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1.
J Hazard Mater ; 480: 136035, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39362119

RESUMO

Melamine (MA) enhanced Cu-Fenton process was developed for the degradation of anthracyclines. Taking daunorubicin (DNR) degradation as an example, we found that the initial first-order apparent constant of Cu2+/MA/H2O2 system with a molar ratio of 1:8 for Cu2+:MA was 5.2 times higher than that of conventional Cu2+/H2O2 system. The in-situ reductive coordination between Cu2+ and MA facilitated the generation and stabilization of Cu+ species, thereby accelerating the rate-limiting step of Cu2+/Cu+ conversion and maintaining high levels of Cu+ during the degradation process. Moreover, pre-synthesized Cu+-MA complexes (e.g., CM-250) further enhanced the efficiency of the Cu-Fenton reaction by increasing both the Cu+ proportion and MA chelation. The apparent activation energy for DNR degradation in CM-250 mediated Fenton reaction (15.9 kJ mol-1) was lower than that in systems involving Cu2+/MA (41.2 kJ mol-1) and Cu2+ (65.6 kJ mol-1). Enhanced generation of various reactive oxygen species (·OH,·O2-, and 1O2) was confirmed, with 1O2 playing a dominant role, significantly improving both degradation rate and mineralization degree for DNR. MA-enhanced Cu-Fenton process also offers a convenient alternative to effectively remove other anthracyclines and organic micropollutants, holding great promise for advancing advanced oxidation processes as well as practical large-scale degradation applications targeting multiple pollutants.

2.
Environ Sci Technol ; 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39373333

RESUMO

Human exposure to polycyclic aromatic hydrocarbons (PAHs) as mutagenic and carcinogenic pollutants in the environment often occurs in the form of mixtures. Although the mixture effects of PAHs have been previously recognized, the toxicological mechanisms to explain them still remain quite unclear. This study combined metabolomics and chemical proteomics methods to comprehensively understand the mixture effects of a PAH mixture including benzo(a)anthracene (BaA), benzo(b)fluoranthene (BbF), benzo(a)pyrene (BaP), and chrysene (CHR). Among them, BaA has shown a strong synergistic effect with other PAHs. Interestingly, BaA alone is not a potent oxidative stress inducer in liver cells but dose-dependently amplifies oxidative damage caused by the PAH mixture. Global metabolomics analysis results revealed damage to the antioxidant glutathione synthesis, which was caused by the glutamine depletion caused by BaA in the mixture. Subsequently, the label-free chemical proteomics and cellular thermal shift analysis (CETSA) demonstrated that the PAH mixture altered the thermal shift of glutamine transporter SLC1A5. Furthermore, Western blotting and the isothermal titration calorimetry (ITC) interaction measurements showed nanomolar KD values between BaA and SLC1A5. Overall, this study showed that BaA synergistically contributed to PAH mixture induced oxidative damage by targeting SLC1A5 to inhibit glutamate transport into cells, resulting in the inhibition of glutathione synthesis.

3.
Heliyon ; 10(17): e37638, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39290277

RESUMO

Background: Ferroptosis and disulfidptosis are regulatory forms of cell death that play an important role in tumorigenesis and progression. However, few biomarkers about disulfidptosis and ferroptosis related genes (DFRGs) have been developed to predict the prognosis of bladder cancer (BC). Methods: We conducted a bioinformatics analysis using public BC datasets to examine the prognostic significance of differentially expressed DFRGs. A Lasso regression was employed to create a prognostic prediction model from these DFRGs. Hub DFRGs that play a role in immunotherapy response and immunoregulation were pinpointed. Immunohistochemistry (IHC) experiment was performed to assess NUBPL and c-MYC expression in BC patients who underwent surgery or received immune checkpoint inhibitor (ICI) immunotherapy at Peking University Cancer Hospital. Results: We constructed a valid model to predict the prognosis of BC based on DFRGs and performed relevant validation, the results demonstrated that the model was an independent prognostic factor for BC. Further analysis indicated that the model score, combined with the expression of various immune factors and tumor mutation burden (TMB), could predict the prognosis for BC. In addition, we also found that NUBPL was strongly associated with prognosis and response to ICI treatment, and NUBPL may influence BC malignant progression through the c-MYC pathway. Conclusions: Our research findings highlight the satisfactory predictive value of DFRGs in the immune microenvironment and suggest that NUBPL may be a highly promising biomarker for predicting the prognosis and efficacy of ICI treatment in BC patients.

4.
Lipids Health Dis ; 23(1): 321, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39342327

RESUMO

BACKGROUND: Periodontitis, a persistent inflammatory condition, significantly impairs individuals' overall quality of life. Lymphocyte-to-high-density lipoprotein cholesterol ratio (LHR), monocyte-to-high-density lipoprotein cholesterol ratio (MHR), neutrophil-to-high-density lipoprotein cholesterol ratio (NHR), and platelet-to-high-density lipoprotein cholesterol ratio (PHR) are new convenient and economical biomarkers. However, whether the above high-density lipoprotein-related inflammatory biomarkers are associated with periodontitis has rarely been investigated. Therefore, the research endeavor focused on uncovering potential relationships. METHODS: The research encompassed a diverse and extensive sample, comprising 9,470 participants, selected from the National Health and Nutrition Examination Survey spanning the years 2009 to 2014. The association between high-density lipoprotein-related inflammatory biomarkers and periodontitis was explored utilizing a multivariable logistic regression model with weighted analysis. Additionally, the study employed smoothed curve fitting to explore potential nonlinear relationships. Further stratified analyses and interaction tests were performed. RESULTS: This study indicated no apparent association between MHR and PHR with periodontitis, whereas LHR and NHR demonstrated a statistically significant positive relationship with the prevalence of periodontitis. In the fully adjusted model, participants belonging to the highest tertile of both LHR and NHR showed a notably higher likelihood of having periodontitis compared to those in the lowest tertile (LHR: OR = 1.22, 95% CI: 1.06, 1.39; NHR: OR = 1.27, 95% CI: 1.09, 1.49). Furthermore, smooth curve fitting was employed to investigate the potential nonlinear relationship between LHR, NHR, and periodontitis. The results indicated that there was a significant increase in the occurrence of periodontitis when Log2 (LHR) exceeded 1.01 and Log2(NHR) surpassed 2.16 (Log2(LHR): OR = 1.42; 95% CI: 1.19, 1.69; Log2(NHR): OR = 1.40; 95% CI: 1.15, 1.71). The subgroup analysis revealed that the associations between periodontitis and either LHR or NHR, separately, were more pronounced among individuals under the age of 50 and those without hypertension. CONCLUSIONS: This cross-sectional study revealed a positive relationship between LHR、NHR and periodontitis, particularly when these indicators exceeded their thresholds. LHR and NHR may serve as potential inflammatory markers for identifying periodontitis, thereby facilitating early warning for both patients and dentists, and enabling early intervention in the oral environment. Besides, extensive prospective cohort investigations are essential to confirm and solidify this observation.


Assuntos
Biomarcadores , Inflamação , Inquéritos Nutricionais , Periodontite , Humanos , Periodontite/sangue , Periodontite/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Inflamação/sangue , Biomarcadores/sangue , HDL-Colesterol/sangue , Monócitos/metabolismo , Neutrófilos , Idoso , Linfócitos/metabolismo , Lipoproteínas HDL/sangue , Estudos Transversais , Plaquetas/patologia , Modelos Logísticos
5.
Clin Transl Med ; 14(9): e1772, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39270064

RESUMO

Tumour cell senescence can be induced by various factors, including DNA damage, inflammatory signals, genetic toxins, ionising radiation and nutrient metabolism. The senescence-associated secretory phenotype (SASP), secreted by senescent tumour cells, possesses the capacity to modulate various immune cells, including macrophages, T cells, natural killer cells and myeloid-derived suppressor cells, as well as vascular endothelial cells and fibroblasts within the tumour microenvironment (TME), and this modulation can result in either the promotion or suppression of tumorigenesis and progression. Exploring the impact of SASP on the TME could identify potential therapeutic targets, yet limited studies have dissected its functions. In this review, we delve into the causes and mechanisms of tumour cell senescence. We then concentrate on the influence of SASP on the tumour immune microenvironment, angiogenesis, extracellular matrix and the reprogramming of cancer stem cells, along with their associated tumour outcomes. Last, we present a comprehensive overview of the diverse array of senotherapeutics, highlighting their prospective advantages and challenge for the treatment of cancer patients. KEY POINTS: Senescence-associated secretory phenotype (SASP) secretion from senescent tumour cells significantly impacts cancer progression and biology. SASP is involved in regulating the remodelling of the tumour microenvironment, including immune microenvironment, vascular, extracellular matrix and cancer stem cells. Senotherapeutics, such as senolytic, senomorphic, nanotherapy and senolytic vaccines, hold promise for enhancing cancer treatment efficacy.


Assuntos
Neoplasias , Fenótipo Secretor Associado à Senescência , Microambiente Tumoral , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Humanos , Neoplasias/imunologia , Neoplasias/metabolismo , Senescência Celular
6.
ACS Appl Mater Interfaces ; 16(37): 49985-49992, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39231168

RESUMO

The organisms of animals with full spatial motion ability present fine and complex 3D structures, showing reliable adhesion ability to the substrate. As core issues, the design and manufacture of complex morphology are essential in bionic adhesion technology. Specifically, the end-expanded microstructure array of high adhesion under low preload has widespread potential in the nondestructive fixation and handling of fragile objects. In the fabrication of end-expanded microstructures, the design and manufacture of metal molds with good mechanical strength are the key. In this paper, a microfabrication technology for manufacturing nickel molds based on three-dimensional printing and electroplating was proposed. The effect of the electric field inhomogeneity on the electrodeposition morphology was systematically studied. Typical bionic adhesives with expanded ends were obtained by a roll-to-roll hot embossing (R2R-HE) process. The normal adhesion force of the bionic adhesives is 9.5 N/cm2, which is comparable to that of the gecko. The electroplating process assisted by 3D printing provides a new approach for the fabrication of complex bionic morphologies and large-area bionic adhesion structures.

7.
Inorg Chem ; 63(37): 17005-17013, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39230951

RESUMO

Developing a synthesis-free, multifunctional, and effective colorimetric assay system based on 3,3',5,5'-tetramethylbenzidine (TMB) oxidation is attractive yet challenging. Herein, we established a synergetic Cu2+/Cr6+-promoting strategy for TMB-based colorimetric detection of Cr6+. By introducing Cu2+, critical TMB·+···Cu(I/II)···TMB charge transfer complex (TMC) intermediates were in situ formed to reduce the activation energy of TMB oxidation, thereby accelerating Cr6+-mediated TMB oxidation. TMC intermediates also played a pivotal role in H2O2-participated TMB oxidation, clarifying the secondary responsibility of reactive oxygen species frequently caused by Fenton-like reactions. Leveraging the synergetic capacity between Cu2+ and Cr6+ for TMB oxidation, we demonstrated sensitive and specific colorimetric detections for Cr6+ with a limit of detection of 0.006 µM. With its convenient operation and rapid responsiveness, this strategy successfully enabled the practical detection of Cr6+ in real water samples. This work not only enhances the understanding of the internal acceleration mechanism in colorimetric sensing but also provides valuable opportunities to advance synthesis-free detection platforms.

8.
Cell Rep ; 43(8): 114640, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39163202

RESUMO

Functional enhancer annotation is critical for understanding tissue-specific transcriptional regulation and prioritizing disease-associated non-coding variants. However, unbiased enhancer discovery in disease-relevant contexts remains challenging. To identify enhancers pertinent to diabetes, we conducted a CRISPR interference (CRISPRi) screen in the human pluripotent stem cell (hPSC) pancreatic differentiation system. Among the enhancers identified, we focused on an enhancer we named ONECUT1e-664kb, ∼664 kb from the ONECUT1 promoter. Previous studies have linked ONECUT1 coding mutations to pancreatic hypoplasia and neonatal diabetes. We found that homozygous deletion of ONECUT1e-664kb in hPSCs leads to a near-complete loss of ONECUT1 expression and impaired pancreatic differentiation. ONECUT1e-664kb contains a type 2 diabetes-associated variant (rs528350911) disrupting a GATA motif. Introducing the risk variant into hPSCs reduced binding of key pancreatic transcription factors (GATA4, GATA6, and FOXA2), supporting its causal role in diabetes. This work highlights the utility of unbiased enhancer discovery in disease-relevant settings for understanding monogenic and complex disease.


Assuntos
Diferenciação Celular , Elementos Facilitadores Genéticos , Pâncreas , Humanos , Elementos Facilitadores Genéticos/genética , Diferenciação Celular/genética , Pâncreas/metabolismo , Pâncreas/patologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Células-Tronco Pluripotentes/metabolismo , Sistemas CRISPR-Cas/genética , Fator de Transcrição GATA6/metabolismo , Fator de Transcrição GATA6/genética
10.
Acta Biomater ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39122136

RESUMO

Sympathetic hyperactivation and inflammatory responses are the main causes of myocardial ischemia‒reperfusion (I/R) injury and myocardial I/R-related ventricular arrhythmias (VAs). Previous studies have demonstrated that light-emitting diodes (LEDs) could modulate post-I/R neuroinflammation, thus providing protection against myocardial I/R injury. Nevertheless, further applications of LEDs are constrained due to the low penetration depth (<1 cm) and potential phototoxicity. Low-intensity focused ultrasound (LIFU), an emerging noninvasive neuromodulation strategy with deeper penetration depth (∼10 cm), has been confirmed to modulate sympathetic nerve activity and inflammatory responses. Sonodynamic therapy (SDT), which combines LIFU with sonosensitizers, confers additional advantages, including superior therapeutic efficacy, precise localization of neuronal modulation and negligible side effects. Herein, LIFU and SDT were introduced to modulate post-myocardial I/R neuroinflammation to protect against myocardial I/R injury. The results indicated that LIFU and SDT inhibited sympathetic neural activity, suppressed the activation of astrocytes and microglia, and promoted microglial polarization towards the M2 phenotype, thereby attenuating myocardial I/R injury and preventing I/R-related malignant VAs. These insights suggest that LIFU and SDT inspire a noninvasive and efficient neuroinflammatory modulation strategy with great clinical translation potential thus benefiting more patients with myocardial I/R in the future. STATEMENT OF SIGNIFICANCE: Myocardial ischemia-reperfusion (I/R) may cause I/R injury and I/R-induced ventricular arrhythmias. Sympathetic hyperactivation and inflammatory response play an adverse effect in myocardial I/R injury. Previous studies have shown that light emitting diode (LED) can regulate I/R-induced neuroinflammation, thus playing a myocardial protective role. However, due to the low penetration depth and potential phototoxicity of LED, it is difficult to achieve clinical translation. Herein, we introduced sonodynamic modulation of neuroinflammation to protect against myocardial I/R injury, based on mitochondria-targeted nanosonosensitizers (CCNU980 NPs). We demonstrated that sonodynamic modulation could promote microglial autophagy, thereby preventing myocardial I/R injury and I/R-induced ventricular arrhythmias. This is the first example of sonodynamic modulation of myocardial I/R-induced neuroinflammation, providing a novel strategy for clinical translation.

11.
Gland Surg ; 13(6): 802-811, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39015702

RESUMO

Background: There is inconsistent evidence regarding obesity's effect on surgical outcomes following retroperitoneal laparoscopic adrenalectomy (RLA). This study aimed to investigate the influence of obesity on surgical outcomes in patients undergoing RLA, with an emphasis on operative time, drainage tube removal time, postoperative hospital stays and perioperative complications. Methods: In this retrospective, single-center, observational study, all consecutive cases of unilateral RLA for adrenal disease from January 2012 to December 2021 were incorporated. The patients were divided into two groups based on their body mass index (BMI) of 28 kg/m2. To mitigate selection bias, propensity score matching (PSM) was conducted, using logistic regression to calculate propensity scores for balancing baseline characteristics. A multivariate logistic regression analysis was performed to assess how obesity affects operative time and intraoperative blood loss as well. The linear correlation between BMI and surgical outcomes, including prolonged operative time and increased intraoperative blood loss, was also examined using restricted cubic spline (RCS) analysis. Results: A total of 569 patients who underwent RLA were included. After PSM, 122 patients were apportioned to each group. Statistically significant differences were observed between the obese and non-obese group in operative time (97.5 vs. 115 min, P<0.001). There were no statistically significant differences between the two groups regarding hospital stay (6.7 vs. 6.8 days, P=0.58), drainage tube removal time (3.0 vs. 3.0 days, P=0.19), nor postoperative complications (9.0% vs. 12.3%, P=0.41). Furthermore, univariate logistic regression analysis revealed that, obese patients undergoing RLA were linked to prolonged operative time and increased intraoperative blood loss. After adjusting for potential confounders, the obese group showed a 67% increased risk of prolonged operative time and a 69% increased intraoperative blood loss. The RCS analysis revealed that BMI had a linear relationship with operative time (P for nonlinearity =0.47) and blood loss during surgery (P for linearity =0.89). Conclusions: In patients undergoing RLA, obesity exerts a significant influence on surgical outcomes, particularly with regard to operative time and intraoperative blood loss, as shown in multivariable logistic regression analysis and PSM to balance baseline characteristics.

12.
Nat Commun ; 15(1): 5659, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969646

RESUMO

Fully targeted mRNA therapeutics necessitate simultaneous organ-specific accumulation and effective translation. Despite some progress, delivery systems are still unable to fully achieve this. Here, we reformulate lipid nanoparticles (LNPs) through adjustments in lipid material structures and compositions to systematically achieve the pulmonary and hepatic (respectively) targeted mRNA distribution and expression. A combinatorial library of degradable-core based ionizable cationic lipids is designed, following by optimisation of LNP compositions. Contrary to current LNP paradigms, our findings demonstrate that cholesterol and phospholipid are dispensable for LNP functionality. Specifically, cholesterol-removal addresses the persistent challenge of preventing nanoparticle accumulation in hepatic tissues. By modulating and simplifying intrinsic LNP components, concurrent mRNA accumulation and translation is achieved in the lung and liver, respectively. This targeting strategy is applicable to existing LNP systems with potential to expand the progress of precise mRNA therapy for diverse diseases.


Assuntos
Lipídeos , Fígado , Pulmão , Nanopartículas , RNA Mensageiro , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Nanopartículas/química , Animais , Fígado/metabolismo , Pulmão/metabolismo , Lipídeos/química , Humanos , Camundongos , Colesterol/metabolismo , Colesterol/química , Biossíntese de Proteínas , Camundongos Endogâmicos C57BL , Fosfolipídeos/química , Fosfolipídeos/metabolismo , Lipossomos
13.
Anal Chem ; 96(32): 13285-13290, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39078708

RESUMO

Accurate detection of site-specific 5-hydroxymethylcytosine (5hmC) in genomic DNA is of great significance, but it is technically challenging to directly distinguish very low levels of 5hmC from their abundant cytosine/5-methylcytosine (C/5mC) analogues. Herein, we wish to propose a selective ligase-mediated mechanism (SLim) that can directly discriminate 5hmC from C/5mC with a high specificity without the use of any sample processing protocol. In this new design, we discovered that HiFi Taq DNA Ligase can well tolerate the mismatched 5hmC/A base-pairing and then effectively ligate the associated nicking site while the mismatched 5mC/A or C/A pairs cannot be recognized by HiFi Taq DNA Ligase, providing a new way for direct and selective discriminating 5hmC from its similar analogues. Ultrasensitive and selective quantification of site-specific 5hmC is realized by coupling the SLim with polymerase chain reaction (PCR) or loop-mediated isothermal amplification (LAMP).


Assuntos
5-Metilcitosina , DNA Ligases , DNA , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/análise , 5-Metilcitosina/química , DNA/química , DNA/análise , DNA Ligases/metabolismo , Técnicas de Amplificação de Ácido Nucleico/métodos , Humanos , Reação em Cadeia da Polimerase
14.
J Family Med Prim Care ; 13(6): 2477-2484, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39027832

RESUMO

Objective: This study aims to explore the relationship between different endometrial preparations and pregnancy outcomes among patients with regular ovulatory cycles in order to find the best endometrial preparation methods in the freeze-thaw embryo transfer (FET) cycle. Materials and Methods: This is a retrospective study to investigate FET pregnancy outcomes in women who had a regular menstrual cycle, were younger than 35 years old, and underwent a modified natural cycle (mNC), ovulation induction (OI), or a hormone replacement treatment (HRT) cycle. A total of 1071 frozen cycles were included for analysis. Results: The implantation rate and live birth rate (LBR) in the OI group show a significant difference when compared to the mNC and HRT groups (P < 0.01). After adjusting for confounding factors, the logistic regression analysis revealed that the number of embryos transferred, the embryo stage, and quality were significantly associated with clinical pregnancy rate and LBR. The LBR was additionally affected by the mode of the endometrial preparation; the OI cycle could increase LBR. Conclusions: Endometrial preparation methods affect the LBR in women with a regular menstrual cycle. The OI cycle had an advantage in the LBR of FET.

15.
Sci Rep ; 14(1): 15650, 2024 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977905

RESUMO

To assess the agreement and repeatability of scotopic pupil size measurement using 2WIN-S (Adaptica, Padova, Italy) portable refractor in Chinese adults. This prospective non-randomized open-label controlled study assessed the scotopic pupil size of 100 right eyes using OPD-Scan III (Optical path difference) (Nidek Technologies, Gamagori, Japan) and 2WIN-S. OPD-Scan III and 2WIN-S measure pupil size using infrared light and detector, while 2WIN-S measures bilateral eyes simultaneously, OPD-Scan III measures unilateral eyes individually. Participants were first measured once using OPD-Scan III and two consecutive measurements were performed using 2WIN-S after 15 min of rest interval. The primary outcome was to evaluate the agreement between 2WIN-S and OPD-Scan III, and the secondary outcome was to evaluate the repeatability of 2WIN-S. Scotopic pupil size of 100 right eyes of 100 adults (28 male and 72 female) aged 18-53 years (mean 36 ± 12 years) was assessed using OPD-Scan III and 2WIN-S, respectively. The mean scotopic pupil size of OPD-Scan III and 2WIN-S was recorded to be 6.24 ± 0.88 mm and 6.27 ± 0.81 mm, respectively. For the mean scotopic pupil size of OPD-Scan III and 2WIN-S the difference was - 0.03 mm (95%CI - 0.10 to 0.04 mm), p = 0.445, the 95% limits of agreement (LOA) was - 0.71 to 0.66 mm. ICC between the two devices was 0.92 (95% CI 0.88-0.94) (ICC > 0.9 indicates excellent consistency). Coefficients of repeatability (CoR) of 2WIN-S was 0.37, which has a high repeatability. For the mean scotopic pupil size of 2WIN-S of the repeated measurements, the difference was -0.04 mm (95%CI - 0.08 to 0.01 mm), p = 0.019, the 95% limits of agreement (LOA) was - 0.41 to 0.32 mm, with a narrow LOA. However, the majority of the variations were less than ± 0.50 mm (98% of scotopic pupil size measurements were below this threshold), within the clinically acceptable range (± 0.50 mm). Our study showed excellent agreement between 2WIN-S and OPD-Scan III (ICC > 0.9) and a good repeatability of 2WIN-S (CoR = 0.37). This study suggests a novel technique for measuring pupillary responses in low light conditions, which can be considered an alternative to OPD-Scan III in clinical settings.


Assuntos
Pupila , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , China , População do Leste Asiático , Estudos Prospectivos , Pupila/fisiologia , Reprodutibilidade dos Testes
16.
Front Oncol ; 14: 1338661, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952555

RESUMO

Breast cancer remains one of the predominant malignancies worldwide. In the context of inoperable advanced or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer, systemic management primarily relies on HER2-targeting monoclonal antibodies. With the successful development of anti-HER2 antibody-drug conjugates (ADCs), these agents have been increasingly integrated into therapeutic regimens for metastatic breast cancer. Here, we present the case of a 42-year-old female patient with HER2-positive pulmonary metastatic breast cancer who underwent an extensive treatment protocol. This protocol included chemotherapy, radiation therapy, hormonal therapy, surgical intervention on the breast, and anti-HER2 therapies. The anti-HER2 therapies involved both singular and dual targeting strategies using trastuzumab and the ADC disitamab vedotin (RC48) over an 8-year period. After experiencing disease progression following HER2-targeted therapy with RC48, the patient achieved noticeable partial remission through a therapeutic regimen that combined trastuzumab deruxtecan (DS8201) and tislelizumab. The data suggest a promising role for DS8201 in managing advanced stages of HER2-amplified metastatic breast cancer, especially in cases that demonstrate progression after initial HER2-directed therapies using ADCs. Furthermore, its combination with anti-PD-1 agents enhances therapeutic efficacy by augmenting the anti-tumoral immune response.

17.
CNS Neurosci Ther ; 30(7): e14818, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38946682

RESUMO

Glycogen synthase kinase-3 (GSK3), consisting of GSK3α and GSK3ß subtypes, is a complex protein kinase that regulates numerous substrates. Research has observed increased GSK3 expression in the brains of Alzheimer's disease (AD) patients and models. AD is a neurodegenerative disorder with diverse pathogenesis and notable cognitive impairments, characterized by Aß aggregation and excessive tau phosphorylation. This article provides an overview of GSK3's structure and regulation, extensively analyzing its relationship with AD factors. GSK3 overactivation disrupts neural growth, development, and function. It directly promotes tau phosphorylation, regulates amyloid precursor protein (APP) cleavage, leading to Aß formation, and directly or indirectly triggers neuroinflammation and oxidative damage. We also summarize preclinical research highlighting the inhibition of GSK3 activity as a primary therapeutic approach for AD. Finally, pending issues like the lack of highly specific and affinity-driven GSK3 inhibitors, are raised and expected to be addressed in future research. In conclusion, GSK3 represents a target in AD treatment, filled with hope, challenges, opportunities, and obstacles.


Assuntos
Doença de Alzheimer , Quinase 3 da Glicogênio Sintase , Animais , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/enzimologia , Precursor de Proteína beta-Amiloide/metabolismo , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Quinase 3 da Glicogênio Sintase/metabolismo , Proteínas tau/metabolismo , Proteínas tau/antagonistas & inibidores
18.
J Environ Manage ; 365: 121611, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38959769

RESUMO

Ultrafiltration technology, separating water from impurities by the core membrane, is an effective strategy for treating wastewater to meet the ever-growing requirement of clean and drinking water. However, the similar nature of hydrophobic organic pollutants and the membrane surface leads to severe adsorption and aggregation, resulting unavoidable membrane degradation of penetration and rejection. The present study presents a novel block amphiphilic polymer, polyethersulfone-g-carboxymethyl chitosan@MWCNT (PES-g-CMC@MWCNT), which is synthesized by grafting hydrophobic polyethersulfone to hydrophilic carboxymethyl chitosan in order to suspend CMC in organic solution. A mixture of hydrophilic carboxymethyl chitosan and hydrophobic polymers (polyethersulfone), in which hydrophilic segments are bonded to hydrophobic segments, could provide hydrophilic groups, as well as gather and remain stable on membrane surfaces by their hydrophobic interaction for improved compatibility and durability. The resultant ultrafiltration membranes exhibit high water flux (198.10 L m-2·h-1), suitable hydrophilicity (64.77°), enhanced antifouling property (82.96%), while still maintains excellent rejection of bovine serum albumin (91.75%). There has also been an improvement in membrane cross-sectional morphology, resulting in more regular pores size (47.64 nm) and higher porosity (84.60%). These results indicate that amphiphilic polymer may be able to significantly promote antifouling and permeability of ultrafiltration membranes.


Assuntos
Quitosana , Interações Hidrofóbicas e Hidrofílicas , Membranas Artificiais , Polímeros , Sulfonas , Ultrafiltração , Polímeros/química , Quitosana/química , Quitosana/análogos & derivados , Sulfonas/química , Adsorção , Purificação da Água/métodos , Incrustação Biológica/prevenção & controle
19.
Adv Biol (Weinh) ; : e2400223, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39051423

RESUMO

Inner ear organoids play a crucial role in hearing research. In comparison to other animal models and 2D cell culture systems, inner ear organoids offer significant advantages for studying the mechanisms of inner ear development and exploring novel approaches to disease treatment. Inner ear organoids derived from human cells are more closely resemble normal human organs in development and function. The 3D culture system of the inner ear organoid enhances cell-cell interactions and mimics the internal environment. In this review, the progress and limitations of organoid culture methods derived from tissue-specific progenitors and pluripotent stem cells (PSCs) are summarized, which may offer new insights into generating organoids that closely resemble the inner ear in terms of morphology and function.

20.
ACS Sens ; 9(8): 4166-4175, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39037034

RESUMO

Among the various hazardous substances, formaldehyde (HCHO), produced worldwide from wood furniture, dyeing auxiliaries, or as a preservative in consumer products, is harmful to human health. In this study, a sensitive room-temperature HCHO sensor, MTiNCs/Pd, has been developed by integrating Pd nanoclusters (PdNCs) into mesoporous MIL-125(Ti)-decorated TiO2 nanochannel arrays (TiNCs). Thanks to the enrichment effect of the mesoporous structure of MIL-125 and the large surface area offered by TiNCs, the resulting gas sensor accesses significantly enhanced HCHO adsorption capacity. The sufficient energetic active defects formed on PdNCs further allow an electron-extracting effect, thus effectively separating the photogenerated electrons and holes at the interface. The resulting HCHO sensor exhibits a short response/recovery time (37 s/12 s) and excellent sensitivity with a low limit of detection (4.51 ppb) under ultraviolet (UV) irradiation. More importantly, the cyclic redox reactions of Pdδ+ in PdNCs facilitated the regeneration of O2-(ads), thus ensuring a stable and excellent gas sensing performance even under a high-humidity environment. As a proof-of-principle of this design, a wearable gas sensing band is developed for the real-time and on-site detection of HCHO in cigarette smoke, with the potential as an independent device for environmental monitoring and other smart sensing systems.


Assuntos
Formaldeído , Umidade , Paládio , Temperatura , Titânio , Titânio/química , Formaldeído/análise , Formaldeído/química , Paládio/química , Nanopartículas Metálicas/química , Limite de Detecção
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