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1.
Cell Mol Immunol ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740925

RESUMO

The NLRP3 inflammasome functions as an inflammatory driver, but its relationship with lipid metabolic changes in early sepsis remains unclear. Here, we found that GITR expression in monocytes/macrophages was induced by lysophosphatidylcholine (LPC) and was positively correlated with the severity of sepsis. GITR is a costimulatory molecule that is mainly expressed on T cells, but its function in macrophages is largely unknown. Our in vitro data showed that GITR enhanced LPC uptake by macrophages and specifically enhanced NLRP3 inflammasome-mediated macrophage pyroptosis. Furthermore, in vivo studies using either cecal ligation and puncture (CLP) or LPS-induced sepsis models demonstrated that LPC exacerbated sepsis severity/lethality, while conditional knockout of GITR in myeloid cells or NLRP3/caspase-1/IL-1ß deficiency attenuated sepsis severity/lethality. Mechanistically, GITR specifically enhanced inflammasome activation by regulating the posttranslational modification (PTM) of NLRP3. GITR competes with NLRP3 for binding to the E3 ligase MARCH7 and recruits MARCH7 to induce deacetylase SIRT2 degradation, leading to decreasing ubiquitination but increasing acetylation of NLRP3. Overall, these findings revealed a novel role of macrophage-derived GITR in regulating the PTM of NLRP3 and systemic inflammatory injury, suggesting that GITR may be a potential therapeutic target for sepsis and other inflammatory diseases. GITR exacerbates LPC-induced macrophage pyroptosis in sepsis via posttranslational regulation of NLRP3. According to the model, LPC levels increase during the early stage of sepsis, inducing GITR expression on macrophages. GITR not only competes with NLRP3 for binding to the E3 ligase MARCH7 but also recruits MARCH7 to induce the degradation of the deacetylase SIRT2, leading to decreasing ubiquitination but increasing acetylation of NLRP3 and therefore exacerbating LPC-induced NLRP3 inflammasome activation, macrophage pyroptosis and systemic inflammatory injury.

2.
Inorg Chem ; 63(19): 8863-8878, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38695487

RESUMO

The determination of the site occupancy of activators in phosphors is essential for precise synthesis, understanding the relationship between their luminescence properties and crystal structure, and tailoring their properties by modifying the host composition. Herein, one simple method was proposed to help determine the sites at which the doping of rare earth ions or transition metal ions occupies in the host lattice through site occupancy theory (SOT) for ions doped into the matrix lattice. SOT was established based on the fact that doping ions preferentially occupy the sites with the lowest bonding energy deviations. In order to provide detailed experimental evidence to prove the feasibility of SOT, several scheelite-type compounds were successfully synthesized using a high-temperature solid-phase method. When Eu3+ ions occupy a similar surrounding environment site, the photoluminescence spectra of the activators Eu3+ are similar. Therefore, by comparing the intensity ratio of photoluminescence spectra and the mechanism of all transitions of KEu(WO4)2, KY(WO4)2:Eu3+, Na5Eu(WO4)4, and Na5Y(WO4)4:Eu3+, it was proved that SOT can successfully confirm the site occupation when doped ions enter the matrix lattice. SOT was further applied to the sites occupied by Eu3+ ion-doped LiAl(MoO4)2 and LiLu(MoO4)2.

3.
Chemphyschem ; : e202300880, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38705870

RESUMO

Recent research on mechano-radicals has provided valuable insights into self-growth and adaptive responsive materials. Typically, mechanophores must remain inert in the absence of force but respond quickly to external tension before other linkages within the polymer network. Azo compounds exhibit promising combinations of mechanical stability and force-triggered reactivity, making them widely used as mechano-radicals in force-responsive materials. However, the activation conditions and behavior of azo compounds have yet to be quantitatively explored. In this study, we investigated the mechanical strength of three azo compounds using single-molecule force spectroscopy. Our results revealed that these compounds exhibit rupture forces ranging from ~500 to 1000 pN, at a loading rate of 3×104 pN s-1. Importantly, these mechanophores demonstrate distinct kinetic properties. Their unique mechanical attributes enable azo bond scission and free radical generation before causing major polymer backbone damage of entire material during polymer network deformation. This fundamental understanding of mechanophores holds significant promise for the development of self-growth materials and their related applications.

4.
Cardiology ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38648752

RESUMO

INTRODUCTION: Heart failure (HF) is a major global public health concern. The application of machine learning (ML) to identify individuals at high risk and enable early intervention is a promising approach for improving HF prognosis. We aim to systematically evaluate the performance and value of ML models for predicting HF prognosis. METHODS: PubMed, Web of Science, Scopus, and Embase online databases were searched up to April 30, 2023, to identify studies on the use of ML models to predict HF prognosis. HF prognosis primarily encompasses readmission and mortality. The meta-analysis was conducted by MedCalc software. Subgroup analyses include grouping based on types of ML models, time interval, sample sizes, the number of predictive variables, validation methods, whether to conduct hyperparameter optimization and calibration, data set partitioning methods. RESULTS: A total of 31 studies were included. The most common ML models were random forest, boosting, support vector machine, neural network. The area under the receiver operating characteristic curve (AUC) for predicting HF readmission was 0.675 (95% CI 0.651-0.699, P<0.001), and the AUC for predicting HF mortality was 0.790 (95% CI 0.765-0.816, P<0.001). Subgroup analyses revealed that models with the prediction time interval of 1 year, sample sizes =10,000, the number of predictive variables =100, external validation, hyperparameter tuning, calibration adjustment, and data set partitioning using 10-fold cross-validation exhibited favorable performance within their respective subgroups. CONCLUSION: The performance of ML models in predicting HF readmission is relatively poor, while its performance in predicting HF mortality is moderate. The quality of the relevant studies is generally low, it is essential to enhance the predictive capabilities of ML models through targeted improvements in practical applications.

5.
Int Immunopharmacol ; 133: 112157, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38678671

RESUMO

In non-small cell lung cancer (NSCLC), identifying a component with certain molecular targets can aid research on cancer treatment. Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin which induced the anti-cancer effects via the STAT3 signaling pathway, but the underlying molecular mechanism is still elusive. In this study, we first proved that DHA prohibits the growth of tumors both in vitro and in vivo. Data from transcriptomics showed that DHA reduced the expression level of the genes involved in cell cycle-promoting and anti-apoptosis, and most importantly, DHA restricted the expression level of receptor tyrosine kinase-like orphan receptor 1 (ROR1) which has been reported to have abnormal expression on tumor cells and had close interaction with STAT3 signaling. Then, we performed comprehensive experiments and found that DHA remarkably decreased the expression of ROR1 at both mRNA and protein levels and it also diminished the phosphorylation level of STAT3 in NSCLC cell lines. In addition, our data showed that exogenously introduced ROR1 could significantly enhance the phosphorylation of STAT3 while blocking ROR1 had the opposite effects indicating that ROR1 plays a critical role in promoting the activity of STAT3 signaling. Finally, we found that ROR1 overexpression could partially reverse the decreased activity of STAT3 induced by DHA which indicates that DHA-induced anti-growth signaling is conferred, at least in part, through blocking ROR1-mediated STAT3 activation. In summary, our study indicates that in NSCLC, ROR1 could be one of the critical molecular targets mediating DHA-induced STAT3 retardation.


Assuntos
Artemisininas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase , Fator de Transcrição STAT3 , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/genética , Animais , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus , Apoptose/efeitos dos fármacos , Camundongos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células A549 , Camundongos Endogâmicos BALB C
6.
Aging (Albany NY) ; 16(8): 7357-7386, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38656892

RESUMO

BACKGROUND: Heart failure (HF) has been reported to affect cerebral cortex structure, but the underlying cause has not been determined. This study used Mendelian randomization (MR) to reveal the causal relationship between HF and structural changes in the cerebral cortex. METHODS: HF was defined as the exposure variable, and cerebral cortex structure was defined as the outcome variable. Inverse-variance weighted (IVW), MR-Egger regression and weighted median (WME) were performed for MR analysis; MR-PRESSO and Egger's intercept was used to test horizontal pleiotropy; and "leave-one-out" was used for sensitivity analysis. RESULTS: Fifty-two single nucleotide polymorphisms (SNPs) were defined as instrumental variables (IVs), and there was no horizontal pleiotropy in the IVs. According to the IVW analysis, the OR and 95% CI of cerebral cortex thickness were 0.9932 (0.9868-1.00) (P=0.0402), and the MR-Egger intercept was -15.6× 10-5 (P = 0.7974) and the Global test pval was 0.078. The P-value of the cerebral cortex surface was 0.2205, and the MR-Egger intercept was -34.69052 (P= 0.6984) and the Global Test pval was 0.045. HF had a causal effect on the surface area of the caudal middle frontal lobule (P=0.009), insula lobule (P=0.01), precuneus lobule (P=0.049) and superior parietal lobule (P=0.044). CONCLUSIONS: HF was potentially associated with changes in cortical thickness and in the surface area of the caudal middle frontal lobule, insula lobule, precuneus lobule and superior parietal lobule.


Assuntos
Córtex Cerebral , Insuficiência Cardíaca , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Humanos , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/genética , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Imageamento por Ressonância Magnética , Masculino
7.
Chem Biodivers ; : e202400258, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581076

RESUMO

We presented a strategy utilizing 2D NMR-based metabolomic analysis of crude extracts, categorized by different pharmacological activities, to rapidly identify the primary bioactive components of TCM. It was applied to identify the potential bioactive components from Scutellaria crude extracts that exhibit anti-non-small cell lung cancer (anti-NSCLC) activity. Four Scutellaria species were chosen as the study subjects because of their close phylogenetic relationship, but their crude extracts exhibit significantly different anti-NSCLC activity. Cell proliferation assay was used to assess the anti-NSCLC activity of four species of Scutellaria. 1H-13C HSQC spectra were acquired for the chemical profiling of these crude extracts. Based on the pharmacological classification (PCA, OPLS-DA and univariate hypothesis test) were performed to identify the bioactive constituents in Scutellaria associated with the anti-NSCLC activity. As a result, three compounds, baicalein, wogonin and scutellarin were identified as bioactive compounds. The anti-NSCLC activity of the three potential active compounds were further confirmed via cell proliferation assay. The mechanism of the anti-NSCLC activity by these active constituents was further explored via flow cytometry and western blot analyses. This study demonstrated 2D NMR-based metabolomic analysis of pharmacologically classified crude extracts to be an efficient approach to the identification of active components of herbal medicine.

8.
Anal Chem ; 96(18): 7187-7193, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38671557

RESUMO

Despite the significant importance of blood lithium (Li) detection in the treatment of bipolar disorder (BD), its point-of-care testing (POCT) remains a great challenge due to tedious sample preparation and the use of large-footprint atomic spectrometers. Herein, a system coupling dried blood spots (DBS) with a point discharge optical emission spectrometer equipped with a miniaturized ultrasonic nebulizer (MUN-µPD-OES) was developed for POCT of blood Li. Three microliters of whole blood were used to prepare a dried blood spot on a piece of filter paper to which 10 µL of eluent (1% (v/v) formic acid and 0.05% (v/v) Triton-X) was added. Subsequently, the paper was placed onto the vibrating steel membrane of the ultrasonic nebulizer and powered on to generate aerosol. The aerosol was directly introduced to the µPD-OES for quantification of Li by monitoring its atomic emission line at 670.8 nm. The proposed method minimized matrix interference caused by high levels of salts and protein. It is worth noting that the MUN suitably matches the needs of DBS sampling and can provide aerosolized introduction of Li into the assembled µPD-OES, thus eliminating all tedious sample preparation and the need for a commercial atomic spectrometer. Calibration response is linear in the therapeutic range and a limit of detection (LOD) of 1.3 µg L-1 is well below the Li minimum therapeutic concentration (2800 µg L-1). Li in mouse blood was successfully detected in real-time using MUN-µPD-OES after intraperitoneal injection of lithium carbonate, confirming that the system holds great potential for POCT of blood Li for patients with BD.


Assuntos
Teste em Amostras de Sangue Seco , Lítio , Testes Imediatos , Lítio/sangue , Humanos , Teste em Amostras de Sangue Seco/instrumentação , Teste em Amostras de Sangue Seco/métodos , Animais , Camundongos , Nebulizadores e Vaporizadores , Miniaturização , Ultrassom , Limite de Detecção
9.
J Phys Chem Lett ; 15(17): 4705-4710, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38656800

RESUMO

Electrochemical CO2 reduction (CO2R) to feedstocks competes with the hydrogen evolution reaction (HER). Cobalt phthalocyanine (CoPc) immobilized onto carbon driven by π-π interaction represents a classical type of heterogeneous molecular catalyst for CO2R. However, the impacts of π conjugation on the electrocatalysis have not been clarified. Herein, the electrochemical properties of CoPc were investigated by comparison of its analogue to 2,3-naphthalocyanine cobalt (NapCo) having extended π conjugation. It is found that CoPc is redox-active on carbon to provide low oxidized Co sites for improving the CO2R activity and selectivity, while NapCo on carbon turned out to be redox-inert leading to lower performance. In addition, the redox-mediated mechanism for CO2R on CoPc tends to operate with increasing electrolyte alkalinity, which further enhances the reaction selectivity. We speculated that moderate π conjugation allows the redox-mediated mechanism on CoPc, which is critical to promote CO2R performance while depressing the competing HER.

10.
Dev Cell ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38688276

RESUMO

Photoperiod sensitivity is crucial for soybean flowering, adaptation, and yield. In soybean, photoperiod sensitivity centers around the evening complex (EC) that regulates the transcriptional level of the core transcription factor E1, thereby regulating flowering. However, little is known about the regulation of the activity of EC. Our study identifies how E2/GIGANTEA (GI) and its homologs modulate photoperiod sensitivity through interactions with the EC. During long days, E2 interacts with the blue-light receptor flavin-binding, kelch repeat, F box 1 (FKF1), leading to the degradation of J/ELF3, an EC component. EC also suppresses E2 expression by binding to its promoter. This interplay forms a photoperiod regulatory loop, maintaining sensitivity to photoperiod. Disruption of this loop leads to losing sensitivity, affecting soybean's adaptability and yield. Understanding this loop's dynamics is vital for molecular breeding to reduce soybean's photoperiod sensitivity and develop cultivars with better adaptability and higher yields, potentially leading to the creation of photoperiod-insensitive varieties for broader agricultural applications.

11.
Drug Des Devel Ther ; 18: 781-799, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500692

RESUMO

Purpose: This study aimed to elucidate the protective mechanism of Traditional Chinese Medicine (TCM) Qifu Yixin formula (QFYXF) to improve heart failure (HF) by promoting ß-arrestin2 (ß-arr2)-mediated SERCA2a SUMOylation. Materials and Methods: The transverse aortic constriction (TAC)-induced HF mice were treated with QFYXF or carvedilol for 8 weeks. ß-arr2-KO mice and their littermate wild-type (WT) mice were used as controls. Neonatal rat cardiomyocytes (NRCMs) were used in vitro. Cardiac function was evaluated by echocardiography and serum NT-proBNP. Myocardial hypertrophy and myocardial fibrosis were assessed by histological staining. ß-arr2, SERCA2a, SUMO1, PLB and p-PLB expressions were detected by Western blotting, immunofluorescence and immunohistochemistry. SERCA2a SUMOylation was detected by Co-IP. The molecular docking method was used to predict the binding ability of the main active components of QFYXF to ß-arr2, SERCA2a, and SUMO1, and the binding degree of SERCA2a to SUMO1 protein. Results: The HF model was constructed 8 weeks after TAC. QFYXF ameliorated cardiac function, inhibiting myocardial hypertrophy and fibrosis. QFYXF promoted SERCA2a expression and SERCA2a SUMOylation. Further investigation showed that QFYXF promoted ß-arr2 expression, whereas Barbadin (ß-arr2 inhibitor) or ß-arr2-KO reduced SERCA2a SUMOylation and attenuated the protective effect of QFYXF improved HF. Molecular docking showed that the main active components of QFYXF had good binding activities with ß-arr2, SERCA2a, and SUMO1, and SERCA2a had a high binding degree with SUMO1 protein. Conclusion: QFYXF improves HF by promoting ß-arr2 mediated SERCA2a SUMOylation and increasing SERCA2a expression.


Assuntos
Insuficiência Cardíaca , Sumoilação , Ratos , Camundongos , Animais , Simulação de Acoplamento Molecular , Miócitos Cardíacos , Cardiomegalia/tratamento farmacológico , Cardiomegalia/metabolismo
12.
Sci Total Environ ; 922: 171270, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38428603

RESUMO

Although triclosan has been ubiquitously detected in aquatic environment and is known to have various adverse effects to fish, details on its uptake, bioconcentration, and elimination in fish tissues are still limited. This study investigated the uptake and elimination toxicokinetics, bioconcentration, and biotransformation potential of triclosan in Nile tilapia (Oreochromis niloticus) exposed to environmentally-relevant concentrations under semi-static regimes for 7 days. For toxicokinetics, triclosan reached a plateau concentration within 5-days of exposure, and decreased to stable concentration within 5 days of elimination. Approximately 50 % of triclosan was excreted by fish through feces, and up to 29 % of triclosan was excreted through the biliary excretion. For fish exposed to 200 ng·L-1, 2000 ng·L-1, and 20,000 ng·L-1, the bioconcentration factors (log BCFs) of triclosan in fish tissues obeyed similar order: bile ≈ intestine > gonad ≈ stomach > liver > kidney ≈ gill > skin ≈ plasma > brain > muscle. The log BCFs of triclosan in fish tissues are approximately maintained constants, no matter what triclosan concentrations in exposure water. Seven biotransformation products of triclosan, involved in both phase I and phase II metabolism, were identified in this study, which were produced through hydroxylation, bond cleavages, dichlorination, and sulfation pathways. Metabolite of triclosan-O-sulfate was detected in all tissues of tilapia, and more toxic product of 2,4-dichlorophenol was also found in intestine, gonad, and bile of tilapia. Meanwhile, two metabolites of 2,4-dichlorophenol-O-sulfate and monohydroxy-triclosan-O-sulfate were firstly discovered in the skin, liver, gill, intestine, gonad, and bile of tilapia in this study. These findings highlight the importance of considering triclosan biotransformation products in ecological assessment. They also provide a scientific basis for health risk evaluation of triclosan to humans, who are associated with dietary exposure through ingesting fish.


Assuntos
Clorofenóis , Ciclídeos , Tilápia , Triclosan , Poluentes Químicos da Água , Animais , Humanos , Tilápia/metabolismo , Triclosan/toxicidade , Triclosan/metabolismo , Distribuição Tecidual , Ciclídeos/metabolismo , Biotransformação , Sulfatos/metabolismo , Poluentes Químicos da Água/análise
13.
Proc Natl Acad Sci U S A ; 121(11): e2316553121, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38437553

RESUMO

Developing cost-effective and high-performance electrocatalysts for oxygen reduction reaction (ORR) is critical for clean energy generation. Here, we propose an approach to the synthesis of iron phthalocyanine nanotubes (FePc NTs) as a highly active and selective electrocatalyst for ORR. The performance is significantly superior to FePc in randomly aggregated and molecularly dispersed states, as well as the commercial Pt/C catalyst. When FePc NTs are anchored on graphene, the resulting architecture shifts the ORR potentials above the redox potentials of Fe2+/3+ sites. This does not obey the redox-mediated mechanism operative on conventional FePc with a Fe2+-N moiety serving as the active sites. Pourbaix analysis shows that the redox of Fe2+/3+ sites couples with HO- ions transfer, forming a HO-Fe3+-N moiety serving as the ORR active sites under the turnover condition. The chemisorption of ORR intermediates is appropriately weakened on the HO-Fe3+-N moiety compared to the Fe2+-N state and thus is intrinsically more ORR active.

14.
Stress Biol ; 4(1): 15, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363398

RESUMO

Tea plant [Camellia sinensis (L.) O. Kuntze] is one of the important foliar cash crops in China, and its root system absorbs heavy metal (HM) elements enriched in the soil and transports them to the over ground part. In order to ensure the safety of the soil ecological environment and tea raw materials in the tea production area, the HM contents of soil and tea plant leaves in Suzhou tea plantations were detected, the relationship between HMs and soil physicochemical properties was analyzed, and the ecological risk of HMs in tea plantation soils was evaluated by using relevant detection techniques and evaluation models. The results showed that the average pH of tea plantation soils around Tai Lake in Suzhou was within the range suitable for the growth of tea plants. The pH, soil organic matter, total nitrogen, available phosphorus and available potassium of tea plantation soil satisfying the requirements of high quality, high efficiency and high yield ('3H') tea plantation accounted for 47.06%, 26.47%, 8.82%, 79.41% and 67.65%, respectively. Site 2 fully met the requirements of '3H' tea plantation. In addition, the contents of cadmium (Cd) and mercury (Hg) were extremely variable, and the average contents exceeded the background value of soil in Jiangsu Province, but the HM contents of tea leaves all met the pollution-free standard, and the HM contents of tea leaves around Tai Lake in Suzhou were generally at a safe level. The composite ecological risk index ranged from 0.05 to 0.60, and 32 of the 34 sample sites (except site 21 and site 23) are the most suitable agricultural land for tea plantations.

15.
Nat Chem ; 16(3): 446-455, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38052946

RESUMO

Azobenzene has been widely explored as a photoresponsive element in materials science. Although some studies have investigated the force-induced isomerization of azobenzene, the effect of force on the rupture of azobenzene has not been explored. Here we show that the light-induced structural change of azobenzene can also alter its rupture forces, making it an ideal light-responsive mechanophore. Using single-molecule force spectroscopy and ultrasonication, we found that cis and trans para-azobenzene isomers possess contrasting mechanical properties. Dynamic force spectroscopy experiments and quantum-chemical calculations in which azobenzene regioisomers were pulled from different directions revealed that the distinct rupture forces of the two isomers are due to the pulling direction rather than the energetic difference between the two isomers. These mechanical features of azobenzene can be used to rationally control the macroscopic fracture behaviours of polymer networks by photoillumination. The use of light-induced conformational changes to alter the mechanical response of mechanophores provides an attractive way to engineer polymer networks of light-regulatable mechanical properties.

16.
Life Sci ; 336: 122279, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37995935

RESUMO

Necrotizing enterocolitis (NEC) is one of the most common acute gastrointestinal diseases in preterm infants. Recent studies have found that NEC is not only caused by changes in the intestinal environment but also by the failure of multiple systems and organs, including the liver. The accumulation of bile acids (BAs) in the ileum and the disorder of ileal BA transporters are related to the ileum injury of NEC. Inflammatory factors such as tumor necrosis factor (TNF)-α and interleukin (IL)-18 secreted by NEC also play an important role in regulating intrahepatic BA transporters. As an important link connecting the liver and intestinal circulation, the bile acid metabolic pathway plays an important role in the regulation of intestinal microbiota, cell proliferation, and barrier protection. In this review, we focus on how bile acids explore the dynamic changes of bile acid metabolism in necrotizing enterocolitis and the potential therapeutic value of targeting the bile acid signaling pathways.


Assuntos
Enterocolite Necrosante , Recém-Nascido Prematuro , Recém-Nascido , Humanos , Ácidos e Sais Biliares/metabolismo , Enterocolite Necrosante/etiologia , Enterocolite Necrosante/metabolismo , Enterocolite Necrosante/patologia , Íleo/metabolismo , Intestinos/patologia , Fator de Necrose Tumoral alfa/metabolismo
17.
Materials (Basel) ; 16(23)2023 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-38068098

RESUMO

Most failures in steel materials are due to fatigue damage, so it is of great significance to analyze the key features of fatigue strength (FS) in order to improve fatigue performance. This study collected data on the fatigue strength of steel materials and established a predictive model for FS based on machine learning (ML). Three feature-construction strategies were proposed based on the dataset, and compared on four typical ML algorithms. The combination of Strategy Ⅲ (composition, heat-treatment, and atomic features) and the GBT algorithm showed the best performance. Subsequently, input features were selected step by step using methods such as the analysis of variance (ANOVA), embedded method, recursive method, and exhaustive method. The key features affecting FS were found to be TT, mE, APID, and Mo. Based on these key features and Bayesian optimization, an ML model was established, which showed a good performance. Finally, Shapley additive explanations (SHAP) and symbolic regression (SR) are introduced to improve the interpretability of the prediction model. It had been discovered through SHAP analysis that TT and Mo had the most significant impact on FS. Specifically, it was observed that 160 < TT < 500 and Mo > 0.15 was beneficial for increasing the value of FS. SR was used to establish a significant mathematical relationship between these key features and FS.

18.
World J Microbiol Biotechnol ; 40(1): 31, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38057682

RESUMO

Pyrroloquinoline quinone (PQQ) is a peptide-modified natural product. PQQ has important physiological functions such as anti-oxidation, anti-aging, and immunity enhancement. However, due to the lack of in-depth understanding of PQQ biosynthesis and regulation, inefficient PQQ production level limits its wide application. Accordingly, there is still an urgent need to develop high-yielding strains for synthesis of PQQ. This paper reviewed the research and development trends on the PQQ biosynthetic pathways, catalytic reaction mechanism of key enzymes, and the selection of high-yielding strains, which also prospects for the future construction of PQQ biosynthetic microbial cell factories.


Assuntos
Cofator PQQ , Oxirredução
19.
Plants (Basel) ; 12(24)2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38140455

RESUMO

Glycine soja is the wild relative species of cultivated soybean. In this study, we investigated the population divergence and genetic basis of the local adaptation of wild soybean in China using genome-wide single-nucleotide polymorphisms (SNPs) of a population of 72 G. soja accessions. Using phylogenetic analysis, we observed that G. soja accessions clustered into three distinct groups, each corresponding to a specific geographic region, the northeastern region (NER), central region (CR), and southern region (SR), consistent with previous studies. Notably, we found a significant positive correlation between genetic and geographic distances. Further population structure analysis revealed each group was associated with an ancestral population and a specific geographic area. By utilizing the genome sequencing data of accessions from 16 different locations, we inferred the population history of these wild soybean groups. Our results indicate that the three groups diverged ~25,000 years ago, coinciding with the time of the last glacial maximum. The effective population size of the SR group expanded first, and subsequently, the NER and CR groups expanded approximately 5000 and 2500 years ago, respectively. Moreover, 83, 104, and 101 significant associated loci (SALs) were identified using genome-wide association analysis for annual mean temperature, annual precipitation, and latitude, respectively. Functional analysis of genes located in SALs highlighted candidate genes related to local adaptation. This study highlights the significant role of geographic isolation and environmental factors in shaping the genetic structure and adaptability of wild soybean populations. Furthermore, it emphasizes the value of wild soybean as a crucial genetic resource for enhancing the adaptability of cultivated soybeans, which have experienced a loss of genetic diversity due to domestication and intensive breeding practices. The insights gained from our research provide valuable information for the protection, conservation, and utilization of this important genetic resource.

20.
PLoS One ; 18(11): e0287650, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38019729

RESUMO

BACKGROUND: Aerobic exercise is widely recognized for improving mental health and reducing negative emotions, including anxiety. However, research on its role in preventing and treating postpartum depression (PPD) has yielded inconsistent results. Some studies show positive effects on PPD symptoms, while others find limited impact, suggesting various factors at play, such as exercise type, intensity, and individual differences. To address this gap, our study aims to comprehensively gather evidence on the preventive and therapeutic effects of aerobic exercise for PPD. We'll focus on differences in exercise program design and implementation, exploring how these factors impact intervention outcomes. By identifying effective exercise approaches, we aim to provide more comprehensive exercise prescription recommendations for this vulnerable population. METHODS: We conducted a quantitative systematic review of the study in 5 representative databases for the effect of aerobic exercise on PPD. Meta-analysis and network meta-analysis were performed with Review-Manager.5.4 and Stata.16.0 software, respectively. This study has been registered on the official Prospero website, and the registration code is CRD42023398221. RESULTS: Twenty-six studies with 2,867 participants were eventually included and the efficacy of aerobic exercise in preventing and treating postpartum depression is significant compared to standard care. (MD = -1.90; 95%CL: -2.58 to -1.21; I2 = 86%). Subgroup analysis suggests that the intervention objective (prevention vs. treatment) of exercise could potentially be a source of heterogeneity in this study, as the "Test for subgroup difference" revealed the presence of significant distinctions (p = 0.02<0.05). The "Test for subgroup difference" yielded non-significant results for both the supervised vs. unsupervised subgroup comparison (p = 0.55 > 0.05) and the individual vs. team subgroup comparison (p = 0.78 > 0.05). Nonetheless, when assessing their effect sizes [Subtotal (95%CL)], the supervised exercise group [-1.66 (-2.48, -0.85)] exhibited a slightly better performance than the unsupervised exercise group [-1.37 (-1.86, -0.88)], while the team exercise group [-1.43 (-1.94, -0.93)] slightly outperformed the individual exercise group [-1.28 (-2.23, -0.33)]. Network meta-analysis indicated that moderate intensity (35~45 min) group demonstrated a more pronounced intervention effect compared to low intensity (50~60 min) group [-2.63 (-4.05, -1.21)] and high intensity (20~30 min) group [-2.96 (-4.51, -1.41)], while the 3~4 times/week group had a more significant intervention effect compared to 1~2 times/week groups [-2.91 (-3.99, -1.83)] and 5~6 times/week groups [-3.28 (-4.75, -1.81)]. No significant differences were observed in pairwise comparisons of intervention effects among the five common types of aerobic exercises. (95%CL including 0). The Surface Under the Cumulative Ranking curve (SUCRA) results align with the findings mentioned above and will not be reiterated here. CONCLUSION: The efficacy of aerobic exercise in preventing and treating postpartum depression is significant compared to standard care, with a greater emphasis on prevention. The optimal prescribed exercise volume for intervention comprises a frequency of 3~4 exercise sessions per week, moderate intensity (35~45 minutes). Currently, several uncharted internal factors influence the optimal intervention effect of aerobic exercise, such as the potential enhancement brought by team-based and supervised exercise. Given the absence of significant differences in certain results and the limitations of the study, it is essential to exercise caution when interpreting the outcomes. Further research is needed in the future to provide a more comprehensive understanding.


Assuntos
Depressão Pós-Parto , Feminino , Humanos , Depressão Pós-Parto/prevenção & controle , Metanálise em Rede , Exercício Físico , Terapia por Exercício
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