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1.
Quant Imaging Med Surg ; 14(5): 3473-3488, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38720847

RESUMO

Background: The combination therapy of immunotherapy and drug-eluting bead bronchial artery chemoembolization (DEB-BACE) or microwave ablation (MWA) has been attempted as an effective and safe approach for advanced non-small cell lung cancer (NSCLC). However, the outcomes of immunotherapy plus multiple interventional techniques for advanced NSCLC remain unclear. This retrospective study thus aimed to investigate the effectiveness and safety of the maintenance treatment of programmed cell death protein 1 (PD-1) blockade after MWA plus DEB-BACE for advanced NSCLC. Methods: This retrospective cohort study consists of 95 patients with advanced NSCLC who were treated with DEB-BACE between April 2017 and October 2022 and who were allocated to three groups: group A (MWA + DEB-BACE + PD-1 blockade; n=15), group B (MWA + DEB-BACE; n=25), and group C (DEB-BACE alone; n=55). The adverse events (AEs) were compared between the three groups. The outcomes were compared via Kaplan-Meier methods, including median progression-free survival (PFS) and overall survival (OS). Survival analyses were performed via the univariate and multivariate analyses to investigate the prognostic predictors. Results: The overall incidence of AEs in the groups A-C was 53.3% (8/15), 36.0% (9/25), and 32.7% (18/55), respectively, which did not represent a significant difference (P=0.42). No severe AEs (SAEs) occurred. Group A, compared with group B and group C, had a significantly longer estimated median PFS (33.0 vs. 7.0 vs. 3.0 months; P<0.001) and OS (33.0 vs. 13.0 vs. 6.0 months; P=0.002). PD-1 blockade (P=0.006), tumor number (P=0.01), and DEB-BACE/bronchial artery infusion (BAI) chemotherapy cycles (P=0.04) were identified as the predictors of PFS, while the predictors of OS were PD-1 blockade (P<0.001), number of metastases (P<0.001), tumor diameter (P<0.001), and DEB-BACE/BAI cycles (P=0.02). Conclusions: Compared with that of advanced NSCLC treated with MWA plus DEB-BACE or DEB-BACE alone, the maintenance treatment of immunotherapy after MWA plus DEB-BACE might provide a superior prognosis without increasing the risk of AEs.

2.
Front Pharmacol ; 15: 1379338, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38738180

RESUMO

Background: Chinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3-5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear. Methods: Patients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)<5 mL/min/1.73 m2, ≥50% decline in the eGFR from the baseline, and doubling of SCr) in individuals consuming Niaoduqing granules. Results: A total of 1,271 patients were included, with a median follow-up duration of 29.71 (12.10, 56.07) months. The mean SCr Z-scores for the non-NDQ group and NDQ group were -0.175 and 0.153, respectively, at baseline (p = 0.015). The coefficients of the NDQ group from visit 1 to visit 5 were -0.207 (95% CI: -0.346, -0.068, p = 0.004), -0.214 (95% CI: 0.389, -0.039, p = 0.017), -0.324 (95% CI: 0.538, -0.109, p = 0.003), -0.502 (95% CI: 0.761, -0.243, p = 0.000), and -0.252 (95% CI: 0.569, 0.065, p = 0.119), respectively. The survival probability was significantly higher in the NDQ group (p = 0.0039). Taking Niaoduqing granules was a significant protective factor for thwarting disease progression (model 1: HR 0.654 (95% CI 0.489-0.875, p = 0.004); model 2: HR 0.646 (95% CI 0.476, 0.877, p = 0.005); and model 3: HR 0.602 (95% CI 0.442, 0.820, p = 0.001)). Conclusion: The long-term use of Niaoduqing granules improved SCr variation and lowered the risk of CKD progression by 39.8%.

3.
Chem Commun (Camb) ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38742271

RESUMO

A new macrocyclic arene, dibenzofuran[3]arene, was synthesized, which could be conveniently transformed to an O-doped aromatic belt with a rigid ring-shaped structure and deep cavity. Moreover, the O-doped aromatic belt also showed a high HOMO energy and a narrow HOMO-LUMO gap experimentally and theoretically.

4.
Environ Res ; 252(Pt 3): 119040, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38692424

RESUMO

Floods in global large rivers modulate the transport of dissolved organic carbon (DOC) and estuarine hydrological characteristics significantly. This study investigated the impact of a severe flood on the sources and age of DOC in the Yangtze River Estuary (YRE) in 2020. Comparing the flood period in 2020 to the non-flood period in 2017, we found that the flood enhanced the transport of young DOC to the East China Sea (ECS), resulting in significantly enriched Δ14C-DOC values. During the flood period, the proportion of modern terrestrial organic carbon (OC) was significantly higher compared to the non-flood period. Conversely, the proportion of pre-aged sediment OC was significantly lower during the flood period. The high turbidity associated with the flood facilitated rapid transformation and mineralization of sedimentary and fresh terrestrial OC, modifying the sources of DOC. The flux of modern terrestrial OC transported to the ECS during the flood period was 1.58 times higher than that of the non-flood period. These findings suggest that floods can modulate the sources and decrease the age of DOC, potentially leading to increased greenhouse gas emissions. Further research is needed to understand the long-term impacts of floods on DOC dynamics in global estuaries.

5.
Angew Chem Int Ed Engl ; : e202405620, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709194

RESUMO

Manganese-based layered oxides are currently of significant interest as cathode materials for sodium-ion batteries due to their low toxicity and high specific capacity. However, the practical applications are impeded by sluggish intrinsic Na+ migration and poor structure stability as a result of Jahn-Teller distortion and complicated phase transition. In this study, a high-entropy strategy is proposed to enhance the high-voltage capacity and cycling stability. The designed P2-Na0.67Mn0.6Cu0.08Ni0.09Fe0.18Ti0.05O2 achieves a deeply desodiation and delivers charging capacity of 158.1 mA h g-1 corresponding to 0.61 Na with a high initial Coulombic efficiency of 98.2%. The charge compensation is attributed to the cationic and anionic redox reactions conjunctively. Moreover, the crystal structure is effectively stabilized, leading to a slight variation of lattice parameters. This research carries implications for the expedited development of low-cost, high-energy-density cathode materials for sodium-ion batteries.

7.
J Mol Graph Model ; 130: 108786, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38710130

RESUMO

In this research, the wetting behavior of SiO2 modified with dodecyltrimethoxysilane (DTMS) was explored using both experimental and molecular dynamics (MD) simulation approaches. The experimental results reveal that DTMS can chemically bond to the SiO2 surface, and the contact angle (CA) reaches the maximum value of 157.7° when the mass of DTMS is twice that of SiO2. The different wetting behaviors caused by DTMS grafting were analyzed by CA fitting, ionic pairs, concentration distribution, molecule orientation, and interfacial interaction energy. The results demonstrate that a 25 % DTMS grafting rate resulted in a maximum CA of 158.2°, which is ascribed to the disruption of interfacial hydrogen bonding and changes in the hydration structure caused by DTMS grafting. Moreover, the above hydrophobic SiO2 model shows a slight decrease in CA as the water temperature increases, which is consistent with the experimental findings. In contrast, an opposite change was observed for the pristine SiO2 model. Although the higher water temperature enhances the diffusion capacity of water molecules in both models, the difference in interfacial interactions is responsible for the change in CA. We hope this finding will contribute to a deeper understanding of the wetting adjustment of SiO2.

8.
J Orthop ; 54: 143-147, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38576728

RESUMO

Aims: To establish cut-off values for Patient-Acceptable Symptom States (PASS) in three Patient Reported Outcome Measures (PROMs), the Constant-Murley Score (CMS) and University of California Los Angeles (UCLA) Shoulder Score and Oxford Shoulder Score (OSS) at 3, 6, and 12-months following reverse shoulder arthroplasty (RSA). Methods: A retrospective study was conducted for individuals who were treated for massive rotator cuff tear, rotator cuff arthropathy or proximal humerus fractures with RSA from January 2011 and February 2020. This study included patients who have completed the patient reported outcome measures (PROMs) and satisfaction questions preoperatively, and at 3, 6 and 12-months after the procedure. Functional outcome were evaluated by CMS, UCLA shoulder score and OSS, with one anchoring question regarding satisfaction. PASS thresholds for each PROM were obtained with the Youden method, by using the receiver operating characteristic analysis, and secondary analysis was performed with the 80% specificity and 75th percentile method. Results: 129 patients were included. 74.2%, 83.9%, and 89.3% of patients were found to have a satisfactory symptom state at 3, 6 and 12-months postoperatively. At 3, 6 and 12-month intervals, the respective PASS thresholds were 42, 39 and 52 for CMS, 17, 21 and 26 for UCLA score and 28, 25 and 18 for OSS. Conclusions: PASS thresholds for RSA at 3, 6 and 12-months were found for CMS (42, 39, 52), UCLA (17, 21, 26) and OSS (28, 25, 18). These thresholds suggest increasing expectations with a trend towards higher functional requirements at each time point.

9.
Opt Express ; 32(6): 10252-10264, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571241

RESUMO

Near-eye displays are widely recognized as a groundbreaking technological advancement with the potential to significantly impact daily life. Within the realm of near-eye displays, micro-LEDs have emerged as a highly promising technology owing to their exceptional optical performance, compact form factor, and low power consumption. However, a notable challenge in integrating micro-LEDs into near-eye displays is the efficient light collimation across a wide spectrum range. In this paper, we propose what we believe to be a novel design of a broadband beam collimation metasurface for full-color micro-LEDs by harnessing wavefront phase modulation based on Huygens' principle. Our results demonstrate a substantial reduction in the full width at half maximum (FWHM) angles, achieving a reduction to 1/10, 1/10, and 1/20 for red, green, and blue micro-LEDs compared to those without the metasurface, which is the best collimation result as far as we know. The central light intensity increases by 24.60, 36.49, and 42.15 times. Furthermore, the significant enhancement in the light energy within ±10° is achieved, with the respective multiplication factors of 14.16, 15.60, and 13.00. This metasurface has the potential to revolutionize the field by enabling high-performance, compact, and lightweight micro-LED displays, with applications in near-eye displays, micro-projectors, and beyond.

10.
J Toxicol Environ Health A ; 87(11): 471-479, 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38590254

RESUMO

Cannabidiol (CBD), a natural component extracted from Cannabis sativa L. exerts neuroprotective, antioxidant, and anti-inflammatory effects in Alzheimer's disease (AD), a disease characterized by impaired cognition and accumulation of amyloid-B peptides (Aß). Interactions between the gut and central nervous system (microbiota-gut-brain axis) play a critical role in the pathogenesis of neurodegenerative disorder AD. At present investigations into the mechanisms underlying the neuroprotective action of CBD in AD are not conclusive. The aim of this study was thus to examine the influence of CBD on cognition and involvement of the microbiota-gut-brain axis using a senescence-accelerated mouse prone 8 (SAMP8) model. Data demonstrated that administration of CBD to SAMP8 mice improved cognitive function as evidenced from the Morris water maze test and increased hippocampal activated microglia shift from M1 to M2. In addition, CBD elevated levels of Bacteriodetes associated with a fall in Firmicutes providing morphologically a protective intestinal barrier which subsequently reduced leakage of intestinal toxic metabolites. Further, CBD was found to reduce the levels of hippocampal and colon epithelial cells lipopolysaccharide (LPS), known to be increased in AD leading to impaired gastrointestinal motility, thereby promoting neuroinflammation and subsequent neuronal death. Our findings demonstrated that CBD may be considered a beneficial therapeutic drug to counteract AD-mediated cognitive impairment and restore gut microbial functions associated with the observed neuroprotective mechanisms.


Assuntos
Doença de Alzheimer , Canabidiol , Disfunção Cognitiva , Camundongos , Animais , Doença de Alzheimer/tratamento farmacológico , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Eixo Encéfalo-Intestino , Cognição , Disfunção Cognitiva/tratamento farmacológico , Modelos Animais de Doenças
11.
J Orthop ; 53: 156-162, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38601892

RESUMO

Introduction: The preclusion of obese patients from unicompartmental knee arthroplasty (UKA) has increasingly been challenged. This study aimed to evaluate the impact of Body Mass Index (BMI) on UKA at 15-year follow-up. Materials and methods: 169 unilateral UKA patients from 2003 to 2007 were followed-up prospectively for at least 15 years. 70 patients were left for analysis after accounting for patient demise, revision surgery and loss to follow-up. 48 of these patients (69%) were in the Control group (BMI <30 kg/m2) and 22 (31%) were in the Obese group (BMI ≥30 kg/m2). Patients were assessed before and after operation using the Knee Society Function Score (KSFS), Knee Society Knee Score (KSKS), Oxford Knee Score (OKS), and Physical (PCS) and Mental (MCS) component of the Short Form 12. Survivorship analysis was also performed. Results: Obese patients went through UKA at an earlier age than the non-obese patients (54.7 ± 4.7 years compared to 59.9 ± 7.8 years, p = 0.005). At 2, 10, and 15-year follow-up, both groups achieved clinically significant improvements in outcomes. There was no significant association found between obesity and outcome using multiple linear regression. While propensity matching found PCS improvement at 2 years to be greater in obese patients, no significant association between obesity and 15-year outcome was found. All 13 patients who required revision, underwent total knee arthroplasty (TKA). The overall 15-year survivorship was 74.2% within the obese group and 92.4% within the control group. Conclusion: Compared to non-obese patients, obese patients had poorer 15-year survivorship with greater odds of requiring revision surgery. However, assuming implant survival, obese patients can expect a non-inferior outcome relative to their non-obese counterparts in all patient reported outcome measures 15 years after surgery.

12.
PLoS One ; 19(4): e0301724, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38625978

RESUMO

BACKGROUNDS: Oral squamous cell carcinoma is a malignant tumor of the head and neck, and its molecular mechanism remains to be explored. METHODS: By analyzing the OSCC data from the TCGA database, we found that SLC2A3 is highly expressed in OSCC patients. The expression level of SLC2A3 was verified by RT-PCR and western blotting in OSCC cell lines. The function of SLC2A3 in OSCC cell lines and Lactic acid in SLC2A3-knockdown OSCC cells were detected by colony formation, CCK8, transwell, and wound healing assays. The effect of SLC2A3 on tumor growth and metastasis was tested in vivo. GSEA and Western blot were used to analyze and validate tumor phenotypes and signaling pathway molecules. RESULTS: We analyzed OSCC datasets in the TCGA database and found that SLC2A3 had abnormally high expression and was associated with poor prognosis. We also found that oral squamous cell carcinoma cells had increased proliferation, migration, invasion, EMT phenotype, and glycolysis due to SLC2A3 overexpression. Conversely, SLC2A3 knockdown had the opposite effect. Our in vivo experiments confirmed that SLC2A3 overexpression promoted tumor growth and metastasis while knockdown inhibited it. We also observed that high SLC2A3 expression led to EMT and the activation of the TGF-ß signaling pathway, while knockdown inhibited it. Interestingly, exogenous lactic acid restored the EMT, proliferation, migration, and invasion abilities of oral cancer cells inhibited by knocking down SLC2A3. CONCLUSIONS: Our study reveals that SLC2A3 expression was up-regulated in OSCC. SLC2A3 activates the TGF-ß signaling pathway through lactic acid generated from glycolysis, thus regulating the biological behavior of OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Proliferação de Células , Transdução de Sinais , Neoplasias de Cabeça e Pescoço/genética , Fator de Crescimento Transformador beta/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Transportador de Glucose Tipo 3/genética
13.
J Toxicol Environ Health A ; 87(10): 448-456, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38557302

RESUMO

Cerebral ischemia-reperfusion injury (CIRI) occurs frequently clinically as a complication following cardiovascular resuscitation resulting in neuronal damage specifically to the hippocampal CA1 region with consequent cognitive impairment. Apoptosis and oxidative stress were proposed as major risk factors associated with CIRI development. Previously, glycosides obtained from Cistanche deserticola (CGs) were shown to play a key role in counteracting CIRI; however, the underlying mechanisms remain to be determined. This study aimed to investigate the neuroprotective effect of CGs on subsequent CIRI in rats. The model of CIRI was established for 2 hr and reperfusion for 24 hr by middle cerebral artery occlusion (MCAO) model. The MCAO rats were used to measure the antioxidant and anti-apoptotic effects of CGs on CIRI. Neurological function was evaluated by the Longa neurological function score test. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to detect the area of cerebral infarction. Nissl staining was employed to observe neuronal morphology. TUNEL staining was used to detect neuronal apoptosis, while Western blot determined protein expression levels of factors for apoptosis-related and PI3K/AKT/Nrf2 signaling pathway. Data demonstrated that CGs treatment improved behavioral performance, brain injury, and enhanced antioxidant and anti-apoptosis in CIRI rats. In addition, CGs induced activation of PI3K/AKT/Nrf2 signaling pathway accompanied by inhibition of the expression of apoptosis-related factors. Evidence indicates that CGs amelioration of CIRI involves activation of the PI3K/AKT/Nrf2 signaling pathway associated with increased cellular viability suggesting these glycosides may be considered as an alternative compound for CIRI treatment.


Assuntos
Isquemia Encefálica , Cistanche , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Ratos , Animais , Ratos Sprague-Dawley , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antioxidantes/farmacologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Fosfatidilinositol 3-Quinases/farmacologia , Glicosídeos/farmacologia , Glicosídeos/uso terapêutico , Fator 2 Relacionado a NF-E2/farmacologia , Apoptose , Isquemia Encefálica/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Fármacos Neuroprotetores/farmacologia
14.
J Toxicol Environ Health A ; 87(10): 436-447, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38557424

RESUMO

One of the main pathological features noted in Alzheimer's disease (AD) is the presence of plagues of aggregated ß-amyloid (Aß1-42)-peptides. Excess deposition of amyloid-ß oligomers (AßO) are known to promote neuroinflammation. Sequentially, following neuroinflammation astrocytes become activated with cellular characteristics to initiate activated astrocytes. The purpose of this study was to determine whether total flavonoids derived from Dracocephalum moldavica L. (TFDM) inhibited Aß1-42-induced damage attributed to activated C8-D1A astrocytes. Western blotting and ELISA were used to determine the expression of glial fibrillary acidic protein (GFAP), and complement C3 to establish the activation status of astrocytes following induction from exposure to Aß1-42. Data demonstrated that stimulation of C8-D1A astrocytes by treatment with 40 µM Aß1-42 for 24 hr produced significant elevation in protein expression and protein levels of acidic protein (GFAP) and complement C3 accompanied by increased expression and levels of inflammatory cytokines. Treatment with TFDM or the clinically employed drug donepezil in AD therapy reduced production of inflammatory cytokines, and toxicity initiated following activation of C8-D1A astrocytes following exposure to Aß1-42. Therefore, TFDM similar to donepezil inhibited inflammatory secretion in reactive astrocytes, suggesting that TFDM may be considered as a potential compound to be utilized in AD therapy.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Lamiaceae , Humanos , Peptídeos beta-Amiloides/farmacologia , Doença de Alzheimer/tratamento farmacológico , Flavonoides/farmacologia , Complemento C3/metabolismo , Complemento C3/farmacologia , Complemento C3/uso terapêutico , Doenças Neuroinflamatórias , Astrócitos/metabolismo , Donepezila/metabolismo , Donepezila/farmacologia , Donepezila/uso terapêutico , Citocinas/metabolismo , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/toxicidade
15.
Sci Rep ; 14(1): 9881, 2024 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-38688977

RESUMO

RAB3B is essential for the transportation and secretion within cells. Its increased expression is linked to the development and progression of various malignancies. However, understanding of RAB3B's involvement in carcinogenesis is mostly limited to specific cancer subtypes. Hence, exploring RAB3B's regulatory roles and molecular mechanisms through comprehensive cancer datasets might offer innovative approaches for managing clinical cancer. To examine the potential involvement of RAB3B in the development of cancer, we analyzed data from various sources including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), cBioPortal, HPA, UALCAN, and tissue microarray (TAM). Using bioinformatics techniques, we examined the correlation between RAB3B expression and prognosis, tumor heterogeneity, methylation modifications, and immune microenvironment across different cancer types. Our findings indicate that elevated RAB3B expression can independently predict prognosis in many tumors and has moderate accuracy for diagnosing most cancers. In most cancer types, we identified RAB3B mutations that showed a significant correlation with tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and microsatellite instability (MSI). Abnormal DNA methylation patterns were also observed in most cancers compared to normal tissues. Additionally, we found significant correlations between RAB3B expression, immune cell infiltration, and immune scores across various cancers. Through pan-cancer analysis, we observed significant differences in RAB3B expression levels between tumors and normal tissues, making it a potential primary factor for cancer diagnosis and prognosis. The IHC results revealed that the expression of RAB3B in six types of tumors was consistent with the results of the pan-cancer analysis of the database. Furthermore, RAB3B showed potential associations with tumor heterogeneity and immunity. Thus, RAB3B can be utilized as an auxiliary diagnostic marker for early tumor detection and a prognostic biomarker for various tumor types.


Assuntos
Biomarcadores Tumorais , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias , Microambiente Tumoral , Proteínas rab3 de Ligação ao GTP , Humanos , Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Mutação , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/diagnóstico , Neoplasias/patologia , Prognóstico , Proteínas rab3 de Ligação ao GTP/genética , Proteínas rab3 de Ligação ao GTP/metabolismo , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética
16.
Signal Transduct Target Ther ; 9(1): 87, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38584157

RESUMO

The gasdermin (GSDM) family has garnered significant attention for its pivotal role in immunity and disease as a key player in pyroptosis. This recently characterized class of pore-forming effector proteins is pivotal in orchestrating processes such as membrane permeabilization, pyroptosis, and the follow-up inflammatory response, which are crucial self-defense mechanisms against irritants and infections. GSDMs have been implicated in a range of diseases including, but not limited to, sepsis, viral infections, and cancer, either through involvement in pyroptosis or independently of this process. The regulation of GSDM-mediated pyroptosis is gaining recognition as a promising therapeutic strategy for the treatment of various diseases. Current strategies for inhibiting GSDMD primarily involve binding to GSDMD, blocking GSDMD cleavage or inhibiting GSDMD-N-terminal (NT) oligomerization, albeit with some off-target effects. In this review, we delve into the cutting-edge understanding of the interplay between GSDMs and pyroptosis, elucidate the activation mechanisms of GSDMs, explore their associations with a range of diseases, and discuss recent advancements and potential strategies for developing GSDMD inhibitors.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular , Sepse , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Gasderminas , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Piroptose
17.
Chem Commun (Camb) ; 60(37): 4962-4965, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38629394

RESUMO

A calix[3]carbazole-based cavitand was conveniently synthesized. It was found that the cavitand with adjustable conformation could show excellent complexation with fullerenes C60 and C70 in both solution and the solid state. Moreover, the crystal structures of the host-guest complexes show that the cavitand can stack into channel-like architectures, in which fullerenes are orderly arranged inside.

18.
Sci Adv ; 10(13): eadl4842, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38552028

RESUMO

The high-capacity advantage of lithium metal anode was compromised by common use of copper as the collector. Furthermore, lithium pulverization associated with "dead" Li accumulation and electrode cracking deteriorates the long-term cyclability of lithium metal batteries, especially under realistic test conditions. Here, we report an ultralight, integrated anode of polyimide-Ag/Li with dual anti-pulverization functionality. The silver layer was initially chemically bonded to the polyimide surface and then spontaneously diffused in Li solid solution and self-evolved into a fully lithiophilic Li-Ag phase, mitigating dendrites growth or dead Li. Further, the strong van der Waals interaction between the bottommost Li-Ag and polyimide affords electrode structural integrity and electrical continuity, thus circumventing electrode pulverization. Compared to the cutting-edge anode-free cells, the batteries pairing LiNi0.8Mn0.1Co0.1O2 with polyimide-Ag/Li afford a nearly 10% increase in specific energy, with safer characteristics and better cycling stability under realistic conditions of 1× excess Li and high areal-loading cathode (4 milliampere hour per square centimeter).

19.
J Med Chem ; 67(8): 6738-6748, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526421

RESUMO

The development and optimization of metal-based anticancer drugs with novel cytotoxic mechanisms have emerged as key strategies to overcome chemotherapeutic resistance and side effects. Agents that simultaneously induce ferroptosis and autophagic death have received extensive attention as potential modalities for cancer therapy. However, only a limited set of drugs or treatment modalities can synergistically induce ferroptosis and autophagic tumor cell death. In this work, we designed and synthesized four new cycloplatinated (II) complexes harboring an isoquinoline alkaloid C∧N ligand. On screening the in vitro activity of these agents, we found that Pt-3 exhibited greater selectivity of cytotoxicity, decreased resistance factors, and improved anticancer activity compared to cisplatin. Furthermore, Pt-3, which we demonstrate can initiate potent ferritinophagy-dependent ferroptosis, exhibits less toxic and better therapeutic activity than cisplatin in vivo. Our results identify Pt-3 as a promising candidate or paradigm for further drug development in cancer treatment.


Assuntos
Antineoplásicos , Ferroptose , Isoquinolinas , Neoplasias de Mama Triplo Negativas , Ferroptose/efeitos dos fármacos , Humanos , Isoquinolinas/farmacologia , Isoquinolinas/química , Isoquinolinas/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Animais , Feminino , Linhagem Celular Tumoral , Ferritinas/metabolismo , Autofagia/efeitos dos fármacos , Camundongos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Alcaloides/farmacologia , Alcaloides/química , Alcaloides/síntese química , Relação Estrutura-Atividade , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células/efeitos dos fármacos , Camundongos Nus
20.
J Plant Physiol ; 296: 154218, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38490054

RESUMO

Jasmonates (JAs) are among the main phytohormones, regulating plant growth and development, stress responses, and secondary metabolism. As the major regulator of the JA signaling pathway, MYC2 also plays an important role in plant secondary metabolite synthesis and accumulation. In this study, we performed a comparative transcriptome analysis of Lycoris aurea seedlings subjected to methyl jasmonate (MeJA) at different treatment times. A total of 31,193 differentially expressed genes (DEGs) were identified by RNA sequencing. Among them, 732 differentially expressed transcription factors (TFs) comprising 51 TF families were characterized. The most abundant TF family was WRKY proteins (80), followed by AP2/ERF-EFR (67), MYB (59), bHLH (52), and NAC protein (49) families. Subsequently, by calculating the Pearson's correlation coefficient (PCC) between the expression level of TF DEGs and the lycorine contents, 41 potential TF genes (|PCC| >0.8) involved in lycorine accumulation were identified, including 36 positive regulators and 5 negative regulators. Moreover, a MeJA-inducible MYC2 gene (namely LaMYC2) was cloned on the basis of transcriptome sequencing. Bioinformatic analyses revealed that LaMYC2 proteins contain the bHLH-MYC_N domain and bHLH-AtAIB_like motif. LaMYC2 protein is localized in the cell nucleus, and can partly rescue the MYC2 mutant in Arabidopsis thaliana. LaMYC2 protein could interact with most LaJAZs (especially LaJAZ3 and LaJAZ4) identified previously. Transient overexpression of LaMYC2 increased lycorine contents in L. aurea petals, which might be associated with the activation of the transcript levels of tyrosine decarboxylase (TYDC) and phenylalanine ammonia lyase (PAL) genes. By isolating the 887-bp-length promoter fragment upstream of the start codon (ATG) of LaTYDC, we found several different types of E-box motifs (CANNTG) in the promoter of LaTYDC. Further study demonstrated that LaMYC2 was indeed able to bind the E-box (CACATG) present in the LaTYDC promoter, verifying that the pathway genes involved in lycorine biosynthesis could be regulated by LaMYC2, and that LaMYC2 has positive roles in the regulation of lycorine biosynthesis. These findings demonstrate that LaMYC2 is a positive regulator of lycorine biosynthesis and may facilitate further functional research of the LaMYC2 gene, especially its potential regulatory roles in Amaryllidaceae alkaloid accumulation in L. aurea.


Assuntos
Acetatos , Alcaloides de Amaryllidaceae , Arabidopsis , Lycoris , Fenantridinas , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Alcaloides de Amaryllidaceae/metabolismo , Lycoris/genética , Lycoris/metabolismo , Ciclopentanos/farmacologia , Ciclopentanos/metabolismo , Oxilipinas/farmacologia , Oxilipinas/metabolismo , Transcriptoma , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas
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