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1.
Front Microbiol ; 15: 1367877, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933026

RESUMO

Introduction: This study was conducted to evaluate the effects of dietary galacto-oligosaccharides (GOS) and hyocholic acids (HCA) during late gestation and lactation on reproductive performance, colostrum quality, antioxidant capacity and gut microbiota in multiparous sows. Methods: A total of 60 healthy multiparous cross-bred sows (Landrace × Yorkshire) were randomly fed 4 groups diets as follows: the basal diets (CTRL group), or the basal diets containing only 600 mg/kg GOS (GOS group), 600 mg/kg GOS + 100 mg/kg HCA (GOS + Low HCA group), and 600 mg/kg + 200 mg/kg HCA (GOS + High HCA group) from d 85 of gestation to weaning. Multiple parameters of sows were determined. Results: There was a trend of shortening the labor process of sows (p = 0.07) in the GOS group and GOS + Low/High HCA group. Compared with the CTRL group, the GOS + Low/High HCA group increased the average piglets weight at birth (p < 0.05), and increased the IgA concentration of colostrum (p < 0.05). In addition, serum triglyceride (TG) concentration was lower (p < 0.05), and serum total antioxidant capacity (T-AOC) was higher (p < 0.05) in the GOS and GOS + Low/High HCA groups than in the CTRL group at farrowing. Serum catalase (CAT) activities was higher in the GOS and GOS + High HCA groups than in the CTRL group at farrowing. The 16S rRNA analysis showed that GOS combination with high-dose HCA shaped the composition of gut microbiota in different reproductive stages (d 107 of gestation, G107; d 0 of lactation, L0; d 7 of lactation, L7). At the phylum level, the relative abundance of Bacteroidota and Desulfobacterota in G107, Bacteroidota, and Proteobacteria in L0, and Planctomycetota in L7 was increased in GOS + High HCA group (p < 0.05). Spearman correlation analysis showed that Streptococcus was positively correlated with the serum TG but negatively correlated with the average piglets weight at birth (p < 0.05). Conclusion: This investigation demonstrated that the administration of galacto-oligosaccharides (GOS) in conjunction with hyocholic acids (HCA), to sows with nutrient restrictions during late gestation and lactation, further improved their antioxidant capacity and milk quality. The observed beneficial effects of GOS + HCA supplementation could potentially be linked to an improvement in gut microbiota disorders of the sows.

2.
J Transl Med ; 22(1): 554, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858785

RESUMO

BACKGROUND: The molecular complexity of colorectal cancer poses a significant challenge to the clinical implementation of accurate risk stratification. There is still an urgent need to find better biomarkers to enhance established risk stratification and guide risk-adapted treatment decisions. METHODS: we systematically analyzed cancer dependencies of 17 colorectal cancer cells and 513 other cancer cells based on genome-scale CRISPR-Cas9 knockout screens to identify colorectal cancer-specific fitness genes. A regression model was built using colorectal cancer-specific fitness genes, which was validated in other three independent cohorts. 30 published gene expression signatures were also retrieved. FINDINGS: We defined a total of 1828 genes that were colorectal cancer-specific fitness genes and identified a 22 colorectal cancer-specific fitness gene (CFG22) score. A high CFG22 score represented unfavorable recurrence and mortality rates, which was validated in three independent cohorts. Combined with age, and TNM stage, the CFG22 model can provide guidance for the prognosis of colorectal cancer patients. Analysis of genomic abnormalities and infiltrating immune cells in the CFG22 risk stratification revealed molecular pathological difference between the subgroups. Besides, drug analysis found that CFG22 high patients were more sensitive to clofibrate. INTERPRETATION: The CFG22 model provided a powerful auxiliary prediction tool for identifying colorectal cancer patients with high recurrence risk and poor prognosis, optimizing precise treatment and improving clinical efficacy.


Assuntos
Sistemas CRISPR-Cas , Neoplasias Colorretais , Técnicas de Inativação de Genes , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/diagnóstico , Humanos , Sistemas CRISPR-Cas/genética , Medição de Risco , Linhagem Celular Tumoral , Prognóstico , Masculino , Aptidão Genética , Feminino , Genoma Humano , Regulação Neoplásica da Expressão Gênica
3.
J Med Chem ; 67(10): 8060-8076, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38722184

RESUMO

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a promising therapeutic target in inflammation-related diseases. However, the inhibition of IRAK4 kinase activity may lead to moderate anti-inflammatory efficacy owing to the dual role of IRAK4 as an active kinase and a scaffolding protein. Herein, we report the design, synthesis, and biological evaluation of an efficient and selective IRAK4 proteolysis-targeting chimeric molecule that eliminates IRAK4 scaffolding functions. The most potent compound, LC-MI-3, effectively degraded cellular IRAK4, with a half-maximal degradation concentration of 47.3 nM. LC-MI-3 effectively inhibited the activation of downstream nuclear factor-κB signaling and exerted more potent pharmacological effects than traditional kinase inhibitors. Furthermore, LC-MI-3 exerted significant therapeutic effects in lipopolysaccharide- and Escherichia coli-induced acute and chronic inflammatory skin models compared with kinase inhibitors in vivo. Therefore, LC-MI-3 is a candidate IRAK4 degrader in alternative targeting strategies and advanced drug development.


Assuntos
Quinases Associadas a Receptores de Interleucina-1 , Quinases Associadas a Receptores de Interleucina-1/antagonistas & inibidores , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Animais , Humanos , Camundongos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/uso terapêutico , Administração Oral , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , NF-kappa B/antagonistas & inibidores , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacocinética , Disponibilidade Biológica , Descoberta de Drogas , Proteólise/efeitos dos fármacos , Relação Estrutura-Atividade , Masculino , Camundongos Endogâmicos C57BL
4.
J Vis Exp ; (206)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38647274

RESUMO

The developmental origins of health and disease concept highlights the impact of early environments on chronic non-communicable diseases like diabetes, cardiovascular disease, and cancer. Studies using animal models have investigated how maternal factors such as undernutrition, overnutrition, obesity, and exposure to chemicals or hypoxia affect fetal development and offspring health, leading to issues like low birth weight, high blood pressure, dyslipidemia, and insulin resistance. Given the increasing prevalence of overweight and obesity among reproductive-age women, effective interventions are critical. Maternal exercise during pregnancy has emerged as a key intervention, benefiting both mother and offspring and reducing the risk of disease. This study compares the differences of three exercise models on pregnant rats: voluntary wheel running, motorized treadmills, and swimming. Swimming is the most beneficial option due to its safe and controlled intensity levels. This protocol details the rat breeding methods, swimming training during pregnancy, and post-breeding nursing protocols. This model, suitable for various rat and mouse species, is useful for studying the benefits of maternal exercise on offspring health and intergenerational wellness.


Assuntos
Condicionamento Físico Animal , Natação , Animais , Feminino , Natação/fisiologia , Gravidez , Ratos , Condicionamento Físico Animal/métodos , Condicionamento Físico Animal/fisiologia , Modelos Animais
5.
Arterioscler Thromb Vasc Biol ; 44(6): 1202-1221, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38602101

RESUMO

BACKGROUND: Hypertension is a major, prevalent risk factor for the development and progression of cerebrovascular disease. Regular exercise has been recommended as an excellent choice for the large population of individuals with mild-to-moderate elevations in blood pressure, but the mechanisms that underlie its vascular-protective and antihypertensive effects remain unknown. Here, we describe a mechanism by which myocyte AKAP150 (A-kinase anchoring protein 150) inhibition induced by exercise training alleviates voltage-dependent L-type Ca2+ channel (CaV1.2) activity and restores cerebral arterial function in hypertension. METHODS: Spontaneously hypertensive rats and newly generated smooth muscle-specific AKAP150 knockin mice were used to assess the role of myocyte AKAP150/CaV1.2 channel in regulating cerebral artery function after exercise intervention. RESULTS: Activation of the AKAP150/PKCα (protein kinase Cα) signaling increased CaV1.2 activity and Ca2+ influx of cerebral arterial myocyte, thus enhancing vascular tone in spontaneously hypertensive rats. Smooth muscle-specific AKAP150 knockin mice were hypertensive with higher CaV1.2 channel activity and increased vascular tone. Furthermore, treatment of Ang II (angiotensin II) resulted in a more pronounced increase in blood pressure in smooth muscle-specific AKAP150 knockin mice. Exercise training significantly reduced arterial myocyte AKAP150 expression and alleviated CaV1.2 channel activity, thus restoring cerebral arterial function in spontaneously hypertensive rats and smooth muscle-specific AKAP150 knockin mice. AT1R (AT1 receptor) and AKAP150 were interacted closely in arterial myocytes. Exercise decreased the circulating Ang II and Ang II-involved AT1R-AKAP150 association in myocytes of hypertension. CONCLUSIONS: The current study demonstrates that aerobic exercise ameliorates CaV1.2 channel function via inhibiting myocyte AKAP150, which contributes to reduced cerebral arterial tone in hypertension.


Assuntos
Proteínas de Ancoragem à Quinase A , Canais de Cálcio Tipo L , Artérias Cerebrais , Modelos Animais de Doenças , Hipertensão , Músculo Liso Vascular , Miócitos de Músculo Liso , Ratos Endogâmicos SHR , Animais , Proteínas de Ancoragem à Quinase A/metabolismo , Proteínas de Ancoragem à Quinase A/genética , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo L/genética , Hipertensão/fisiopatologia , Hipertensão/metabolismo , Hipertensão/genética , Artérias Cerebrais/metabolismo , Artérias Cerebrais/fisiopatologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiopatologia , Masculino , Miócitos de Músculo Liso/metabolismo , Condicionamento Físico Animal/fisiologia , Proteína Quinase C-alfa/metabolismo , Proteína Quinase C-alfa/genética , Sinalização do Cálcio , Camundongos Endogâmicos C57BL , Camundongos , Ratos , Ratos Endogâmicos WKY , Angiotensina II , Pressão Sanguínea , Transdução de Sinais
6.
Clin Respir J ; 18(3): e13746, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38529683

RESUMO

OBJECTIVES: The aim of this study is to evaluate the diagnostic value of rapid on-site evaluation (ROSE) combined with computed tomography-guided percutaneous needle biopsy (CT-PNB) or radial endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) for pulmonary cryptococcosis (PC). METHODS: Clinical data of 33 patients diagnosed with PC at the Third Affiliated Hospital of Soochow University between February 2018 and June 2023 were retrospectively analysed. Patients were divided into the CT-PNB and EBUS-TBLB groups based on the intervention method, and the diagnostic positivity rate and incidence of complications were compared between the two groups. RESULTS: Compared with the final diagnosis, the positive diagnostic rates of ROSE, histopathology and serum CrAg of all patients were 81.8% (27/33), 72.7% (24/33) and 63.6% (21/33), respectively. The average turnaround times of the three methods were 0.1 (0.1-0.2) h, 96.0 (48.0-120.0) h and 7.8 (4.5-13.6) h, respectively (P < 0.001). The coincidence rate between histopathology and ROSE was 84.8% with a kappa value of 0.574. The positive diagnostic rate for PC was significantly higher in the CT-PNB group than in the EBUS-TBLB group (92.9% vs. 57.9%), and the difference was statistically significant (P < 0.05). Combined with the ROSE results, the positive diagnostic rate in the EBUS-TBLB group increased to 84.2% (16/19). CONCLUSION: ROSE has commendable accuracy and timeliness, and CT-PNB offers further advantages in this regard. ROSE enhances the diagnostic efficiency of EBUS-TBLB for PC and is safe and effective.


Assuntos
Criptococose , Neoplasias Pulmonares , Pneumologia , Humanos , Avaliação Rápida no Local , Estudos Retrospectivos , Broncoscopia/métodos , Biópsia Guiada por Imagem/métodos , Criptococose/diagnóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia
7.
BMC Pulm Med ; 24(1): 117, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448907

RESUMO

BACKGROUND: Sex difference in the incidence rate of idiopathic pulmonary fibrosis (IPF) indicates that estrogen has a certain protective effect on the disease. Nevertheless, there is a dearth of study investigating the association between factors pertaining to endogenous estrogen exposure level, such as age at menarche (AAM) in women, and IPF. Our study intended to employ Mendelian randomization (MR) method to elucidate the causal association between AAM and IPF. METHODS: Our study utilized AAM as a measure of endogenous estrogen exposure and investigated its causal effect on the risk of IPF through MR. We employed the inverse variance weighted (IVW) method to assess the causal relationship between AAM and IPF risk, with supplementary analyses conducted using the weighted median estimator (WME) and MR-Egger method. Several sensitivity analyses were performed to assess the dependability of MR estimates. RESULTS: A total of 9 selected single nucleotide polymorphisms (SNPs) significantly associated with AAM were selected as instrumental variables. The IVW method showed that genetically later AAM was associated with an increased risk of IPF (odds ratio [OR] = 1.0014, 95%confidence interval [CI] = 1.0005-1.0023, p = 0.001). The median weighting method and the MR-Egger method obtained similar estimates, and no heterogeneity or pleiotropy was found, indicating that the results were robust. CONCLUSIONS: Our MR study suggested a causal relationship between a later onset of menarche and a heightened susceptibility to IPF.


Assuntos
Fibrose Pulmonar Idiopática , Menarca , Humanos , Feminino , Masculino , Menarca/genética , Análise da Randomização Mendeliana , Estrogênios , Fibrose Pulmonar Idiopática/epidemiologia , Fibrose Pulmonar Idiopática/genética , Razão de Chances
8.
Opt Express ; 32(5): 6929-6944, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38439387

RESUMO

The support vector regression (SVR) algorithm is presented to demodulate the torsion angle of an optical fiber torsion sensor based on the Sagnac interferometer with the panda fiber. Experimental results demonstrate that with the aid of SVR algorithm, the information in the transmission spectrum of the sensor can be used fully to realize the regression prediction of the directional torsion angle. The full torsion angle ranges from -360° to 360° can be predicted with a mean absolute error (MAE) of 2.24° and determination coefficient (R2) of 0.9996. The impact of the angle sampling interval and wavelength resolution of the spectrometer on the prediction accuracy of the directional torsion angle and the suitability of the SVR algorithm for compact optical fiber sensor and other optical fiber torsion sensors based on the Sagnac interferometer are discussed. Moreover, the multi-objective SVR algorithm is used to eliminate the interference of strain during torsion angle measurement. The SVR algorithm can efficiently enlarge the measurement range of the torsion angle and break through the challenge of demodulating sensing signal for compact fiber torsion sensor. Compared to the prediction accuracy of common machine learning algorithms of artificial neural network (ANN) algorithm, random forest (RF) algorithm, and K-nearest neighbor (KNN) algorithm, the SVR algorithm has the advantages of higher measurement accuracy and shorter testing time.

9.
J Colloid Interface Sci ; 663: 532-540, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38422978

RESUMO

The performance of thin lithium metal anodes is affected due to issues that weaken the electrode-electrolyte interphase. In this work, a coating layer serving as a Li+ traffic controller based on hexadecyl trimethyl ammonium bis(trifluoromethanesulphonyl)imide ([CTA][TFSI]) and poly (vinylidene difluoride co-hexafluoropropylene) (P(VDF-HFP)) is used to stabilize the thin lithium metal interface. The CTA+ ions in the coating layer can effectively regulate the distribution of Li+ concentration to promote uniform deposition of lithium. The anion of [CTA][TFSI] can optimize solid electrolyte interphase (SEI) with inorganic-rich components, which improve the ionic conductivity and reaction kinetics. Furthermore, the flexible polymer skeleton can fortify the fragile SEI, facilitating the consistent operation of the battery. Due to these improvements, a thin Li metal anode (4 mAh cm-2) with a coating layer in a Li||Li symmetric cell demonstrates a lifespan of 600 h at 1 mA cm-2 and 1 mAh cm-2. Notably, full cells with an ultra-low negative electrode/positive electrode = 1 (N/P = 1) demonstrate a stable performance over 200 cycles and 90 cycles at 0.5C and 1C (1C = 170 mA g-1), respectively.

10.
Phys Chem Chem Phys ; 26(9): 7783-7793, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38375586

RESUMO

The study of active systems, especially in the presence of a chemical background field, is garnering significant attention. Traditionally, the self-propelled velocity of active colloids was assumed to be constant, independent of the local density of colloids. In this work, we introduce a chemotactic active system that features quorum sensing (QS), wherein particles act as chemorepellents. Interestingly, these particles lose their activity in regions of high local particle density. Our findings reveal that QS leads to a transition from an oscillatory colloidal wave to a Turing-like pattern, with the observation of an intermediate state. With the variation of the sensing threshold, both the mean oscillation frequency of the system and the number of clusters exhibit non-monotonic dependence. Furthermore, the QS-induced pattern differs markedly from systems without QS, primarily due to the competitive interplay between diffusion and chemotaxis. The dynamics of this phenomenon are explained using a coarse-grained mean field model.

11.
Nat Commun ; 15(1): 1354, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355652

RESUMO

Exploiting thin Li metal anode is essential for high-energy-density battery, but is severely plagued by the poor processability of Li, as well as the uncontrollable Li plating/stripping behaviors and Li/electrolyte interface. Herein, a thickness/capacity-adjustable thin alloy-type Li/LiZn@Cu anode is fabricated for high-energy-density Li metal batteries. The as-formed lithophilic LiZn alloy in Li/LiZn@Cu anode can effectively regulate Li plating/stripping and stabilize the Li/electrolyte interface to deliver the hierarchical Li electrochemistry. Upon charging, the Li/LiZn@Cu anode firstly acts as Li source for homogeneous Li extraction. At the end of charging, the de-alloy of LiZn nanostructures further supplements the Li extraction, actually playing the Li compensation role in battery cycling. While upon discharging, the LiZn alloy forms just at the beginning, thereby regulating the following Li homogeneous deposition. The reversibility of such an interesting process is undoubtedly verified from the electrochemistry and in-situ XRD characterization. This work sheds light on the facile fabrication of practical Li metal anodes and useful Li compensation materials for high-energy-density Li metal batteries.

12.
Opt Express ; 31(23): 38205-38215, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-38017932

RESUMO

A high sensitivity optical fiber twist sensor based on Suspend Core Fiber Sagnac Interference (SCFSI) is proposed and experimentally demonstrated. By filling the air hole of the Suspend Core Fiber (SCF) with alcohol, the twist sensitivity of the twist sensor is greatly improved to 8.37 nm/°. Moreover, the valid angle measurement range of the sensor can be expanded by utilizing the combination of intensity demodulation and wavelength demodulation. The sensor not only has high twist angle sensitivity but also exhibits a capability of temperature calibration. Since the wavelength shifts of the interference fringes of Mach-Zehnder Interferometer (MZI) formed in the suspend core of SCF appears insensitive to twist angle, the parasitic interference formed by MZI can be used for temperature calibration. Due to compact structure, easy fabrication and low temperature cross sensitivity, the proposed sensor has a great potential for structural health monitoring, such as buildings, towers, bridges, and many other infrastructures.

13.
Heliyon ; 9(11): e21683, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37954366

RESUMO

Industrial structure markedly affects the level of carbon emissions generated in a region. It is imperative to study the industrial structure of the Chengdu-Chongqing region to obtain information to achieve regional high-quality development by promoting low-carbon development. We selected 16 cities in Chengdu-Chongqing area as the research object in this study. The total carbon emissions (CE), carbon intensity (CI) and per capita carbon emissions (PCE) were calculated for each city. The green industry development (GI) evaluation indexes were then extracted, and the comprehensive evaluation value was determined using the entropy weight-TOPSIS model (EWM-TOPSIS). The green industry development was used as the core explanatory variable to construct a system representing the dynamic relationship between green industry development and carbon intensity using the quantile regression (QR) model. The results of the study showed that: (1) the total carbon emissions of Chengdu-Chongqing region increased whereas the carbon intensity decreased from 2010 to 2020. (2) The green industry development evaluation results showed that Chengdu-Chongqing had unevenly distributed green industry development during the study period, and Chengdu and Chongqing cities had higher green industry development values than other cities. (3) The green industry development of the region had a significant negative effect on carbon intensity at low quantile and a significant positive effect on carbon intensity at high quantile. Energy supply (ES) was positively correlated with the carbon intensity of the region at 1 % level of significance, whereas urbanization rate (U) and power consumption (PEC) were negatively correlated with the carbon intensity at 1 % level of significance. We comprehensively evaluated the development of green industry and introduced it as a core explanatory variable into the quantile regression model to explore the relationship between regional carbon emission intensity and industrial development. The results provide a reference for designing strategies to promote high-quality development in the cities in the Chengdu-Chongqing region.

14.
BMC Genomics ; 24(1): 633, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872493

RESUMO

Nitrate is a primary nitrogen source for plant growth, and previous studies have indicated a correlation between nitrogen and browning. Nitrate transporters (NRTs) are crucial in nitrate allocation. Here, we utilized a genome-wide approach to identify and analyze the expression pattern of 74 potential GbNRTs under nitrate treatments during calluses browning in Ginkgo, including 68 NITRATE TRANSPORTER 1 (NRT1)/PEPTIDE TRANSPORTER (PTR) (NPF), 4 NRT2 and 2 NRT3. Conserved domains, motifs, phylogeny, and cis-acting elements (CREs) were analyzed to demonstrate the evolutionary conservation and functional diversity of GbNRTs. Our analysis showed that the NPF family was divided into eight branches, with the GbNPF2 and GbNPF6 subfamilies split into three groups. Each GbNRT contained 108-214 CREs of 19-36 types, especially with binding sites of auxin and transcription factors v-myb avian myeloblastosis viral oncogene homolog (MYB) and basic helix-loop-helix (bHLH). The E1X1X2E2R motif had significant variations in GbNPFs, indicating changes in the potential dynamic proton transporting ability. The expression profiles of GbNRTs indicated that they may function in regulating nitrate uptake and modulating the signaling of auxin and polyphenols biosynthesis, thereby affecting browning in Ginkgo callus induction. These findings provide a better understanding of the role of NRTs during NO3- uptake and utilization in vitro culture, which is crucial to prevent browning and develop an efficient regeneration and suspension production system in Ginkgo.


Assuntos
Nitratos , Proteínas de Plantas , Nitratos/farmacologia , Nitratos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ginkgo biloba/genética , Proteínas de Transporte de Ânions/genética , Proteínas de Transporte de Ânions/química , Proteínas de Transporte de Ânions/metabolismo , Transportadores de Nitrato , Nitrogênio/metabolismo , Ácidos Indolacéticos , Regulação da Expressão Gênica de Plantas , Filogenia
15.
J Agric Food Chem ; 71(41): 14911-14930, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37800676

RESUMO

With the development of artificial intelligence (AI), tailoring methods for enzyme engineering have been widely expanded. Additional protocols based on optimized network models have been used to predict and optimize lipase production as well as properties, namely, catalytic activity, stability, and substrate specificity. Here, different network models and algorithms for the prediction and reforming of lipase, focusing on its modification methods and cases based on AI, are reviewed in terms of both their advantages and disadvantages. Different neural networks coupled with various algorithms are usually applied to predict the maximum yield of lipase by optimizing the external cultivations for lipase production, while one part is used to predict the molecule variations affecting the properties of lipase. However, few studies have directly utilized AI to engineer lipase by affecting the structure of the enzyme, and a set of research gaps needs to be explored. Additionally, future perspectives of AI application in enzymes, including lipase engineering, are deduced to help the redesign of enzymes and the reform of new functional biocatalysts. This review provides a new horizon for developing effective and innovative AI tools for lipase production and engineering and facilitating lipase applications in the food industry and biomass conversion.


Assuntos
Inteligência Artificial , Lipase , Lipase/química , Algoritmos , Redes Neurais de Computação
16.
Opt Lett ; 48(19): 4929-4932, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37773352

RESUMO

An omnidirectional bending sensor comprising cascaded asymmetric dual-core photonic crystal fibers (ADCPCFs) is designed and demonstrated experimentally. Upon cascading and splicing two ADCPCFs at a lateral rotation angle, the transmission spectrum of the sensor becomes highly dependent on the bending direction. Machine learning (ML) is employed to predict the curvature and bending orientation of the bending sensor for the first time, to the best of our knowledge. The experimental results demonstrate that the ADCPCF sensor used in combination with machine learning can predict the curvature and omnidirectional bending orientation within 360° without requiring any post-processing fabrication steps. The prediction accuracy is 99.85% with a mean absolute error (MAE) of 2.7° for bending direction measurement and 98.08% with an MAE of 0.03 m-1 for the curvature measurement. This promising strategy utilizes the global features (full spectra) in combination with machine learning to overcome the dependence of the sensor on high-quality transmission spectra, the wavelength range, and a special wavelength dip in the conventional dip tracking method. This excellent omnidirectional bending sensor has large potential for structural health monitoring, robotic arms, medical instruments, and wearable devices.

17.
J Med Chem ; 66(11): 7438-7453, 2023 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-37220310

RESUMO

Abnormal activation of fibroblast growth factor receptors (FGFRs) results in the development and progression of human cancers. FGFR2 is frequently amplified or mutated in cancers; therefore, it is an attractive target for tumor therapy. Despite the development of several pan-FGFR inhibitors, their long-term therapeutic efficacy is hindered by acquired mutations and low isoform selectivity. Herein, we report the discovery of an efficient and selective FGFR2 proteolysis-targeting chimeric molecule, LC-MB12, that incorporates an essential rigid linker. LC-MB12 preferentially internalizes and degrades membrane-bound FGFR2 among the four FGFR isoforms; this may promote greater clinical benefits. LC-MB12 exhibits superior potency in FGFR signaling suppression and anti-proliferative activity compared to the parental inhibitor. Furthermore, LC-MB12 is orally bioavailable and shows significant antitumor effects in FGFR2-dependent gastric cancer in vivo. Taken together, LC-MB12 is a candidate FGFR2 degrader for alternative FGFR2-targeting strategies and offers a promising starting point for drug development.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , Mutação , Transdução de Sinais , Inibidores de Proteínas Quinases/farmacologia , Fosforilação , Linhagem Celular Tumoral
18.
Aquat Toxicol ; 259: 106549, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37150124

RESUMO

Ammonia stress in aquaculture systems poses a great threat to the growth and survival of the Pacific whiteleg shrimp Litopenaeus vannamei. Although the ammonia stress tolerance capacity of L. vannamei has been found to vary significantly among different breeding families, the underneath mechanisms are still largely unknown. In this study, the ammonia tolerance capacity of different L. vannamei breeding families was compared. Results confirmed the significant differences in the ammonia adaptability among different families. To ascertain the underlying adaptive strategies, ATP status, ATP synthase activity, expression and activities of ammonia excretion and metabolism-related enzymes, and apoptosis in shrimp gills were analyzed. Furthermore, transcriptomic analyses were also performed to elucidate the molecular mechanisms. Our results indicated that ammonia-tolerant L. vannamei may possess (1) enhanced ability to excrete ammonia, (2) better capacity to convert ammonia into less toxic products, and (3) sufficient energy reserves for ammonia-compensating processes.


Assuntos
Penaeidae , Poluentes Químicos da Água , Humanos , Animais , Estresse Fisiológico , Amônia/toxicidade , Poluentes Químicos da Água/toxicidade , Perfilação da Expressão Gênica , Penaeidae/genética , Trifosfato de Adenosina
19.
Biochem Genet ; 61(6): 2382-2400, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37060482

RESUMO

Oil palm (Elaeis guineensis) is the most important tropical oil-bearing crop species worldwide. MADS-box proteins, which play crucial roles in plant growth and development and are involved in various physiological and biochemical processes, compose one of the largest families of plant transcription factors. In this study, 42 MADS-box genes were screened from the mesocarp transcriptome database of oil palm fruit, and their phylogenetic relationships with Arabidopsis thaliana MADS-box genes were analyzed. Based on the results, MADS-box genes from oil palm mesocarp were classified into four groups: MIKCc-type, MIKC*-type, Mα-type, and Mγ-type MADS-box genes. Members of the subfamilies were classified according to the presence of three specific protein motifs. To explore the differential expression of the MADS-box genes, the dynamic expression of all selected MADS-box genes in oil palm was measured by RNA-seq. The high expression of specific MADS-box genes in the mesocarp of oil palm during different developmental stages indicates that those genes may play important roles in the cell division of and metabolite accumulation in the fruit and could become important targets for fruit development and oil accumulation research in oil palm.


Assuntos
Arecaceae , Frutas , Frutas/metabolismo , Filogenia , Fatores de Transcrição/genética , Motivos de Aminoácidos , Arecaceae/genética , Arecaceae/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
20.
Life Sci Alliance ; 6(3)2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36625204

RESUMO

Baroreceptors are nerve endings located in the adventitia of the carotid sinus and aortic arch. They act as a mechanoelectrical transducer that can sense the tension stimulation exerted on the blood vessel wall by the rise in blood pressure and transduce the mechanical force into discharge of the nerve endings. However, the molecular identity of mechanical signal transduction from the vessel wall to the baroreceptor is not clear. We discovered that exogenous integrin ligands, such as RGD, IKVAV, YIGSR, PHSRN, and KNEED, could restrain pressure-dependent discharge of the aortic nerve in a dose-dependent and reversible manner. Perfusion of RGD at the baroreceptor site in vivo can block the baroreceptor reflex. An immunohistochemistry study showed the binding of exogenous RGD to the nerve endings under the adventitia of the rat aortic arch, which may competitively block the binding of integrins to ligand motifs in extracellular matrix. These findings suggest that connection of integrins with extracellular matrix plays an important role in the mechanical coupling process between vessel walls and arterial baroreceptors.


Assuntos
Mecanotransdução Celular , Pressorreceptores , Ratos , Animais , Pressorreceptores/fisiologia , Aorta/inervação , Artérias
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