Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 78
Filtrar
1.
Adv Mater ; : e2401473, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38663859

RESUMO

Lithium-sulfur (Li-S) batteries offer high theoretical capacity but are hindered by poor rate capability and cycling stability due to sluggish Li2S precipitation kinetics. Here a sulfonate-group-rich liquid crystal polymer (poly-2,2'-disulfonyl-4,4'-benzidine terephthalamide, PBDT) is designed and fabricated to accelerate Li2S precipitation by promoting the desolvation of Li+ from electrolyte. PBDT-modified separators are employed to assemble Li-S batteries, which deliver a remarkable rate capacity (761 mAh g-1 at 4 C) and cycling stability (500 cycles with an average decay rate of 0.088% per cycle at 0.5 C). A PBDT-based pouch cell even delivers an exceptional capacity of ≈1400 mAh g-1 and an areal capacity of ≈11 mAh cm-2 under lean-electrolyte and high-sulfur-loading condition, demonstrating promise for practical applications. Results of Raman spectra, molecular dynamic (MD) and density functional theory (DFT) calculations reveal that the abundant anionic sulfonate groups of PBDT aid in Li+ desolvation by attenuating Li+-solvent interactions and lowering the desolvation energy barrier. Plus, the polysulfide adsorption/catalysis is also excluded via electrostatic repulsion. This work elucidates the critical impact of Li+ desolvation on Li-S batteries and provides a new design direction for advanced Li-S batteries.

2.
J Cardiothorac Surg ; 19(1): 141, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504347

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of morality among all malignant tumors. Smoking is one of the most important causes of NSCLC, which contributes not only to the initiation of NSCLC but also to its progression. The identification of specific biomarkers associated with smoking will promote diagnosis and treatment. METHODS: Data mining was used to identify the smoking associated gene SERPINB12. CCK8 assays, colony formation assays, a mouse xenograft model and transwell assays were performed to measure the biological functions of SERPINB12 in NSCLC. GSEA, luciferase reporter assays and immunofluorescence were conducted to explore the potential molecular mechanisms of SERPINB12 in NSCLC. RESULTS: In this study, by data mining the TCGA database, we found that SERPINB12 was greatly upregulated in NSCLC patients with cigarette consumption behavior, while the expression level was positively correlated with disease grade and poor prognosis. SERPINB12 is a kind of serpin peptidase inhibitor, but its function in malignant tumors remains largely unknown. Functionally, knockdown of SERPINB12 observably inhibited the proliferation and metastasis of NSCLC cells in vitro and in vivo. Moreover, downregulation of SERPINB12 attenuated Wnt signaling by inhibiting the nuclear translocation of ß-catenin, which explained the molecular mechanism underlying tumor progression. CONCLUSIONS: In conclusion, SERPINB12 functions as a tumorigenesis factor, which could be a promising biomarker for NSCLC patients with smoking behavior, as well as a therapeutic target.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Serpinas , Humanos , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Via de Sinalização Wnt/genética , Regulação para Cima , Linhagem Celular Tumoral , Fumar/efeitos adversos , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Movimento Celular , Serpinas/genética
3.
Adv Mater ; 36(4): e2307218, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37972344

RESUMO

Costly data movement in terms of time and energy in traditional von Neumann systems is exacerbated by emerging information technologies related to artificial intelligence. In-memory computing (IMC) architecture aims to address this problem. Although the IMC hardware prototype represented by a memristor is developed rapidly and performs well, the sneak path issue is a critical and unavoidable challenge prevalent in large-scale and high-density crossbar arrays, particularly in three-dimensional (3D) integration. As a perfect solution to the sneak-path issue, a self-rectifying memristor (SRM) is proposed for 3D integration because of its superior integration density. To date, SRMs have performed well in terms of power consumption (aJ level) and scalability (>102  Mbit). Moreover, SRM-configured 3D integration is considered an ideal hardware platform for 3D IMC. This review focuses on the progress in SRMs and their applications in 3D memory, IMC, neuromorphic computing, and hardware security. The advantages, disadvantages, and optimization strategies of SRMs in diverse application scenarios are illustrated. Challenges posed by physical mechanisms, fabrication processes, and peripheral circuits, as well as potential solutions at the device and system levels, are also discussed.

4.
RSC Adv ; 13(50): 35689-35694, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38077978

RESUMO

Co-Mo-S based catalysts have promising applications in both the hydrogen evolution reaction (HER) and hydrodesulfurization (HDS). Herein, Co-Mo-S catalyst and Co-Mo-S catalyst with and without NaBH4 modification have been successfully synthesized by a simple hydrothermal synthesis method. Co-Mo-S catalysts with NaBH4 modification show better catalytic activity towards both HDS and the HER. The phase purity, morphology, crystal structures and electron valence distribution of the catalysts with and without NaBH4 modification were studied by experimental characterizations and theoretical calculations. The catalysts without NaBH4 modification are mostly 2H-MoS2, while the catalysts without NaBH4 modification have 1T-MoS2, and 1T-MoS2 is exposed to more active sites, which will be conducive to the results of HDS performance of the catalyst. DFT calculations investigated the required activation energies of 1T-MoS2 and 2H-MoS2 for HDS and HER, respectively. The activation energy required for both HDS and H2 generation of 1T-MoS2 is significantly lower than that for the 2H-MoS2 structure.

5.
BMC Genomics ; 24(1): 591, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37798722

RESUMO

BACKGROUND: Circular RNAs (circRNAs), as important non-coding RNAs (ncRNAs), are involved in many biological activities. However, the exact chemical mechanism behind fat accumulation is unknown. In this paper, we obtained the expression profiles of circRNAs using high-throughput sequencing and investigated their differential expression in subcutaneous fat tissue of Duolang and Small Tail Han sheep. RESULTS: From the transcriptomic analysis, 141 differentially expressed circRNAs were identified, comprising 61 up-regulated circRNAs and 80 down-regulated circRNAs. These host genes were primarily enriched in the MAPK and AMPK signaling pathways which is closely associated with fat deposition regulation. We identified circRNA812, circRNA91, and circRNA388 as vital genes in fat deposition by miRNA-circRNA target gene prediction. The functional annotation results of target genes of key circRNAs showed that the signaling pathways mainly included PI3K-Akt and AMPK. We constructed the competing endogenous RNA (ceRNA) regulatory network to study the role of circRNAs in sheep lipid deposition, and circRNA812, circRNA91, and circRNA388 can adsorb more miRNAs. NC_040253.1_5757, as the source of miRNA response element (MRE) among the three, may play an important role during the process of sheep fat deposition. CONCLUSIONS: Our study gives a systematic examination of the circRNA profiles expressed in sheep subcutaneous fat. These results from this study provide some new basis for understanding circRNA function and sheep fat metabolism.


Assuntos
MicroRNAs , RNA Circular , Animais , Ovinos/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Quinases Ativadas por AMP/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Gordura Subcutânea/metabolismo , Redes Reguladoras de Genes
6.
J Cell Mol Med ; 28(5): e17856, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37461162

RESUMO

The highly expressed oncogenic factor Krüppel-like factor 5 (KLF5) promotes various cancerous processes, such as cell growth, survival, anti-apoptosis, migration and metastasis, particularly in lung cancer. Nevertheless, the modifications to KLF5 after translation are poorly understood. Protein arginine methyltransferase 5 (PRMT5) is considered as an oncogene known to be involved in different types of carcinomas, including lung cancer. Here, we show that the expression levels of PRMT5 and KLF5 are highly expressed lung cancer. Moreover, PRMT5 interacts with KLF5 and facilitates the dimethylation of KLF5 at Arginine 41 in a manner that depends on methyltransferase activity. Downregulation or pharmaceutical suppression of PRMT5 reduces the expression of KLF5 and its downstream targets both in vitro and in vivo. Mechanistically, the dimethylation of KLF5 by PRMT5 promotes the maintenance and proliferation of lung cancer cells at least partially by stabilising KLF5 via regulation of the Akt/GSK3ß signalling axis. In summary, PRMT5 methylates KLF5 to prevent its degradation, thereby promoting the maintenance and proliferation of lung cancer cells. These results suggest that targeting PRMT5/KLF5 axis may offer a potential therapeutic strategy for lung cancer.

7.
J Surg Oncol ; 128(5): 743-748, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37243870

RESUMO

BACKGROUND: Papillary thyroid cancer (PTC) is the most common type of differentiated thyroid cancer. Early identification of patients at higher risk of recurrence may allow to improve relevant follow-up strategies and plan tailored treatment. Inflammation play an important role in the prognosis of cancer. We aimed to explore the predictive value of systemic inflammatory markers in PTC recurrence. METHODS: We retrospectively enrolled 200 consecutive patients who were diagnosed with PTC and underwent curative resection at Lianyungang Oriental Hospital between January 2006 and December 2018. Clinicopathological characteristics, preoperative hematologic results were analyzed. The optimal cutoff values were calculated using x-tile software. The multivariate logistic regression and univariable survival analysis were performed by SPSS. RESULTS: Multivariable analysis showed that lymph node metastases (odds ratio [OR] = 2.506, 95% confidence interval [CI]: 1.226-5.119, p = 0.012) and higher monocyte-to-lymphocyte ratio (MLR) (OR = 2.100, 95% CI: 1.042-4.233, p = 0.038) were independent prognostic factors for tumor recurrence. The cutoff value 0.22 of MLR significantly predicted recurrence at 53.3% sensitivity and 67.9% specificity. Patients with MLR ≥ 0.22 exhibited significantly poor long-term prognosis (46.8%) compared to the counterpart (76.8%, p = 0.0004). CONCLUSIONS: Preoperative MLR significantly predicted PTC recurrence after curative resection, which may provide clues for early identification of patients at higher risk of PTC recurrence.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/patologia , Estudos Retrospectivos , Carcinoma Papilar/cirurgia , Neoplasias da Glândula Tireoide/patologia , Prognóstico , Recidiva Local de Neoplasia/cirurgia , Tireoidectomia
8.
Int J Surg ; 109(5): 1318-1329, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37068793

RESUMO

BACKGROUND: Anastomotic stricture is a common underlying cause of long-term morbidity after hepaticojejunostomy (HJ) for bile duct injury (BDI) following cholecystectomy. However, there are no methods for predicting stricture risk. This study was aimed at establishing two online calculators for predicting anastomotic stricture occurrence (ASO) and stricture-free survival (SFS) in this patient population. METHODS: The clinicopathological characteristics and follow-up information of patients who underwent HJ for BDI after cholecystectomy from a multi-institutional database were reviewed. Univariate and multivariate analyses of the risk factors of ASO and SFS were performed in the training cohort. Two nomogram-based online calculators were developed and validated by internal bootstrapping resamples ( n =1000) and an external cohort. RESULTS: Among 220 screened patients, 41 (18.64%) experienced anastomotic strictures after a median follow-up of 110.7 months. Using multivariate analysis, four variables, including previous repair, sepsis, HJ phase, and bile duct fistula, were identified as independent risk factors associated with both ASO and SFS. Two nomogram models and their corresponding online calculators were subsequently developed. In the training cohort, the novel calculators achieved concordance indices ( C -indices) of 0.841 and 0.763 in predicting ASO and SFS, respectively, much higher than those of the above variables. The predictive accuracy of the resulting models was also good in the internal ( C -indices: 0.867 and 0.821) and external ( C -indices: 0.852 and 0.823) validation cohorts. CONCLUSIONS: The two easy-to-use online calculators demonstrated optimal predictive performance for identifying patients at high risk for ASO and with dismal SFS. The estimation of individual risks will help guide decision-making and long-term personalized surveillance.


Assuntos
Doenças dos Ductos Biliares , Ductos Biliares , Humanos , Ductos Biliares/cirurgia , Ductos Biliares/lesões , Estudos Retrospectivos , Colecistectomia/efeitos adversos , Doenças dos Ductos Biliares/etiologia , Fatores de Risco , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
9.
RSC Adv ; 13(4): 2600-2610, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36741148

RESUMO

Exploring the design strategy of new energetic materials is crucial to promote the development of energetic materials. In this study, a method for designing polycyclic energetic materials is proposed by combining the azetidine structure with azobis-1,2,4-triazole or bi-1,2,4-triazole. A series of typical triazolyl polycyclic compounds were designed and synthesized by simple nucleophilic reaction, which included 5,5'-dichloro-3,3'-bis(3,3'-difluoroazetidine)-4,4'-azobis-1,2,4-triazole (1), 5,5'-dichloro-3,3'-bis(3,3'-difluoroazetidine)-4,4'-bi-1,2,4-triazole (2), 5,5'-dichloro-3-(N,N-dimethyl)-3'-(3,3'-difluoroazetidine)-4,4'-bi-1,2,4-triazole (3) 5,5'-dichloro-3,3'-bis(3,3'-dinitroazetidine)-4,4'-bi-1,2,4-triazole (4), 5,5'-dichloro-3-(N,N-dimethyl)-3'-(3,3'-dinitroazetidine)-4,4'-bi-1,2,4-triazole (5), and 5,5'-diazido-3,3'-bis(3,3'-difluoroazetidine)-4,4'-azo-1,2,4-triazole (6). These designed and synthesized polycyclic compounds (1, 2, 3) have high decomposition temperatures (>200 °C). The molecular van der Waals surface electrostatic potentials suggested the reactivity of compounds 1, 2, and 3 when attacked by nucleophiles. The natural bond orbital and Hirshfeld surface analysis proved the essential reason for the stability of these compounds in theory. The formula design example suggests that some triazolyl polycyclic compounds (4, 5, and 6) are potentially explosives, suggesting that this strategy is feasible for constructing the triazolyl polycyclic energetic compounds.

10.
Cell Discov ; 9(1): 20, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36810288

RESUMO

Immune checkpoint blockade (ICB) therapy targeting PD-1/PD-L1 has shown durable clinical benefits in lung cancer. However, many patients respond poorly to ICB treatment, underscoring an incomplete understanding of PD-L1 regulation and therapy resistance. Here, we find that MTSS1 is downregulated in lung adenocarcinoma, leading to PD-L1 upregulation, impairment of CD8+ lymphocyte function, and enhanced tumor progression. MTSS1 downregulation correlates with improved ICB efficacy in patients. Mechanistically, MTSS1 interacts with the E3 ligase AIP4 for PD-L1 monoubiquitination at Lysine 263, leading to PD-L1 endocytic sorting and lysosomal degradation. In addition, EGFR-KRAS signaling in lung adenocarcinoma suppresses MTSS1 and upregulates PD-L1. More importantly, combining AIP4-targeting via the clinical antidepressant drug clomipramine and ICB treatment improves therapy response and effectively suppresses the growth of ICB-resistant tumors in immunocompetent mice and humanized mice. Overall, our study discovers an MTSS1-AIP4 axis for PD-L1 monoubiquitination and reveals a potential combinatory therapy with antidepressants and ICB.

11.
Allergol Immunopathol (Madr) ; 51(1): 159-167, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36617836

RESUMO

INTRODUCTION: Inflammatory bowel disease (IBD), which mainly leads to diarrhea, fatigue, stool blood, abdominal pain, and cramping, is threatening public health. Tripartite motif-containing 52 (TRIM52) has been reported to play an important role in inflammatory responses via activating the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway. However, the causes of IBD need to be elucidated, and the function of TRIM52 in IBD remains unclear. Here, we demonstrated that TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium (DSS)-induced IBD by activating TLR4/NF-κBs pathway. METHODS: The colitis model was established on mice through DSS induction. For the TRIM52 knockdown, the mice were infected with a recombinant adenoviral vector expressing sgRNAs targeting TRIM52. RT-qPCR, western blot, and immunohistochemistry were performed to verify TRIM52 expression in DSS-induced IBD. The body weight, disease activity index, colon length, and H&E staining were used to assess the IBD symptoms in mice with TRIM52 knockdown. The inflammatory responses were examined by RT-qPCR and ELISA measuring tumor necrosis factor-α (TNF-α), inter-leukin 6 (IL-6), and interleukin 1ß (IL-1ß). Furthermore, the pyroptosis in colon tissue was detected by western blot. Finally, the TLR4/NF-κBs pathway activity was also examined by western blot. RESULTS: TRIM52 expression was up-regulated in DSS-induced IBD, and knockdown of TRIM52 could alleviate the symptoms of IBD. TRIM52 knockdown retarded DSS-induced inflammatory response and inhibited DSS-induced pyroptosis in colon tissue. In addition, TRIM52 played a role in activating TLR4/NF-κBs pathway. CONCLUSION: Knockdown of TRIM52 alleviated inflammation and pyroptosis in IBD by regulating TLR4/NF-κBs pathway. TRIM52 is expected to be a novel diagnostic indicator for IBD and a target of therapeutic treatment.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Piroptose , Proteínas com Motivo Tripartido , Animais , Camundongos , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Inflamação , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Proteínas com Motivo Tripartido/metabolismo
12.
Adv Mater ; 35(14): e2211790, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36632699

RESUMO

Precisely tailoring the oxidation state of single-atomic metal in heterogeneous catalysis is an efficient way to stabilize the single-atomic site and promote their activity, but realizing this approach remains a grand challenge to date. Herein, a class of stable single-atomic catalysts with well-tuned oxidation state of Pt by forming PtFe atomic bonds is reported, which are supported by defective Fe2 O3  nanosheets on reduced graphene oxide (PFARFNs). These as-synthesized materials can greatly enhance the catalytic activity, stability, and selectivity for the diboration of alkynes. The PFARFNs exhibit high conversion of 99% at 100 °C with an outstanding turnover frequency (TOF) of 545 h-1 , and a relatively high conversion of 58% at room temperature (25 °C) with a TOF of 310 h-1 , which has been hardly achieved previously. Through both experimental and theoretical investigation, it is demonstrated that the fast electron transfer from Fe to Pt in Fe-Pt-O atomic sites in PFARFNs can not only stabilize the single-atomic Pt, but also significantly improve their catalytic activity.

13.
Allergol. immunopatol ; 51(1): 159-167, ene. 2023. tab, graf
Artigo em Inglês | IBECS | ID: ibc-214032

RESUMO

Introduction: Inflammatory bowel disease (IBD), which mainly leads to diarrhea, fatigue, stool blood, abdominal pain, and cramping, is threatening public health. Tripartite motif-containing 52 (TRIM52) has been reported to play an important role in inflammatory responses via activating the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway. However, the causes of IBD need to be elucidated, and the function of TRIM52 in IBD remains unclear. Here, we demonstrated that TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium (DSS)-induced IBD by activating TLR4/NF-κBs pathway. Methods: The colitis model was established on mice through DSS induction. For the TRIM52 knockdown, the mice were infected with a recombinant adenoviral vector expressing sgRNAs targeting TRIM52. RT-qPCR, western blot, and immunohistochemistry were performed to verify TRIM52 expression in DSS-induced IBD. The body weight, disease activity index, colon length, and H&E staining were used to assess the IBD symptoms in mice with TRIM52 knockdown. The inflammatory responses were examined by RT-qPCR and ELISA measuring tumor necrosis factor-α (TNF-α), inter-leukin 6 (IL-6), and interleukin 1β (IL-1β). Furthermore, the pyroptosis in colon tissue was detected by western blot. Finally, the TLR4/NF-κBs pathway activity was also examined by western blot. Results: TRIM52 expression was up-regulated in DSS-induced IBD, and knockdown of TRIM52 could alleviate the symptoms of IBD. TRIM52 knockdown retarded DSS-induced inflammatory response and inhibited DSS-induced pyroptosis in colon tissue. In addition, TRIM52 played a role in activating TLR4/NF-κBs pathway. Conclusion: Knockdown of TRIM52 alleviated inflammation and pyroptosis in IBD by regulating TLR4/NF-κBs pathway. TRIM52 is expected to be a novel diagnostic indicator for IBD and a target of therapeutic treatment (AU)


Assuntos
Animais , Camundongos , Proteínas com Motivo Tripartido/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Receptor 4 Toll-Like/metabolismo , NF-kappa B/metabolismo , Colite/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Transdução de Sinais , Camundongos Transgênicos , Sulfato de Dextrana
14.
Adv Mater ; 35(50): e2206402, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36062873

RESUMO

Solid-state batteries (SSBs) are considered as one of the most promising candidates for the next-generation energy-storage technology, because they simultaneously exhibit high safety, high energy density, and wide operating temperature range. The replacement of liquid electrolytes with solid electrolytes produces numerous solid-solid interfaces within the SSBs. A thorough understanding on the roles of these interfaces is indispensable for the rational performance optimization. In this review, the interface issues in the SSBs, including internal buried interfaces within solid electrolytes and composite electrodes, and planar interfaces between electrodes and solid electrolyte separators or current collectors are discussed. The challenges and future directions on the investigation and optimization of these solid-solid interfaces for the production of the SSBs are also assessed.

15.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-993192

RESUMO

Objective:To analyze the clinical efficacy and prognostic factors of intracranial primary diffuse large B-cell lymphoma (DLBCL).Methods:Clinical data of 205 patients pathologically diagnosed with intracranial primary DLBCL at Sun Yat-sen University Cancer center from March 2001 to September 2020 were retrospectively analyzed. Among them, 101 patients were male and 104 female, the median age was 54 years old. Non-germinal center B cell (GCB) subtype accounted for 74.1%(126/170). A total of 177 patients received high-dose methotrexate (HD-MTX) and 91 patients received rituximab. After induction chemotherapy, 59 patients (30.4%) achieved complete response (CR), 112 patients (57.7%) achieved partial response (PR) or stable disease (SD). A total of 83 patients received consolidation or salvage radiotherapy, and only 14 patients received autologous stem cell transplantation (ASCT). The influence of pathological type, chemotherapy, rituximab treatment, radiotherapy and radiotherapy mode, ASCT and other factors on the overall survival (OS) and progression free survival (PFS) was evaluated. The survival rate was calculated by Kaplan-Meier method. Univariate prognostic analysis was performed by log-rank test. Multivariate prognostic analysis was conducted by COX model.Results:The median follow-up time was 34 months. The 5-year OS and PFS rates were 55.6% and 44.2%, respectively. GCB subtype, chemotherapy with HD-MTX, rituximab treatment, remission status after induction chemotherapy, and radiotherapy were favorable prognostic factors for OS or PFS, in which the last three were the independent prognostic factors. Consolidation radiotherapy in patients who obtained CR after induction chemotherapy did not significantly improve survival, while salvage radiotherapy in patients who achieved PR/SD after induction chemotherapy significantly improved both OS and PFS(both P<0.01). Consolidation radiotherapy showed no significant survival difference compared with consolidation ASCT. Conclusions:The non-GCB subtype of intracranial primary DLBCL is related to poor prognosis. The addition of rituximab to HD-MTX based induction chemotherapy can improve survival. Radiotherapy is still an important treatment for intracranial primary DLBCL, and there are limitations of ASCT in practical clinical application.

16.
Nat Commun ; 13(1): 7281, 2022 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-36435834

RESUMO

Chronic inflammation and an immunosuppressive microenvironment promote prostate cancer (PCa) progression and diminish the response to immune checkpoint blockade (ICB) therapies. However, it remains unclear how and to what extent these two events are coordinated. Here, we show that ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, functions downstream of inflammation-induced IKKß activation to shape the immunosuppressive tumor microenvironment (TME). Prostate-specific deletion of Arid1a cooperates with Pten loss to accelerate prostate tumorigenesis. We identify polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) as the major infiltrating immune cell type that causes immune evasion and reveal that neutralization of PMN-MDSCs restricts the progression of Arid1a-deficient tumors. Mechanistically, inflammatory cues activate IKKß to phosphorylate ARID1A, leading to its degradation via ß-TRCP. ARID1A downregulation in turn silences the enhancer of A20 deubiquitinase, a critical negative regulator of NF-κB signaling, and thereby unleashes CXCR2 ligand-mediated MDSC chemotaxis. Importantly, our results support the therapeutic strategy of anti-NF-κB antibody or targeting CXCR2 combined with ICB for advanced PCa. Together, our findings highlight that the IKKß/ARID1A/NF-κB feedback axis integrates inflammation and immunosuppression to promote PCa progression.


Assuntos
Células Supressoras Mieloides , Neoplasias da Próstata , Masculino , Humanos , Próstata/metabolismo , Quimiotaxia , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Neoplasias da Próstata/metabolismo , NF-kappa B/metabolismo , Receptores de Interleucina-8B/metabolismo , Proteínas Serina-Treonina Quinases , Inflamação/genética , Inflamação/metabolismo , Microambiente Tumoral/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
17.
Front Vet Sci ; 9: 938311, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35880040

RESUMO

microRNAs are a class of important non-coding RNAs, which can participate in the regulation of biological processes. In recent years, miRNA has been widely studied not only in humans and mice, but also in animal husbandry. However, compared with other livestock and poultry breeds, the study of miRNA in subcutaneous adipose tissue of sheep is not comprehensive. Transcriptome analysis of miRNAs in subcutaneous adipose tissue of Duolang sheep, and Small Tail Han sheep was performed using RNA-Seq technology. Differentially expressed miRNAs were screened between different breeds. Target genes were predicted, and then the joint analysis of candidate genes were conducted based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, the RNA-Seq data were verified by real-time quantitative polymerase chain reaction (qRT-PCR). Herein, we identified 38 differentially expressed miRNAs (9 novel miRNAs and 29 known miRNAs). In addition, a total of 854 target genes were predicted by miRanda software. GO and KEGG pathway analysis demonstrated that regulation of lipolysis in adipocytes plays a key role in the deposition of subcutaneous adipose tissue in Duolang sheep and Small Tail Han sheep. The miRNAs might regulate fat deposits by regulating genes involved in regulation of lipolysis in adipocytes. Specifically, NC_ 040278.1_ 37602, oar-mir-493-3p, NC_ 040278.1_ 37521 and NC_ 040255.1_ 11627 might target PTGS2, AKT2, AKT3, and PIK3CA, respectively, and then play critical regulatory role. In conclusion, all the results provide a good idea for further revealing the mechanism of subcutaneous adipose tissue deposition and improving the meat production performance of sheep, and lay a foundation for promoting the development of animal husbandry.

18.
Mater Horiz ; 9(3): 1036-1044, 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35022629

RESUMO

Phase engineering of two-dimensional transition metal dichalcogenides has received increasing attention in recent years due to its atomically thin nature and polymorphism. Here, we first realize an electric-field-induced controllable phase transition between semiconducting 2H and metallic 1T' phases in MoTe2 memristive devices. The device performs stable bipolar resistive switching with a cycling endurance of over 105, an excellent retention characteristic of over 105 s at an elevated temperature of 85 °C and an ultrafast switching of ∼5 ns for SET and ∼10 ns for RESET. More importantly, the device works in different atmospheres including air, vacuum and oxygen, and even works with no degradation after being placed in air for one year, indicating excellent surrounding and time stability. In situ Raman analysis reveals that the stable resistive switching originates from a controllable phase transition between 2H and 1T' phases. Density functional theory calculations reveal that the Te vacancy facilitates the phase transition in MoTe2 through decreasing the barrier between 2H and 1T' phases, and serving as nucleation sites due to the elimination of repulsive forces. This electric-field-induced controllable phase transition in MoTe2 devices offers new opportunities for developing reliable and ultrafast phase transition devices based on atomically thin membranes.

19.
World J Gastrointest Surg ; 14(12): 1432-1437, 2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36632116

RESUMO

BACKGROUND: Common diseases after radical gastrectomy include cholecystitis and pancreatitis, but the sudden onset of acute appendicitis in a short period following radical gastrectomy is very rare, and its clinical symptoms are easily misdiagnosed as duodenal stump leakage. CASE SUMMARY: This is a case report of a 77-year-old woman with lower right abdominal pain 14 d after radical resection of gastric cancer. Her pain was not relieved by conservative treatment, and her inflammatory markers were elevated. Computed tomography showed effusion in the perihepatic and hepatorenal spaces, right paracolic sulcus and pelvis, as well as exudative changes in the right iliac fossa. Ultrasound-guided puncture revealed a slightly turbid yellow-green fluid. Laparoscopic exploration showed a swollen appendix with surrounding pus moss and no abnormalities of the digestive anastomosis or stump; thus, laparoscopic appendectomy was performed. The patient recovered well after the operation. Postoperative pathology showed acute purulent appendicitis. The patient continued adjuvant chemotherapy after surgery, completing three cycles of oxaliplatin plus S-1 (SOX regimen). CONCLUSION: Acute appendicitis in the short term after radical gastrectomy needs to be differentiated from duodenal stump leakage, and early diagnosis and surgery are the most important means of treatment.

20.
Cell Death Dis ; 13(1): 1, 2021 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-34911928

RESUMO

Fulminant hepatic failure (FHF) is a potentially fatal liver disease that is associated with intrahepatic infiltration of inflammatory cells. As the receptor of polyunsaturated long chain fatty acids, GPR120 can regulate cell differentiation, proliferation, metabolism, and immune response. However, whether GPR120 is involved in FHF remains unknown. Using Propionibacterium acnes (P. acnes)-primed, LPS-induced FHF in mice, we found that interference with GPR120 activity using pharmacological agonist attenuated the severity of the liver injury and mortality of FHF in mice, while a lack of GPR120 exacerbated the disease. GPR120 activation potently alleviated FHF and led to decreased T helper (Th) 1 cell response and expansion of regulatory T cells (Tregs). Interestingly, GPR120 agonist didn't directly target T cells, but dramatically induced a distinct population of CD11c+MHC IIlowCD80lowCD86low regulatory DCs in the livers of FHF mice. GPR120 was found to restrict HIF-1α-dependent glycolysis. The augmented HIF-1α stabilization caused by GPR120 antagonism or deletion could be attenuated by the inhibition of ERK or by the activation of AMPK. Through the analysis of the clinical FHF, we further confirmed the activation of GPR120 was negatively associated with the severity in patients. Our findings indicated that GPR120 activation has therapeutic potential in FHF. Strategies to target GPR120 using agonists or free fatty acids (FFAs) may represent a novel approach to FHF treatment.


Assuntos
Células Dendríticas/metabolismo , Falência Hepática Aguda/genética , Receptores Acoplados a Proteínas G/metabolismo , Animais , Estudos de Casos e Controles , Modelos Animais de Doenças , Feminino , Glicólise , Humanos , Camundongos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...