other interventions and sort candidates for further investigation. Significance Statement One approach to Glucose transporter I (Glut1) deficiency syndrome (G1D), dementia and cancer treatment is modulation of glucose transport. Using lung adenocarcinoma cells rich in Glut1, we identified, in high-throughput fashion, activators and inhibitors of fluorescent glucose analog transport. We also developed a gait testing platform for the deep learning neural network analysis of G1D mice that quantifies drug impact on 49 gait parameters, thus evaluating the potential preclinical efficacy of these drugs and other interventions via analysis of locomotion.

6.
Int Immunopharmacol ; 115: 109693, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36638660

RESUMO

BACKGROUND: An imbalance in Th17/regulatory T (Treg) cells is the major pathogenic mechanism underlying myasthenia gravis (MG). JAK2 inhibitors selectively inhibit JAK2 and reduce inflammatory responses. However, there have been no studies examining the therapeutic effects of JAK2 inhibitors in the context of MG. METHODS: Here, an experimental autoimmune MG (EAMG) rat model was established to explore the therapeutic effect of JAK2 inhibitors on EAMG rats immunized with the AChR α-subunit (97-116 peptide). A JAK2 inhibitor was administered to EAMG rats both in vivo and in vitro. The following experimental methods were used to evaluate the effects of JAK2 inhibitors. The behavioral scores and body weights of the rats were assessed on alternate days. Serum anti-AChR (97-116) IgG and cytokine levels were detected using ELISA. CD4+ T cell subsets and related transcription factors in mononuclear cells were detected using flow cytometry and qPCR, respectively. The expression levels of protein molecules in the signaling pathway were detected by western blotting, and the neuromuscular junctions were observed using immunofluorescence. RESULTS: The results revealed that JAK2 inhibitors could regulate Th17/Treg balance in vivo and in vitro. JAK2 inhibitors reduced the immune response in EAMG rats (including reducing pro-inflammatory cytokines and postsynaptic membrane complement deposition), improved clinical symptoms, and increased AChR aggregation in the postsynaptic membrane. Meanwhile, this study demonstrated that JAK2 inhibitor treatment suppressed the phosphorylation of JAK2/STAT3 and AKT/mTOR pathways and decreased the expression level of the IL-23 receptor. CONCLUSIONS: This study reveals that there is crosstalk between the JAK2/STAT3 and AKT/mTOR pathways in EAMG rats. JAK2 inhibitors can ameliorate EAMG by regulating Th17/Treg balance by inhibiting both signaling pathways. Our study provides new potential therapeutic targets for MG immunotherapy.

7.
Carbohydr Polym ; 302: 120423, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36604085

RESUMO

Understanding the effect of nitrogen fertilization on the quality of proso millet is key to expanding the use of this crop to address water scarcity and food security. Therefore, this study determined the impact of nitrogen fertilization on the proso millet quality. Nitrogen fertilization significantly increased the NR and GS activities and decreased the GBSSase activity, resulting in an increase in protein content and reduction in amylose content and L*, which decreased the appearance quality. Nitrogen fertilization increased the proportion of short amylopectin chains, resulting in a more disordered carbohydrate structure, and decreased the proportion of hydrophilic functional groups, contributing to an increase in setback viscosity and decrease in pasting temperature in the waxy (w139) variety. In contrast, the non-waxy (n297) variety exhibited a larger proportion of long amylopectin chains, lower ordered structure and hydrophobic functional groups after nitrogen fertilization, which strengthened the inter- and intramolecular forces of starch colloids.


Assuntos
Amilopectina , Panicum , Panicum/química , Panicum/metabolismo , Fertilizantes , Nitrogênio/metabolismo , Ceras , Amido/química , Amilose
8.
Ecotoxicol Environ Saf ; 250: 114506, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36608571

RESUMO

Cadmium (Cd) is a persistent heavy metal that poses environmental and public health concerns. This study aimed to identify the potential biomarkers responsible for Cd tolerance and accumulation by investigating the response of the content of essential metal elements, transporter gene expression, and root exudates to Cd stress in broomcorn millet (Panicum miliaceum). A hydroponics experiment was conducted using two broomcorn millet cultivars with distinct Cd tolerance levels and accumulation phenotypes (Cd-tolerant and Cd-sensitive cultivars). Cd stress inhibited lateral root growth, especially in the Cd-sensitive cultivar. Furthermore, Cd accumulation was significantly greater in the Cd-tolerant cultivar than in the Cd-sensitive cultivar. Cd stress significantly inhibited the absorption of essential metal elements and significantly increased the calcium concentration. Differentially expressed genes involved in metal ion transport were identified via transcriptome analysis. Cd stress altered the composition of root exudates, thus increasing lipid species and decreasing alkaloid, lignan, sugar, and alcohol species. Moreover, Cd stress significantly reduced most alkaloid, organic acid, and phenolic acid exudates in the Cd-tolerant cultivar, while it increased most lipid and phenolic acid exudates in the Cd-sensitive cultivar. Some significantly changed root exudates (ferulic acid, O-coumaric acid, and spermine) are involved in the phenylalanine biosynthesis, and arginine and proline metabolic pathways, thus, may be potential biomarkers of Cd stress response. Overall, metal ion absorption and root exudates are critical for Cd tolerance and accumulation in broomcorn millet. These findings provide valuable insights into improving Cd phytoremediation by applying mineral elements or metabolites.


Assuntos
Panicum , Poluentes do Solo , Cádmio/metabolismo , Panicum/metabolismo , Exsudatos e Transudatos/metabolismo , Lipídeos , Raízes de Plantas/metabolismo , Poluentes do Solo/análise
9.
Artigo em Inglês | MEDLINE | ID: mdl-36472739

RESUMO

The future trends and development trajectory of China's carbon emissions trading scheme (ETS), one of the key policy instruments for curbing peak carbon emissions and achieving carbon neutrality, have drawn a lot of interest. However, the Porter hypothesis (PH) and its validity boundary have not been explored sufficiently. We use micro-firm data from 2010 to 2019 to investigate whether the triple-difference (DDD) method could reveal the weak PH on the policy viewing ETS as a quasi-natural experiment in this work. Meanwhile, we use the panel threshold model and the moderated mediation effect model to assess the scientific border of the PH on the ETS. The findings show that by verifying the weak PH, the ETS may greatly enhance investment and foster the inventiveness of heavy-polluting industries (HPE). In contrast, the strong PH on the ETS has unstable validity and has non-linear characteristics. In particular, the ETS shows a U-shaped link between innovation and profitability by first decreasing and then increasing HPE's profitability through R&D. The cost of R&D and compliance costs being combined negatively impacts HPE's profitability. Further analysis shows that ETS will have different effects on the profitability of HPE due to R&D level and the threshold change of the compliance cost. This paper will offer some insightful points of view for the implementation of carbon market mechanisms in developing nations like China.

10.
Front Endocrinol (Lausanne) ; 13: 957010, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465614

RESUMO

Background: Effectively predicting the risk of adverse pregnancy outcome (APO) in women with systemic lupus erythematosus (SLE) during early and mid-pregnancy is a challenge. This study was aimed to identify potential markers for early prediction of APO risk in women with SLE. Methods: The GSE108497 gene expression dataset containing 120 samples (36 patients, 84 controls) was downloaded from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was performed, and differentially expressed genes (DEGs) were screened to define candidate APO marker genes. Next, three individual machine learning methods, random forest, support vector machine-recursive feature elimination, and least absolute shrinkage and selection operator, were combined to identify feature genes from the APO candidate set. The predictive performance of feature genes for APO risk was assessed using area under the receiver operating characteristic curve (AUC) and calibration curves. The potential functions of these feature genes were finally analyzed by conventional gene set enrichment analysis and CIBERSORT algorithm analysis. Results: We identified 321 significantly up-regulated genes and 307 down-regulated genes between patients and controls, along with 181 potential functionally associated genes in the WGCNA analysis. By integrating these results, we revealed 70 APO candidate genes. Three feature genes, SEZ6, NRAD1, and LPAR4, were identified by machine learning methods. Of these, SEZ6 (AUC = 0.753) showed the highest in-sample predictive performance for APO risk in pregnant women with SLE, followed by NRAD1 (AUC = 0.694) and LPAR4 (AUC = 0.654). After performing leave-one-out cross validation, corresponding AUCs for SEZ6, NRAD1, and LPAR4 were 0.731, 0.668, and 0.626, respectively. Moreover, CIBERSORT analysis showed a positive correlation between regulatory T cell levels and SEZ6 expression (P < 0.01), along with a negative correlation between M2 macrophages levels and LPAR4 expression (P < 0.01). Conclusions: Our preliminary findings suggested that SEZ6, NRAD1, and LPAR4 might represent the useful genetic biomarkers for predicting APO risk during early and mid-pregnancy in women with SLE, and enhanced our understanding of the origins of pregnancy complications in pregnant women with SLE. However, further validation was required.


Assuntos
Lúpus Eritematoso Sistêmico , Resultado da Gravidez , Gravidez , Feminino , Humanos , Resultado da Gravidez/epidemiologia , Lúpus Eritematoso Sistêmico/genética , Marcadores Genéticos , Área Sob a Curva , Curva ROC
11.
Orphanet J Rare Dis ; 17(1): 431, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36494820

RESUMO

BACKGROUND: Congenital cranial dysinnervation disorders (CCDDs) are a group of diseases with high clinical and genetic heterogeneity. Clinical examinations combined with Magnetic resonance imaging (MRI) and whole exome sequencing (WES) were performed to reveal the phenotypic and genotypic characteristics in a cohort of Chinese CCDDs patients. RESULTS: A total of 122 CCDDs patients from 96 families were enrolled. All patients showed restrictive eye movements, and 46 patients from 46 families (47.9%, 46/96) were accompanied by multiple congenital malformations. Multi-positional high-resolution MRI was performed in 94 patients from 88 families, of which, all patients had hypoplasia of the cranial nerves except HGPPS patients and 15 patients from 15 families (17.0%,15/88) were accompanied by other craniocerebral malformations. WES was performed in 122 CCDDs patients. Ten pathogenic variants were detected in KIF21A, TUBB3, and CHN1 genes in 43 families. Three variants were unreported, including KIF21A (c.1064T > C, p.F355S), TUBB3 (c.232T > A, p.S78T) and CHN1 (c.650A > G, p.H217R). Of the 43 probands harboring pathogenic variants, 42 were diagnosed with Congenital Fibrosis of Extraocular Muscles (CFEOM) and one was Duane Retraction Syndrome (DRS). No definite pathogenic variants in known candidate genes of CCDDs were found in sporadic DRS, Möbius Syndrome (MBS) and Horizontal Gaze Palsy with Progressive Scoliosis (HGPPS) patients. The CFEOM patients harboring R380C, E410K and R262H variants in TUBB3 gene and F355S variant in KIF21A gene exhibited syndromic phenotypes. CONCLUSIONS: This study broadened the phenotypic and genotypic spectrums of CCDDs, and it was the largest clinical and genetic investigation for CCDDs patients from China. KIF21A and TUBB3 were the common pathogenic genes in Chinese CFEOM. MRI coupled with WES can provide a supportive diagnosis in patients with clinically suspected CCDDs.


Assuntos
Síndrome da Retração Ocular , Síndrome de Möbius , Oftalmoplegia , Humanos , Síndrome da Retração Ocular/diagnóstico , Síndrome da Retração Ocular/genética , Síndrome de Möbius/diagnóstico , Fibrose
12.
Adv Sci (Weinh) ; : e2202416, 2022 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-36529695

RESUMO

Early noninvasive screening and regression therapy for vulnerable atherosclerotic plaques remain challenging. In this study, it is aimed to develop a new approach for the active targeting of atherosclerotic plaques with nano-agents to aid imaging and treatment. Biocompatible hyaluronic acid (HA)-guided cerasomes are generated to selectively target CD44-positive cells within the plaque in in vitro studies and in vivo testing in Apoe-/- mice. Rosuvastatin (RST) is encapsulated in the HA-guided cerasome nano-formulation to produce HA-CC-RST, which results in significant plaque regression as compared to treatment with the free drug. Moreover, gadodiamide-loaded HA-CC enhances magnetic resonance images of vulnerable plaques, thereby attaining the goal of improved simultaneous treatment and imaging. Transcriptomic analysis confirms plaque regression with HA-CC-RST treatment, which potentially benefits from the anti-inflammatory effect of RST. In summary, a safe and efficient nano-formulation for the targeted delivery of active agents to atherosclerotic plaques is developed and may be applicable to other diagnostic and therapeutic agents for atherosclerosis treatment.

13.
Respir Res ; 23(1): 362, 2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36536402

RESUMO

BACKGROUND: Little is known about the relationship between N6-methyladenosine (m6A)-related genes and tumor immune microenvironment (TIME) in non-small cell lung cancer (NSCLC). It is unclear which m6A regulators are essential for NSCLC progression. The aim of this work was to excavate the role of m6A-related genes in the TIME and progression of NSCLC. METHODS: Based on bioinformatics analysis, heterogeneous nuclear ribonucleoprotein C (HNRNPC) was considered as the most influential m6A regulator. Further study was investigated using patient samples, stable cell lines, and xenograft mice models. RESULTS: The differentially expressed profiles of m6A-related genes were established in NSCLC, and the NSCLC samples were clustered into two subtypes with different immune infiltration and survival time. Next, we found that the risk score (RS) based on m6A-related genes was a predictor of prognosis and immunotherapy response for NSCLC, in which HNRNPC was considered as the most influential m6A regulator. In NSCLC patients, we confirmed that HNRNPC predicted poor prognosis and correlated with tumor invasion and lymph node metastasis. RNA-seq data revealed that HNRNPC was involved in cell growth, cell migration, extracellular matrix organization and angiogenesis. In vitro, we verified that HNRNPC knockdown attenuated the cell proliferation, clonogenicity, invasion and migration. In vivo, HNRNPC knockdown inhibited the tumor growth and lung metastasis. Additionally, HNRNPC knockdown was associated with high CD8 + T cell infiltration, along with elevated CD4 + T cell infiltration, collagen production and angiogenesis. CONCLUSIONS: M6A regulator HNRNPC, a predictor of prognosis and immunotherapy response based on bioinformatics analysis, is related to proliferation and invasion of NSCLC cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Ribonucleoproteínas Nucleares Heterogêneas Grupo C , Prognóstico , Proliferação de Células , Biologia Computacional , Microambiente Tumoral
15.
RSC Adv ; 12(55): 36063-36071, 2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36545075

RESUMO

Some of the metal vanadates have special self-activated luminescence. In order to further enrich its luminous color, luminescent impurity ions can be introduced into its lattice. The interaction between the self-activated emission and the impurity-related emission remains to be studied. In this work, the synergism between the two kinds of emission in LiCa3ZnV3O12 was explored from these three aspects: lattice distortion, energy transfer and temperature effect. Eu3+ ions replace Ca2+ ions in the lattice of LiCa3ZnV3O12, leading to a lattice contraction of the LCZV host, which depresses the self-activating emission around 500 nm. The characteristic linear emissions of Eu3+ ions are also observed benefiting from the energy transfer from [VO4]3- to Eu3+. Since the temperature quenching effect is more sensitive for the self-activated emission than that for the Eu3+-related ones, the phosphor can be applied as a luminescent temperature sensor, with the absolute and relative temperature sensitivities of 0.012 K-1 and 1.56% K-1, respectively.

16.
Int J Biol Sci ; 18(16): 6084-6101, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439880

RESUMO

Background: Chloride channel 3 (CLCN3) is regulated by transcription-coactivator, however, it is unclear which core transcription factor regulates CLCN3. The role of CLCN3 in lung adenocarcinoma (LUAD) is unexplored and the relationship between CLCN3 and tumor microenvironment is unknown. Methods: A 5'-biotin-labeled promoter probe of CLCN3 was used to pull down the promoter-binding transcription factor. Further study was investigated using LUAD samples, cell lines, and xenograft mice models, and the mechanism was explored. Results: CLCN3 was upregulated in human LUAD, and CLCN3 knockdown inhibited tumor proliferation and migration in vitro. Next, heterogeneous nuclear ribonucleoprotein K (HNRNPK) was first validated as a CLCN3 promoter-binding transcription factor. Mechanistically, HNRNPK knockdown suppressed the promoter activity of CLCN3, thus regulating CLCN3 expression at the transcriptional level, and the binding motif 'GCGAGG' and binding site '-538/-248 bp' were identified. Subsequently, the RNA-seq data illustrated that the primary functions of HNRNPK were similar to those of CLCN3. The results from in vitro and in vivo trials indicated that the expression and function of CLCN3 were regulated by HNRNPK. By isolating primary cancer-associated fibroblasts (CAFs) from human LUAD, we confirmed that decreased extracellular CLCN3 secretion induced by HNRNPK knockdown inhibited CAFs activation and TGF-ß1 production, thus suppressing nuclear HNRNPK expression and LUAD progression in a feedback way. Furthermore, this phenomenon was rescued after the addition of TGF-ß1, revealing that the HNRNPK/CLCN3 axis facilitated LUAD progression through intercellular interactions. Finally, we identified that CLCN3 and HNRNPK were upregulated and correlated with poor prognosis in LUAD patients. Conclusions: HNRNPK/CLCN3 axis facilitates the progression of LUAD through CAF-tumor interaction.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Camundongos , Animais , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Adenocarcinoma de Pulmão/metabolismo , Fatores de Transcrição/metabolismo , Neoplasias Pulmonares/metabolismo , Microambiente Tumoral
17.
Front Cardiovasc Med ; 9: 989527, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36440015

RESUMO

Objective: Several clinical trials have indicated that statins stabilize and reverse atherosclerotic plaque. However, different studies have provided inconsistent findings regarding mechanisms and influencing factors of plaque regression under statin therapy. Apart from lipid-lowering effect, statins have pleiotropic effects including anti inflammation in humans. In this study, meta-analysis and meta-regression were used to determine the effects of statin medications on coronary plaque volume. Meanwhile, to assess whether statins promote plaque regression effect was related to their anti-inflammatory ability, the impact of CRP/hsCRP reduction during statin therapy on plaque regression was investigated. Methods: Up to June 15, 2022, a systematic PubMed, EMBASE, and Cochrane search was performed for randomized controlled trials that assessed treatment effect using total atheroma volume (TAV), percent atheroma volume (PAV), or plaque volume (PV). Only CRP/hsCRP and LDL-C values reported before and after treatment were considered. Results: 12 studies (2,812 patients with heart and/or vascular disease) fulfilled the inclusion criteria and were included in the systematic review. A meta-analysis of 15 statin-treated arms reported a significant reduction in change of TAV/PV [standardized mean difference (SMD): -0.27, 95% confidence intervals (-CI): -0.42, -0.12, p < 0.001], compared with the control arms. Another meta-analysis of 7 trials also found that patients in the intervention group had a significant reduction in change of PAV (SMD: -0.16, 95% CI: -0.29, -0.03, p = 0.019), compared with those in the control group. Meta-regressionanalysis revealed that the percent change of CRP/hsCRP was significantly associated with SMD in change of TAV/PV after adjusting for percent change of LDL-C, age, gender and study duration. Meta-regression analysis showed that percent change of CRP/hsCRP statistically influenced SMD in change of PAV, when percent change of CRP/hsCRP was included separately. However, the percent change of CRP/hsCRP was not significantly associated with SMD of PAV change after adjusting for all covariates. Conclusion: In conclusion, statin therapy is beneficial for plaque regression. Statins promote plaque regression, which might be associated to their anti-inflammatory ability.

18.
Ecotoxicol Environ Saf ; 248: 114298, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36403299

RESUMO

Land alkalization is an abiotic stress that affects global sustainable agricultural development and the balance of natural ecosystems. In this study, two broomcorn millet cultivars, T289 (alkaline-tolerant) and S223 (alkaline-sensitive), were selected to investigate the response of broomcorn millet to alkaline stress and the role of brassinolide (BR) in alkaline tolerance. Phenotypes, physiologies, and transcriptomes of T289 and S223 plants under only alkaline stress (AS) and alkaline stress with BR (AB) were compared. The results showed that alkaline stress inhibited growth, promoted the accumulation of soluble sugars and malondialdehyde, enhanced electrolyte leakage, and destroyed the integrity of broomcorn millet stomata. In contrast, BR lessened the negative effects of alkaline stress on plants. Transcriptome sequencing analysis showed that relative to control groups (CK, nutrient solution), in AS groups, 21,113 and 12,151 differentially expressed genes (DEGs) were identified in S223 and T289, respectively. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed various terms and pathways related to metabolism. Compared to S223, alkaline stress strongly activated the brassinosteroid biosynthesis pathway in T289. Conversely, ARF, TF, and TCH4, associated with cell growth and elongation, were inhibited by alkaline stress in S223. Moreover, alkaline stress induced the activation of the mitogen-activated protein kinase (MAPK) pathway, the abscisic acid signaling pathway that initiates stomatal closure, as well as the starch and sucrose metabolism. The EG and BGL genes, which are associated with cellulose degradation, were notably activated. BR enhanced alkaline tolerance, thereby alleviating the transcriptional responses of the two cultivars. Cultivar T289 is better in alkalized regions. Taken together, these results reveal how broomcorn millet responds to alkaline stress and BR mitigates alkaline stress, thus promoting agriculture in alkalized regions.


Assuntos
Brassinosteroides , Panicum , Transcriptoma , Ecossistema
19.
ISA Trans ; 2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36319509

RESUMO

This paper investigates dynamic output feedback H∞ control for singular Markovian jump systems with partly unknown transition rates and input saturation. Necessary and sufficient conditions that singular Markovian jump system satisfies stochastic admissibility and H∞ performance index are successfully deduced in terms of linear matrix inequalities under the two different conditions of completely known transition rates and partly unknown transition rates. Mode-dependent dynamic output feedback controller is designed to ensure that the closed-loop singular Markovian jump system satisfies stochastic admissibility and H∞ performance index. Novel set invariant condition is proposed, and it not only provides an estimate of the attractive domain of the closed-loop system but also allows the analysis of performance outside the stability region within this invariant set. Furthermore, the estimation of the attraction domain comes down to the determination of the largest contractively invariant ellipsoid satisfying the necessary and sufficient conditions and the novel set invariant condition, and it is solved as an optimization problem with linear matrix inequality constraints. Finally, the effectiveness and utility of the proposed method are verified by a numerical example and an oil catalytic cracking process.

20.
BMC Cardiovasc Disord ; 22(1): 494, 2022 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-36404328

RESUMO

BACKGROUND: In patients with heart failure, anxiety disorder is common and associated with adverse prognosis. This study intended to find more confounding factors of Chinese heart failure patients. METHODS: We enrolled 284 hospitalized heart failure patients, whose New York Heart Association (NYHA) classed as II-IV and left ventricular ejection fraction (LVEF) ≤ 45%. All the patients were scaled in Hamilton Rating Scale for Anxiety (14-items) (HAM-A14). Ordinal logistic regression analysis was performed to examine the association of correlated factors with anxiety disorder. RESULTS: There were 184 patients had anxiety accounting for 64.8% of all 284 hospitalized heart failure patients. The neutrophilic granulocyte percentage, urea nitrogen, total bilirubin and brain natriuretic peptide were positively associated with HAM-A14 score, meanwhile, the hemoglobin, red blood cells counts, albumin and LVEF were negatively associated with HAM-A14 score (All P < 0.05). After the adjustments of sex, hemoglobin, urea nitrogen, total bilirubin, albumin and brain natriuretic peptide, the neutrophilic granulocyte percentage was significantly associated with anxiety (OR = 43.265, P = 0.012). The neutrophilic granulocyte percentage was 0.616 ± 0.111, 0.640 ± 0.102, 0.681 ± 0.106 and 0.683 ± 0.113 in heart failure patients with no anxiety, possible anxiety, confirmed anxiety and obvious anxiety, respectively. CONCLUSIONS: Neutrophilic granulocyte percentage as well as the traditional risk factors such as sex, urea nitrogen and brain natriuretic peptide is associated with anxiety in hospitalized heart failure patients.


Assuntos
Insuficiência Cardíaca , Peptídeo Natriurético Encefálico , Humanos , Volume Sistólico , Função Ventricular Esquerda , Insuficiência Cardíaca/diagnóstico , Transtornos de Ansiedade , Granulócitos/química , Bilirrubina , Albuminas/análise , Nitrogênio/análise , China/epidemiologia , Ureia
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