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1.
Cancer Lett ; 598: 217101, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38969156

RESUMO

The tumor microenvironment (TME) consists of tumor cells, non-tumor cells, extracellular matrix, and signaling molecules, which can contribute to tumor initiation, progression, and therapy resistance. In response to starvation, hypoxia, and drug treatments, tumor cells undergo a variety of deleterious endogenous stresses, such as hypoxia, DNA damage, and oxidative stress. In this context, to survive the difficult situation, tumor cells evolve multiple conserved adaptive responses, including metabolic reprogramming, DNA damage checkpoints, homologous recombination, up-regulated antioxidant pathways, and activated unfolded protein responses. In the last decades, the protein O-GlcNAcylation has emerged as a crucial causative link between glucose metabolism and tumor progression. Here, we discuss the relevant pathways that regulate the above responses. These pathways are adaptive adjustments induced by endogenous stresses in cells. In addition, we systematically discuss the role of O-GlcNAcylation-regulated stress-induced adaptive response pathways (SARPs) in TME remodeling, tumor progression, and treatment resistance. We also emphasize targeting O-GlcNAcylation through compounds that modulate OGT or OGA activity to inhibit tumor progression. It seems that targeting O-GlcNAcylated proteins to intervene in TME may be a novel approach to improve tumor prognosis.

2.
J Cancer Res Ther ; 20(2): 633-641, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38687934

RESUMO

OBJECTIVE: To determine the effectiveness and safety of neoadjuvant therapy in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) and provide evidence-based suggestions for clinical treatment. METHODS: The Cochrane Library, Embase, PubMed, and Web of Science were searched for articles published that analyzed the effectiveness and safety of GEP-NEN-targeted neoadjuvant therapy before March 2023. A confidence interval (CI) of 95%, a subgroup analysis, heterogeneity, and effect size (ES) were analyzed, and a meta-analysis of the literature was performed using the Stata BE17 software. RESULTS: A total of 417 patients from 13 studies were included in this meta-analysis. The primary variables comprised the objective response rate (ORR), disease control rate (DCR), surgical resection rate, and R0 resection rate with ES values of 0.42 (95% CI: 0.25-0.60), 0.96 (95% CI: 0.93-0.99), 0.67 (95% CI: 0.50-0.84), and 0.60 (95% CI: 0.54-0.67), respectively. The secondary variables were the incidence rates of treatment-related adverse events (TRAEs), Grade 3 or higher TRAEs, and surgical complications with ES values of 0.29 (95% CI: -0.03-0.21), 0.13 (95% CI: -0.07-0.33), and 0.35 (95% CI: 0.27-0.44), respectively. CONCLUSION: Neoadjuvant therapy is an effective and safe treatment method for GEP-NENs. However, further studies are required to determine the optimal regimen for this therapy in these tumors.


Assuntos
Neoplasias Intestinais , Terapia Neoadjuvante , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Tumores Neuroendócrinos/terapia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/tratamento farmacológico , Terapia Neoadjuvante/métodos , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Gástricas/terapia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Intestinais/patologia , Neoplasias Intestinais/terapia , Neoplasias Intestinais/tratamento farmacológico , Resultado do Tratamento
3.
J Int Med Res ; 52(3): 3000605241232968, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38460542

RESUMO

OBJECTIVE: To retrospectively compare the differences in the surgical efficacy and prognosis of laparoscopic pyeloplasty for hydronephrosis caused by symptomatic versus asymptomatic ureteropelvic junction obstruction (UPJO) in children and determine whether clinical symptoms affect the surgical outcome and prognosis. METHODS: Children who underwent laparoscopic pyeloplasty in our hospital from January 2018 to December 2022 were retrospectively analyzed. The children were divided into symptomatic and asymptomatic groups according to their main symptoms. The primary outcomes were the surgical success rate, change in renal parenchymal thickness, and change in renal pelvis anteroposterior diameter. The secondary outcomes were postoperative complications, reoperation rate, operative duration, intraoperative blood loss, and drainage tube indwelling time. RESULTS: In total, 224 children with UPJO were enrolled; 148 (66.1%) were symptomatic and 76 (33.9%) were asymptomatic. The symptomatic group showed a significantly greater mean change in renal parenchymal thickness, significantly higher surgical success rate, and significantly lower postoperative complication rate. CONCLUSIONS: In the present study, asymptomatic children had a lower surgical success rate, less postoperative imaging improvement, and more postoperative complications than symptomatic children. The presence or absence of clinical symptoms may affect the surgical outcome and prognosis.


Assuntos
Hidronefrose , Laparoscopia , Obstrução Ureteral , Humanos , Criança , Estudos Retrospectivos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Procedimentos Cirúrgicos Urológicos/métodos , Hidronefrose/diagnóstico por imagem , Hidronefrose/cirurgia , Hidronefrose/complicações , Obstrução Ureteral/cirurgia , Obstrução Ureteral/etiologia , Complicações Pós-Operatórias/cirurgia , Resultado do Tratamento
4.
J Ultrasound Med ; 43(7): 1245-1250, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38477076

RESUMO

OBJECTIVES: Ultrasound (US) imaging has been observed to underestimate tumor size in clinical practice. This study aims to compare the size measurements of breast cancer and benign tumors using two-dimensional ultrasound (2DUS) and contrast-enhanced ultrasound (CEUS). METHODS: The study included 42 clinically confirmed breast cancer and 47 benign breast tumors. Two experienced physicians independently measured the maximal longitudinal and transverse diameters of the masses in 2DUS and CEUS. All analyses were performed in R (4.2.2) and GraphPad Prism 6. RESULTS: The maximal longitudinal and transverse diameters of breast cancer measured by CEUS were 26.61 ± 0.21% and 26.24 ± 0.19% larger compared with 2DUS, and benign breast tumors had an 11.74 ± 0.21% and 11.06 ± 0.14% increase in size compared with 2DUS. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) for the difference between 2DUS and CEUS was 0.870 for longitudinal diameters (95% CI: 0.795-0.945, sensitivity 0.842, specificity 0.783, threshold value 0.215), and 0.863 for transverse diameters (95% CI: 0.785-0.942, sensitivity 0.667, specificity 0.936, threshold value 0.203). CONCLUSIONS: The size measurements of both breast cancer and benign tumors were larger in CEUS compared with 2DUS, with CEUS measurements of breast cancer being more pronounced than those of benign breast tumors. These findings suggest that CEUS may provide a more precise assessment of tumor size, which is crucial for determining optimal treatment strategies and improving patient outcomes in breast cancer management.


Assuntos
Neoplasias da Mama , Mama , Meios de Contraste , Aumento da Imagem , Sensibilidade e Especificidade , Ultrassonografia Mamária , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Ultrassonografia Mamária/métodos , Aumento da Imagem/métodos , Adulto , Reprodutibilidade dos Testes , Mama/diagnóstico por imagem , Mama/patologia , Idoso , Diagnóstico Diferencial , Carga Tumoral
5.
BMC Cancer ; 24(1): 69, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216936

RESUMO

OBJECTIVE: To evaluate the value of an integrated model incorporating deep learning (DL), hand-crafted radiomics and clinical and US imaging features for diagnosing central lymph node metastasis (CLNM) in patients with papillary thyroid cancer (PTC). METHODS: This retrospective study reviewed 613 patients with clinicopathologically confirmed PTC from two institutions. The DL model and hand-crafted radiomics model were developed using primary lesion images and then integrated with clinical and US features selected by multivariate analysis to generate an integrated model. The performance was compared with junior and senior radiologists on the independent test set. SHapley Additive exPlanations (SHAP) plot and Gradient-weighted Class Activation Mapping (Grad-CAM) were used for the visualized explanation of the model. RESULTS: The integrated model yielded the best performance with an AUC of 0.841. surpassing that of the hand-crafted radiomics model (0.706, p < 0.001) and the DL model (0.819, p = 0.26). Compared to junior and senior radiologists, the integrated model reduced the missed CLNM rate from 57.89% and 44.74-27.63%, and decreased the rate of unnecessary central lymph node dissection (CLND) from 29.87% and 27.27-18.18%, respectively. SHAP analysis revealed that the DL features played a primary role in the diagnosis of CLNM, while clinical and US features (such as extrathyroidal extension, tumour size, age, gender, and multifocality) provided additional support. Grad-CAM indicated that the model exhibited a stronger focus on thyroid capsule in patients with CLNM. CONCLUSION: Integrated model can effectively decrease the incidence of missed CLNM and unnecessary CLND. The application of the integrated model can help improve the acceptance of AI-assisted US diagnosis among radiologists.


Assuntos
Carcinoma Papilar , Aprendizado Profundo , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Estudos Retrospectivos , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Radiômica , Carcinoma Papilar/patologia , Fatores de Risco , Linfonodos/patologia
6.
Clin Endocrinol (Oxf) ; 100(2): 116-123, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38146598

RESUMO

OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects many populations, and screening out the high-risk populations at an early stage is a challenge. As a sarcopenia index, the relationship between creatinine to cystatin C ratio (CCR) and MASLD remains unclear. This cross-sectional, prospective study aimed to explore the relationship between CCR and MASLD. Design Firstly, explored the correlation between CCR and MASLD in cross-sectional analyses. Then excluded the population with baseeline diagnosis of MASLD and analyzed the association with baseline CCR levels and the onset of MASLD in the population with available follow-up data. Univariate and multivariate logistic regression analyses were used to calculate odds ratios (ORs) to evaluate the association between CCR levels and MASLD. PATIENTS AND MEASUREMENTS: This study included 368,634 participants from the UK Biobank for cross-sectional and prospective analyses. The demographic characteristics and laboratory measurements of all participants were obtained from the UK Biobank. MASLD was diagnosed according to the multi-society consensus nomenclature. Hepatic steatosis was defined as FLI  ≥60. RESULTS: We grouped the study participants according to CCR tertiles. In cross-sectional analyses, participants in CCR tertile 1 had the highest MASLD risk (OR: 1.070, 95% CI: 1.053-1.088, p < .001). And the similar association was observed in the prospective analyses (CCR tertile 1 OR: 1.340, 95% CI: 1.077-1.660, p = .009; CCR tertile 2 OR: 1.217, 95% CI: 1.021-1.450, p = .029, respectively). After stratification by gender, the significant association between CCR and the onset of MASLD was only observed in males (CCR tertile 1 OR: 1.639, 95% CI: 1.160-2.317, p = .005; CCR tertile 2 OR: 1.322, 95% CI: 1.073-1.628, p = .005, respectively). CONCLUSION: Our results indicated that lower CCR was significantly associated with higher risk of MASLD, based on which predictive models can be developed to screen populations at high risk of developing MASLD.


Assuntos
Cistatina C , Fígado Gorduroso , Masculino , Humanos , Estudos Prospectivos , Creatinina , Estudos Transversais , Bancos de Espécimes Biológicos , Biobanco do Reino Unido
7.
Photodiagnosis Photodyn Ther ; 45: 103934, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38097120

RESUMO

Photodynamic therapy (PDT) uses light energy to excite a photosensitizing agent, leading to production of reactive oxygen species, which exert cytotoxic effects on targeted cells. PDT has emerged as a promising therapeutic modality for the treatment of flat warts caused by human papillomavirus (HPV) infection, by targeting infected keratinocytes and inactivating nonenveloped viral particles. Some patients with recalcitrant flat warts on the face who have poor response to traditional treatment often seek effective therapy to have the warts removed. In this report, we retrospectively evaluated the efficacy of topical 10% 5-aminolevulinic acid PDT (ALA-PDT) in the treatment of 15 patients with recalcitrant facial flat warts. Patients received treatment once every two weeks for a total of two or three sessions. At 24 weeks after the start of treatment, 86.67% of patients showed complete or excellent response. Further more, the remission rate of 100% lesion clearance was 46.67% (seven patients), and the remission rate of 70-100% lesion clearance was 40.00% (six patients). None of the patients experienced disease recurrence or progression. The adverse reactions were generally well tolerated by the patients and mostly resolved in a few days without special treatment. Our findings showed that topical 10% ALA-PDT is a safe and effective treatment for recalcitrant facial flat warts.


Assuntos
Infecções por Papillomavirus , Fotoquimioterapia , Verrugas , Humanos , Ácido Aminolevulínico/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Retrospectivos , Fotoquimioterapia/métodos , Verrugas/tratamento farmacológico
9.
BMC Plant Biol ; 23(1): 591, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38008764

RESUMO

BACKGROUND: Kiwifruit bacterial canker, caused by Pseudomonas syringae pv. actinidiae (Psa), is a destructive disease worldwide. Resistance genes that respond to Psa infection urgently need to be identified for controlling this disease. Laccase is mainly involved in the synthesis of lignin in the plant cell wall and plays a prominent role in plant growth and resistance to pathogen infection. However, the role of laccase in kiwifruit has not been reported, and whether laccase is pivotal in the response to Psa infection remains unclear. RESULTS: We conducted a bioinformatics analysis to identify 55 laccase genes (AcLAC1-AcLAC55) in the kiwifruit genome. These genes were classified into five cluster groups (I-V) based on phylogenetic analysis, with cluster groups I and II having the highest number of members. Analysis of the exon-intron structure revealed that the number of exons varied from 1 to 8, with an average of 5 introns. Our evolutionary analysis indicated that fragment duplication played a key role in the expansion of kiwifruit laccase genes. Furthermore, evolutionary pressure analysis suggested that AcLAC genes were under purifying selection. We also performed a cis-acting element analysis and found that AcLAC genes contained multiple hormone (337) and stress signal (36) elements in their promoter regions. Additionally, we investigated the expression pattern of laccase genes in kiwifruit stems and leaves infected with Psa. Our findings revealed that laccase gene expression levels in the stems were higher than those in the leaves 5 days after inoculation with Psa. Notably, AcLAC2, AcLAC4, AcLAC17, AcLAC18, AcLAC26, and AcLAC42 showed significantly higher expression levels (p < 0.001) compared to the non-inoculated control (0 d), suggesting their potential role in resisting Psa infection. Moreover, our prediction indicated that 21 kiwifruit laccase genes are regulated by miRNA397, they could potentially act as negative regulators of lignin biosynthesis. CONCLUSIONS: These results are valuable for further analysis of the resistance function and molecular mechanism of laccases in kiwifruit.


Assuntos
Actinidia , Lacase , Lacase/genética , Filogenia , Lignina , Evolução Biológica , Actinidia/genética , Actinidia/microbiologia , Pseudomonas syringae/fisiologia , Doenças das Plantas/genética , Doenças das Plantas/microbiologia
10.
Int J Mol Sci ; 24(14)2023 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-37511299

RESUMO

Kiwifruit canker disease, caused by Pseudomonas syringae pv. actinidiae (Psa), is the main threat to kiwifruit production worldwide. Currently, there is no safe and effective disease prevention method; therefore, biological control technologies are being explored for Psa. In this study, Bacillus velezensis WL-23 was isolated from the leaf microbial community of kiwifruit and used to control kiwifruit cankers. Indoor confrontation experiments showed that both WL-23 and its aseptic filtrate had excellent inhibitory activity against the main fungal and bacterial pathogens of kiwifruit. Changes in OD600, relative conductivity, alkaline proteinase, and nucleic acid content were recorded during Psa growth after treatment with the aseptic filtrate, showing that Psa proliferation was inhibited and the integrity of the cell membrane was destroyed; this was further verified using scanning electron microscopy and transmission electron microscopy. In vivo, WL-23 promoted plant growth, increased plant antioxidant enzyme activity, and reduced canker incidence. Therefore, WL-23 is expected to become a biological control agent due to its great potential to contribute to sustainable agriculture.


Assuntos
Actinidia , Bacillus , Pseudomonas syringae , Doenças das Plantas/prevenção & controle , Doenças das Plantas/microbiologia , Actinidia/microbiologia
11.
Front Surg ; 10: 1023329, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37035572

RESUMO

This was an initial effort to treat hemophiliac hematoma by ultrasound-guided intratumoral drainage and lavage with urokinase after adequate supplementation of coagulation factors. Two patients with severe hemophilia underwent ultrasound-guided percutaneous drainage in combination with lavage using urokinase. After 5-day and 3-day treatments, respectively, intramuscular hematomas in both patients disappeared, compression symptom was relieved, and no obvious adverse reactions or serious complications were observed during the treatment or follow-up. These findings suggest that ultrasound-guided drainage combined with lavage using urokinase is an immediate, safe, effective, and minimally invasive treatment for intramuscular hematomas in hemophiliacs, avoiding potential complications by surgical resection with relatively low treatment cost.

12.
Ann Transl Med ; 10(18): 958, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36267736

RESUMO

Background: De novo lipogenesis (DNL) is a dynamic process that converts excess carbohydrates into fatty acids to maintain cellular homeostasis. Dysregulation of DNL is associated with diverse obesity-related diseases and many tumor types. Therefore, monitoring DNL in real-time with high sensitivity should be highly beneficial when screening therapeutic agents for their potential use as obesity treatments. Methods: A sequence coding for Gaussia luciferase (GLuc) preceded by a 2A peptide was inserted into the murine fatty acid synthase (FASN) genetic locus by homologous recombination to generate FASN-2A-GLuc mice. The luciferase mouse model was evaluated in conditions of physical and pharmacological stimuli by in vivo and ex vivo imaging. Results: The distribution of bioluminescence signals in different organs was identical to the FASN expression: high in white fat, brown fat, and the lungs. In addition, the bioluminescence signals accurately recapitulated the dynamic change of FASN in response to fasting and refeeding conditions. Moreover, with this murine reporter model, we also discovered that fatostatin, a synthetic inhibitor of sterol regulatory element-binding proteins, effectively inhibited DNL in multiple organs, especially in adipose tissues under a high-carbohydrate diet. Conclusions: Our FASN-2A-GLuc reporter mouse model proved to be a sensitive visualization tool for monitoring both systemic and organ-specific DNL in real time.

13.
Ann Transl Med ; 10(9): 524, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35928748

RESUMO

Background: Hepatocellular carcinoma (HCC) is a malignant tumor with a poor prognosis, however, biomarkers for the prognostic assessment of HCC remain suboptimal. Consequently, we aimed to develop a reliable tool for prognostic estimation of HCC. Methods: Differentially expressed genes (DEGs) between HCC and adjacent normal tissues in 3 Gene Expression Omnibus (GEO) datasets were identified, followed by hub gene selection and least absolute shrinkage and selection operator (LASSO) Cox regression to develop a prognostic gene signature. Kaplan-Meier survival analysis, univariate and multivariate Cox regression, time-dependent area under the curve (AUC), and integrated value of time-dependent AUC (iAUC) were used to assess the relationship between predictors and clinical outcomes in the training and validation datasets. Then we built nomograms including gene signature and clinicopathological factors to forecast the probability of death. Moreover, we performed quantitative real-time PCR (qPCR) to compare the expression of prognostic genes between HCC and adjacent normal tissues. Finally, the relationship between prognostic genes and tumor microenvironment (TME) was investigated using immune cell infiltration algorithms and single cell transcriptomic database. Results: Eight prognostic genes (CDC20, PTTG1, TOP2A, CXCL2, CXCL14, CYP2C9, MT1F, and GHR) were finally identified to construct the gene signature. Each patient's risk score was calculated according to the gene signature. Patients with high-risk scores showed worse outcomes in the training set [hazard ratio (HR) =3.404, P<0.001]. Risk score, age, body mass index (BMI), and TNM stage were identified as independent prognostic factors for overall survival (OS) in the training set. The nomogram including risk score and other independent prognostic factors showed better performance as opposed to the clinicopathological model. In the validation dataset, we obtained the similar results as well. Moreover, we found a close relationship between risk score and immune cell infiltration. Patients with high-risk scores had elevated expression of immune checkpoint genes, indicating that these patients may be more suitable for immunotherapy. Conclusions: We have established and validated an eight-gene based prognostic model, which could be an effective tool for the prognostic evaluation of HCC patients.

14.
Org Lett ; 24(34): 6321-6325, 2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-35993566

RESUMO

The Friedel-Crafts type alkylation of C2-tethered thiophenes has been reported to be nonregioselective. Taking advantage of the highly regioselective 5-exo-trig spirocyclization of an electrochemically generated amidyl radical, we have unraveled an electrochemical dearomative spirocyclization of N-acyl thiophene-2-sulfonamides. Various nucleophilic agents, including carboxylates, alcohols, and fluoride, are readily incorporated to afford the remotely functionalized spirocyclic dihydrothiophenes, and their novel spirocyclic scaffolds have been shown to exhibit promising antitumor activities.


Assuntos
Sulfonamidas , Tiofenos , Álcoois , Alquilação , Estereoisomerismo
15.
Stat Methods Med Res ; 31(10): 2021-2034, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35837741

RESUMO

In phase II clinical trials on cancer, it is of great interest to establish the efficacy and safety of a new treatment simultaneously. Existing hypotheses may not achieve this goal effectively. We introduce two new sets of hypotheses that consider the association between the two factors, then construct the optimal two-stage designs for the hypotheses. The proposed designs strictly control the maximum type I error rate at the given nominal level α, maintain the minimum power at least the given 1-ß, and have the smallest expected total sample size under the null hypothesis. Furthermore, an algorithm is provided to compute these designs. R-codes are given in the Supplemental Material.


Assuntos
Neoplasias , Algoritmos , Humanos , Neoplasias/tratamento farmacológico , Projetos de Pesquisa , Tamanho da Amostra
16.
Ann Transl Med ; 10(12): 698, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35845527

RESUMO

Background: Gastric cancer (GC) has a high incidence and high mortality rate among Asian countries, and distinguishing predictive prognosis biomarkers for GC are essential. Cancer-associated fibroblasts (CAFs) play a significant role in the progression, immune evasion, and therapeutic resistance of GC. Therefore, CAF-associated genes might have huge potential as prognostic biomarkers for predicting tumor progression and survival rate in GC pateints. Methods: A sum of 1,134 GC patients from the The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD), GSE62254, and GSE84437 datasets as well as GC cohorts from Xijing hospital were included. Firstly, we performed univariate Cox regression analysis to identify CAF-associated prognostic genes. Subsequently, the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was used to develop a CAF gene signature (CAFGS) in the TCGA-STAD training cohort. CAFGS's predictive performance was examined in both the training and validation cohorts, and the relationship between CAFGS and the tumor microenvironment (TME) was investigated by ssGSEA, CIBERSORT, TIMER, and ESTIMATE. Finally, a nomogram of CAFGS was established. Results: Ten CAF-associated genes (ANGPTL4, CPNE8, CST2, HTR1F, IL1RAP, NR1D1, NTAN1, OLFML2B, TMEM259, and VTN) were identified to develop CAFGS. A high CAFGS score represented a worse outcome for GC patients in four cohorts, and a strong correlation was found between CAFGS and the infiltration of immune cells. We showed that CAFs contribute to immune evasion and unfavorable prognoses of GC patients by promoting the formation of an immunosuppressive microenvironment, and a high level of CAF infiltration may attenuate the efficacy of immunotherapy. The nomogram based on CAFGS showed reasonable predictive ability and may deliver great clinical net benefits. Conclusions: We established a CAFGS model with 10 CAF-associated genes that had a great predictive value for GC prognosis and survival rate evaluation. This study could provide a novel insight for investigating the role of CAFs in GC.

17.
Int J Biol Macromol ; 208: 720-730, 2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35364202

RESUMO

Phytophthora capsici is a destructive plant pathogen that infects a wide range of hosts worldwide. The P. capsici cell wall, rich in cellulose, is vital for hyphal growth and host interactions. However, the enzymes involved in its synthesis remain largely unelucidated. In the current study, we functionally characterized the cellulose synthase gene PcCesA1, which is highly conserved in Phytophthora. By using CRISPR/Cas9-mediated gene replacement and in situ complementation system, it was found PcCesA1 is essential for the mycelial growth, cystospore germination, and pathogenicity of P. capsici. The normal deposition of newly synthesized cell wall components and the polar growth point formation were disrupted in PcCesA1 knockout mutants, suggesting that PcCesA1 plays an important role in the polar growth of P. capsici. Compared with the wild-type strains, PcCesA1 knockout mutants displayed a thicker inner layer cell wall and were more sensitive to carboxylic acid amide fungicides (CAAs). The contents of the cell wall polysaccharides 1,4-Glc, 1,4,6-Glc, and 1,3,4-Glc were reduced in PcCesA1 knockout mutants, suggesting that PcCesA1 affected cellulose content and glycosidic linkage crosslinking in the cell wall. Our findings demonstrate that PcCesA1 is required for cell wall biogenesis. Therefore, PcCesA1 may be a potential target for Phytophthora disease control.


Assuntos
Phytophthora , Parede Celular , Celulose , Glicosídeos , Doenças das Plantas
18.
Front Microbiol ; 12: 673784, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690942

RESUMO

Patched (Ptc) and Patched-related (Ptr) proteins containing sterol-sensing domains (SSD) and Patched domains are highly conserved in eukaryotes for lipid transport and metabolism. Four proteins containing predicted SSD and Patched domains were simultaneously found by searching the Phytophthora sojae genome database, and one of them was identified as a Patched-like (PTL) protein. Here, we investigated the biological function of PsPTL. The expression level of PsPTL was higher during mycelial and sporulation stages, compared to zoospore (ZO), cyst, and germinated-cyst stages, without significant change during infection. However, deletion of PsPTL using CRISPR/Cas9 had no significant effect on the growth, development, or virulence of P. sojae. Further investigations showed that PsPTL is not essential for P. sojae to cope with external stresses such as temperature, pH, oxidative and osmotic pressure. In addition, this gene did not appear to play an essential role in P. sojae's response to exogenous sterols. The transcript levels of the other three proteins containing predicted SSD and Patched domains were also not significantly upregulated in PsPTL deletion transformants. Our studies demonstrated that PsPTL is not an essential protein for P. sojae under the tested conditions, and more in-depth research is required for revealing the potential functions of PsPTL under special conditions or in other signaling pathways.

19.
J Hazard Mater ; 416: 126224, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492978

RESUMO

Engineering functional defects in support materials has gained ever-increasing attention as a novel approach to boosting the catalytic performance of oxide-supported catalysts. Herein, we demonstrate the feasibility of engineering oxygen vacancy in iron oxide through amorphization in conjunction with foreign cation doping and elucidate the important role of support functionality in the catalytic oxidation of formaldehyde (HCHO). A supported Pt catalyst on Fe-W-O amorphous nanosheets (denoted as Pt/a-Fe-W-O) was synthesized using a one-step solvothermal method. This simple method allowed us to simultaneously create abundant oxygen vacancies in the substrate and to ensure uniform dispersion of tiny Pt nanoparticles with an average diameter of 1.4 nm on the high-surface-area substrate. This renders an increased possibility of Pt/O-vacancy coexistence in close proximity, which synergistically boosts the formation of active oxygen and surface hydroxyl species. Consequently, the Pt/a-Fe-W-O catalyst with an optimal W/Fe molar ratio of 0.08:1 and a 1.51 wt% Pt loading exhibited a high specific reaction rate of 68.3 µmol gPt-1 s-1 and excellent stability during 24 h continuous test, outperforming most existing HCHO oxidation catalysts. Our study highlights the importance of functional oxygen defects in construction of synergistic active sites for promoting the reactions requiring multiple active species.

20.
Front Oncol ; 11: 604480, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34084740

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is an aggressive type of cancer, associated with poor prognosis. The development of an accurate and non-invasive method to evaluate the pathologic response of patients with ESCC to chemoradiotherapy remains a critical issue. Therefore, the aim of this study was to assess the importance of vascular permeability and texture parameters in predicting the response to neoadjuvant chemoradiotherapy (NACRT) in patients with ESCC. METHODS: This prospective analysis included patients with T1-T2 stage of ESCC, without either lymphatic or metastasis, and distant metastasis. All patients underwent surgery having received two rounds of NACRT. All patients underwent dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) twice, i.e., before the first NACRT and after the second NACRT. Patients were assessed for treatment response at 30 days after the second NACRT. Patients were divided into the complete response (CR) and partial response (PR) groups based on their responses to NACRT. Vascular permeability and texture parameters were extracted from the DCE-MRI scans. After assessing the diagnostic performance of individual parameters, a combined model with vascular permeability and texture parameters was generated to predict the response to NACRT. RESULTS: In this study, the CR and PR groups included 16 patients each. The volume transfer constant (Ktrans), extracellular extravascular volume fraction (ve), and entropy values, as well as changes to each of these parameters, extracted from the second DCE-MRI scans, showed significant differences between the CR and PR groups. The area under the curve (AUC) of Ktrans, ve, and entropy values showed good diagnostic ability (0.813, 0.789, and 0.707, respectively). A logistic regression model combining Ktrans, ve, and entropy had significant diagnostic ability (AUC=0.977). CONCLUSIONS: The use of a combined model with vascular permeability and texture parameters can improve post-NACRT prognostication in patients with ESCC.

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