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1.
Cancer Immunol Immunother ; 73(7): 125, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733402

RESUMO

BACKGROUND: Despite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC  plus cisplatin CCRT ) for LANPC patients. METHODS: From January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors. RESULTS: After PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3-4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064). CONCLUSION: Additiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.


Assuntos
Quimiorradioterapia , Quimioterapia de Indução , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Pontuação de Propensão , Humanos , Masculino , Feminino , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/tratamento farmacológico , Pessoa de Meia-Idade , Quimiorradioterapia/métodos , Adulto , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/tratamento farmacológico , Quimioterapia de Indução/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/uso terapêutico , Idoso , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Desoxicitidina/administração & dosagem , Estudos Retrospectivos , Gencitabina
2.
Biomed Environ Sci ; 37(4): 367-376, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38727159

RESUMO

Objective: This study aimed to clarify the intervention effect of salidroside (SAL) on lung injury caused by PM 2.5 in mice and illuminate the function of SIRT1-PGC-1ɑ axis. Methods: Specific pathogen-free (SPF) grade male C57BL/6 mice were randomly assigned to the following groups: control group, SAL group, PM 2.5 group, SAL+PM 2.5 group. On the first day, SAL was given by gavage, and on the second day, PM 2.5 suspension was given by intratracheal instillation. The whole experiment consist of a total of 10 cycles, lasting 20 days. At the end of treatment, blood samples and lung tissues were collected and analyzed. Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy. The expression of inflammatory, antioxidants, apoptosis, and SIRT1-PGC-1ɑ proteins were detected by Western blotting. Results: Exposure to PM 2.5 leads to obvious morphological and pathologica changes in the lung of mice. PM 2.5 caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1, Nrf2, SOD2, SIRT1 and PGC-1ɑ, and an increase in the protein expressions of IL-6, IL-1ß, Bax, caspase-9 and cleaved caspase-3. However, SAL reversed the aforementioned changes caused by PM 2.5 by activating the SIRT1-PGC-1α pathway. Conclusion: SAL can activate SIRT1-PGC-1ɑ to ameliorate PM 2.5-induced lung injury.


Assuntos
Glucosídeos , Lesão Pulmonar , Camundongos Endogâmicos C57BL , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Fenóis , Sirtuína 1 , Animais , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Sirtuína 1/metabolismo , Sirtuína 1/genética , Masculino , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Camundongos , Lesão Pulmonar/tratamento farmacológico , Material Particulado/toxicidade , Material Particulado/efeitos adversos , Tamanho da Partícula , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo
3.
CNS Neurosci Ther ; 30(4): e14721, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38644578

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder distinguished by a swift cognitive deterioration accompanied by distinctive pathological hallmarks such as extracellular Aß (ß-amyloid) peptides, neuronal neurofibrillary tangles (NFTs), sustained neuroinflammation, and synaptic degeneration. The elevated frequency of AD cases and its proclivity to manifest at a younger age present a pressing challenge in the quest for novel therapeutic interventions. Numerous investigations have substantiated the involvement of C/EBPß in the progression of AD pathology, thus indicating its potential as a therapeutic target for AD treatment. AIMS: Several studies have demonstrated an elevation in the expression level of C/EBPß among individuals afflicted with AD. Consequently, this review predominantly delves into the association between C/EBPß expression and the pathological progression of Alzheimer's disease, elucidating its underlying molecular mechanism, and pointing out the possibility that C/EBPß can be a new therapeutic target for AD. METHODS: A systematic literature search was performed across multiple databases, including PubMed, Google Scholar, and so on, utilizing predetermined keywords and MeSH terms, without temporal constraints. The inclusion criteria encompassed diverse study designs, such as experimental, case-control, and cohort studies, restricted to publications in the English language, while conference abstracts and unpublished sources were excluded. RESULTS: Overexpression of C/EBPß exacerbates the pathological features of AD, primarily by promoting neuroinflammation and mediating the transcriptional regulation of key molecular pathways, including δ-secretase, apolipoprotein E4 (APOE4), acidic leucine-rich nuclear phosphoprotein-32A (ANP32A), transient receptor potential channel 1 (TRPC1), and Forkhead BoxO (FOXO). DISCUSSION: The correlation between overexpression of C/EBPß and the pathological development of AD, along with its molecular mechanisms, is evident. Investigating the pathways through which C/EBPß regulates the development of AD reveals numerous multiple vicious cycle pathways exacerbating the pathological progression of the disease. Furthermore, the exacerbation of pathological progression due to C/EBPß overexpression and its molecular mechanism is not limited to AD but also extends to other neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and multiple sclerosis (MS). CONCLUSION: The overexpression of C/EBPß accelerates the irreversible progression of AD pathophysiology. Additionally, C/EBPß plays a crucial role in mediating multiple pathways linked to AD pathology, some of which engender vicious cycles, leading to the establishment of feedback mechanisms. To sum up, targeting C/EBPß could hold promise as a therapeutic strategy not only for AD but also for other degenerative diseases.


Assuntos
Doença de Alzheimer , Proteína beta Intensificadora de Ligação a CCAAT , Progressão da Doença , Humanos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/genética , Animais , Peptídeos beta-Amiloides/metabolismo
4.
Behav Brain Res ; 466: 114979, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38582409

RESUMO

OBJECTIVE: Reward anticipation is important for future decision-making, possibly due to re-evaluation of prior decisions. However, the exact relationship between reward anticipation and prior effort-expenditure decision-making, and its neural substrates are unknown. METHOD: Thirty-three healthy participants underwent fMRI scanning while performing the Effort-based Pleasure Experience Task (E-pet). Participants were required to make effort-expenditure decisions and anticipate the reward. RESULTS: We found that stronger anticipatory activation at the posterior cingulate cortex was correlated with slower reaction time while making decisions with a high-probability of reward. Moreover, the substantia nigra was significantly activated in the prior decision-making phase, and involved in reward-anticipation in view of its strengthened functional connectivity with the mammillary body and the putamen in trial conditions with a high probability of reward. CONCLUSIONS: These findings support the role of reward anticipation in re-evaluating decisions based on the brain-behaviour correlation. Moreover, the study revealed the neural interaction between reward anticipation and decision-making.


Assuntos
Antecipação Psicológica , Tomada de Decisões , Imageamento por Ressonância Magnética , Tempo de Reação , Recompensa , Humanos , Masculino , Tomada de Decisões/fisiologia , Antecipação Psicológica/fisiologia , Feminino , Adulto Jovem , Adulto , Tempo de Reação/fisiologia , Giro do Cíngulo/fisiologia , Giro do Cíngulo/diagnóstico por imagem , Mapeamento Encefálico , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Substância Negra/fisiologia , Substância Negra/diagnóstico por imagem
5.
Int J Pharm ; 656: 124096, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38583821

RESUMO

Pulmonary fibrosis (PF) is a chronic, progressive and irreversible interstitial lung disease that seriously threatens human life and health. Our previous study demonstrated the unique superiority of traditional Chinese medicine cryptotanshinone (CTS) combined with sustained pulmonary drug delivery for treating PF. In this study, we aimed to enhance the selectivity, targeting efficiency and sustained-release capability based on this delivery system. To this end, we developed and evaluated CTS-loaded modified liposomes-chitosan (CS) microspheres SM(CT-lipo) and liposome-exosome hybrid bionic vesicles-CS microspheres SM(LE). The prepared nano-in-micro particles system integrates the advantages of the carriers and complements each other. SM(CT-lipo) and SM(LE) achieved lung myofibroblast-specific targeting through CREKA peptide binding specifically to fibronectin (FN) and the homing effect of exosomes on parent cells, respectively, facilitating efficient delivery of anti-fibrosis drugs to lung lesions. Furthermore, compared with daily administration of conventional microspheres SM(NC) and positive control drug pirfenidone (PFD), inhaled administration of SM(CT-lipo) and SM(LE) every two days still attained similar efficacy, exhibiting excellent sustained drug release ability. In summary, our findings suggest that the developed SM(CT-lipo) and SM(LE) delivery strategies could achieve more accurate, efficient and safe therapy, providing novel insights into the treatment of chronic PF.


Assuntos
Quitosana , Exossomos , Fibronectinas , Lipossomos , Fibrose Pulmonar , Piridonas , Animais , Fibronectinas/administração & dosagem , Fibrose Pulmonar/tratamento farmacológico , Exossomos/química , Quitosana/química , Quitosana/administração & dosagem , Administração por Inalação , Microesferas , Liberação Controlada de Fármacos , Masculino , Preparações de Ação Retardada , Fenantrenos/administração & dosagem , Fenantrenos/química , Fenantrenos/farmacocinética , Camundongos , Sistemas de Liberação de Medicamentos/métodos , Humanos , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Ratos Sprague-Dawley , Antifibróticos/administração & dosagem , Antifibróticos/química
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 428-433, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38660847

RESUMO

OBJECTIVE: To summarize the clinical characteristics, therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma (HL). METHODS: A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled, and their clinical data, including sex, age, pathological type, Ann Arbor stage, ECOG score, blood test, ß2-microglobulin, lactate dehydrogenase level, albumin level were collected. The clinical characteristics, therapeutic effect and long-term prognosis of the patients were summarized and analyzed. RESULTS: In classical HL, nodular sclerosis HL accounted for the highest proportion of 51.6%, followed by mixed cellularity HL (36.5%), lymphocyte-rich classical HL (3.2%), and lymphocyte depletion HL (0.7%), while nodular lymphocyte predominant HL accounted for 4.8%. The 3-year overall survival (OS) rate of HL patients was 89.8%, and 5-year OS was 85.0%. The 3-year progression-free survival (PFS) rate was 73.4%, and 5-year PFS was 63.1%. Multivariate regression analysis indicated that IPI score was an independent negative factor, while hemoglobin (Hb) level was an independent positive factor for OS in HL patients. When the mediastinal mass size was 9.2 cm, it was most significant to judge the survival status of HL patients. 5-year OS and 5-year PFS were 97.4% and 76.0% in early-stage HL patients without large mass, respectively, while in patients with advanced-stage HL was 83.4% and 55.9% (both P < 0.05). After 2-4 courses of treatment, the overall response rate (ORR) of patients who received chemotherapy combined with radiotherapy was 95.0%, while that was 89.6% in those with chemotherapy alone. CONCLUSIONS: The overall prognosis of patients with HL is satisfactory, especially those in early-stage without large mass. IPI score and Hb level are independent risk factors for the prognosis of HL patients. A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.


Assuntos
Doença de Hodgkin , Humanos , Doença de Hodgkin/terapia , Adulto , Masculino , Prognóstico , Feminino , Taxa de Sobrevida , Adulto Jovem
7.
Neurosci Lett ; 826: 137712, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38447888

RESUMO

Glaucoma is a kind of neurodegenerative disorder characterized by irreversible loss of retinal ganglion cells (RGCs) and permanent visual impairment. It is reported that resveratrol (RES) is a promising drug for neurodegenerative diseases. However, the detailed molecular mechanisms underlying its protective potential have not yet been fully elucidated. The present study sought to investigate whether resveratrol could protect RGCs and retinal function triggered by acute ocular hypertension injury through the SIRT1/NF-κB pathway. An experimental glaucoma model was generated in C57BL/6J mice. Resveratrol was intraperitoneally injected for 5 days. Sirtinol was injected intravitreally on the day of retinal AOH injury. RGC survival was determined using immunostaining. TUNEL staining was conducted to evaluate retinal cell apoptosis. ERG was used to evaluate visual function. The proteins Brn3a, SIRT1, NF-κB, IL-6, Bax, Bcl2, and Cleaved Caspase3 were determined using western blot. The expression and localisation of SIRT1 and NF-κB in the retina were detected by immunofluorescence. Our data indicated that resveratrol treatment significantly increased Brn3a-labelled RGCs and reduced RGC apoptosis caused by AOH injury. Resveratrol administration also remarkably decreased NF-κB, IL-6, Bax, and Cleaved Caspase3 proteins and increased SIRT1 and Bcl2 proteins. Furthermore, resveratrol treatment obviously inhibited the reduction in ERG caused by AOH injury. Importantly, simultaneous administration of resveratrol and sirtinol abrogated the protective effect of resveratrol, decreased NF-κB protein expression, and increased SIRT1 protein levels. These results suggest that resveratrol administration significantly mitigates retinal AOH-induced RGCs loss and retinal dysfunction, and that this neuroprotective effect is partially regulated through the SIRT1/NF-κB pathway.


Assuntos
Benzamidas , Glaucoma , Naftóis , Hipertensão Ocular , Camundongos , Animais , Resveratrol/farmacologia , Resveratrol/uso terapêutico , NF-kappa B/metabolismo , Sirtuína 1/metabolismo , Proteína X Associada a bcl-2 , Interleucina-6 , Camundongos Endogâmicos C57BL , Hipertensão Ocular/tratamento farmacológico , Glaucoma/tratamento farmacológico
8.
Front Immunol ; 15: 1358719, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38533497

RESUMO

Neuroinflammation is a common pathological process in various neurological disorders, including stroke, Alzheimer's disease, Parkinson's disease, and others. It involves the activation of glial cells, particularly astrocytes, and the release of inflammatory mediators. Lipocalin-2 (Lcn-2) is a secretory protein mainly secreted by activated astrocytes, which can affect neuroinflammation through various pathways. It can also act as a pro-inflammatory factor by modulating astrocyte activation and polarization through different signaling pathways, such as NF-κB, and JAK-STAT, amplifying the inflammatory response and aggravating neural injury. Consequently, Lcn-2 and astrocytes may be potential therapeutic targets for neuroinflammation and related diseases. This review summarizes the current knowledge on the role mechanisms, interactions, and therapeutic implications of Lcn-2 and astrocytes in neuroinflammation.


Assuntos
Astrócitos , Doenças Neuroinflamatórias , Humanos , Astrócitos/metabolismo , Lipocalina-2/metabolismo , Inflamação/metabolismo , Neuroglia/metabolismo
9.
Int Immunopharmacol ; 131: 111809, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38484666

RESUMO

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that is characterized by persistent morning stiffness, joint pain, and swelling. However, there is a lack of reliable diagnostic markers and therapeutic targets that are both effective and trustworthy. METHODS: In this study, gene expression profiles (GSE89408, GSE55235, GSE55457, and GSE77298) were obtained from the Gene Expression Omnibus database. Differentially expressed necroptosis-related genes were attained from intersection of necroptosis-related gene set, differentially expressed genes, and weighted gene co-expression network analysis. The LASSO, random forest, and SVM-RFE machine learning algorithms were utilized to further screen potential diagnostic genes for RA. Immune cell infiltration was analyzed using the CIBERSORT method. The expressions of diagnostic genes were validated through quantitative real-time PCR, western blotting, immunohistochemistry, and immunofluorescence staining in synovial tissues collected from three trauma controls and three RA patients. RESULTS: Five core necroptosis-related genes (FAS, CYBB, TNFSF10, EIF2AK2, and BIRC2) were identified as potential biomarkers for RA. Two different necroptosis patterns based on these five genes were confirmed to significantly correlated with immune cells (especially macrophages). In vitro experiments showed significantly higher mRNA and protein expression levels of CYBB and EIF2AK2 in RA patients compared to normal controls, consistent with the bioinformatics analysis results. CONCLUSION: Our study identified a novel necroptosis-related subtype and five diagnostic biomarkers of RA, revealed vital roles in the development and occurrence of RA, and offered potential targets for clinical diagnosis and immunotherapy.


Assuntos
Artrite Reumatoide , Necroptose , Humanos , Necroptose/genética , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/genética , Membrana Sinovial , Algoritmos , Biologia Computacional , Biomarcadores
10.
ACS Nano ; 18(8): 6623-6637, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38348825

RESUMO

Cell-free RNAs and extracellular vesicles (EVs) are valuable biomarkers in liquid biopsies, but they are prone to preanalytical variabilities such as nonstandardized centrifugation or ex vivo blood degradation. Herein, we report a high-throughput and label-free inertial microfluidic device (ExoArc) for isolation of platelet-free plasma from blood for RNA and EV analysis. Unlike conventional inertial microfluidic devices widely used for cell sorting, a submicrometer size cutoff (500 nm) was achieved which completely removed all leukocytes, RBCs, platelets, and cellular debris based on differential lateral migration induced by Dean vortices. The single-step operation also reduced platelet-associated miRNAs (∼2-fold) compared to centrifugation. We clinically validated ExoArc for plasma miRNA profiling (39 samples) and identified a 7-miRNA panel that detects non-small cell lung cancer with ∼90% sensitivity. ExoArc was also coupled with size exclusion chromatography (SEC) to isolate EVs within 50 min with ∼10-fold higher yield than ultracentrifugation. As a proof-of-concept for EV-based transcriptomics analysis, we performed miRNA analysis in healthy and type 2 diabetes mellitus (T2DM) subjects (n = 3 per group) by coupling ExoArc and ExoArc+SEC with quantitative polymerase chain reaction (RT-qPCR) assay. Among 293 miRNAs detected, plasmas and EVs showed distinct differentially expressed miRNAs in T2DM subjects. We further demonstrated automated in-line EV sorting from low volume culture media for continuous EV monitoring. Overall, the developed ExoArc offers a convenient centrifugation-free workflow to automate plasma and EV isolation for point-of-care diagnostics and quality control in EV manufacturing.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Diabetes Mellitus Tipo 2 , Vesículas Extracelulares , Neoplasias Pulmonares , MicroRNAs , Humanos , MicroRNAs/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Microfluídica , Neoplasias Pulmonares/metabolismo , Vesículas Extracelulares/metabolismo
11.
Bone ; 182: 117050, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38367924

RESUMO

Postmenopausal osteoporosis (PMOP) is a common kind of osteoporosis that is associated with excessive osteocyte death and bone loss. Previous studies have shown that TNF-α-induced osteocyte necroptosis might exert a stronger effect on PMOP than apoptosis, and TLR4 can also induce cell necroptosis, as confirmed by recent studies. However, little is known about the relationship between TNF-α-induced osteocyte necroptosis and TLR4. In the present study, we showed that TNF-α increased the expression of TLR4, which promoted osteocyte necroptosis in PMOP. In patients with PMOP, TLR4 was highly expressed at skeletal sites where exists osteocyte necroptosis, and high TLR4 expression is correlated with enhanced TNF-α expression. Osteocytes exhibited robust TLR4 expression upon exposure to necroptotic osteocytes in vivo and in vitro. Western blotting and immunofluorescence analyses demonstrated that TNF-α upregulated TLR4 expression in vitro, which might further promote osteocyte necroptosis. Furthermore, inhibition of TLR4 by TAK-242 in vitro effectively blocked osteocyte necroptosis induced by TNF-α. Collectively, these results suggest a novel TLR4-mediated process of osteocyte necroptosis, which might increase osteocyte death and bone loss in the process of PMOP.


Assuntos
Osteócitos , Osteoporose Pós-Menopausa , Receptor 4 Toll-Like , Fator de Necrose Tumoral alfa , Feminino , Humanos , Necroptose , Osteócitos/metabolismo , Osteoporose Pós-Menopausa/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
12.
J Phys Chem Lett ; 15(6): 1694-1701, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38316030

RESUMO

Perovskite solar cells (PSCs) have attracted significant attention due to their high efficiencies that are closely associated with the optimized interface of perovskite (PVK) films. However, during film deposition, tremendous interfacial defects are generated in PVK films, which suppress device performance. Herein, we employ an organic molten chloride salt of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) on the PVK surface to regulate the interface properties through surface reconstruction by heating to 110 °C, during which DMTMM undergoes an obvious phase transition from a solid to liquid molten salt. The mobile phase coordinates with unsaturated Pb2+ and halide vacancies to heal the structural defects. After the mixture cools to room temperature, a compact DMTMM interlayer is formed to protect PVKs from degradation in the air. Consequently, the DMTMM-treated MAPbI3-based PSCs yield a champion PCE approaching 20% with optimized stability. This molten-salt-assisted surface reconstruction strategy provides a new approach to establish highly stable hybrid perovskite films for high-performance PSCs.

13.
Onco Targets Ther ; 17: 131-144, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38405176

RESUMO

Objective: This work aimed to explore the prognostic risk factors of lung cancer (LC) patients and establish a line chart prediction model. Methods: A total of 322 LC patients were taken as the study subjects. They were randomly divided into a training set (n = 202) and a validation set (n = 120). Basic information and laboratory indicators were collected, and the progression-free survival (PFS) and overall survival (OS) were followed up. Single-factor and cyclooxygenase (COX) multivariate analyses were performed on the training set to construct a Nomogram prediction model, which was validated with 120 patients in the validation set, and Harrell's consistency was analyzed. Results: Single-factor analysis revealed significant differences in PFS (P<0.05) between genders, body mass index (BMI), carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), squamous cell carcinoma antigen (SCCA), treatment methods, treatment response evaluation, smoking status, presence of pericardial effusion, and programmed death ligand 1 (PD-L1) at 0 and 1-50%. Significant differences in OS (P<0.05) were observed for age, tumor location, treatment methods, White blood cells (WBC), uric acid (UA), CA125, pro-gastrin-releasing peptide (ProGRP), SCCA, cytokeratin fragment 21 (CYFRA21), and smoking status. COX analysis identified male gender, progressive disease (PD) as treatment response, and SCCA > 1.6 as risk factors for LC PFS. The consistency indices of the line chart models for predicting PFS and OS were 0.782 and 0.772, respectively. Conclusion: Male gender, treatment response of PD, and SCCA > 1.6 are independent risk factors affecting the survival of LC patients. The PFS line chart model demonstrates good concordance.

14.
J Hepatocell Carcinoma ; 11: 285-304, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38344425

RESUMO

Objective: Thermal ablation is a commonly used therapy for hepatocellular carcinoma (HCC). Nevertheless, inadequate ablation can lead to the survival of residual HCC, potentially causing rapid progression. The underlying mechanisms for this remain unclear. This study explores the molecular mechanism responsible for the rapid progression of residual HCC. Methods: We established an animal model of inadequate ablation in BALB/c nude mice and identified a key transcriptional regulator through high-throughput sequencing. Subsequently, we conducted further investigations on RAD21. We evaluated the expression and clinical significance of RAD21 in HCC and studied its impact on HCC cell function through various assays, including CCK-8, wound healing, Transwell migration and invasion. In vitro experiments established an incomplete ablation model verifying RAD21 expression and function. Using ChIP-seq, we determined potential molecules regulated by RAD21 and investigated how RAD21 influences residual tumor development. Results: High RAD21 expression in HCC was confirmed and correlated with low tumor cell differentiation, tumor growth, and portal vein thrombosis. Silencing RAD21 inhibited the migration, invasion, and proliferation significantly in liver cancer cells. Patients with high RAD21 levels showed elevated multiple inhibitory immune checkpoint levels and a lower response rate to immune drugs. Heat treatment intensified the malignant behavior of liver cancer cells, resulting in increased migration, invasion, and proliferation. After subjecting it to heat treatment, the results indicated elevated RAD21 levels in HCC. Differentially expressed molecules regulated by RAD21 following incomplete ablation were primarily associated with the VEGF signaling pathway, focal adhesion, angiogenesis, and hepatocyte growth factor receptor signaling pathway etc. Conclusion: The upregulation of RAD21 expression after incomplete ablation may play a crucial role in the rapid development of residual tumors and could serve as a novel therapeutic target.

15.
Soft Robot ; 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38422187

RESUMO

This article describes development of a crab biorobot that is capable of traversing diverse environments including both land and water. We have transformed a living rainbow crab into a walking biorobot by attaching wireless controller. An anatomical and physiological investigation revealed the rainbow crabs have sensory system on the carapace. Based on this finding, we implanted electrodes into the carapace. The walking direction of the robot is controlled through electrical stimulation provided by the controller. Depending on this site, the crab biorobot is induced to walk forward, leftward, and rightward in both terrestrial and underwater conditions. There is no significant difference in the mean walking direction between the two conditions. Smooth transition from land to water of the crab biorobot further demonstrates the adaptability to amphibious environment. This biorobot is compact, measuring 5 cm in carapace and weighing 50 g including the wireless controller. The crab biorobot in this scale has a potential for application narrow and unstructured in waterfront environments.

16.
APMIS ; 132(6): 416-429, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38403979

RESUMO

Histology slide, tissue microbes, and the host gene expression can be independent prognostic factors of colorectal cancer (CRC), but the underlying associations and biological significance of these multimodal omics remain unknown. Here, we comprehensively profiled the matched pathological images, intratumoral microbes, and host gene expression characteristics in 527 patients with CRC. By clustering these patients based on histology slide features, we classified the patients into two histology slide subtypes (HSS). Onco-microbial community and tumor immune microenvironment (TIME) were also significantly different between the two subtypes (HSS1 and HSS2) of patients. Furthermore, variation in intratumoral microbes-host interaction was associated with the prognostic heterogeneity between HSS1 and HSS2. This study proposes a new CRC classification based on pathological image features and elucidates the process by which tumor microbes-host interactions are reflected in pathological images through the TIME.


Assuntos
Neoplasias Colorretais , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/imunologia , Prognóstico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso
17.
Spine J ; 24(5): 858-866, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38272127

RESUMO

BACKGROUND CONTEXT: Cellular schwannoma (CS) is a rare tumor that accounts for 2.8%-5.2% of all benign schwannomas. There is a dearth of up-to-date information on spinal CS in the literature. PURPOSE: The aims of this study were to identify the proportion of CS cases amongst spinal benign schwannoma, describe the clinical features of spinal CS, and identify prognostic factors for local recurrence by analyzing data from 93 consecutive CS cases. STUDY DESIGN: Retrospective review. PATIENT SAMPLE: We analyzed 93 PSGCT screened from 1,706 patients with spine CS who were treated at our institute between 2008 and 2021. OUTCOME MEASURES: Demographic, radiographic, operative and postoperative data were recorded and analyzed. METHODS: We compared the clinical features of spinal CS from the cervical, thoracic, lumbar and sacral segments. Prognostic factors for local recurrence-free survival (RFS) were identified by the Kaplan-Meier method. Factors with p≤.05 in univariate analysis were subjected to multivariate analysis by Cox regression analysis. RESULTS: The proportion of spinal CS in all benign schwannomas was 6.7%. The mean and median follow-up times for the 93 patients in this study were 92.2 and 91.0 months respectively (range 36-182 months). Local recurrence was detected in 11 cases, giving an overall recurrence rate of 11.7%, with one patient death. Statistical analysis revealed that tumor size ≥5 cm, intralesional resection, and Ki-67 ≥5% were independent negative prognostic factors for RFS in spinal CS. CONCLUSIONS: Whenever possible, en bloc resection is recommended for spinal CS. Long-term follow-up should be carried out for patients with tumor size ≥5 cm and postoperative pathological Ki-67 ≥5%.


Assuntos
Neurilemoma , Neoplasias da Coluna Vertebral , Humanos , Neurilemoma/cirurgia , Neurilemoma/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/patologia , Idoso , Estudos Retrospectivos , Recidiva Local de Neoplasia/epidemiologia , Resultado do Tratamento , Adulto Jovem , Adolescente , Prognóstico
18.
Spine (Phila Pa 1976) ; 49(10): 715-725, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38239008

RESUMO

STUDY DESIGN: A retrospective case series. OBJECTIVE: This study developed a novel classification system based on imaging and anatomy to select optimal surgical approaches and reconstruction strategies to achieve total resection of cervical dumbbell tumors and restore spinal stability. SUMMARY OF BACKGROUND DATA: Total resection is necessary to decrease the recurrence rate of cervical dumbbell tumors. Previous cervical dumbbell tumor classifications are insufficient for determining surgical strategies; therefore, a practical classification is needed. MATERIALS AND METHODS: This study included 295 consecutive patients with cervical dumbbell tumors who underwent total surgical resection. A novel classification of cervical dumbbell tumors was developed based on magnetic resonance imaging and computed tomography. Continuous variables were expressed as mean±SD and were compared using an unpaired two-tailed Student t test. The χ 2 test or the Fisher exact test was used for categorical variables. Kendall's W test assessed three independent raters' inter-rater and intrarater reliabilities on 140 cervical dumbbell tumors. RESULTS: The inter-rater and intrarater consistency coefficient was 0.969 (χ 2 =404.3, P <0.001) and 0.984 (χ 2 =273.7, P <0.001). All patients with type I and II tumors underwent single-posterior surgeries to achieve total resection. Of the patients in this study, 86.1%, 25.9%, 75.9%, and 76.9% underwent posterior surgeries for types IIIa, IIIb, IVa, and V tumors, respectively. All patients with type IVb tumors underwent a combined anterior and posterior approach. Posterior internal fixation was used for all patients in posterior surgery. Anterior reconstruction was applied for patients with type IVb tumors (20/20, 100%) and some with type V tumors (3/13, 23.1%). The mean follow-up duration was 93.6±2.6 months. A recurrence was observed in 19 (6.4%) patients. CONCLUSION: The authors describe a novel classification system that is of practical use for planning the complete resection of cervical dumbbell tumors.


Assuntos
Vértebras Cervicais , Procedimentos de Cirurgia Plástica , Humanos , Vértebras Cervicais/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Idoso , Procedimentos de Cirurgia Plástica/métodos , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/classificação , Adulto Jovem , Imageamento por Ressonância Magnética/métodos , Reprodutibilidade dos Testes , Adolescente , Tomografia Computadorizada por Raios X
19.
Chembiochem ; 25(5): e202300828, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38236789

RESUMO

An efficient and easy-to-use approach is presented for obtaining biocompatible polysaccharide-based nanoparticles (NP) that can act as tumor-specific drug delivery agents. Two antibodies are directly immobilized onto reactive xylan phenyl carbonate (XPC) NP; namely Cetuximab (CTX) that binds to human epidermal growth factor receptor (EGFR) and Atezolizumab (ATZ) that binds to programmed death-ligand 1 (PD-L1). High coupling efficiency (up to 100 %) are achieved without any pre-activation and no aggregation occurs during antibody immobilization. By quartz crystal microbalance experiments with dissipation monitoring (QCM-D), flow cytometry assays, and confocal laser scanning microscopy imaging it is demonstrated that the functionalized XPC-NP specifically bind to cells carrying the corresponding antigens. Moreover, the NP retain the antibody specific bioactivities (growth inhibition for CTX and induction of T-cell cytotoxicity for ATZ).


Assuntos
Polissacarídeos , Xilanos , Humanos , Especificidade de Anticorpos , Bioensaio , Carbonatos , Cetuximab/farmacologia
20.
ACS Omega ; 9(1): 283-293, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38222604

RESUMO

Microengines driven by catalytic decomposition of a fuel have been an interesting research area recently due to their diverse applications, such as environmental monitoring and drug delivery. Literature reports a number of studies on this topic where researchers have made various attempts to manufacture such microengines. Some such methods are deposition of catalytic metal layers on sacrificial photoresists, electrochemical deposition of metal layers on polymeric structures, or 3D printing of structures followed by multi-step loading of structures with catalysts. These methods, even though proven to be effective, are tedious, time-consuming, and expensive. To address these issues, herein we report a 3D printing technique to realize microengines in a simple, rapid, and inexpensive single-step process. The printing of various shapes of microengines is achieved using digital light processing printing of a catalyst resin, where Pd(II) acts as a catalyst resin. The proposed integrated molding process can achieve cost-effective preparation of high-efficiency microengines. We demonstrate the locomotion of these microengines in 30% (w/w) H2O2 through the decomposition of H2O2 to generate oxygen to facilitate the self-propelled locomotion. The study characterizes the microengine based on several factors, such as the role of H2O2, Pd, shape, and design of the microengine, to get a full picture of the self-locomotion of microengines. The study shows that the developed method is feasible to manufacture microengines in a simple, rapid, and inexpensive manner to be suitable for numerous applications such as environmental monitoring, remediation, drug delivery, diagnosis, etc., through the modification of the catalyst resin and fuel, as desired.

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