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1.
Nat Prod Bioprospect ; 14(1): 29, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38740677

RESUMO

A catalytic diastereoselective Prins reaction for hydroxymethylation and hydroxylation of 1,3-diarylpropene was successfully utilized to prepare various 1,3-dioxanes 7 in 14-88% yields. Take advantage of the synthetic intermediate 7h, the key B/C rings in brazilin core could be constructed by the sequential of Friedel-Crafts/Ullmann-Ma rather than Ullmann-Ma/Friedel-Crafts reactions.

2.
Phys Rev Lett ; 132(16): 165002, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38701476

RESUMO

We report the experimental measurement of millijoule terahertz (THz) radiation emitted in the backward direction from laser wakefields driven by a femtosecond laser pulse of few joules interacting with a gas target. By utilizing frequency-resolved energy measurement, it is found that the THz spectrum exhibits two peaks located at about 4.5 and 9.0 THz, respectively. In particular, the high frequency component emerges when the drive laser energy exceeds 1.26 J, at which electron acceleration in the forward direction is detected simultaneously. Theoretical analysis and particle-in-cell simulations indicate that the THz radiation is generated via mode conversion from the laser wakefields excited in plasma with an up-ramp profile, where radiations both at the local electron plasma frequency and its harmonics are produced. Such intense THz sources may find many applications in ultrafast science, e.g., manipulating the transient states of matter.

3.
Acta Derm Venereol ; 104: adv22146, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738772

RESUMO

There are no standard treatment guidelines for hidradenocarcinoma, and the immune microenvironment and genomic data are very limited. Thus, in this study the immune microenvironment and genomic indicators in hidradenocarcinoma was investigated, and immunotherapy for hidradenocarcinoma was initially explored. Forty-seven hidradenocarcinoma patients were retrospectively collected. Immunohistochemical staining was performed to identify CD3/CD8+ T cells and programmed death ligand-1 expression. In total, 89.4% and 10.6% of samples had Immunoscores of 0-25% and 25-70%. Tumour proportion score distribution was as follows: tumour proportion score < 1% in 72.4%, 1-5% in 17.0%, and > 5% in 10.6%. Combined positive score distribution was as follows: combined positive score < 1 in 63.8%, 1-5 in 14.9%, and > 5 in 21.3%. Next-generation sequencing revealed that TP53 (33%), PI3KCA (22%), and ERBB3 (22%) were the most frequently mutated genes. The PI3K-Akt signalling pathway, growth, and MAPK signalling pathways were significantly enriched. Five patients had a low TMB (< 10 muts/Mb), and 9 patients had MSS. Three patients treated with immune combined with chemotherapy achieved significant tumour regression, and the progression-free survival was 28.8 months. In conclusion, the hidradenocarcinoma immune microenvironment tends to be noninflammatory. Evidence-based targets for targeted therapy are lacking. Immunotherapy combined with chemotherapy may be better for most advanced hidradenocarcinoma patients with a noninflammatory microenvironment.


Assuntos
Biomarcadores Tumorais , Neoplasias das Glândulas Sudoríparas , Microambiente Tumoral , Humanos , Estudos Retrospectivos , Neoplasias das Glândulas Sudoríparas/genética , Neoplasias das Glândulas Sudoríparas/patologia , Neoplasias das Glândulas Sudoríparas/terapia , Neoplasias das Glândulas Sudoríparas/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Mutação , Resultado do Tratamento , Linfócitos do Interstício Tumoral/imunologia , Antígeno B7-H1 , Imunoterapia/métodos , Adulto Jovem , Antineoplásicos Imunológicos/uso terapêutico
4.
Transl Cancer Res ; 13(3): 1382-1393, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38617513

RESUMO

Background: Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor prognosis. Thus, this study aimed to identify a prognostic molecular signature to predict the overall survival (OS) of patients with EAC. Methods: The mRNA microarray data sets GSE13898 and GSE26886 were downloaded from the Gene Expression Omnibus (GEO) database. RNA sequencing profile and clinical data of EAC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) between EAC tissues and adjacent non-cancerous tissues were obtained using R software. DEGs associated with prognosis of OS were assessed by univariate Cox analysis, and a prognostic signature was built using stepwise multivariate Cox analysis. Time-dependent receiver operating characteristic (ROC) analysis and stratification analysis were conducted to evaluate its predictive performance. Functional enrichment analysis was performed for genes co-expressed with the signature to explore its biological functions in EAC. Results: A total of 336 genes were identified to be differentially expressed between EAC tissues and adjacent non-cancerous tissues. After univariate and multivariate Cox regression analysis, four genes (ALAD, ABLIM3, IL17RB and IFI6) were screened out to construct a prognostic signature. According to this signature, patients could be assigned into high-risk and low-risk group with significantly different OS (P=4.92e-05<0.0001). Multivariate Cox regression analysis suggested that the four-gene signature served as an independent factor in OS prediction. In the time-dependent ROC analysis, the areas under the curves (AUCs) were 0.804, 0.792 and 0.695 for 1-, 3- and 5-year survival prediction, respectively, suggesting a good performance. Functional enrichment analysis showed that the signature was mainly clustered in cell proliferation related biological processes or pathways. Conclusions: The four-gene signature identified in the current study may be a potential prognostic factor for predicting OS of EAC patients.

5.
Clin Transl Oncol ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662170

RESUMO

PURPOSE: Although immunotherapy improves outcomes in extensive-stage small-cell lung cancer (ES-SCLC), the search for biomarkers predicting treatment success is crucial. Natural killer (NK) cells are potential indicators in various cancers, however, their precise role in ES-SCLC prognosis remains unclear. METHODS: In this retrospective study, 33 patients with ES-SCLC treated with first-line immuno-chemotherapy were enrolled. The peripheral NK cell percentage and its longitudinal dynamics were analyzed using flow cytometry. Progression-free survival (PFS) and overall survival (OS) were calculated as hazard ratio (HR) and compared statistically. RESULTS: The median PFS was better in the group with normal baseline NK cell levels than the low group (7.0 vs. 4.6 months; HR = 0.17; 95% CI 0.07-0.41; P < 0.0001), but there was no association with OS (14.9 vs. 10.3 months; HR = 0.55; 95% CI 0.23-1.31; P = 0.171). Furthermore, the NK cell% for 95.0% of patients increased after immunochemotherapy in the clinical response group (P = 0.0047), which led to a better median PFS (6.3 vs. 2.1 months; HR = 0.23; 95% CI 0.05-0.98; P < 0.0001) and OS (14.9 vs. 5.9 months; HR = 0.20; 95% CI 0.04-1.02; P < 0.0001). Similar trends were observed with NK cell% changes up to disease progression, improving PFS (6.5 vs. 4.3; HR = 0.41; 95% CI 0.12-0.92; P = 0.0049) and OS (17.4 vs. 9.7; HR = 0.42; 95% CI 0.17-1.02; P < 0.0001). CONCLUSION: In patients with ES-SCLC, the percentage and changes in peripheral NK cells can predict the response to combined immunotherapy and chemotherapy.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38581336

RESUMO

This paper comprehensively analyzes the caregiver burden and its influencing factors on primary caregivers in autologous hematopoietic stem cell transplantation (Auto-HSCT) with bendamustine preconditioning. Auto-HSCT refers to the transplantation of cells back to the patient, aiming to eliminate tumor cells and prolong the patient's life. Bendamustine, while enhancing the success rate of transplantation, has drawn considerable attention to the primary caregivers of patients. Due to the complex nature of the transplantation process, patients have diverse caregiving needs, which caregivers must address to support the entire treatment journey. The caregiver burden of primary caregivers is influenced by various factors, including the patient's disease condition, various aspects of the caregiver as an individual, and psychological factors. The article emphasizes the need for personalized care plans and psychological support to minimize caregiver burden and improve overall quality of life. This study has positive implications for optimizing the implementation of Auto-HSCT therapy.

7.
Am J Cancer Res ; 14(3): 1363-1375, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590409

RESUMO

Tetrachlorobisphenol A (TCBPA), widely used as a substitute for tetrabromobisphenol A (TBBPA), has been detected in various environmental media. Therefore, a detailed evaluation of the toxicological properties of TCBPA is necessary. In this study, we used hepatoma and normal liver cell models in vitro to investigate the effects of TCBPA. Our findings indicate that TCBPA promotes the proliferation of liver cancer cells, as evidenced by MTT and EdU assays, and enhances the expression levels of molecules related to hepatoma proliferation. Further investigation into the molecular mechanism revealed that TCBPA-induced hepatoma proliferation is regulated by an NLRP3-mediated inflammatory process. Additionally, TCBPA was found to promote the epithelial-mesenchymal transition (EMT) process in liver cancer cells. Conversely, TCBPA inhibited the proliferation of normal liver cells. Mechanistic studies showed that TCBPA induced cell pyroptosis in normal liver cells by evaluating a series of related markers, including NLRP3, IL-1ß, ASC, GASDMD, and Caspase 1. In vivo models further showed that TCBPA causes liver tissue damage. In summary, this study demonstrates that TCBPA has a dual effect: promoting the occurrence and development of liver tumor cells in vitro, while inhibiting the proliferation of normal liver cells, like two sides of a coin. These opposite cellular outcomes are regulated by NLRP3-mediated inflammatory processes, providing valuable insights for evaluating the potential health impacts of TCBPA.

8.
Stat Med ; 43(10): 1883-1904, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38634277

RESUMO

Biomarker stratified clinical trial designs are versatile tools to assess biomarker clinical utility and address its relationship with clinical endpoints. Due to imperfect assays and/or classification rules, biomarker status is prone to errors. To account for biomarker misclassification, we consider a two-stage stratified design for survival outcomes with an adjustment for misclassification in predictive biomarkers. Compared to continuous and/or binary outcomes, the test statistics for survival outcomes with an adjustment for biomarker misclassification is much more complicated and needs to take special care. We propose to use the information from the observed biomarker status strata to construct adjusted log-rank statistics for true biomarker status strata. These adjusted log-rank statistics are then used to develop sequential tests for the global (composite) hypothesis and component-wise hypothesis. We discuss the power analysis with the control of the type-I error rate by using the correlations between the adjusted log-rank statistics within and between the design stages. Our method is illustrated with examples of the recent successful development of immunotherapy in nonsmall-cell lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Biomarcadores/análise , Projetos de Pesquisa , Ensaios Clínicos como Assunto
9.
Clinics (Sao Paulo) ; 79: 100361, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38678873

RESUMO

OBJECTIVE: Early diagnosis of Severity Mycoplasma Pneumoniae Pneumonia (SMPP) has been a worldwide concern in clinical practice. Two cytokines, soluble Triggering Receptor Expressed on Myeloid cells (sTREM-1) and Interferon-Inducible Protein-10 (IP-10), were proved to be implicated in bacterial infection diseases. However, the diagnostic value of sTREM-1 and IP-10 in MPP was poorly known. This study aimed to investigate the diagnostic value of sTREM-1 and IP-10 for SMPP. METHODS: In this prospective study, the authors enrolled 44 children with MPP, along with their clinical information. Blood samples were collected, and cytokine levels of sTREM-1 and IP-10 were detected with ELISA assay. RESULTS: Serum levels of sTREM-1 and IP-10 were positively correlated with the severity of MPP. In addition, sTREM-1 and IP-10 have significant potential in the diagnosis of SMPP with an Area Under Curve (AUC) of 0.8564 (p-value = 0.0001, 95% CI 0.7461 to 0.9668) and 0.8086 (p-value = 0.0002, 95% CI 0.6918 to 0.9254) respectively. Notably, the combined diagnostic value of sTREM-1 and IP-10 is up to 0.911 in children with SMPP (p-value < 0.001, 95% CI 0.830 to 0.993). CONCLUSIONS: Serum cytokine levels of sTREM-1 and IP-10 have a great potential diagnostic value in children with SMPP.


Assuntos
Biomarcadores , Quimiocina CXCL10 , Ensaio de Imunoadsorção Enzimática , Pneumonia por Mycoplasma , Receptores Imunológicos , Índice de Gravidade de Doença , Receptor Gatilho 1 Expresso em Células Mieloides , Humanos , Receptor Gatilho 1 Expresso em Células Mieloides/sangue , Feminino , Masculino , Pneumonia por Mycoplasma/diagnóstico , Pneumonia por Mycoplasma/sangue , Criança , Estudos Prospectivos , Pré-Escolar , Quimiocina CXCL10/sangue , Receptores Imunológicos/sangue , Biomarcadores/sangue , Glicoproteínas de Membrana/sangue , Mycoplasma pneumoniae , Lactente , Sensibilidade e Especificidade , Curva ROC , Adolescente
10.
BMC Psychol ; 12(1): 149, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486331

RESUMO

The Academic Grit Scale (AGS) is a novel measure of academic-specific grit. However, its factor structure and measurement invariance have yet to be thoroughly supported. The present study tested the factor structure and measurement invariance of the AGS with a large sample of early adolescents (aged 9-14 years) from China (N = 1,894). The bifactor model showed that the AGS was predominately accounted for by the general factor rather than the domain-specific factors; the parallel model from the AGS's one-factor model showed good fit indices; thus, the AGS should be described as a univocal solution and reported as the total score. Gender and grade measurement invariance were supported at a scalar level, warranting further mean difference comparisons. In addition, academic grit was significantly associated with positive academic emotions and academic achievement, yielding evidence of good criteria-related validity. The current study contributes additional evidence to the construct validity of the Chinese version of the AGS among middle- and upper-grade primary school students in China.


Assuntos
Sucesso Acadêmico , População do Leste Asiático , Estudantes , Adolescente , Humanos , China , Psicometria , Instituições Acadêmicas , Estudantes/psicologia , Criança
11.
Arterioscler Thromb Vasc Biol ; 44(5): e145-e167, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38482696

RESUMO

BACKGROUND: New blood vessel formation requires endothelial cells to transition from a quiescent to an invasive phenotype. Transcriptional changes are vital for this switch, but a comprehensive genome-wide approach focused exclusively on endothelial cell sprout initiation has not been reported. METHODS: Using a model of human endothelial cell sprout initiation, we developed a protocol to physically separate cells that initiate the process of new blood vessel formation (invading cells) from noninvading cells. We used this model to perform multiple transcriptomics analyses from independent donors to monitor endothelial gene expression changes. RESULTS: Single-cell population analyses, single-cell cluster analyses, and bulk RNA sequencing revealed common transcriptomic changes associated with invading cells. We also found that collagenase digestion used to isolate single cells upregulated the Fos proto-oncogene transcription factor. Exclusion of Fos proto-oncogene expressing cells revealed a gene signature consistent with activation of signal transduction, morphogenesis, and immune responses. Many of the genes were previously shown to regulate angiogenesis and included multiple tip cell markers. Upregulation of SNAI1 (snail family transcriptional repressor 1), PTGS2 (prostaglandin synthase 2), and JUNB (JunB proto-oncogene) protein expression was confirmed in invading cells, and silencing JunB and SNAI1 significantly reduced invasion responses. Separate studies investigated rounding 3, also known as RhoE, which has not yet been implicated in angiogenesis. Silencing rounding 3 reduced endothelial invasion distance as well as filopodia length, fitting with a pathfinding role for rounding 3 via regulation of filopodial extensions. Analysis of in vivo retinal angiogenesis in Rnd3 heterozygous mice confirmed a decrease in filopodial length compared with wild-type littermates. CONCLUSIONS: Validation of multiple genes, including rounding 3, revealed a functional role for this gene signature early in the angiogenic process. This study expands the list of genes associated with the acquisition of a tip cell phenotype during endothelial cell sprout initiation.


Assuntos
Perfilação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Neovascularização Fisiológica , Proteínas Proto-Oncogênicas c-fos , Transcriptoma , Proteínas rho de Ligação ao GTP , Animais , Humanos , Camundongos , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Ciclo-Oxigenase 2/genética , Células Endoteliais/metabolismo , Perfilação da Expressão Gênica/métodos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Neovascularização Fisiológica/genética , Fenótipo , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Proteínas rho de Ligação ao GTP/genética , Transdução de Sinais , Análise de Célula Única , Fatores de Transcrição da Família Snail/metabolismo , Fatores de Transcrição da Família Snail/genética
12.
Indian J Microbiol ; 64(1): 82-91, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38468732

RESUMO

Children obesity is a serious public health problem drawing much attention around the world. Recent research indicated that gut microbiota plays a vital role in children obesity, and disturbed gut microbiota is a prominent characteristic of obese children. Diet and exercise are efficient intervention for weight loss in obesity children, however, how the gut microbiota is modulated which remains largely unknown. To characterize the feature of gut microbiota in obese children and explore the effect of dietary and exercise on gut microbiota in simple obese children, 107 healthy children and 86 obese children were recruited, and among of the obese children 39 received the dietary-exercise combined weight loss intervention (DEI). The gut microbiota composition was detected by the 16S amplicon sequencing method. The gut microbiota composition was significantly different between obese children and the healthy cohort, and DEI significantly reduced the body weight and ameliorated the gut microbiota dysbiosis. After DEI, the abundance of the Akkermansia muciniphila was increased, while the abundance of the Sutterella genus was decreased in simple obese children. Our results may provide theoretical reference for future personalized obesity interventions based on gut microbiota. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01088-3.

13.
J Agric Food Chem ; 72(14): 7943-7953, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38529919

RESUMO

Fusarium wilt is a worldwide soil-borne fungal disease caused by Fusarium oxysporum that causes serious damage to agricultural products. Therefore, preventing and treating fusarium wilt is of great significance. In this study, we purified ten single lipopeptide fengycin components from Bacillus subtilis FAJT-4 and found that C17 fengycin B inhibited the growth of F. oxysporum FJAT-31362. We observed early apoptosis hallmarks, including reactive oxygen species accumulation, mitochondrial dysfunction, and phosphatidylserine externalization in C17 fengycin B-treated F. oxysporum cells. Further data showed that C17 fengycin B induces cell apoptosis in a metacaspase-dependent manner. Importantly, we found that the expression of autophagy-related genes in the TOR signaling pathway was significantly upregulated; simultaneously, the accumulation of acidic autophagy vacuoles in F. oxysporum cell indicated that the autophagy pathway was activated during apoptosis induced by C17 fengycin B. Therefore, this study provides new insights into the antifungal mechanism of fengycin.


Assuntos
Antifúngicos , Fusarium , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Lipopeptídeos/farmacologia , Lipopeptídeos/metabolismo , Apoptose , Doenças das Plantas/microbiologia
14.
Biology (Basel) ; 13(2)2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38392335

RESUMO

United States commercial beekeepers prepare honey bee colonies for almond pollination in California each year in late January to early February. This represents the largest managed pollination event in the world and involves more than half of all U.S. honey bee colonies. In winter 2023, numerous colonies in Florida, which were graded as suitable for almonds (larger than ten frames of bees), dwindled suddenly or altogether died within several weeks, just prior to movement for almonds. The timing of these losses and the resulting morbidity caused severe economic harm to affected operations. This study reports interviews with affected stakeholders, their economic harm, and analyses of pathogens and parasites found in their colonies.

15.
Indian J Pathol Microbiol ; 67(1): 21-28, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38358184

RESUMO

Objective: To explore the relationships among the epithelial to mesenchymal transition (EMT)-related factors (SNAIL, TWIST, and E-Cadherin) and clinicopathological parameters and gastric mesangial tumor deposits (TDs) in advanced gastric cancer (AGC) patients and their value in gastric cancer prognosis judgment. Materials and Methods: The data of 190 patients who underwent radical resection of ACG were analyzed retrospectively, including 75 cases of TDs (+) and 115 cases of TDs (-). The expression of EMT-related transforming factors Snail, Twist, and E-cadherin in the primary tumor, paracancerous normal tissues, and TDs was detected by immunohistochemistry. Results: SNAIL and TWIST were overexpressed in primary tumors and TDs, whereas E-Cadherin was down-expressed in primary tumors. SNAIL was correlated significantly with tumor differentiation, lymph node metastases, and TDs (P < 0.05); TWIST was correlated strongly with tumor location, lymph node metastases, and TDs (P < 0.05); E-Cadherin was correlated closely with tumor differentiation and lymph node metastases (P < 0.05). Kaplan-Meier curves showed that SNAIL expression was correlated with DFS (P < 0.05), and TWIST expression was correlated with OS (P < 0.05). Tumor differentiation, lymph node metastasis, and TWIST expression were prognostic-independent risk factors of AGC patients (P < 0.05). Conclusion: The occurrence and development of gastric cancer and the formation of TDs may be related to EMT, analyzing the expression of EMT-related transforming proteins may be helpful to judge the prognosis of gastric cancer.


Assuntos
Neoplasias Gástricas , Fatores de Transcrição , Humanos , Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , Relevância Clínica , Transição Epitelial-Mesenquimal , Extensão Extranodal , Metástase Linfática , Prognóstico , Estudos Retrospectivos , Fatores de Transcrição da Família Snail/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Fatores de Transcrição/metabolismo
16.
Curr Med Chem ; 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38310394

RESUMO

BACKGROUND: Acute lung injury (ALI) is a serious complication that may accompany severe pneumonia in children. Derived from exosomes of human umbilical cord mesenchymal stem cell exosome (HucMSC-Exo) can contribute to the regeneration of damaged lung tissue. This study aims to investigate the impact of HucMSC-Exo on ALI and its potential mechanisms. METHODS: Firstly, RT-qPCR was performed to assess the expression of miR-335-5p. Subsequently, Pearson correlation analysis was performed to examine the correlation between METTL14 and miR-335-5p, as well as the correlation between METTL14 and ITGB4., while RNA immunoprecipitation (RIP) was used to determine the m6A modification level of ITGß4. Additionally, molecular biology techniques were employed to evaluate the expression of glycolysis-related factors. Definitively, an LPS-induced ALI model was established to investigate the effect of miR-335-5p on mice lung tissue. RESULTS: miR-335-5p was found to be highly expressed in HucMSC-Exo. Transfection with miR-335-5p mimics resulted in increased glucose uptake. Pearson correlation analysis revealed a negative correlation between METTL14 and miR-335-5p, as well as between METTL14 and ITGß4. The m6A level of ITGß4 was elevated in ALI. Overexpression of METTL14 was found to reduce the expression and glucose uptake of ITGß4, while overexpression of ITGß4 reversed the effects of METTL14 overexpression. in vivo, results demonstrated that miR-335-5p can improve the extent of lung tissue lesions and reduce glycolytic levels. CONCLUSION: This study reveals the mechanism by which miR-335-5p derived from HucMSC-Exo could alleviate LPS-induced ALI by regulating the m6A modification of ITGß4, providing a new direction for the treatment of ALI.

17.
J Control Release ; 366: 596-610, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38184232

RESUMO

Insufficient delivery of therapeutic agents into solid tumors by systemic administration remains a major challenge in cancer treatment. Secreted protein acidic and rich in cysteine (SPARC) has high binding affinity to albumin and has been shown to enhance the penetration and uptake of albumin-based drug carriers in tumors. Here, we developed a strategy to alter the tumor microenvironment (TME) by upregulating SPARC to enhance the delivery efficiency of albumin-based drug carriers into tumors. We prepared albumin nanoparticles encapsulating an NF-κB controllable CRISPR activation system (SP-NPs). SP-NPs achieved tumor-selective SPARC upregulation by responding to the highly activated NF-κB in tumor cells. Whereas a single dose of SP-NPs only modestly upregulated SPARC expression, serial administration of SP-NPs created a positive feedback loop that induced progressive increases in SPARC expression as well as tumor cell uptake and tumor penetration of the nanoparticles in vitro, in organoids, and in subcutaneous tumors in vivo. Additionally, pre-treatment with SP-NPs significantly enhanced the anti-tumor efficacy of Abraxane, a commercialized albumin-bound paclitaxel nanoformulation. Our data provide evidence that modulating SPARC in the TME can enhance the efficiency of albumin-based drug delivery to solid tumors, which may result in new strategies to increase the efficacy of nanoparticle-based cancer drugs.


Assuntos
NF-kappa B , Neoplasias , Humanos , Osteonectina , Albuminas , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Portadores de Fármacos , Paclitaxel Ligado a Albumina , Microambiente Tumoral
18.
Sensors (Basel) ; 24(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38203151

RESUMO

The accurate and efficient detection of defective insulators is an essential prerequisite for ensuring the safety of the power grid in the new generation of intelligent electrical system inspections. Currently, traditional object detection algorithms for detecting defective insulators in images face issues such as excessive parameter size, low accuracy, and slow detection speed. To address the aforementioned issues, this article proposes an insulator defect detection model based on the lightweight Faster R-CNN (Faster Region-based Convolutional Network) model (Faster R-CNN-tiny). First, the Faster R-CNN model's backbone network is turned into a lightweight version of it by substituting EfficientNet for ResNet (Residual Network), greatly decreasing the model parameters while increasing its detection accuracy. The second step is to employ a feature pyramid to build feature maps with various resolutions for feature fusion, which enables the detection of objects at various scales. In addition, replacing ordinary convolutions in the network model with more efficient depth-wise separable convolutions increases detection speed while slightly reducing network detection accuracy. Transfer learning is introduced, and a training method involving freezing and unfreezing the model is employed to enhance the network's ability to detect small target defects. The proposed model is validated using the insulator self-exploding defect dataset. The experimental results show that Faster R-CNN-tiny significantly outperforms the Faster R-CNN (ResNet) model in terms of mean average precision (mAP), frames per second (FPS), and number of parameters.

19.
RSC Adv ; 14(4): 2214-2225, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38213961

RESUMO

Fe2O3-loaded NiFe2O4 nanoblocks were successfully developed under a straightforward one-step hydrothermal synthesis method, aiming to detect trace amounts of n-butanol at the parts per billion (ppb) concentration range. The synthesized samples were comprehensively characterized using various techniques, including XRD, SEM, XPS, TEM and SAED. At a tantalizingly low temperature of 130 °C, the Ni/Fe-2 gas sensor demonstrated the optimum response (Ra/Rg = 29.747 @ 10 ppm) to n-butanol. Furthermore, Ni/Fe-2 sensor exhibited remarkable stability and reproducibility and an ultra-low detection limit. The enhanced gas sensitivity was primarily due to the assembly of Ni/Fe-2 nanoblocks from differently sized nanospheres, which exhibited a rich surface porosity conducive to gas adsorption. Besides, the formation of heterojunctions and the augmentation of oxygen vacancy content are also conducive to enhancing gas sensing capabilities. The Ni/Fe-2 sensor is expected to successfully detect trace amounts of n-butanol.

20.
BMC Infect Dis ; 24(1): 75, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212688

RESUMO

BACKGROUND: Hantaan virus (HTNV), Seoul virus (SEOV) and Puumala virus (PUUV) are major serotypes of the Hantavirus, which can cause hemorrhagic fever with renal syndrome (HFRS). The pathophysiology of HFRS in humans is complex and the determinants associated with mortality, especially the coagulation and fibrinolysis disorders, are still not been fully elucidated. Severe patients usually manifest multiple complications except for acute kidney injury (AKI). The aim of this study was to observe the levels of peripheral blood routine, biochemical and coagulation parameters during the early stage, so as to find independent risk factors closely related to the prognosis, which may provide theoretical basis for targeted treatment and evaluation. METHODS: A total of 395 HFRS patients from December 2015 to December 2018 were retrospectively enrolled. According to prognosis, they were divided into a survival group (n = 368) and a death group (n = 27). The peripheral blood routine, biochemical and coagulation parameters were compared between the two groups on admission. The relationship between the parameters mentioned above and prognosis was analyzed, and the dynamic changes of the coagulation and fibrinolysis parameters during the first week after admission were further observed. RESULTS: In addition to AKI, liver injury was also common among the enrolled patients. Patients in the death group manifested higher levels of white blood cell counts (WBC) on admission. 27.30% (107/392) of the patients enrolled presented with disseminated intravascular coagulation (DIC) on admission and DIC is more common in the death group; The death patients manifested longer prothrombin time (PT) and activated partial thromboplastin time (APTT), higher D-dimer and fibrinogen degradation product (FDP), and lower levels of platelets (PLT) and fibrinogen (Fib) compared with those of the survival patients. The proportion of D-dimer and FDP abnormalities are higher than PT, APTT and Fib. Prolonged PT, low level of Fib and elevated total bilirubin (TBIL) on admission were considered as independent risk factors for prognosis (death). CONCLUSIONS: Detection of PT, Fib and TBIL on admission is necessary, which might be benefit to early predicting prognosis. It is also important to pay attention to the dynamic coagulation disorders and hyperfibrinolysis during the early stage in the severe HFRS patients.


Assuntos
Injúria Renal Aguda , Coagulação Intravascular Disseminada , Febre Hemorrágica com Síndrome Renal , Humanos , Estudos Retrospectivos , Testes de Coagulação Sanguínea , Prognóstico , Fibrinogênio , Coagulação Intravascular Disseminada/etiologia
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