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1.
Pest Manag Sci ; 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39096093

RESUMO

BACKGROUND: The highland barley, Hordeum vulgare L., is a staple food crop with superior nutritional functions in Xizang, China. It is often damaged by the black cutworm, Agrotis ipsilon (Hufnagel), which is an underground pest and difficult to effectively manage. To introduce a novel insecticide with unique mode of action, broflanilide (BFL) and its binary mixtures with chlorantraniliprole (CAP), fluxametamide, ß-cypermethrin or imidacloprid were screened out as seed treatment to control black cutworm in highland barley in the present study. RESULTS: In the laboratory bioassays, BFL had outstanding insecticidal activity to black cutworm with a median lethal dose (LD50) of 0.07 mg kg-1. The mixture of BFL × CAP at the concentration ratio of 7:40 exhibited the highest synergistic effect with a co-toxicity coefficient of 280.48. In the greenhouse pot experiments, BFL and BFL × CAP seed treatments at 8 g a.i. kg-1 seed could effectively control black cutworm, with a low percentage of injured seedlings <20% and high control efficacies of 93.33-100% during a period of 3-12 days after seed emergence. Moreover, BFL and BFL × CAP seed treatments could promote the seed germination and seedling growth of highland barley at the tested temperatures of 15, 20 and 25 °C. CONCLUSION: Our results indicated that BFL and BFL × CAP were effective and promising insecticides as seed treatment to control black cutworm in highland barley. © 2024 Society of Chemical Industry.

2.
Am J Med Sci ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38969288

RESUMO

BACKGROUND: MicroRNA (miRNA)-processing machinery may modify the risk of primary Sjögren's syndrome (pSS) by altering miRNA expression profiles. Inflammatory cytokines and reactive oxygen species (ROS) are also involved in pSS; however, the role of altered miRNAs expression in its pathogenesis is still unclear. We aimed to evaluate the relationship between single-nucleotide polymorphisms (SNPs) in miRNA processing machinery genes, including XPO5 (rs11077), RAN (rs14035), Dicer (rs3742330), TNRC6B (rs9623117), GEMIN3 (rs197412), and GEMIN4 (rs2740348), and the risk of pSS in female patients. The potential associations of cytokines and ROS with pSS-susceptible SNPs were also evaluated. MATERIALS AND METHODS: The SNPs confirmed by polymerase chain reaction ligase detection reaction were genotyped in 74 female patients with pSS and 77 controls. The relationship was analyzed by Student's t-test, Wilcoxon rank-sum test, chi-square test, Pearson's correlation test, and binary logistic regression analysis. RESULTS: For rs197412 of the GEMIN3 gene, the genotype TT carrier was associated with a 2.172-fold increased risk for pSS when compared with that of CT+CC carrier (odds ratio: 2.172, 95% CI, 1.133-4.166, p=0.019). Simultaneously, the pSS-susceptible TT carriers were associated with increased interferon-γ (IFN-γ) (P < 0.001) and tumor necrosis factor-α (TNF-α) (P = 0.003) levels when compared with that of CT+CC genotype carriers in female patients with pSS. The subsequent analysis also showed a weak positive correlation between IFN-γ and TNF-α levels (r=0.271, P = 0.019). CONCLUSION: The predictors of GEMIN3 SNPs might modify pSS development in females by mediating the expression of miRNAs and therefore regulate the levels of IFN-γ and TNF-α.

3.
Int J Biol Macromol ; 277(Pt 1): 134010, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39032891

RESUMO

Capsular polysaccharide (CPS) as a probiotic component has the ability to regulate the function of the host's immune system. However, how the structure and function of heat-killed CPS are altered remains unclear. In the present study, CPS were isolated and purified from live (LCPS) and heat-killed (HCPS) Lacticaseibacillus paracasei 6235. The differences in structure and immunomodulation between LCPS and HCPS were compared and analyzed. The results demonstrate that after heat killed, the molecular weight of CPS decreased from 23.4 kDa to 17.5 kDa, with the disappearance of galactosamine in the monosaccharide composition, and changes in the microstructure. Methylation analysis and nuclear magnetic resonance analysis revealed that the LCPS and HCPS are similar in structure, which main units of →3,4)-α-D-Glcp-(1→4)-α-D-Galp-(1→3)-ß-L-Rhap-(1→6)-ß-D-Galp-(1→, and repeating units of →3,4)-α-D-Glcp-(1→, →3)-ß-L-Rhap-(1→, and →4)-α-D-Galp-(1→ residues. Furthermore, both LCPS and HCPS significantly downregulated the expression of pro-inflammatory cytokines in RAW264.7 cells induced by LPS. Specifically, HCPS reduced the levels of IL-6 and IL-1ß by 79.38 % and 88.42 %, respectively, compared to LCPS. Concurrently, both LCPS and HCPS effectively mitigated inflammatory responses through the NF-κB and MAPK signaling pathways. Moreover, compared to LCPS, HCPS increased the protein expression levels of NF-κB/p-NF-κB and IκB/p-IκB by 26.14 % and 28.92 %, respectively. These results suggest that CPS has a role in modulating immune responses and that HCPS is more effective. This study can be further developed into new products related to postbiotics.

4.
Discov Oncol ; 15(1): 209, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834851

RESUMO

Colorectal cancer is a leading cause of cancer-related mortality worldwide. Traditionally, colorectal cancer has been recognized as a disease caused by genetic mutations. However, recent studies have revealed the significant role of epigenetic alterations in the progression of colorectal cancer. Epithelial-mesenchymal transition, a critical step in cancer cell metastasis, has been found to be closely associated with the tumor microenvironment and immune factors, thereby playing a crucial role in many kinds of biological behaviors of cancers. In this review, we explored the impact of N6-methyladenosine and post-translational modifications (like methylation, acetylation, ubiquitination, SUMOylation, glycosylation, etc.) on the process of epithelial-mesenchymal transition in colorectal cancer and the epigenetic regulation for the transcription factors and pathways correlated to epithelial-mesenchymal transition. Furthermore, we emphasized that the complex regulation of epithelial-mesenchymal transition by epigenetics can provide new strategies for overcoming drug resistance and improving treatment outcomes. This review aims to provide important scientific evidence for the prevention and treatment of colorectal cancer based on epigenetic modifications.

5.
Polymers (Basel) ; 16(12)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38932105

RESUMO

The adsorption mechanism of superabsorbent polymer (SAP) can provide theoretical guidance for their practical applications in different environments. However, there has been limited research on the mechanism of attapulgite-sodium polyacrylate. This research aimed to compare the Cd(II) adsorption characteristics and water retention properties of organic-inorganic composite SAP (attapulgite-sodium polyacrylate, OSAP) and organic SAP (polyacrylamide, JSAP). Batch experiments were used to investigate the kinetics of Cd(II) adsorption, as well as the thermodynamic properties and factors influencing these properties. The results show that the Cd(II) adsorption capacity was directly proportional to the pH value. The maximum adsorption capacities of OSAP and JSAP were of 770 and 345 mg·g-1. The Cd(II) adsorption for OSAP and JSAP conformed to the Langmuir and the quasi-second-order kinetic model. This indicates that chemical adsorption is the primary mechanism. The adsorption process was endothermic (ΔH0 > 0) and spontaneous (ΔG0 < 0). The water adsorption ratios of OSAP and SAP were 474.8 and 152.6 in pure water. The ratio decreases with the increase in Cd(II) concentration. OSAP and JSAP retained 67.23% and 38.37% of the initial water adsorption after six iterations of water adsorption. Hence, OSAP is more suitable than JSAP for agricultural and environmental ecological restoration in arid and semi-arid regions.

6.
Am J Cancer Res ; 14(5): 2124-2140, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38859826

RESUMO

Alpha-fetoprotein-producing gastric cancer (AFPGC) is a rare and aggressive subtype of gastric cancer associated with poor prognosis. This study aimed to investigate the recurrent metastatic patterns and prognostic factors in AFPGC patients undergoing radical surgical resection. Data from 241 AFPGC patients diagnosed between January 2017 and January 2020 who underwent surgical resection were analyzed across multiple centers. Recurrence patterns, metastatic sites, and survival outcomes were evaluated. Univariate and multivariate analyses were performed to identify risk factors for recurrent metastasis, overall survival (OS), and disease-free survival (DFS). There is an annual increase in the proportion of AFPGC cases, rising from 3.45% in 2017 to 7.88% in 2023. Higher serum AFP level was associated with increased likelihood of lymph node metastasis (P=0.006), deeper invasion depth (P=0.000) and greater tumor diameter (P=0.036). Independent predictors of recurrent metastasis included T4 infiltration, lymph node metastasis, tumor diameter >5 cm, poorly differentiated-undifferentiated pathology, preoperative AFP>1000 ng/mL, and postoperative increasing trend in AFP levels. The 5-year OS and DFS rates were 36.5% and 34.2%, respectively, with poorer survival linked to higher preoperative AFP levels and postoperative increasing trend in AFP level. Independent risk factors for poor OS and DFS included T4 infiltration, lymph node metastasis, poorly differentiated-undifferentiated pathology, preoperative AFP>1000 ng/mL, and postoperative increasing trend in AFP. Serum AFP level can serve as a potential predictive and prognostic biomarker. Identifying independent risk factors informs risk stratification and personalized treatment for AFPGC patients.

7.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167292, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38871031

RESUMO

Post-translational modification and fine-tuned protein turnover are of great importance in mammalian early embryo development. Apart from the classic protein degradation promoting ubiquitination, new forms of ubiquitination-like modification are yet to be fully understood. Here, we demonstrate the function and potential mechanisms of one ubiquitination-like modification, neddylation, in mouse preimplantation embryo development. Treated with specific inhibitors, zygotes showed a dramatically decreased cleavage rate and almost all failed to enter the 4-cell stage. Transcriptional profiling showed genes were differentially expressed in pathways involving cell fate determination and cell differentiation, including several down-regulated zygotic genome activation (ZGA) marker genes. A decreased level of phosphorylated RNA polymerase II was detected, indicating impaired gene transcription inside the embryo cell nucleus. Proteomic data showed that differentially expressed proteins were enriched in histone modifications. We confirmed the lowered in methyltransferase (KMT2D) expression and a decrease in histone H3K4me3. At the same time, acetyltransferase (CBP/p300) reduced, while deacetylase (HDAC6) increased, resulting in an attenuation in histone H3K27ac. Additionally, we observed the up-regulation in YAP1 and RPL13 activities, indicating potential abnormalities in the downstream response of Hippo signaling pathway. In summary, we found that inhibition of neddylation induced epigenetic changes in early embryos and led to abnormalities in related downstream signaling pathways. This study sheds light upon new forms of ubiquitination regulating mammalian embryonic development and may contribute to further investigation of female infertility pathology.


Assuntos
Desenvolvimento Embrionário , Regulação da Expressão Gênica no Desenvolvimento , Histonas , Zigoto , Animais , Camundongos , Zigoto/metabolismo , Desenvolvimento Embrionário/genética , Desenvolvimento Embrionário/efeitos dos fármacos , Histonas/metabolismo , Feminino , Proteína NEDD8/metabolismo , Proteína NEDD8/genética , Processamento de Proteína Pós-Traducional , Código das Histonas , Embrião de Mamíferos/metabolismo , Ubiquitinação , Ciclopentanos , Pirimidinas
8.
Environ Pollut ; 355: 124210, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38795815

RESUMO

Pesticide residue and thermal stress resulting from global climate change are parallel stressors for soil fauna. However, it remains ambiguous how elevated temperatures and pesticides can interact to threaten soil fauna. In the study, the acute and chronic clothianidin (CTD) toxicity to earthworms (Eisenia fetida) at different temperatures, and the effect of increasing temperature on antioxidant defense mechanisms in response to CTD were investigated. The acute toxicity of CTD was exacerbated by increased temperature in both filter paper contact tests (a decrease in the 48-h median lethal concentration (LC50) from 0.077 µg/cm2 at 20 °C to 0.009 µg/cm2 at 30 °C) and natural soil tests (a decrease in the 48-h LC50 from 0.774 mg/kg at 20 °C to 0.199 mg/kg at 30 °C). Exposure to CTD or high temperature (30 °C) triggered reactive oxygen species (ROS) overgeneration and increased antioxidant enzyme activities in earthworms; and the effect was particularly pronounced after exposure to both higher temperatures and CTD. At 20 and 25 °C, there was no significant change in the growth and reproduction of E. fetida after 56-d exposure to CTD-contaminated soil. However, the combined effect of CTD and high temperature (30 °C) significantly reduced the weight change rate, cocoon number, hatching rate, and number of juveniles on day 56. These results indicated that elevated temperature could aggravate acute and chronic CTD toxicity to earthworms. The findings emphasize that evaluating changes in pesticide toxicity under global warming is worth further investigation.


Assuntos
Guanidinas , Neonicotinoides , Oligoquetos , Poluentes do Solo , Tiazóis , Oligoquetos/efeitos dos fármacos , Animais , Neonicotinoides/toxicidade , Guanidinas/toxicidade , Tiazóis/toxicidade , Poluentes do Solo/toxicidade , Inseticidas/toxicidade , Temperatura Alta , Espécies Reativas de Oxigênio/metabolismo , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica , Solo/química
9.
Zookeys ; 1197: 43-55, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38616923

RESUMO

Due to the detrimental effect of formaldehyde on DNA, ethanol has replaced formalin as the primary preservative for animal specimens. However, short-term formalin fixation of specimens might be applied during field collection. In an increasing number of studies, DNA extraction and sequencing have been successfully conducted from formalin-fixed specimens. Here the DNA from five specimens of Triplophysadalaica (Kessler, 1876) were extracted and performed high-throughput sequencing. Four of the specimens underwent short-term fixation with formalin and were subsequently transferred to ethanol. One was continuously stored in ethanol. No significant difference of DNA quality and amount were observed among these samples. Followed by assembly and annotation, five mitochondrial genomes ranging in length from 16,569 to 16,572 bp were obtained. Additionally, previously published data of other individuals or species were included to perform phylogenetic analyses. In the reconstructed trees, all eight individuals of T.dalaica form a monophyletic group within the Triplophysa branch. The group is divided into three clades: (1) samples from the Yellow River, (2) those from the Yangtze River, and (3) those from the Haihe River, and the Lake Dali Nur. This study sheds initial light on the phylogeographic relationships among different populations of T.dalaica, and will support the research about its evolutionary history in the future.

10.
Sci Rep ; 14(1): 9086, 2024 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643222

RESUMO

The survival significance of the number of positive lymph nodes in salivary gland carcinoma remains unclear. Thus, the current study aimed to determine the effect of the number of positive lymph nodes on disease-specific survival (DSS) and overall survival (OS) in cN0 mucoepidermoid carcinoma (MEC) of the major salivary gland. Patients surgically treated for MEC of the major salivary gland between 1975 and 2019 were retrospectively enrolled from the surveillance, epidemiology, and end results database. The total population was randomly divided into training and test groups (1:1). Primary outcome variables were DSS and OS. Prognostic models were constructed based on the independent prognostic factors determined using univariate and multivariate Cox analyses in the training group and were validated in the test group using C-index. A total of 3317 patients (1624 men and 1693 women) with a mean age of 55 ± 20 years were included. The number of positive lymph nodes was an independent prognostic factor for both DSS and OS, but the effect began when at least two positive lymph nodes for DSS and three positive lymph nodes for OS were found. Predictive models for DSS and OS in the training group had C-indexes of 0.873 (95% confidence interval [CI] 0.853-0.893) and 0.835 (95% CI 0.817-0.853), respectively. The validation of the test group showed C-indexes of 0.877 (95% CI 0.851-0.902) for DSS and 0.820 (95% CI 0.798-0.842) for OS. The number of positive lymph nodes was statistically associated with survival in cN0 major salivary gland MEC. The current prognostic model could provide individualized follow-up strategies for patients with high reliability.


Assuntos
Carcinoma Mucoepidermoide , Neoplasias das Glândulas Salivares , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Carcinoma Mucoepidermoide/cirurgia , Estudos Retrospectivos , Reprodutibilidade dos Testes , Glândulas Salivares/patologia , Prognóstico , Neoplasias das Glândulas Salivares/patologia , Linfonodos/patologia , Estadiamento de Neoplasias
11.
Sci Total Environ ; 928: 172444, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38615769

RESUMO

The development of antibiotic resistance threatens human and environmental health. Non-antibiotic stressors, including fungicides, may contribute to the spread of antibiotic resistance genes (ARGs). We determined the promoting effects of tebuconazole on ARG dissemination using a donor, Escherichia coli MG1655, containing a multidrug-resistant fluorescent plasmid (RP4) and a recipient (E. coli HB101). The donor was then incorporated into the soil to test whether tebuconazole could accelerate the spread of RP4 into indigenous bacteria. Tebuconazole promoted the transfer of the RP4 plasmid from the donor into the recipient via overproduction of reactive oxygen species (ROS), enhancement of cell membrane permeability and regulation of related genes. The dissemination of the RP4 plasmid from the donor to soil bacteria was significantly enhanced by tebuconazole. RP4 plasmid could be propagated into more genera of bacteria in tebuconazole-contaminated soil as the exposure time increased. These findings demonstrate that the fungicide tebuconazole promotes the spread of the RP4 plasmid into indigenous soil bacteria, revealing the potential risk of tebuconazole residues enhancing the dissemination of ARGs in soil environments.


Assuntos
Fungicidas Industriais , Plasmídeos , Microbiologia do Solo , Poluentes do Solo , Triazóis , Plasmídeos/genética , Triazóis/toxicidade , Poluentes do Solo/toxicidade , Fungicidas Industriais/toxicidade , Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Bactérias/genética , Farmacorresistência Bacteriana Múltipla/genética
12.
J Int Med Res ; 52(3): 3000605241233988, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38483129

RESUMO

Gastric metastasis from breast cancer has a high rate of misdiagnosis and missed diagnosis. Data of patients who had gastric metastasis from breast cancer were retrieved from our hospital between 2014 and 2020. The gastric metastasis from breast cancer incidence was 0.04% (5/14,169 cases of breast cancer). Four patients had invasive lobular carcinoma, and the other patient had invasive ductal carcinoma. The time from the initial diagnosis of breast cancer to the appearance of gastric metastasis ranged from 0 to 12 years. One patient's endoscopic presentation was similar to mucosal-associated lymphoid tissue lymphoma and presented with gastric mucosal congestion and edema, widened wrinkles, mixed color fading, and redness. The initial pathological diagnosis of this patient was mucosal-associated lymphoid tissue lymphoma, and breast cancer was finally confirmed by immunohistochemistry. Hormonal receptors were highly expressed in four patients with primary and metastasis lesions and were negative in one patient. Human epidermal growth factor receptor 2 was negative in all patients. Mammaglobin and GATA3 were positive in all patients. In conclusion, the gastric metastasis of breast cancer incidence rate is low, and misdiagnosis can lead to insufficient or excessive treatment. Multiple biopsies and immunohistochemistry should be performed to diagnose gastric metastasis of breast cancer.


Assuntos
Neoplasias da Mama , Carcinoma Lobular , Linfoma , Neoplasias Gástricas , Humanos , Feminino , Neoplasias da Mama/patologia , Carcinoma Lobular/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia
13.
Aging (Albany NY) ; 16(7): 6098-6117, 2024 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-38546403

RESUMO

PURPOSE: Necroptosis plays an important role in the tumorigenesis, development, metastasis, and drug resistance of malignant tumors. This study explored the new model for assessing stomach adenocarcinoma (STAD) prognosis and immunotherapy by combining long noncoding RNAs associated with necroptosis. METHODS: Patient clinical data and STAD gene expression profiles were curated from The Cancer Genome Atlas (TCGA). Immune-related genes were sourced from a specialized molecular database. Perl software and R software were used for data processing and analysis. Necroptosis-related lncRNAs in STAD were pinpointed via R's correlation algorithms. These lncRNAs, in conjunction with clinical data, informed the construction of a prognostic lncRNA-associated risk score model using univariate and multivariate Cox regression analyses. The model's prognostic capacity was evaluated by Kaplan-Meier survival curves and validated as an independent prognostic variable. Further, a nomogram incorporating this model with clinical parameters was developed, offering refined individual survival predictions. Subsequent analyses of immune infiltration and chemosensitivity within necroptosis-related lncRNA clusters utilized an arsenal of bioinformatic tools, culminating in RT-PCR validation of lncRNA expression. RESULTS: Through rigorous Cox regression, 21 lncRNAs were implicated in the risk score model. Stratification by median risk scores delineated patients into high- and low-risk cohorts, with the latter demonstrating superior prognostic outcomes. The risk model was corroborated as an independent prognostic indicator for STAD. The integrative nomogram displayed high concordance between predicted and observed survival rates, as evidenced by calibration curves. Differential immune infiltration in risk-defined groups was illuminated by the single sample GSEA (ssGSEA), indicating pronounced immune presence in higher-risk patients. Tumor microenvironment (TME) analysis showed that cluster-C3 had the highest score in the analysis of the three TMEs. Through the differential analysis of immune checkpoints, it was found that almost all immune checkpoint-related genes were expressed differently in various tumor clusters. Among them, CD44 expression was the highest. By comparing all drug sensitivities, we screened out 29 drugs with differences in drug sensitivity across different clusters. Risk score gene expression identification results showed that these lncRNAs were abnormally expressed in gastric cancer cell lines. CONCLUSIONS: This investigation provides a robust methodological advance in prognosticating and personalizing immunotherapy for STAD, leveraging quantitatively derived tumor cluster risk scores. It posits the use of necroptosis-related lncRNAs as pivotal molecular beacons for guiding therapeutic strategies and enhancing clinical outcomes in STAD.


Assuntos
Adenocarcinoma , Necroptose , RNA Longo não Codificante , Neoplasias Gástricas , Microambiente Tumoral , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Adenocarcinoma/tratamento farmacológico , Prognóstico , Necroptose/genética , Regulação Neoplásica da Expressão Gênica , Masculino , Feminino , Resistencia a Medicamentos Antineoplásicos/genética , Nomogramas , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Estimativa de Kaplan-Meier
14.
Nat Med ; 30(4): 1035-1043, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38438735

RESUMO

Epigenetic modifications of chromatin, including histone acetylation, and tumor angiogenesis play pivotal roles in creating an immunosuppressive tumor microenvironment. In the randomized phase 2 CAPability-01 trial, we investigated the potential efficacy of combining the programmed cell death protein-1 (PD-1) monoclonal antibody sintilimab with the histone deacetylase inhibitor (HDACi) chidamide with or without the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab in patients with unresectable chemotherapy-refractory locally advanced or metastatic microsatellite stable/proficient mismatch repair (MSS/pMMR) colorectal cancer. Forty-eight patients were randomly assigned to either the doublet arm (sintilimab and chidamide, n = 23) or the triplet arm (sintilimab, chidamide and bevacizumab, n = 25). The primary endpoint of progression-free survival (PFS) rate at 18 weeks (18wPFS rate) was met with a rate of 43.8% (21 of 48) for the entire study population. Secondary endpoint results include a median PFS of 3.7 months, an overall response rate of 29.2% (14 of 48), a disease control rate of 56.3% (27 of 48) and a median duration of response of 12.0 months. The secondary endpoint of median overall survival time was not mature. The triplet arm exhibited significantly improved outcomes compared to the doublet arm, with a greater 18wPFS rate (64.0% versus 21.7%, P = 0.003), higher overall response rate (44.0% versus 13.0%, P = 0.027) and longer median PFS rate (7.3 months versus 1.5 months, P = 0.006). The most common treatment-emergent adverse events observed in both the triplet and doublet arms included proteinuria, thrombocytopenia, neutropenia, anemia, leukopenia and diarrhea. There were two treatment-related fatalities (hepatic failure and pneumonitis). Analysis of bulk RNA sequencing data from the patients suggested that the triplet combination enhanced CD8+ T cell infiltration, resulting in a more immunologically active tumor microenvironment. Our study suggests that the combination of a PD-1 antibody, an HDACi, and a VEGF antibody could be a promising treatment regimen for patients with MSS/pMMR advanced colorectal cancer. ClinicalTrials.gov registration: NCT04724239 .


Assuntos
Aminopiridinas , Benzamidas , Neoplasias Colorretais , Inibidores de Histona Desacetilases , Humanos , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/efeitos adversos , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Inibidores de Histona Desacetilases/efeitos adversos , Inibidores de Histona Desacetilases/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Microambiente Tumoral , Fator A de Crescimento do Endotélio Vascular
15.
Small ; 20(22): e2309448, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38362699

RESUMO

Hydrogen peroxide (H2O2) is a highly value-added and environmental-friendly chemical with various applications. The production of H2O2 by electrocatalytic 2e- oxygen reduction reaction (ORR) has emerged as a promising alternative to the energy-intensive anthraquinone process. High selectivity Catalysts combining with superior activity are critical for the efficient electrosynthesis of H2O2. Earth-abundant transition metal selenides (TMSs) being discovered as a classic of stable, low-cost, highly active and selective catalysts for electrochemical 2e- ORR. These features come from the relatively large atomic radius of selenium element, the metal-like properties and the abundant reserves. Moreover, compared with the advanced noble metal or single-atom catalysts, the kinetic current density of TMSs for H2O2 generation is higher in acidic solution, which enable them to become suitable catalyst candidates. Herein, the recent progress of TMSs for ORR to H2O2 is systematically reviewed. The effects of TMSs electrocatalysts on the activity, selectivity and stability of ORR to H2O2 are summarized. It is intended to provide an insight from catalyst design and corresponding reaction mechanisms to the device setup, and to discuss the relationship between structure and activity.

16.
Int J Mol Sci ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38279341

RESUMO

Universal stress proteins (USPs) play an important regulatory role in responses to abiotic stress. Most of the research related to USPs so far has been conducted on plant models such as Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa L.), and cotton (Gossypium hirsutum L.). The potato (Solanum tuberosum L.) is one of the four major food crops in the world. The potato is susceptible to mechanical damage and infection by pathogenic fungi during transport and storage. Deoxynivalenol (DON) released by Fusarium can seriously degrade the quality of potatoes. As a result, it is of great significance to study the expression pattern of the potato StUSP gene family under abiotic stress conditions. In this study, a total of 108 USP genes were identified from the genome of the Atlantic potato, divided into four subgroups. Based on their genetic structure, the physical and chemical properties of their proteins and other aspects of their biological characteristics are comprehensively analyzed. Collinear analysis showed that the homologous genes of StUSPs and four other representative species (Solanum lycopersicum, Arabidopsis, Oryza sativa L., and Nicotiana attenuata) were highly conserved. The cis-regulatory elements of the StUSPs promoter are involved in plant hormones, environmental stress, mechanical damage, and light response. RNA-seq analysis showed that there are differences in the expression patterns of members of each subgroup under different abiotic stresses. A Weighted Gene Coexpression Network Analysis (WGCNA) of the central gene showed that the differential coexpression gene is mainly involved in the plant-pathogen response process, plant hormone signal transduction, and the biosynthesis process of secondary metabolites. Through qRT-PCR analysis, it was confirmed that StUSP13, StUSP14, StUSP15, and StUSP41 may be important candidate genes involved in the response to adversity stress in potatoes. The results of this study provide a basis for further research on the functional analysis of StUSPs in the response of potatoes to adversity stress.


Assuntos
Arabidopsis , Solanum tuberosum , Tricotecenos , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Proteínas de Choque Térmico/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Estresse Fisiológico/genética , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/metabolismo , Filogenia , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas
17.
Front Oncol ; 13: 1257011, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38162498

RESUMO

In China, gastric cancer is the second most common cause of cancer-related death, after lung cancer. At present, the morbidity and mortality rates of gastric cancer are increasing, and targeted therapy for gastric cancer has become a research hotspot. Herein, we report a patient with multiple metastases from advanced gastric cancer. After identifying MET gene amplification, initial treatment induced regression of the tumor. However, in later stages, due to the overexpression or mutation of HER-2, KRAS, TP53, and other genes, the targeted drug therapy became ineffective, and the disease progressed rapidly, leading to the death of the patient.

18.
Microorganisms ; 12(1)2023 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-38257868

RESUMO

Ecological restoration has notably impacted microbe and soil characteristics in abandoned open pit mines, especially in alpine regions. Yet, the adaptive responses of microbial communities in the initial years of mine site restoration remain largely unexplored. This study endeavors to offer a thorough comprehension of soil properties and microbial dynamics during the initial phases of alpine mining land reclamation. It places emphasis on physicochemical properties and microbial community composition and evaluates the feasibility of phytoremediation, along with proposing subsequent measures. Our study employs spatial sequence instead of time-sequenceal sequence to investigate early-stage changes in soil microbes and physicochemical properties in alpine mining land reclamation. We used high-throughput sequencing for the 16S rRNA amplicon study. Over time, soil physicochemical properties improved noticeably. Soil pH shifted from neutral to alkaline (7.04-8.0), while soil electrical conductivity (EC) decreased to 77 µS·cm-1 in R_6a. Cation exchange capacity (CEC) initially decreased from R_2a (12.30-27.98 cmol·kg-1) and then increased. Soil organic matter increased from 17.7 to 43.2 g·kg-1 over time during mine reclamation and restoration. The dominant bacterial community consisted of Proteobacteria (33.94% to 52.09%), Acidobacteriota (4.94% to 15.88%), Bacteroidota (6.52% to 11.15%), Actinobacteriota (7.18% to 9.61%), and Firmicutes (4.52% to 16.80%) with varying relative abundances. Gene annotation of sequences from various reclamation years revealed general function prediction, translation, ribosome structure, cell wall/membrane/envelope biogenesis, nucleotide translocation, and metabolism, along with other related functions. Mine reclamation improved soil fertility and properties, with the R_6a treatment being the most effective. Starting in the 2nd year of reclamation, the effective phosphorus content and the dominance of microbial bacteria, notably the Bacillus content, decreased. Firmicute fertilization promoted phosphorus and bacterial growth. In conclusion, employing a blend of sequencing and experimental approaches, our study unveils early-stage enhancements in soil microbial and physicochemical properties during the reclamation of alpine mining areas. The results underscore the beneficial impacts of vegetation restoration on key properties, including soil fertility, pore structure, and bacterial community composition. Special attention is given to assessing the effectiveness of the R_6a treatment and identifying deficiencies in the R_2a treatment. It serves as a reference for addressing the challenges associated with soil fertility and microbial community structure restoration in high-altitude mining areas in Qinghai-Tibet. This holds great significance for soil and water conservation as well as vegetation restoration in alpine mining regions. Furthermore, it supports the sustainable restoration of local ecosystems.

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