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2.
J Surg Res ; 296: 472-480, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38320367

RESUMO

INTRODUCTION: We aimed to investigate the association between renal dysfunction at discharge and long-term survival in acute type A aortic dissection (ATAAD) patients following surgery. METHODS: From 2000 to 2021, 784 patients underwent aortic repair for an ATAAD. Patients were stratified based on creatinine (Cr) level at discharge alive or dead: normal Cr (n = 582) and elevated Cr defined as >1.3 mg/dL for males and >1.0 mg/dL for females or on dialysis at discharge (n = 202). RESULTS: Preoperatively, both groups had similar rates of comorbidities except for the elevated-Cr group which had more diabetes, chronic obstructive pulmonary disease, and chronic and acute renal insufficiency. Both groups had similar open ATAAD repair procedures. Postoperative outcomes in the elevated-Cr group were significantly worse, including six times higher operative mortality (20% versus 3.4%, P < 0.0001). The landmark long-term survival after discharge alive was significantly worse in the elevated-Cr group than the normal-Cr group (10-y survival: 48% versus 69%, P = 0.0009). The elevated Cr on dialysis at discharge group had significantly worse five-year survival (40%) than the elevated Cr not on dialysis at discharge group (80%, P = 0.02) and the normal-Cr group (87%, P < 0.0001). Additionally, the elevated Cr not on dialysis had a worse five-year survival than the normal-Cr group (80% versus 87%, P = 0.02). Elevated Cr at discharge on dialysis was a significant risk factor for late mortality (hazard ratio = 4.22, 95% confidence interval: [2.07, 8.61], P < 0.0001). CONCLUSIONS: Renal dysfunction at discharge was associated with significantly decreased short-term and long-term survival following open ATAAD repair. Surgeons should aggressively prevent renal dysfunction, especially new-onset dialysis, at discharge as it is correlated with significantly worse short-term and long-term outcomes.

3.
Psychol Rep ; : 332941241233208, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38334333

RESUMO

A wealth of studies have revealed that foreign experiences affect various cognitive abilities. One well-established finding is that living abroad can increase creative thinking skills. However, there has been little research on the dark side of creativity. Here, we hypothesized that exposure to foreign experiences can also foster malevolent creativity, which refers to the deliberate application of original ideas to turn a profit at someone else's expense. Consistent with our hypotheses, Studies 1 and 2 found that student participants with foreign experiences showed greater malevolent creativity than those without such experiences. Relying on non-student adults, Study 3 replicated the findings of Study 1 using a different behavioral outcome of malevolent creativity. Study 4 found that participants who had decided to move overseas but had not yet done so demonstrated reduced levels of malevolent creativity compared to participants who had lived abroad, which minimized the possibility of reverse causality. Study 5 utilized an experimental design methodology and provided causal evidence for the effect of foreign experiences on malevolent creativity. These findings contribute to understanding about the range of effects that foreign experiences can have on different types of creativity.

4.
Appl Environ Microbiol ; : e0207423, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319094

RESUMO

Bifidobacterium breve, one of the main bifidobacterial species colonizing the human gastrointestinal tract in early life, has received extensive attention for its purported beneficial effects on human health. However, exploration of the mode of action of such beneficial effects exerted by B. breve is cumbersome due to the lack of effective genetic tools, which limits its synthetic biology application. The widespread presence of CRISPR-Cas systems in the B. breve genome makes endogenous CRISPR-based gene editing toolkits a promising tool. This study revealed that Type I-C CRISPR-Cas systems in B. breve can be divided into two groups based on the amino acid sequences encoded by cas gene clusters. Deletion of the gene coding uracil phosphoribosyl-transferase (upp) was achieved in five B. breve strains from both groups using this system. In addition, translational termination of uracil phosphoribosyl-transferase was successfully achieved in B. breve FJSWX38M7 by single-base substitution of the upp gene and insertion of three stop codons. The gene encoding linoleic acid isomerase (bbi) in B. breve, being a characteristic trait, was deleted after plasmid curing, which rendered it unable to convert linoleic acid into conjugated linoleic acid, demonstrating the feasibility of successive editing. This study expands the toolkit for gene manipulation in B. breve and provides a new approach toward functional genome editing and analysis of B. breve strains.IMPORTANCEThe lack of effective genetic tools for Bifidobacterium breve is an obstacle to studying the molecular mechanisms of its health-promoting effects, hindering the development of next-generation probiotics. Here, we introduce a gene editing method based on the endogenous CRISPR-Cas system, which can achieve gene deletion, single-base substitution, gene insertion, and successive gene editing in B. breve. This study will facilitate discovery of functional genes and elucidation of molecular mechanisms of B. breve pertaining to health-associated benefits.

6.
Biochem Pharmacol ; 221: 116036, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38301967

RESUMO

Diminished or lost Major Histocompatibility Complex class I (MHC-I) expression is frequently observed in tumors, which obstructs the immune recognition of tumor cells by cytotoxic T cells. Restoring MHC-I expression by promoting its transcription and improving protein stability have been promising strategies for reestablishing anti-tumor immune responses. Here, through cell-based screening models, we found that cediranib significantly upregulated MHC-I expression in tumor cells. This finding was confirmed in various non-small cell lung cancer (NSCLC) cell lines and primary patient-derived lung cancer cells. Furthermore, we discovered cediranib achieved MHC-I upregulation through transcriptional regulation. interferon regulatory factor 1 (IRF-1) was required for cediranib induced MHC-I transcription and the absence of IRF-1 eliminated this effect. Continuing our research, we found cediranib triggered STAT1 phosphorylation and promoted IRF-1 transcription subsequently, thus enhancing downstream MHC-I transcription. In vivo study, we further confirmed that cediranib increased MHC-I expression, enhanced CD8+ T cell infiltration, and improved the efficacy of anti-PD-L1 therapy. Collectively, our study demonstrated that cediranib could elevate MHC-I expression and enhance responsiveness to immune therapy, thereby providing a theoretical foundation for its potential clinical trials in combination with immunotherapy.

7.
Traffic Inj Prev ; : 1-9, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38346171

RESUMO

OBJECTIVE: Colored pavement is commonly used to reduce the road traffic risk and promote road traffic safety, but its performance in foggy environments has not been fully assessed. The goal of this research is to explore the effectiveness and optimization of colored pavement in a dynamic low-visibility environment. METHODS: A driving simulation experiment is conducted. Three road risk sections in which collisions are common, including a long straight section, a sharp bend section, and a long downslope section, are considered, and three forms of colored pavement are used in five different visibility environments. The effectiveness of the colored pavement is explored by collecting and analyzing driving behavior and physiological characteristic data for 30 drivers in the established driving environment, and information is obtained through a subjective colored evaluation questionnaire. Eight evaluation indexes are selected from the perspectives of driving behavior and physiological characteristics, and the gray premium evaluation method is applied to evaluate the effectiveness of different forms of colored pavement considering the influence of visibility. Finally, the optimal colored pavement under various visibility and road alignment conditions is proposed. RESULTS: The results show that reasonably selecting colored pavement can effectively improve drivers' behaviors and physiological characteristics under foggy conditions. For different road alignments and visibility conditions, different forms of colored pavement should be used to ensure road traffic safety. CONCLUSIONS: The findings provide a theoretical reference for the optimization of colored pavement in foggy conditions.

8.
Phytother Res ; 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349045

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive and lethal clinical subtype and lacks effective targeted therapies at present. Isobavachalcone (IBC), the main active component of Psoralea corylifolia L., has potential anticancer effects. Herein, we identified IBC as a natural sirtuin 2 (SIRT2) inhibitor and characterized the potential mechanisms underlying the inhibition of TNBC. Molecular dynamics analysis, enzyme activity assay, and cellular thermal shift assay were performed to evaluate the combination of IBC and SIRT2. The therapeutic effects, mechanism, and safety of IBC were analyzed in vitro and in vivo using cellular and xenograft models. IBC effectively inhibited SIRT2 enzyme activity with an IC50 value of 0.84 ± 0.22 µM by forming hydrogen bonds with VAL233 and ALA135 within its catalytic domain. In the cellular environment, IBC bound to and stabilized SIRT2, consequently inhibiting cellular proliferation and migration, and inducing apoptosis and cell cycle arrest by disrupting the SIRT2/α-tubulin interaction and inhibiting the downstream Snail/MMP and STAT3/c-Myc pathways. In the in vivo model, 30 mg/kg IBC markedly inhibited tumor growth by targeting the SIRT2/α-tubulin interaction. Furthermore, IBC exerted its effects by inducing apoptosis in tumor tissues and was well-tolerated. IBC alleviated TNBC by targeting SIRT2 and triggering the reactive oxygen species ROS/ß-catenin/CDK2 axis. It is a promising natural lead compound for future development of SIRT2-targeting drugs.

9.
JTCVS Tech ; 23: 22-23, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38352013
10.
Adv Sci (Weinh) ; : e2306066, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38350725

RESUMO

Acetaminophen overdose is a leading cause of acute liver failure (ALF). Despite the pivotal role of the inflammatory microenvironment in the progression of advanced acetaminophen-induced liver injury (AILI), a comprehensive understanding of the underlying cellular interactions and molecular mechanisms remains elusive. Mas is a G protein-coupled receptor highly expressed by myeloid cells; however, its role in the AILI microenvironment remains to be elucidated. A multidimensional approach, including single-cell RNA sequencing, spatial transcriptomics, and hour-long intravital imaging, is employed to characterize the microenvironment in Mas1 deficient mice at the systemic and cell-specific levels. The characteristic landscape of mouse AILI models involves reciprocal cellular communication among MYC+ CD63+ endothelial cells, MMP12+ macrophages, and monocytes, which is maintained by enhanced glycolysis and the NF-κB/TNF-α signaling pathway due to myeloid-Mas deficiency. Importantly, the pathogenic microenvironment is delineated in samples obtained from patients with ALF, demonstrating its clinical relevance. In summary, these findings greatly enhance the understanding of the microenvironment in advanced AILI and offer potential avenues for patient stratification and identification of novel therapeutic targets.

11.
Sci Rep ; 14(1): 3211, 2024 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332001

RESUMO

Type 2 diabetic kidney disease (T2DKD) is a common microvascular complication of type 2 diabetes mellitus (T2DM), and its incidence is significantly increasing. Microinflammation plays an important role in the development of T2DKD. Based on this, this study investigated the value of inflammatory markers including neutrophil-lymphocyte ratio (NLR), high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1) in the prediction of T2DKD. This was a cross-sectional survey study. A total of 90 patients with T2DM, who were hospitalized in the nephrology and endocrinology departments of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from June 2021 to January 2022, were included and divided into three groups (A1, A2, A3) according to the urinary albumin-to-creatinine ratio (UACR). Observe and compare the basic information, clinical and laboratory data, and the inflammatory markers NLR, hs-CRP, MCP-1. Results revealed that high levels of NLR (OR = 6.562, 95% CI 2.060-20.902, P = 0.001) and MCP-1 (OR = 1.060, 95% CI 1.026-1.095, P < 0.001) were risk factors in the development of T2DKD. Receiver operating characteristic curve analysis showed that the area under curve of NLR and MCP-1 in diagnosing T2DKD were 0.760 (95% CI 0.6577-0.863, P < 0.001) and 0.862 (95% CI 0.7787-0.937, P < 0.001). Therefore, the inflammatory markers NLR and MCP-1 are risk factors affecting the development of T2DKD, which of clinical value may be used as novel markers of T2DKD.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Humanos , Proteína C-Reativa/análise , Quimiocina CCL2/urina , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/urina , Linfócitos/química , Neutrófilos/química , Estudos Retrospectivos , Curva ROC
12.
J Oleo Sci ; 73(2): 135-145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38311404

RESUMO

In the pursuit of reducing oil separation in peanut butter, oleogels synthesized from diacylglycerol (DAG)-rich peanut oils, using glycerol monostearate (GMS) as the gelator, were examined as alternative stabilizers. In comparison to triacylglycerol (TAG)-rich peanut oils, the DAG oil-based oleogels exhibited better oil-binding capacities across increasing GMS concentrations. Intriguingly, thermal and rheological assessments pointed to a weaker network structure in DAG oil oleogels, as evidenced by their lower crystallization temperatures and reduced viscoelastic parameters (G' and G''). Insight from infrared spectroscopy revealed that this could stem from heightened intermolecular hydrogen bonding between the DAG oil and the gelator. When applied to peanut butter, DAG oil oleogels demonstrated efficacy in minimizing oil separation. Extended storage trials affirmed the long-term stability of peanut butter formulations incorporating these oleogels. Furthermore, sensory evaluations by panelists underscored favorable impressions, suggesting potential consumer acceptance. Overall, this study illuminates the promising role of DAG oleogels as effective, alternative stabilizers in peanut butter formulations.


Assuntos
Arachis , Diglicerídeos , Óleos , Compostos Orgânicos/química
13.
Int Dent J ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38368235

RESUMO

OBJECTIVE: This in vitro study aimed to determine whether a newly designed arcuate scan body can improve intraoral scanning accuracy for implant rehabilitation of edentulous jaws. MATERIAL AND METHODS: A master model containing 4 implant abutment replicas was fabricated and digitized with different scan bodies using an intraoral scanner. Four types of scan bodies were evaluated: original scan bodies (group OS), computer-aided design and computer-aided manufacturing (CAD/CAM) scan bodies without extension (group CS), CAD/CAM scan bodies with straight extension (group CSS), and CAD/CAM scan bodies with arcuate extension (group CSA). Conventional splinted open-tray impressions (group CI) were used as controls. The master model and the poured casts were digitized using a laboratory scanner. Impressions were repeated 10 times each in 5 groups. Scans in standard tessellation language format were exported to reverse engineering software and root mean square (RMS) values were used for trueness and precision assessments. In each group, 45 RMS values were acquired for precision evaluation and 10 RMS values were obtained for trueness assessment. Statistical evaluation was performed with the Kruskal-Wallis test and Dunn-Bonferroni test (α = 0.05). RESULTS: The median trueness values were 41.40, 55.95, 39.80, 39.75, and 22.30 µm for group OS, CS, CSS, CSA, and CI, respectively. CI showed better trueness than OS (P = .020), CS (P < .001), and CSS (P = .035). The median precisions for group OS, CS, CSS, CSA, and CI were 47.40, 51.50, 43.90, 25.20, and 24.60 µm. respectively. The precision of CSA and CI were higher than OS (P < .001), CS (P < .001), and CSS (P < .001). Between CI and CSA, there was no significant difference (P = 1.000). CONCLUSIONS: For full-arch implant rehabilitation, the scan body with arcuate extension could improve the intraoral scanning precision and showed similar 3-dimensional discrepancy compared to conventional splinted open-tray impressions.

14.
Biomater Sci ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38374788

RESUMO

To date, organ transplantation remains an effective method for treating end-stage diseases of various organs. In recent years, despite the continuous development of organ transplantation technology, a variety of problems restricting its progress have emerged one after another, and the shortage of donors is at the top of the list. Bioprinting is a very useful tool that has huge application potential in many fields of life science and biotechnology, among which its use in medicine occupies a large area. With the development of bioprinting, advances in medicine have focused on printing cells and tissues for tissue regeneration and reconstruction of viable human organs, such as the heart, kidneys, and bones. In recent years, with the development of organ transplantation, three-dimensional (3D) bioprinting has played an increasingly important role in this field, giving rise to many unsolved problems, including a shortage of organ donors. This review respectively introduces the development of 3D bioprinting as well as its working principles and main applications in the medical field, especially in the applications, and advancements and challenges of 3D bioprinting in organ transplantation. With the continuous update and progress of printing technology and its deeper integration with the medical field, many obstacles will have new solutions, including tissue repair and regeneration, organ reconstruction, etc., especially in the field of organ transplantation. 3D printing technology will provide a better solution to the problem of donor shortage.

15.
Clin Drug Investig ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38376794

RESUMO

BACKGROUND AND OBJECTIVES: Although thromboembolic events (TEEs) have been reported with the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), their association remains largely unknown. In this study, we aimed to provide a comprehensive review of TEEs associated with EGFR-TKIs. METHODS: We collected EGFR-TKIs (gefitinib, erlotinib, afatinib, and osimertinib) adverse reaction reports from 2015 Q1 to 2023 Q1 from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Disproportionality analysis was conducted to identify thromboembolic adverse events associated with EGFR-TKIs by comparing them with the overall FAERS database according to the reporting odds ratio (ROR). Associated factors were explored using univariate logistic regression. RESULTS: We identified 1068 reports of TEEs associated with EGFR-TKIs (1.24% accounts for all TEEs). Affected patients were females (49.72%) and those older than 65 years (41.20%). The reported TEE case fatality was 30.24%. The median time to onset (TTO) of all cases was 39 days [interquartile range (IQR) 11-161], and the median TTO of fatalities [31 days (IQR 10-116)] was significantly shorter than that of non-fatal cases [46 days (IQR 12-186)]. CONCLUSION: This study yielded three key findings. Firstly, EGFR-TKIs seem to exhibit prothrombotic effects, elevating the risk of TEEs. Secondly, the clinical outcomes of TEEs associated with EGFR-TKIs were poor. Thirdly, most TEEs occurred within the initial 3 months, and fatal cases occurred earlier than non-fatal cases.

16.
Acta Pharmacol Sin ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360931

RESUMO

Although ALK tyrosine kinase inhibitors (ALK-TKIs) have shown remarkable benefits in EML4-ALK positive NSCLC patients compared to conventional chemotherapy, the optimal sequence of ALK-TKIs treatment remains unclear due to the emergence of primary and acquired resistance and the lack of potential prognostic biomarkers. In this study, we systematically explored the validity of sequential ALK inhibitors (alectinib, lorlatinib, crizotinib, ceritinib and brigatinib) for a heavy-treated patient with EML4-ALK fusion via developing an in vitro and in vivo drug testing system based on patient-derived models. Based on the patient-derived models and clinical responses of the patient, we found that crizotinib might inhibit proliferation of EML4-ALK positive tumors resistant to alectinib and lorlatinib. In addition, NSCLC patients harboring the G1269A mutation, which was identified in alectinib, lorlatinib and crizotinib-resistant NSCLC, showed responsiveness to brigatinib and ceritinib. Transcriptomic analysis revealed that brigatinib suppressed the activation of multiple inflammatory signaling pathways, potentially contributing to its anti-tumor activity. Moreover, we constructed a prognostic model based on the expression of IL6, CXCL1, and CXCL5, providing novel perspectives for predicting prognosis in EML4-ALK positive NSCLC patients. In summary, our results delineate clinical responses of sequential ALK-TKIs treatments and provide insights into the mechanisms underlying the superior effects of brigatinib in patients harboring ALKG1269A mutation and resistant towards alectinib, lorlatinib and crizotinib. The molecular signatures model based on the combination of IL6, CXCL1 and CXCL5 has the potential to predict prognosis of EML4-ALK positive NSCLC patients.

17.
Mediators Inflamm ; 2024: 5573353, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38361765

RESUMO

As an interstitial fibrosis disease characterized by diffuse alveolitis and structural alveolar disorders, idiopathic pulmonary fibrosis (IPF) has high lethality but lacks limited therapeutic drugs. A hospital preparation used for the treatment of viral pneumonia, Qingfei Tongluo mixture (QFTL), is rumored to have protective effects against inflammatory and respiratory disease. This study aims to confirm whether it has a therapeutic effect on bleomycin-induced IPF in rats and to elucidate its mechanism of action. Male SD rats were randomly divided into the following groups: control, model, CQ + QFTL (84 mg/kg chloroquine (CQ) + 3.64 g/kg QFTL), QFTL-L, M, H (3.64, 7.28, and 14.56 g/kg, respectively) and pirfenidone (PFD 420 mg/kg). After induction modeling and drug intervention, blood samples and lung tissue were collected for further detection. Body weight and lung coefficient were examined, combined with hematoxylin and eosin (H&E) and Masson staining to observe lung tissue lesions. The enzyme-linked immunosorbent assay (ELISA) and the hydroxyproline (HYP) assay kit were used to detect changes in proinflammatory factors (transforming growth factor-ß (TGF-ß), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß)) and HYP. Immunohistochemistry and Western blotting were performed to observe changes in proteins related to pulmonary fibrosis (α-smooth muscle actin (α-SMA) and matrix metalloproteinase 12 (MMP12)) and autophagy (P62 and mechanistic target of rapamycin (mTOR)). Treatment with QFTL significantly improved the adverse effects of bleomycin on body weight, lung coefficient, and pathological changes. Then, QFTL reduced bleomycin-induced increases in proinflammatory mediators and HYP. The expression changes of pulmonary fibrosis and autophagy marker proteins are attenuated by QFTL. Furthermore, the autophagy inhibitor CQ significantly reversed the downward trend in HYP levels and α-SMA protein expression, which QFTL improved in BLM-induced pulmonary fibrosis rats. In conclusion, QFTL could effectively attenuate bleomycin-induced inflammation and pulmonary fibrosis through mTOR-dependent autophagy in rats. Therefore, QFTL has the potential to be an alternative treatment for IPF in clinical practice.


Assuntos
Medicamentos de Ervas Chinesas , Pneumonia , Fibrose Pulmonar , Ratos , Masculino , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Bleomicina/toxicidade , Ratos Sprague-Dawley , Pulmão/metabolismo , Pneumonia/induzido quimicamente , Serina-Treonina Quinases TOR/farmacologia , Peso Corporal , Fator de Crescimento Transformador beta1/metabolismo
18.
Transl Cancer Res ; 13(1): 290-298, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38410203

RESUMO

Background: Lung cancer is currently the world's leading malignancy in terms of morbidity and mortality. Neoadjuvant therapy is widely used in clinic to improve R0 resection rates and long-term survival after surgery, and patients with locally resectable non-small cell lung cancer (NSCLC) may benefit from neoadjuvant therapy. Methods: Data from 78 patients with stage II to IV NSCLC who had received neoadjuvant immunotherapy combined with chemotherapy from January 2019 to May 2022 were collected. The patients were categorized into groups based on their eligibility for posttreatment surgery, the level of pathological remission, and receipt of adjuvant therapy. The progression-free survival (PFS) and survival rates of patients in each group were compared. Efforts were made to identify the factors that influence patients' prognoses. Results: The incidence of adverse events in patients who received neoadjuvant immunotherapy combined with chemotherapy was 19%. The proportion of patients receiving neoadjuvant immunotherapy and chemotherapy undergoing surgery was 83.33%, and the rate of R0 resection was 64.10%. The pathological complete response (pCR) and major pathological response (MPR) rates were 26.25% and 21.87%, respectively. Patients who received adjuvant therapy were less likely to experience recurrent metastases than were those who did not receive adjuvant therapy (χ2=7.183; P=0.007<0.05). Conclusions: Neoadjuvant immunotherapy combined with chemotherapy has a low incidence of adverse events in resectable stage II-IV NSCLC, does not significantly increase the difficulty of surgery, and provides greater benefit in terms of PFS for patients who receive operation and adjuvant therapy.

19.
Dalton Trans ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38411983

RESUMO

Polar cyano fragments and their isomeric isocyano counterparts have attracted great attention as stimuli-responsive luminescent materials in a wide range of fields including organic light-emitting diode devices, chemical fluorescent sensors, photoelectric semiconductors, anti-counterfeit products, etc., mainly because of their typical electron-deficient activity, noncovalent recognition ability, and variable coordination capacity. The electron-deficient and polar nature of these blocks have significant effects on the properties of the cyano/isocyano-based luminophore materials, especially concerning their condensed state-dependent electronic structures. Among them, donor-acceptor (D-A) derived unimolecular and co-assembled luminophores have attracted more attention because their large delocalized structures and noncovalent interaction recognition sites can rebuild the electronic transfer character in the aggregative state, thus endowing them with outstanding stimuli-responsive luminescent behavior via intermolecular and intramolecular charge transfer in polytropic morphologies. In this perspective paper, we give a brief introduction on stimuli-responsive organic and coordinated luminophores and the documented typical design concepts and applications in recent years. It is expected that this perspective article will not only summarize the recent developments of polar cyano/isocyano-derived luminophores and their coordination compounds via structural tailoring and self-assembly but also throw light on the future of the design of more sophisticated stimuli-responsive architectures and their versatile properties.

20.
Sci Adv ; 10(8): eadj6251, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38394207

RESUMO

Chimeric antigen receptor T (CAR-T) cell therapy is a promising and precise targeted therapy for cancer that has demonstrated notable potential in clinical applications. However, severe adverse effects limit the clinical application of this therapy and are mainly caused by uncontrollable activation of CAR-T cells, including excessive immune response activation due to unregulated CAR-T cell action time, as well as toxicity resulting from improper spatial localization. Therefore, to enhance controllability and safety, a control module for CAR-T cells is proposed. Synthetic biology based on genetic engineering techniques is being used to construct artificial cells or organisms for specific purposes. This approach has been explored in recent years as a means of achieving controllability in CAR-T cell therapy. In this review, we summarize the recent advances in synthetic biology methods used to address the major adverse effects of CAR-T cell therapy in both the temporal and spatial dimensions.


Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Neoplasias/genética , Neoplasias/terapia , Terapia Baseada em Transplante de Células e Tecidos
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