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This study explores the bioactive secondary metabolite profiles of the peels of three major cultivars of bananas (Musa acuminata and Musa balbisiana). These cultivars are primarily grown in Southeast Asia and are widely consumed due to their rich nutritional and fiber content. The research utilizes advanced analytical techniques, specifically HPLC-DAD-q-TOF-MS/MS, in conjunction with both univariate and multivariate statistical analyses, to analyze the ethanolic extracts of the banana peels. This study identifies phenolic acids, flavonoids, and proanthocyanidins as significant contributors to the differentiation of the cultivars. The secondary metabolites rutin, chlorogenic acid, and gentisic acid are pinpointed as the key discriminants. Moreover, the research demonstrates a synergistic contribution of certain phytochemicals to the antioxidant and antibacterial properties of the banana peel extracts. The fingerprint profiling tools introduced in this study offer a reliable method for identifying metabolite biomarkers for the discrimination of banana cultivars.
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BACKGROUND: Osteoporotic vertebral compression fracture (OVCF) is a common consequence of osteoporosis and can significantly impact the quality of life for affected individuals. Despite treatment options such as vertebroplasty and kyphoplasty, many patients continue to experience residual back pain (RBP) even after the fracture has healed. The incidence of RBP after OVCF treatment varies among studies, and there is a need for further research to understand the risk factors associated with RBP. METHODS: A systematic review and meta-analysis were conducted following the PRISMA guidelines. Electronic databases were searched, and relevant studies were selected based on inclusion and exclusion criteria. Data extraction and quality assessment were performed independently by two authors. Statistical analysis included single-proportion meta-analyses and pooling of odds ratios (OR) using the inverse-variance method, to calculate the overall incidences of RBP and cement leakage and identify risk factors associated with RBP. RESULTS: A total of 19 studies were included in the analysis. The overall incidences of RBP and cement leakage were found to be 16% and 18%, respectively. Several risk factors were identified, including gender, bone mineral density, depression, baseline visual analog scale (VAS) score, intravertebral vacuum cleft, number of fractured segments, cement distribution, history of vertebral fracture, thoracolumbar fascial injury, and fracture non-union. CONCLUSIONS: This study provides potential value within the scope of the incidence and risk factors of RBP following treatment of OVCFs. The identified risk factors can help clinicians identify high-risk patients and tailor appropriate interventions. Future research should focus on standardizing the definition of RBP and patient selection criteria to improve the accuracy of estimates and facilitate better management strategies for OVCF patients.
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Low flexural strength and toughness have posed enduring challenges to cementitious materials. As the main hydration product of cement, calcium silicate hydrate (C-S-H) plays important roles in the mechanical performance of cementitious materials while exhibiting random microstructures with pores and defects, which hinder mechanical enhancement. Inspired by the "brick-and-mortar" microstructure of natural nacre, this paper presents a method combining freeze casting, freeze-drying, in situ polymerization, and hot pressing to fabricate C-S-H nacre with high flexural strength, high toughness, and lightweight. Poly(acrylamide-co-acrylic acid) was used to disperse C-S-H and toughen C-S-H building blocks, which function as "bricks", while poly(methyl methacrylate) was impregnated as "mortar". The flexural strength, toughness, and density of C-S-H nacre reached 124 MPa, 5173 kJ/m3, and 0.98 g/cm3, respectively. The flexural strength and toughness of the C-S-H nacre are 18 and 1230 times higher than those of cement paste, respectively, with a 60% reduction in density, outperforming existing cementitious materials and natural nacre. This research establishes the relationship between material composition, fabrication process, microstructure, and mechanical performance, facilitating the design of high-performance C-S-H-based and cement-based composites for scalable engineering applications.
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BACKGROUND: Chondrosarcoma (CHS), a bone malignancy, poses a significant challenge due to its heterogeneous nature and resistance to conventional treatments. There is a clear need for advanced prognostic instruments that can integrate multiple prognostic factors to deliver personalized survival predictions for individual patients. This study aimed to develop a novel prediction tool based on recursive partitioning analysis (RPA) to improve the estimation of overall survival for patients with CHS. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) database were analyzed, including demographic, clinical, and treatment details of patients diagnosed between 2000 and 2018. Using C5.0 algorithm, decision trees were created to predict survival probabilities at 12, 24, 60, and 120 months. The performance of the models was assessed through confusion scatter plot, accuracy rate, receiver operator characteristic (ROC) curve, and area under ROC curve (AUC). RESULTS: The study identified tumor histology, surgery, age, visceral (brain/liver/lung) metastasis, chemotherapy, tumor grade, and sex as critical predictors. Decision trees revealed distinct patterns for survival prediction at each time point. The models showed high accuracy (82.40%-89.09% in training group, and 82.16%-88.74% in test group) and discriminatory power (AUC: 0.806-0.894 in training group, and 0.808-0.882 in test group) in both training and testing datasets. An interactive web-based shiny APP (URL: https://yangxg1209.shinyapps.io/chondrosarcoma_survival_prediction/) was developed, simplifying the survival prediction process for clinicians. CONCLUSIONS: This study successfully employed RPA to develop a user-friendly tool for personalized survival predictions in CHS. The decision tree models demonstrated robust predictive capabilities, with the interactive application facilitating clinical decision-making. Future prospective studies are recommended to validate these findings and further refine the predictive model.
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Neoplasias Ósseas , Condrossarcoma , Aprendizado de Máquina , Humanos , Condrossarcoma/mortalidade , Condrossarcoma/patologia , Condrossarcoma/terapia , Masculino , Feminino , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Neoplasias Ósseas/patologia , Pessoa de Meia-Idade , Prognóstico , Idoso , Programa de SEER , Árvores de Decisões , Adulto , Curva ROC , Adulto JovemRESUMO
This umbrella review aimed to summarize and provide a general evaluation of the effectiveness of current treatments for male infertility and assess the quality of evidence and possible biases. An umbrella review of systematic reviews and meta-analyses available in PubMed, Web of Science, and Scopus, covering studies published up to October 2023, was conducted. Sperm concentration, morphology, and motility were used as endpoints to evaluate the effectiveness of the treatments. Of 2998 studies, 18 published meta-analyses were extracted, yielding 90 summary effects on sperm concentration (n = 36), sperm morphology (n = 26), and sperm motility (n = 28) on 28 interventions. None of the meta-analyses were classified as having low methodological quality, whereas 12 (66.7%) and 6 (33.3%) had high and moderate quality, respectively. Of the 90 summary effects, none were rated high-evidence quality, whereas 53.3% (n = 48), 25.6% (n = 23), and 21.1% (n = 19) were rated moderate, low, and very low, respectively. Significant improvements in sperm concentration, morphology, and motility were observed with pharmacological interventions (N-acetyl-cysteine, antioxidant therapy, aromatase inhibitors, selective estrogen receptor modulators, hormones, supplements, and alpha-lipoic acid) and nonpharmacological interventions (varicocele repair and redo varicocelectomy). In addition, vitamin supplementation had no significant positive effects on sperm concentration, motility, or morphology. Treatments for male infertility are increasingly diverse; however, the current evidence is poor because of the limited number of patients. Further well-designed studies on single treatment and high-quality meta-analysis of intertreatment comparisons are recommended.
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Collective excitations including plasmons, magnons, and layer-breathing vibration modes emerge at an ultralow frequency (<1 THz) and are crucial for understanding van der Waals materials. Strain at the nanoscale can drastically change the property of van der Waals materials and create localized states like quantum emitters. However, it remains unclear how nanoscale strain changes collective excitations. Herein, ultralow-frequency tip-enhanced Raman spectroscopy (TERS) with sub-10 nm resolution under ambient conditions is developed to explore the localized collective excitation on monolayer semiconductors with nanoscale strains. A new vibrational mode is discovered at around 12 cm-1 (0.36 THz) on monolayer MoSe2 nanobubbles and it is identified as the radial breathing mode (RBM) of the curved monolayer. The correlation is determined between the RBM frequency and the strain by simultaneously performing deterministic nanoindentation and TERS measurement on monolayer MoSe2. The generality of the RBM in nanoscale curved monolayer WSe2 and bilayer MoSe2 is demonstrated. Using the RBM frequency, the strain of the monolayer MoSe2 on the nanoscale can be mapped. Such an ultralow-frequency vibration from curved van der Waals materials provides a new approach to study nanoscale strains and points to more localized collective excitations to be discovered at the nanoscale.
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The POU2F3-POU2AF2/3 transcription factor complex is the master regulator of the tuft cell lineage and tuft cell-like small cell lung cancer (SCLC). Here, we identify a specific dependence of the POU2F3 molecular subtype of SCLC (SCLC-P) on the activity of the mammalian switch/sucrose non-fermentable (mSWI/SNF) chromatin remodeling complex. Treatment of SCLC-P cells with a proteolysis targeting chimera (PROTAC) degrader of mSWI/SNF ATPases evicts POU2F3 and its coactivators from chromatin and attenuates downstream signaling. B cell malignancies which are dependent on the POU2F1/2 cofactor, POU2AF1, are also sensitive to mSWI/SNF ATPase degraders, with treatment leading to chromatin eviction of POU2AF1 and IRF4 and decreased IRF4 signaling in multiple myeloma cells. An orally bioavailable mSWI/SNF ATPase degrader significantly inhibits tumor growth in preclinical models of SCLC-P and multiple myeloma without signs of toxicity. This study suggests that POU2F-POU2AF-driven malignancies have an intrinsic dependence on the mSWI/SNF complex, representing a therapeutic vulnerability.
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Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Fatores de Transcrição , Humanos , Animais , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologia , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Linhagem Celular Tumoral , Fator 3 de Transcrição de Octâmero/metabolismo , Fator 3 de Transcrição de Octâmero/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Transdução de Sinais , Regulação Neoplásica da Expressão Gênica , Fator 2 de Transcrição de OctâmeroRESUMO
BACKGROUND: Menkes Disease (MD) is a fatal X-linked recessive disorder caused by mutations in the ATP7A gene. Severe cases typically die before the age of three. Mild MD and occipital horn syndrome are variants of MD characterized by a less severe phenotype and longer survival. OBJECTIVE: This case series aims to validate previous findings, expand the clinical phenotype, identify novel ATP7A mutations of MD patients. METHODS: Observational data with follow-up were collected from 17 genetically diagnosed Chinese MD patients. RESULTS: All 17 patients exhibited neurological symptoms, including delayed motor milestones (100%) and seizures (58.8%). Unspecific pregnancy or delivery complications occurred in 9 patients (52.9%). The most prevalent connective tissue problems were abnormal hair (76.5%), followed by skeletal and dental abnormalities (52.9%), skin problems (41.2%) and hernia (35.3%). Sensorineural hearing loss (17.6%) was previously unreported. Coronary artery aneurysm and patent foramen ovale (5.9%) were infrequent. One 16-year-old boy carries pathological exon 3-4 deletion, presents novel mild phenotype including short stature and cerebellar ataxia. Out of 13 patients with follow-up (median: 24 months), 7 patients (53.8%) died with median survival of 40 months (range: 21-48 months), 3 patients (23.1%) show severe motor development delay and 2 (15.4%) have refractory epilepsy, only the mild MD patient shows improved cerebellar ataxia. Sixteen ATP7A mutations were identified including 6 small indels (37.5%), 5 nonsense mutations (31.2%), 2 missense mutations (12.5%), 2 exon deletions (12.5%), and 1 splice site mutation (6.25%). Fourteen mutations were novel. CONCLUSIONS: Our study further broadens the phenotypic and genotypic spectrums of Menkes disease.
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RATIONALE AND OBJECTIVES: Prior to clinical presentations of Alzheimer's Disease (AD), neuropathological changes, such as amyloid-ß and brain atrophy, have accumulated at the earlier stages of the disease. The combination of such biomarkers assessed by multiple modalities commonly improves the likelihood of AD etiology. We aimed to explore the discriminative ability of Aß PET features and whether combining Aß PET and structural MRI features can improve the classification performance of the machine learning model in older healthy control (OHC) and mild cognitive impairment (MCI) from AD. MATERIAL AND METHODS: We collected 94 AD patients, 82 MCI patients, and 85 OHC from three different cohorts. 17 global/regional Aß features in Centiloid, 122 regional volume, and 68 regional cortical thickness were extracted as imaging features. Single or combined modality features were used to train the random forest model on the testing set. The top 10 features were sorted based on the Gini index in each binary classification. RESULTS: The results showed that AUC scores were 0.81/0.86 and 0.69/0.68 using sMRI/Aß PET features on the testing set in differentiating OHC and MCI from AD. The performance was improved while combining two-modality features with an AUC of 0.89 and an AUC of 0.71 in two classifications. Compared to sMRI features, particular Aß PET features contributed more to differentiating AD from others. CONCLUSION: Our study demonstrated the discriminative ability of Aß PET features in differentiating AD from OHC and MCI. A combination of Aß PET and structural MRI features can improve the RF model performance.
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OBJECTIVES: Ground-glass nodules-featured lung cancer have been identified in some teenagers in recent years. This study aims to investigate the characteristics and surgical outcomes of these patients and explore proper management strategy. METHODS: Patients aged ≤20 with incidentally diagnosed lung cancer were retrospectively reviewed from February 2016 to March 2023. Based on lymph node evaluation status, these patients were divided into non-lymph node evaluation and lymph node evaluation groups. The clinical and pathological characteristics were analysed. RESULTS: A total of 139 teenage patients were included, with an obviously increased cases observed from 2019, corresponding to the COVID-19 pandemic. The median age of the 139 patients was 18 years (range 12-20). Eighty-five patients had pure ground-glass nodules, while others had mixed ground-glass nodules. The mean diameter of nodules was 8.87 ± 2.20 mm. Most of the patients underwent wedge resection (64%) or segmentectomy (31.7%). Fifty-two patients underwent lymph node sampling or dissection. None of these patients had lymph node metastasis. The majority of lesions were adenocarcinoma in situ (63 cases) and minimally invasive adenocarcinoma (72 cases), while four lesions were invasive adenocarcinoma. The median follow-up time was 2.46 years, and none of these patients experienced recurrence or death during follow-up. The lymph node evaluation group had longer hospital stays (P < 0.001), longer surgery time (P < 0.001), and greater blood loss (P = 0.047) than the non-lymph node evaluation group. CONCLUSIONS: The COVID-19 pandemic significantly increased the number of teenage patients incidentally diagnosed with lung cancer, presenting as ground-glass nodules on CT scans. These patients have favourable surgical outcomes. We propose a management strategy for teenage patients, and suggest that sub-lobar resection without lymph node dissection may be an acceptable surgical procedure for these patients.
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Adenocarcinoma de Pulmão , COVID-19 , Neoplasias Pulmonares , Pneumonectomia , Humanos , Masculino , Adolescente , Feminino , Estudos Retrospectivos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , COVID-19/epidemiologia , Adulto Jovem , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/patologia , Pneumonectomia/métodos , Criança , SARS-CoV-2 , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Excisão de LinfonodoRESUMO
In the field of perovskite optoelectronics, developing hole-transporting materials (HTMs) on the spiro[fluorene-9,9'-xanthene] (SFX) platform is one of the current research focuses. The SFX inherits the merits of spirobifluorene in terms of the configuration and property, but it is more easily derivatized and regulated by virtue of its binary structure. In this work, we design and synthesize four isomeric SFX-based HTMs, namely m-SFX-mF, p-SFX-mF, m-SFX-oF, and p-SFX-oF, through varying the positions of fluorination on the peripheral aniline units and their substitutions on the SFX core, and the optoelectronic performance of the resulting HTMs is evaluated in both perovskite solar cells (PSCs) and light-emitting diodes (PeLEDs) by the vacuum thermal evaporating hole-transporting layers (HTLs). The HTM p-SFX-oF exhibits an improved power conversion efficiency of 15.21% in an inverted PSC using CH3NH3PbI3 as an absorber, benefiting from the deep HOMO level and good HTL/perovskite interface contact. Meanwhile, the HTM m-SFX-mF provides a maximum external quantum efficiency of 3.15% in CsPb(Br/Cl)3-based PeLEDs, which is attributed to its perched HOMO level and shrunken band-gap for facilitating charge carrier injection and then exciton combination. Through elucidating the synergistic position effect of fluorination on aniline units and their substitutions on the SFX core, this work lays the foundation for developing low-cost and efficient HTMs in the future.
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The difunctionalization of vinylpyridines based on the cyclization strategy remains rare and underdeveloped, in contrast to the well-developed hydrogen functionalization. Current exploration on [4 + 2] cyclization of vinylpyridines mainly relies on extremely high temperatures and the LUMO activation of vinylpyridines using boron trifluoride as a strong Lewis acid. Herein, we established a phosphoric acid-catalyzed [4 + 2] cyclization reaction of 3-vinyl-1H-indoles and 2-vinylpyridines by means of the LUMO/HOMO bifunctional activation model. This protocol features mild reaction conditions, high functional group tolerance, broad substrate compatibility, and high diastereoselectivity, enabling the efficient construction of various functionalized pyridine-substituted tetrahydrocarbazoles with prominent potential in drug discovery.
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OBJECTIVE: To evaluate the safety and efficacy of myomectomy for recurrent uterine fibroids (UFs) after high-intensity focused ultrasound (HIFU) ablation. METHODS: This was a retrospective study. Patients who underwent abdominal myomectomy (AM) and laparoscopic myomectomy (LM) from January 2018 to December 2021 at the Three Gorges Hospital of Chongqing University were included. Among them, 73 had undergone prior HIFU ablation (Group 1), while 120 had not undergone HIFU (Group 2). Outcome measures included operating time, estimated blood loss (EBL), blood transfusion, postoperative activity times (PAT), duration of hospital stay (DOHS), and complications. RESULTS: The operating time was 90.0 min (70.5, 115.0) for Group 1 and 110.0 min (81.5, 130.0) for Group 2 (P < 0.05). During all AM pathways, there were no significant differences observed between the two groups in EBL, blood transfusion, PAT, DOHS, and complications; however, operating time was shorter in Group 1. The operating time, EBL, blood transfusion, PAT, DOHS, and complications were similar in both groups during LM pathway. During the follow-up 40 (range: 24-53) months, the rate of relief, recurrence, and reintervention in Groups 1 and 2 was 78.1% versus 74.1%, 14.6% versus 16.4%, and 3.7% versus 2.6%, respectively (P > 0.05). CONCLUSION: Myomectomy is a safe and effective surgical method for treating recurrent UFs after HIFU. Myomectomy for treating recurrent UFs resulted in a shorter operative and hospital stay, reduced blood loss, faster postoperative recovery, and fewer complications, better symptom relief rates, and lower risk of recurrence or reintervention. These findings indicate that previous HIFU ablation does not worsen the outcomes of the subsequent myomectomy.
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Cancer treatment continues to shift from utilizing traditional therapies to targeted ones, such as protein kinase inhibitors and immunotherapy. Mobilizing dendritic cells (DC) and other myeloid cells with antigen presenting and cancer cell killing capacities is an attractive but not fully exploited approach. Here, we show that PIKFYVE is a shared gene target of clinically relevant protein kinase inhibitors and high expression of this gene in DCs is associated with poor patient response to immune checkpoint blockade (ICB) therapy. Genetic and pharmacological studies demonstrate that PIKfyve ablation enhances the function of CD11c+ cells (predominantly dendritic cells) via selectively altering the non-canonical NF-κB pathway. Both loss of Pikfyve in CD11c+ cells and treatment with apilimod, a potent and specific PIKfyve inhibitor, restrained tumor growth, enhanced DC-dependent T cell immunity, and potentiated ICB efficacy in tumor-bearing mouse models. Furthermore, the combination of a vaccine adjuvant and apilimod reduced tumor progression in vivo. Thus, PIKfyve negatively regulates the function of CD11c+ cells, and PIKfyve inhibition has promise for cancer immunotherapy and vaccine treatment strategies.
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Antígeno CD11c , Células Dendríticas , Morfolinas , Fosfatidilinositol 3-Quinases , Animais , Feminino , Humanos , Camundongos , Antígeno CD11c/metabolismo , Linhagem Celular Tumoral , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/efeitos dos fármacos , Hidrazonas , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Camundongos Endogâmicos C57BL , Morfolinas/farmacologia , Neoplasias/imunologia , Neoplasias/genética , Neoplasias/terapia , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas , Linfócitos T/imunologia , MasculinoRESUMO
BACKGROUND: Patient involvement is crucial to the success of kidney transplants. This study aimed to investigate the knowledge, attitude, and practice (KAP) toward postoperative self-management among kidney transplant recipients. METHODS: A web-based cross-sectional study was conducted in Ruijin Hospital (Shanghai, China) between March 24, 2023, and April 15, 2023 in kidney transplant recipients. A questionnaire was designed to collect data about the characteristics of the participants and their KAP toward postoperative self-management. KAP scores were calculated based on participants' responses, using predefined scoring criteria tailored to evaluate each dimension of KAP effectively. RESULTS: A total of 483 valid questionnaires were collected, including 189 (39.13%) participants aged between 46 and 60 years. The mean score of knowledge, attitude and practice were 23.44 ± 4.87 (possible range: 0-28), 43.59 ± 2.65 (possible range: 10-50), 52.52 ± 4.64 (possible range: 0-58), respectively. The multivariate analysis showed knowledge scores (OR = 1.15, 95% CI = 1.10-1.20, p < 0.001), attitude scores (OR = 1.22, 95% CI = 1.12-1.32, p < 0.001) and undergone transplantation within 1 year (OR = 3.92, 95% CI = 1.60-9.63, p = 0.003) were independently associated with good practice. Knowledge scores (OR = 1.06, 95% CI = 1.02-1.10, p = 0.003), attitude scores (OR = 1.16, 95% CI = 1.08-1.25, p < 0.001), aged 16-35 years (OR = 0.38, 95% CI = 0.18-0.78, p = 0.009), underwent a single kidney transplant surgery (OR = 3.97, 95% CI = 1.28-12.38, p = 0.017) were independently associated with medication adherence. CONCLUSIONS: Kidney transplant recipients had good knowledge, positive attitude and good practice toward postoperative self-management. Implementing personalized education, psychological support, and close monitoring strategies is recommended to optimize postoperative self-management in kidney transplant recipients.
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Conhecimentos, Atitudes e Prática em Saúde , Transplante de Rim , Autogestão , Humanos , Pessoa de Meia-Idade , Estudos Transversais , Masculino , Feminino , Adulto , Transplantados/psicologia , Inquéritos e Questionários , China , Cuidados Pós-OperatóriosRESUMO
Gut Universe Database (GutUDB) provides a comprehensive, systematic, and practical platform for researchers, and is dedicated to the management, analysis, and visualization of knowledge related to intestinal diseases. Based on this database, eight major categories of omics data analyses are carried out to explore the genotype-phenotype characteristics of a certain intestinal disease. The first tool for comprehensive omics data research on intestinal diseases will help each researcher better understand intestinal diseases.
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Fibrosis is a reparative and progressive process characterized by abnormal extracellular matrix deposition, contributing to organ dysfunction in chronic diseases. The tumor suppressor p53 (p53), known for its regulatory roles in cell proliferation, apoptosis, aging, and metabolism across diverse tissues, appears to play a pivotal role in aggravating biological processes such as epithelial-mesenchymal transition (EMT), cell apoptosis, and cell senescence. These processes are closely intertwined with the pathogenesis of fibrotic disease. In this review, we briefly introduce the background and specific mechanism of p53, investigate the pathogenesis of fibrosis, and further discuss p53's relationship and role in fibrosis affecting the kidney, liver, lung, and heart. In summary, targeting p53 represents a promising and innovative therapeutic approach for the prevention and treatment of organ fibrosis.
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Fibrose , Proteína Supressora de Tumor p53 , Humanos , Proteína Supressora de Tumor p53/metabolismo , Animais , Transição Epitelial-Mesenquimal , Apoptose , Terapia de Alvo MolecularRESUMO
This study aims to explore the potential mechanism of action in the intervention of acute lung injury(ALI) based on the blood entry components of Ganke Granules in rats and in conjunction with network pharmacology, molecular docking, and animal experimental validation. The blood entry components of Ganke Granules in rats were imported into the SwissTargetPrediction platform to predict drug targets, and ALI-related targets were collected from the disease database. Intersections were taken, and protein-protein interaction(PPI) networks were constructed to screen the core targets, followed by Gene Ontology(GO) functional and Kyoto encyclopedia of genes and gnomes(KEGG) pathway enrichment analyses. A "blood entry components-target-pathway-disease" network was constructed, and the core components for disease intervention based on their topological parameters were screened. Molecular docking was used to predict the binding ability of the core components to key targets. The key targets of Ganke Granules in the intervention of ALI were verified by the lipopolysaccharide(LPS)-induced ALI mouse model. Through PPI topological parameter analysis, the top six key targets of STAT3, SRC, HSP90AA1, MAPK3, HRAS, and MAPK1 related to ALI were obtained. GO functional analysis showed that it was mainly related to ERK1 and ERK2 cascade, inflammatory response, and response to LPS. KEGG analysis showed that the main enrichment pathways were MAPK, neutrophil extracellular trap(NET) formation, and so on. Six core components(schizantherin B, schisandrin, besigomsin, harpagoside, isotectorigenin, and trachelanthamine) were filtered out by the "blood entry components-target-pathway-disease" network based on the analysis of topological parameters. Molecular docking results showed that the six core components and Tectoridin with the highest content in the granules had a high affinity with the key targets of MAPK3, SRC, MAPK1, and STAT3. In vivo experiment results showed that compared with the model group, Ganke Granules could effectively alleviate LPS-induced histopathological injury in the lungs of mice and reduce the percentage of inflammatory infiltration. The total protein content, nitric oxide(NO) level, myeloperoxidase(MPO) content, tumor necrosis factor-α(TNF-α), gamma interferon(IFN-γ), interleukin-1ß(IL-1ß), interleukin-6(IL-6), vascular endothelial growth factor(VEGF), and chemokine(C-X-C motif) ligand 1(CXCL1) chemokines in bronchoalveolar lavage fluid(BALF) were decreased, and the expression levels of lymphocyte antigen 6G(Ly6G), citrullinated histones 3(Cit-H3), and phosphorylated proteins SRC, ERK1/2, and STAT3 in lung tissue were significantly down-regulated. In conclusion, Ganke Granules could effectively inhibit the inflammatory response of ALI induced by LPS, protect lung tissue, regulate the release of inflammatory factors, and inhibit neutrophil infiltration and NET formation, and the mechanism of action may be related to inhibiting the activation of SRC/ERK1/2/STAT3 signaling pathway.