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1.
Life (Basel) ; 14(6)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38929762

RESUMO

Computer-vision-based plant leaf segmentation technology is of great significance for plant classification, monitoring of plant growth, precision agriculture, and other scientific research. In this paper, the YOLOv8-seg model was used for the automated segmentation of individual leaves in images. In order to improve the segmentation performance, we further introduced a Ghost module and a Bidirectional Feature Pyramid Network (BiFPN) module into the standard Yolov8 model and proposed two modified versions. The Ghost module can generate several intrinsic feature maps with cheap transformation operations, and the BiFPN module can fuse multi-scale features to improve the segmentation performance of small leaves. The experiment results show that Yolov8 performs well in the leaf segmentation task, and the Ghost module and BiFPN module can further improve the performance. Our proposed approach achieves a 86.4% leaf segmentation score (best Dice) over all five test datasets of the Computer Vision Problems in Plant Phenotyping (CVPPP) Leaf Segmentation Challenge, outperforming other reported approaches.

2.
BMC Oral Health ; 24(1): 657, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840138

RESUMO

BACKGROUND: Margin designs and loading conditions can impact the mechanical characteristics and survival of endocrowns. Analyzing the stress distribution of endocrowns with various margin designs and loading conditions can provide evidence for their clinical application. METHODS: Three finite element analysis models were established based on the margin designs: endocrown with a butt-joint type margin (E0), endocrown with a 90° shoulder (E90), and endocrown with a 135° shoulder (E135). The E0 group involved lowering the occlusal surface and preparing the pulp chamber. The E90 group created a 90° shoulder on the margin of model E0, measuring 1.5 mm high and 1 mm wide. The E135 group featured a 135° shoulder. The solids of the models were in fixed contact with each other, and the materials of tooth tissue and restoration were uniform, continuous, isotropic linear elasticity. Nine static loads were applied, with a total load of 225 N, and the maximum von Mises stresses and stress distribution were calculated for teeth and endocrowns with different margin designs. RESULTS: Compared the stresses of different models under the same loading condition. In endocrowns, when the loading points were concentrated on the buccal side, the maximum von Mises stresses were E0 = E90 = E135, and when there was a lingual loading, they were E0 < E90 = E135. In enamel, the maximum von Mises stresses under all loading conditions were E0 > E90 > E135. In dentin, the maximum von Mises stresses of the three models were basically similar except for load2, load5 and load9. Compare the stresses of the same model under different loading conditions. In endocrowns, stresses were higher when lingual loading was present. In enamel and dentin, stresses were higher when loaded obliquely or unevenly. The stresses in the endocrowns were concentrated in the loading area. In enamel, stress concentration occurred at the cementoenamel junction. In particular, E90 and E135 also experienced stress concentration at the shoulder. In dentin, the stresses were mainly concentrated in the upper section of the tooth root. CONCLUSION: Stress distribution is similar among the three margin designs of endocrowns, but the shoulder-type designs, especially the 135° shoulder, exhibit reduced stress concentration.


Assuntos
Análise do Estresse Dentário , Análise de Elementos Finitos , Estresse Mecânico , Humanos , Análise do Estresse Dentário/métodos , Planejamento de Prótese Dentária , Coroas , Fenômenos Biomecânicos , Dentina
3.
Appl Environ Microbiol ; : e0025524, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874338

RESUMO

Marine bacteria contribute substantially to cycle macroalgae polysaccharides in marine environments. Carrageenans are the primary cell wall polysaccharides of red macroalgae. The carrageenan catabolism mechanism and pathways are still largely unclear. Pseudoalteromonas is a representative bacterial genus that can utilize carrageenan. We previously isolated the strain Pseudoalteromonas haloplanktis LL1 that could grow on ι-carrageenan but produce no ι-carrageenase. Here, through a combination of bioinformatic, biochemical, and genetic analyses, we determined that P. haloplanktis LL1 processed a desulfurization-depolymerization sequential pathway for ι-carrageenan utilization, which was initiated by key sulfatases PhSulf1 and PhSulf2. PhSulf2 acted as an endo/exo-G4S (4-O-sulfation-ß-D-galactopyranose) sulfatase, while PhSulf1 was identified as a novel endo-DA2S sulfatase that could function extracellularly. Because of the unique activity of PhSulf1 toward ι-carrageenan rather than oligosaccharides, P. haloplanktis LL1 was considered to have a distinct ι-carrageenan catabolic pathway compared to other known ι-carrageenan-degrading bacteria, which mainly employ multifunctional G4S sulfatases and exo-DA2S (2-O-sulfation-3,6-anhydro-α-D-galactopyranose) sulfatase for sulfate removal. Furthermore, we detected widespread occurrence of PhSulf1-encoding gene homologs in the global ocean, indicating the prevalence of such endo-acting DA2S sulfatases as well as the related ι-carrageenan catabolism pathway. This research provides valuable insights into the enzymatic processes involved in carrageenan catabolism within marine ecological systems.IMPORTANCECarrageenan is a type of linear sulfated polysaccharide that plays a significant role in forming cell walls of marine algae and is found extensively distributed throughout the world's oceans. To the best of our current knowledge, the ι-carrageenan catabolism in marine bacteria either follows the depolymerization-desulfurization sequential process initiated by ι-carrageenase or starts from the desulfurization step catalyzed by exo-acting sulfatases. In this study, we found that the marine bacterium Pseudoalteromonas haloplanktis LL1 processes a distinct pathway for ι-carrageenan catabolism employing a specific endo-acting DA2S-sulfatase PhSulf1 and a multifunctional G4S sulfatase PhSulf2. The unique PhSulf1 homologs appear to be widely present on a global scale, indicating the indispensable contribution of the marine bacteria containing the distinct ι-carrageenan catabolism pathway. Therefore, this study would significantly enrich our understanding of the molecular mechanisms underlying carrageenan utilization, providing valuable insights into the intricate roles of marine bacteria in polysaccharide cycling in marine environments.

4.
Chem Biodivers ; : e202401093, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867371

RESUMO

Two previously undescribed coumarins (1-2) were isolated from the root of Notopterygium incisum. The structures of new findings were elucidated by analyses of spectral evidences in HRESIMS, NMR, as well as ICD. The absolute configurations were further confirmed by chemical calculations. 1-2 exhibits obviously anti-inflammatory activity by inhibiting the expression of inflammatory mediators (COX-2, iNOS), as well as reducing the release of NO and the accumulation of ROS in cells. Western blotting analysis revealed that 2 could inhibit the PI3K/AKT pathway by reducing the expression of p-PI3K and p-AKT.

5.
Dalton Trans ; 53(25): 10403-10415, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38779818

RESUMO

Metal-organic frameworks (MOFs) have emerged as promising electrode materials for supercapacitors (SCs) due to their highly porous structures, tunable chemical compositions, and diverse morphologies. However, their applications are hindered by low conductivity and poor cycling performance. A novel approach for resolving this issue involves the growth of layered double hydroxides (LDHs) using MOFs as efficient templates or precursors for electrode material preparation. This method effectively enhances the stability, electrical conductivity, and mass transport ability of MOFs. The MOF-derived LDH exhibits a well-defined porous micro-/nano-structure, facilitating the dispersion of active sites and preventing the aggregation of LDHs. Firstly, this paper introduces synthesis strategies for converting MOFs into LDHs. Subsequently, recent research progress in MOF-derived LDHs encompassing pristine LDH powders, LDH composites, and LDH-based arrays, along with their applications in SCs, is overviewed. Finally, the challenges associated with MOF-derived LDH electrode materials and potential solutions are discussed.

6.
Asian Nurs Res (Korean Soc Nurs Sci) ; 18(2): 89-96, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38583799

RESUMO

PURPOSE: This study aims to investigate the current status of affiliate stigma among parents of autistic children, analyze the influencing factors, explore the relationship among mindfulness, coping styles, and affiliate stigma, and verify the mediating role of coping styles between mindfulness and affiliate stigma in parents of children with autism in China. METHOD: Between February and April 2023, the Child Development Behaviour Centre of a public hospital in China recruited 345 parents of children with autism. These parents completed the general information questionnaire, the Mindful Attention Awareness Scale, the Affiliate Stigma Scale, and the Simple Coping Style Questionnaire. We then adapted the Hayes Process Macro and Bootstrap methods to examine the mediating effects of coping styles between mindfulness and affiliate stigma. RESULTS: (1) The total affiliate stigma score of parents of children with autism was 48.53 (standard deviation:: 10.74). Parents' age, monthly family income, duration of care, mindfulness, and coping styles were the influencing factors of parental affiliate stigma. (2) Mindfulness was positively correlated with positive coping style (r = 0.33, p < .01) and negatively correlated with negative coping style, affiliate stigma (r = -0.38, -0.39, p < .01), whereas affiliate stigma was negatively correlated with positive coping style (r = -0.34, p < .01) and positively correlated with negative coping style (r = 0.41, p < .01). (3) Positive coping style and negative coping style play a parallel mediating role between mindfulness and affiliate stigma of parents of autistic children. CONCLUSIONS: Parents of children with autism experience significant levels of affiliate stigma. Mindfulness has a direct impact on associated stigma in parents of children with autism and also indirectly predicts associated stigma through the intermediary influence of positive and negative coping styles. Healthcare professionals could perform mindfulness interventions from an optimistic psychology viewpoint to boost parents' mindfulness and coping abilities, thereby accomplishing the objective of mitigating affiliate stigma.


Assuntos
Adaptação Psicológica , Transtorno do Espectro Autista , Atenção Plena , Pais , Estigma Social , Humanos , Masculino , Feminino , Transtorno do Espectro Autista/psicologia , Transtorno do Espectro Autista/enfermagem , China , Pais/psicologia , Adulto , Criança , Pessoa de Meia-Idade , Inquéritos e Questionários , Pré-Escolar
7.
bioRxiv ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38645259

RESUMO

The crab-eating macaques ( Macaca fascicularis ) and rhesus macaques ( M. mulatta ) are widely studied nonhuman primates in biomedical and evolutionary research. Despite their significance, the current understanding of the complex genomic structure in macaques and the differences between species requires substantial improvement. Here, we present a complete genome assembly of a crab-eating macaque and 20 haplotype-resolved macaque assemblies to investigate the complex regions and major genomic differences between species. Segmental duplication in macaques is ∼42% lower, while centromeres are ∼3.7 times longer than those in humans. The characterization of ∼2 Mbp fixed genetic variants and ∼240 Mbp complex loci highlights potential associations with metabolic differences between the two macaque species (e.g., CYP2C76 and EHBP1L1 ). Additionally, hundreds of alternative splicing differences show post-transcriptional regulation divergence between these two species (e.g., PNPO ). We also characterize 91 large-scale genomic differences between macaques and humans at a single-base-pair resolution and highlight their impact on gene regulation in primate evolution (e.g., FOLH1 and PIEZO2 ). Finally, population genetics recapitulates macaque speciation and selective sweeps, highlighting potential genetic basis of reproduction and tail phenotype differences (e.g., STAB1 , SEMA3F , and HOXD13 ). In summary, the integrated analysis of genetic variation and population genetics in macaques greatly enhances our comprehension of lineage-specific phenotypes, adaptation, and primate evolution, thereby improving their biomedical applications in human diseases.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38662556

RESUMO

Multiobject tracking (MOT) is a fundamental problem in computer vision with numerous applications, such as intelligent surveillance and automated driving. Despite the significant progress made in MOT, pedestrian attributes, such as gender, hairstyle, body shape, and clothing features, which contain rich and high-level information, have been less explored. To address this gap, we propose a simple, effective, and generic method to predict pedestrian attributes to support general reidentification (Re-ID) embedding. We first introduce attribute multi-object tracking (AttMOT), a large, highly enriched synthetic dataset for pedestrian tracking, containing over 80k frames and six million pedestrian identity switches (IDs) with different times, weather conditions, and scenarios. To the best of authors' knowledge, AttMOT is the first MOT dataset with semantic attributes. Subsequently, we explore different approaches to fuse Re-ID embedding and pedestrian attributes, including attention mechanisms, which we hope will stimulate the development of attribute-assisted MOT. The proposed method attribute-assisted method (AAM) demonstrates its effectiveness and generality on several representative pedestrian MOT benchmarks, including MOT17 and MOT20, through experiments on the AttMOT dataset. When applied to the state-of-the-art trackers, AAM achieves consistent improvements in multi-object tracking accuracy (MOTA), higher order tracking accuracy (HOTA), association accuracy (AssA), IDs, and IDF1 scores. For instance, on MOT17, the proposed method yields a + 1.1 MOTA, + 1.7 HOTA, and + 1.8 IDF1 improvement when used with FairMOT. To further encourage related research, we release the data and code at https://github.com/HengLan/AttMOT.

9.
Fitoterapia ; 174: 105880, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38431026

RESUMO

An undescribed trichodenone derivative (1), two new diketopiperazines (3 and 4) along with a bisabolane analog (2) were isolated from Trichoderma hamatum b-3. The structures of the new findings were established through comprehensive analyses of spectral evidences in HRESIMS, 1D and 2D NMR, Marfey's analysis as well as comparisons of ECD. The absolute configuration of 2 was unambiguously confirmed by NMR, ECD calculation and Mo2(AcO)4 induced circular dichroism. Compounds 1-4 were tested for their fungicidal effects against eight crop pathogenic fungi, among which 1 showed 51% inhibition against Sclerotinia sclerotiorum at a concentration of 50 µg/mL.


Assuntos
Hypocreales , Trichoderma , Estrutura Molecular , Dicetopiperazinas/química , Trichoderma/química
10.
World J Gastrointest Endosc ; 16(2): 83-90, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38464817

RESUMO

BACKGROUND: Gastric phytobezoars (GPBs) are very common in northern China. Combined therapy involving carbonated beverage consumption and endoscopic lithotripsy has been shown to be effective and safe. Existing studies on this subject are often case reports highlighting the successful dissolution of phytobezoars through Coca-Cola consumption. Consequently, large-scale prospective investigations in this domain remain scarce. Therefore, we conducted a randomized controlled trial to examine the effects of Coca-Cola consumption on GPBs. AIM: To evaluate the impact of Coca-Cola on GPBs, including the dissolution rate, medical expenses, ulcer rate, and operation time. METHODS: A total of 160 consecutive patients diagnosed with GPBs were allocated into two groups (a control group and an intervention group) through computer-generated randomization. Patients in the intervention group received a Coca-Cola-based regimen (Coca-Cola 2000-4000 mL per day for 7 d), while those in the control group underwent emergency fragmentation. RESULTS: Complete dissolution of GPBs was achieved in 100% of the patients in the intervention group. The disparity in expenses between the control group and intervention group (t = 25.791, P = 0.000) was statistically significant, and the difference in gastric ulcer occurrence between the control group and intervention group (χ2 = 6.181, P = 0.013) was also statistically significant. CONCLUSION: Timely ingestion of Coca-Cola yields significant benefits, including a complete dissolution rate of 100%, a low incidence of gastric ulcers, no need for fragmentation and reduced expenses.

11.
Curr Issues Mol Biol ; 46(3): 1851-1864, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38534737

RESUMO

Autism spectrum disorder (ASD) is thought to result from susceptibility genotypes and environmental risk factors. The offspring of women who experience pregnancy infection have an increased risk for autism. Maternal immune activation (MIA) in pregnant animals produces offspring with autistic behaviors, making MIA a useful model for autism. However, how MIA causes autistic behaviors in offspring is not fully understood. Here, we show that NKCC1 is critical for mediating autistic behaviors in MIA offspring. We confirmed that MIA induced by poly(I:C) infection during pregnancy leads to autistic behaviors in offspring. We further demonstrated that MIA offspring showed significant microglia activation, excessive dendritic spines, and narrow postsynaptic density (PSD) in their prefrontal cortex (PFC). Then, we discovered that these abnormalities may be caused by overexpression of NKCC1 in MIA offspring's PFCs. Finally, we ameliorated the autistic behaviors using PFC microinjection of NKCC1 inhibitor bumetanide (BTN) in MIA offspring. Our findings may shed new light on the pathological mechanisms for autism caused by pregnancy infection.

12.
Hortic Res ; 11(3): uhae015, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38544551

RESUMO

The nectar spur is an important feature of pollination and ecological adaptation in flowering plants, and it is a key innovation to promote species diversity in certain plant lineages. The development mechanism of spurs varies among different plant taxa. As one of the largest angiosperm genera, we have little understanding of the mechanism of spur development in Impatiens. Here, we investigated the initiation and growth process of spurs of Impatiens uliginosa based on histology and hormone levels, and the roles of AUXIN BINDING PROTEIN (ABP) and extensin (EXT) in spur development were explored. Our results indicate that the spur development of I. uliginosa is composed of cell division and anisotropic cell elongation. Imbalances in spur proximal-distal cell division lead to the formation of curved structures. Endogenous hormones, such as auxin and cytokinins, were enriched at different developmental stages of spurs. IuABP knockdown led to an increase in spur curves and distortion of morphology. IuEXT knockdown resulted in reduced spur length and loss of curve and inner epidermal papillae structures. This study provides new insights into the mechanism of spur development in core eudicots.

13.
Diabetes Metab J ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38408883

RESUMO

Background: Diabetes-induced cardiac fibrosis is one of the main mechanisms of diabetic cardiomyopathy. As a common histone methyltransferase, enhancer of zeste homolog 2 (EZH2) has been implicated in fibrosis progression in multiple organs. However, the mechanism of EZH2 in diabetic myocardial fibrosis has not been clarified. Methods: In the current study, rat and mouse diabetic model were established, the left ventricular function of rat and mouse were evaluated by echocardiography and the fibrosis of rat ventricle was evaluated by Masson staining. Primary rat ventricular fibroblasts were cultured and stimulated with high glucose (HG) in vitro. The expression of histone H3 lysine 27 (H3K27) trimethylation, EZH2, and myocardial fibrosis proteins were assayed. Results: In STZ-induced diabetic ventricular tissues and HG-induced primary ventricular fibroblasts in vitro, H3K27 trimethylation was increased and the phosphorylation of EZH2 was reduced. Inhibition of EZH2 with GSK126 suppressed the activation, differentiation, and migration of cardiac fibroblasts as well as the overexpression of the fibrotic proteins induced by HG. Mechanical study demonstrated that HG reduced phosphorylation of EZH2 on Thr311 by inactivating AMP-activated protein kinase (AMPK), which transcriptionally inhibited peroxisome proliferator-activated receptor γ (PPAR-γ) expression to promote the fibroblasts activation and differentiation. Conclusion: Our data revealed an AMPK/EZH2/PPAR-γ signal pathway is involved in HG-induced cardiac fibrosis.

14.
Acta Pharmacol Sin ; 45(5): 879-889, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38191914

RESUMO

MORF4-related gene on chromosome 15 (MRG15), a chromatin remodeller, is evolutionally conserved and ubiquitously expressed in mammalian tissues and cells. MRG15 plays vital regulatory roles in DNA damage repair, cell proliferation and division, cellular senescence and apoptosis by regulating both gene activation and gene repression via associations with specific histone acetyltransferase and histone deacetylase complexes. Recently, MRG15 has also been shown to rhythmically regulate hepatic lipid metabolism and suppress carcinoma progression. The unique N-terminal chromodomain and C-terminal MRG domain in MRG15 synergistically regulate its interaction with different cofactors, affecting its functions in various cell types. Thus, how MRG15 elaborately regulates target gene expression and performs diverse functions in different cellular contexts is worth investigating. In this review, we provide an in-depth discussion of how MRG15 controls multiple physiological and pathological processes.


Assuntos
Epigênese Genética , Humanos , Animais
15.
J Biomol Struct Dyn ; 42(3): 1249-1267, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37042992

RESUMO

Vascular endothelial growth factor receptor 2 (VEGFR2) and c-Mesenchymal epithelial transition factor (c-Met) are tyrosine kinase receptors associated with the occurrence of malignant tumors. Studies have shown that inhibition of VEGFR2 promotes a feedback increase in c-Met, a mechanism linked to the emergence of resistance to VEGFR2 inhibitors. Therefore, treatment targeting both VEGFR2 and c-Met will have better application prospects. In this study, hierarchical virtual screening was performed on ZINC15, Molport and Mcule-ULTIMATE databases to identify potential VEGFR2/c-Met dual inhibitors. Firstly, the best pharmacophore model for each target was used to cross-screen the three databases, and the compounds that could match the two pharmacophore models were then retained based on the Fit Value of the respective crystal ligands. Compounds ZINC, MOL, and MLB named after their database sources were retained by binding pattern analysis and docking assessment. ADMET predictions indicated that ZINC had significantly higher oral bioavailability compared to the approved drug cabozantinib. This is likely due to ZINC's unique symmetrical backbone with less structure complexity, which may reduce the occurrence of adverse effects. Molecular dynamics simulations and binding free energy analysis showed that all three hit compounds were able to stably bind at the active site, but only ZINC could form high occupancy of hydrogen bonds with both VEGFR2 and c-Met, and also only ZINC had a higher binding free energy than crystal ligands, suggesting that ZINC was the most likely potential VEGFR2/c-Met dual-target inhibitor. This finding provides a promising starting point for the development of VEGFR2/c-Met dual-target inhibitors.Communicated by Ramaswamy H. Sarma.


Assuntos
Inibidores de Proteínas Quinases , Fator A de Crescimento do Endotélio Vascular , Inibidores de Proteínas Quinases/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Zinco , Ligantes
16.
J Cell Physiol ; 239(1): 97-111, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37921259

RESUMO

Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment, and the M2-type TAMs can promote tumor growth, invasion and angiogenesis, and suppress antitumor immune responses. It has been reported that spectrin beta, non-erythrocytic 1 (SPTBN1) may inhibit the infiltration of macrophages in Sptbn1+/-  mouse liver, but whether tumor SPTBN1 affects TAMs polarization remains unclear. This study investigated the effect and mechanism of tumor cell SPTBN1 on polarization and migration of TAMs in hepatoma and breast cancer. By analyzing tumor immune databases, we found a negative correlation between SPTBN1 and abundance of macrophages and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. By reverse transcription-quantitative real-time PCR assays and cell migration assays, the migration and M2 polarization of macrophages were enhanced by the culture medium from hepatocellular carcinoma cell line PLC/PRF/5, SNU449, and breast cancer cell line MDA-MB-231 with SPTBN1 suppression, which could be reversed by CXCL1 neutralizing antibody MAB275. Meanwhile, the ability of migration and colony formation of PLC/PRF/5, SNU449, and MDA-MB-231 cells were promoted when coculture with M2 macrophages. We also found that SPTBN1 regulated CXCL1 through p65 by cytoplasmic-nuclear protein isolation experiments and ChIP-qPCR. Our data suggest that tumor cell SPTBN1 inhibits migration and M2-type polarization of TAMs by reducing the expression and secretion of CXCL1 via inhibiting p65 nuclear localization.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Espectrina , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Neoplasias Hepáticas/metabolismo , Macrófagos/metabolismo , Microambiente Tumoral , Macrófagos Associados a Tumor/patologia , Humanos , Espectrina/metabolismo , Quimiocina CXCL1
17.
Chinese Pharmacological Bulletin ; (12): 565-573, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013655

RESUMO

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

18.
BMC Gastroenterol ; 23(1): 443, 2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38104065

RESUMO

OBJECTIVES: The objectives of this study were to present an accessible C-shaped partial stapled hemorrhoidopexy (C-PSH) in the treatment of grade IV hemorrhoids and to assess long-term outcomes of this technique compared with circular stapled hemorrhoidopexy (CSH). METHODS: Conventional CSH kits combined with an intestinal spatula were used for performing C-PSH. A total of 256 patients with grade IV hemorrhoids referred to Hangzhou Third People's Hospital between January 2016 and June 2017 were obtained: 122 (47.7%) with C-PSH, and 134 (52.3%) with CSH. After propensity score matching, 222 patients (111 in C-PSH group and 111 in CSH group) were ultimately analyzed. The primary outcome was the five-year recurrence rate of hemorrhoids. Secondary outcomes included intraoperative outcomes, postoperative outcomes and complications. RESULTS: The operative time in the C-PSH group was slightly longer than that in the CSH group (p < 0.01). The vertical length of rectal mucosa specimen in the C-PSH group was shorter than that in the CSH group (p < 0.01). Compared with the CSH group, fecal urgency incidence and numeric rating scale (NRS) score at first defecation were lower in the C-PSH group (p < 0.05). Major complication rate in the CSH group was higher than that in the C-PSH group (p = 0.03). Five-year recurrence rate between the C-PSH group and CSH group was comparable (p > 0.05). Multivariate Cox regression analysis revealed that constipation was an independent prognostic factor for hemorrhoidal recurrence. CONCLUSIONS: The accessible C-PSH seems to be a safe and effective technique in managing grade IV hemorrhoids. It has advantages in alleviating postoperative pain at first defecation, fecal urgency and major complications compared with CSH. It could be an alternative technique in the treatment of grade IV hemorrhoids.


Assuntos
Incontinência Fecal , Hemorroidas , Humanos , Hemorroidas/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Grampeamento Cirúrgico/métodos , Recidiva Local de Neoplasia/cirurgia
19.
Nat Commun ; 14(1): 8428, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38129407

RESUMO

Hepatic insulin resistance is central to the metabolic syndrome. Here we investigate the role of BTB and CNC homology 1 (BACH1) in hepatic insulin signaling. BACH1 is elevated in the hepatocytes of individuals with obesity and patients with non-alcoholic fatty liver disease (NAFLD). Hepatocyte-specific Bach1 deletion in male mice on a high-fat diet (HFD) ameliorates hyperglycemia and insulin resistance, improves glucose homeostasis, and protects against steatosis, whereas hepatic overexpression of Bach1 in male mice leads to the opposite phenotype. BACH1 directly interacts with the protein-tyrosine phosphatase 1B (PTP1B) and the insulin receptor ß (IR-ß), and loss of BACH1 reduces the interaction between PTP1B and IR-ß upon insulin stimulation and enhances insulin signaling in hepatocytes. Inhibition of PTP1B significantly attenuates BACH1-mediated suppression of insulin signaling in HFD-fed male mice. Hepatic BACH1 knockdown ameliorates hyperglycemia and improves insulin sensitivity in diabetic male mice. These results demonstrate a critical function for hepatic BACH1 in the regulation of insulin signaling and glucose homeostasis.


Assuntos
Hiperglicemia , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Animais , Humanos , Masculino , Camundongos , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Dieta Hiperlipídica , Glucose/metabolismo , Homeostase , Hiperglicemia/metabolismo , Insulina/metabolismo , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo
20.
Langmuir ; 39(46): 16244-16260, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37935578

RESUMO

The interfacial bonding of the four cellulose nanocrystals (CNCs) and calcium silicate hydrate (C-S-H) in vacuum and solution conditions was analyzed by molecular dynamics simulation. The binding energies were calculated, and the sources of interface strength were analyzed by the formation and lifetime of hydrogen bonds. The adsorption between CNC/C-S-H was characterized by the movement of interfacial atoms and CNC's adsorption conformation. The types of the functional group determine the bonding of the CNC/C-S-H, and the interface adsorption in two simulation conditions both followed: CNC-C (carboxyl) > CNC-O (hydroxyl) > CNC-N (amino) > CNC-S (sulfonic). The bonding of the interface affects the load transferred between the matrix and CNC, which can be reflected in the overall mechanical properties of the mortar. The mechanical strength of the mortar is in line with the simulation results. CNC-C has the strongest reinforcement effect, while CNC-S has the weakness effect. In the solution simulation, there is almost no chemical adsorption between C-S-H and CNC-S; instead, CNC-S decreased the bonding between the matrix and reduced the strength of the sample. Scanning electron microscopy found that CNC was interspersed in the matrix, riveting the matrix and enhanced the stability of the mortar structure. The influence of CNC on the mortar structure was analyzed by the calcium to silicon ratio (C/S) and it was showed that CNC-C, CNC-O, and CNC-N have an enhancement effect, while CNC-S decreased the coherence of the cement matrix. Durability and nuclear magnetic resonance tests further verified the effect of the four CNCs on the structure of mortar, and results indicated that CNC-C, CNC-O, and CNC-N can control the growth of hydration crystals, fill the cracks, and reduced porosity of samples, while CNC-S reduces the compactness of hydration products and ultimately decreased the mechanical and durability properties of the mortar.

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