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1.
Small ; : e2403606, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940231

RESUMO

Salt deposition is a disturbing problem that limits the development of passive solar-driven interfacial evaporation. Inspired by the passive fluid control mechanism of the Tesla valve, a novel solar evaporator is proposed with a Tesla valve-like water transport structure to prevent salt accumulation at the evaporation interface. A unique "ion diode" salt resistance of this evaporator is significantly achieved by optimizing the two asymmetric water transport structures, consisting of one Tesla valve-like side and one wide-leg side, which establish a reverse-suppressing and forward-accelerating water transport channel. In contrast to the limited ion migration of the typical symmetric solar evaporator, such a channel caused by the water/salt ions transport difference between two water supply structures, reinforces the water/salt ions supply on the wide-leg side, thus leading to an apparent unidirectional salt ions migration from the wide-leg side to bulk water through the Tesla valve-like side. Consequently, an evaporation rate of 3.25 kg m-2 h-1 and a conversion efficiency of 83.27% under 2 suns are achieved in 16 wt% NaCl solution. The development of the Tesla Valve-like evaporator provides a new perspective for solving salt deposition and realizing scalable applications of solar-driven interfacial evaporation.

2.
Antibodies (Basel) ; 13(2)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38920969

RESUMO

Chimeric antigen receptor (CAR) T cell therapy shows promise in treating malignant tumors. However, the use of human epidermal growth factor receptor-2 (HER2) CAR-T cells carries the risk of severe toxicity, including cytokine release syndrome, due to their "on-target off-tumor" recognition of HER2. Enhancing the quality and functionality of HER2 CARs could greatly improve the therapeutic potential of CAR-T cells. In this study, we developed a novel anti-HER2 monoclonal antibody, Ab8, which targets domain III of HER2, distinct from the domain IV recognition of trastuzumab. Although two anti-HER2 mAbs induced similar levels of antibody-dependent cellular cytotoxicity, trastuzumab-based CAR-T cells exhibited potent antitumor activity against HER2-positive cancer cells. In conclusion, our findings provide scientific evidence that antibody recognition of the membrane-proximal domain promotes the anti-tumor response of HER2-specific CAR-T cells.

3.
Int J Hyg Environ Health ; 260: 114407, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38879913

RESUMO

BACKGROUND: Executive functions develop rapidly in childhood, enabling problem-solving, focused attention, and planning. Exposures to environmental toxicants in pregnancy may impair healthy executive function development in children. There is increasing concern regarding polycyclic aromatic hydrocarbons (PAHs) given their ability to transfer across the placenta and the fetal blood-brain barrier, yet evidence from epidemiological studies is limited. METHODS: We examined associations between prenatal PAH exposure and executive functions in 814 children of non-smoking mothers from two U.S. cohorts in the ECHO-PATHWAYS Consortium. Seven mono-hydroxylated PAH metabolites were measured in mid-pregnancy urine and analyzed individually and as mixtures. Three executive function domains were measured at age 8-9: cognitive flexibility, working memory, and inhibitory control. A composite score quantifying overall performance was further calculated. We fitted linear regressions adjusted for socio-demographics, maternal health behaviors, and psychological measures, and examined modification by child sex and stressful life events in pregnancy. Bayesian kernel machine regression was performed to estimate the interactive and overall effects of the PAH mixture. RESULTS: The results from primary analysis of linear regressions were generally null, and no modification by child sex or maternal stress was indicated. Mixture analyses suggested several pairwise interactions between individual PAH metabolites in varied directions on working memory, particularly interactions between 2/3/9-FLUO and other PAH metabolites, but no overall or individual effects were evident. CONCLUSION: We conducted a novel exploration of PAH-executive functions association in a large, combined sample from two cohorts. Although findings were predominantly null, the study carries important implications for future research and contributes to evolving science regarding developmental origins of diseases.


Assuntos
Função Executiva , Hidrocarbonetos Policíclicos Aromáticos , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , Hidrocarbonetos Policíclicos Aromáticos/urina , Gravidez , Função Executiva/efeitos dos fármacos , Criança , Masculino , Estudos de Coortes , Poluentes Ambientais/urina , Adulto , Memória de Curto Prazo/efeitos dos fármacos , Exposição Materna
4.
PLoS One ; 19(6): e0305576, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38917109

RESUMO

OBJECTIVE: This study aimed to understand the health of workers exposed to occupational noise and explore the influencing factors related to workers' health, especially the impact of noise on workers' hearing. This work can provide a basis for formulating relevant measures for occupational noise prevention and control in the future. METHODS: On the basis of the key occupational disease monitoring project in Chongqing, China, in 2021, the data of 1125 workers exposed to occupational noise were analyzed. Data included demographic information, occupational history, clinical physical examination information, and noise detection information of the working environment. Chi-square test and multifactorial logistic regression were used for statistical analysis. RESULTS: The prevalence rates of abnormal electrocardiogram (ECG), blood pressure (BP), and pure tone audiometry (PTA) were 21.9% (246/1125), 27.8% (313/1125), and 18.0% (202/1125), respectively. Male workers accounted for 78.8%. Compared with male workers, female workers had a lower prevalence of abnormal PTA (OR = 0.28, 95% CI = 0.16-0.50). Workers working in medium enterprises had a lower prevalence of abnormal BP than workers in micro enterprises (OR = 0.36, 95% CI = 0.19-0.66). The prevalence of abnormal BP and PTA of workers increased with age. After adjusting for age, sex, and body mass index, the prevalence of abnormal ECG of mining workers was higher than that of manufacturing workers (OR = 1.54, 95% CI = 1.07-2.24), and the prevalence of abnormal PTA had a rising trend with the increase in noise exposure value. CONCLUSION: Noise-exposed workers have a high prevalence of abnormal ECG, BP, and PTA, and factors such as age, enterprise size, and workplace noise exposure are correlated with the aberrant health of workers. Governments, enterprises, and individuals need to attach great importance to the possible adverse effects of noise. They must also actively adopt various effective measures to protect the occupational safety and health of workers.


Assuntos
Ruído Ocupacional , Exposição Ocupacional , Humanos , Ruído Ocupacional/efeitos adversos , Masculino , China/epidemiologia , Feminino , Estudos Transversais , Adulto , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Prevalência , Perda Auditiva Provocada por Ruído/epidemiologia , Perda Auditiva Provocada por Ruído/etiologia , Pressão Sanguínea , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Eletrocardiografia , Audiometria de Tons Puros , Adulto Jovem
5.
J Leukoc Biol ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38922297

RESUMO

Hepatocellular carcinoma (HCC) is a highly malignant tumor characterized by insidious onset and rapid progression, with limited treatment choices. One treatment modality, chimeric antigen receptor (CAR)-modified natural killer (NK) cell immunotherapy, has shown promise for various cancers. In this study, we developed two GPC3-specific CAR-NK-92 cell lines (GPC3-CAR-NK) and explored their antitumor efficacy for the treatment of HCC. Significant levels of cytokine production and in vitro cytotoxicity were produced following co-culture of GPC3+ HCC cells with the developed GPC3-CAR-NK cells. GC33-G2D-NK cells with NK cell-specific signaling domains showed better activation and killing abilities than GC33-CD28-NK cells containing T cell-specific signaling domains. Moreover, GC33-G2D-NK cells efficiently eliminated tumors in cell-derived xenograft and patient-derived xenograft mouse models. In an abdominal metastasis model, intraperitoneally delivered GC33-G2D-NK cells showed better antitumor ability than intravenously injected cells. Finally, the combination of microwave ablation with GC33-G2D-NK cell administration showed greater CAR-NK infiltration and tumor regression in ablated tumors than monotherapy alone. These findings indicate that administration of GPC3-CAR-NK cells may be a potential strategy for the treatment of HCC, and regional delivery or their combination with microwave ablation may optimize their efficacy against HCC and may have translational value.

6.
J Med Chem ; 67(12): 10275-10292, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38842846

RESUMO

Due to the wide application of reporter gene-related visible/NIR-I bioluminescent imaging, multiplexed fluorescence imaging across visible/NIR-I/NIR-II has excellent potential in biomedical research. However, in vivo multiplexed imaging applications across those regions have rarely been reported due to the lack of proper fluorophores. Herein, nine squaraine dyes, which exhibit diverse adsorption and emission wavelengths, were synthesized. Among them, water-soluble SQ 710-5k and SQ 905 were found to have significant absorption differences, which allowed the tumor and lymph nodes to be identified. Then, for the first time, six-channel multiplexed fluorescence imaging across visible/NIR-I/II was achieved by coordination with reporter gene-related bioluminescent phosphors. Additional research revealed that SQ 710-5k exhibited higher-quality blood vessels and tumor imaging in NIR-II. H-aggregates SQ 905 demonstrated a high photothermal conversion efficiency for photothermal therapy. This study proposed an approach to creating small molecular dyes that coordinate with reporter gene-related bioluminescent phosphors for six-color fluorescence imaging.


Assuntos
Ciclobutanos , Corantes Fluorescentes , Imagem Óptica , Fenóis , Terapia Fototérmica , Ciclobutanos/química , Ciclobutanos/síntese química , Animais , Corantes Fluorescentes/química , Humanos , Camundongos , Fenóis/química , Terapia Fototérmica/métodos , Raios Infravermelhos , Camundongos Nus , Linhagem Celular Tumoral , Feminino , Estrutura Molecular , Camundongos Endogâmicos BALB C
7.
Psychol Sport Exerc ; 74: 102685, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38844016

RESUMO

BACKGROUND: Despite existing studies showing that physical exercise improves cognitive function in older adults either concurrently or in a delayed manner, studies examining these associations simultaneously are rare. Additionally, the underlying mechanisms in these associations remain incompletely understood. OBJECTIVE: This study explores the concurrent and delayed (two years later) associations between physical exercise and older adults' cognitive function. This study also investigates the mediating roles of three negative physical, psychological, and social resources: limitations in daily abilities, depressive mood, and isolation from friends, as well as the moderating roles of cognitive reserve on these associations. DESIGN: A cohort sample of 6646 Chinese older adults (Mean age = 69.28, SD = 7.03) is obtained from the 2016 and 2018 waves of the China Longitudinal Aging Social Survey. Regression analysis was employed to test the concurrent and delayed associations between physical exercise and cognitive function. The bootstrap method was utilized to examine the mediating roles of limitations in daily activities, depression mood, and isolation from friends. Interaction terms were generated to investigate the moderating roles of cognitive reserve. RESULTS: Physical exercise presents concurrent and delayed positive associations with cognitive function. Limitations in daily activities, depressive mood and isolation from friends mediate the above associations. Moreover, cognitive reserve plays a significant role in buffering the concurrent and delayed negative links between depressive mood, isolation from friends, and cognitive function, with larger negative relationships observed for older adults with lower rather than higher levels of cognitive reserve. CONCLUSIONS: This study validates the concurrent and delayed benefits of physical exercise on older adults' cognitive function while elucidating the underlying mechanisms. These findings offer practical implications for health policies and intervention programs aimed at enhancing older adults' cognitive function.

8.
J Am Chem Soc ; 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38853354

RESUMO

A piezoelectric polymer membrane based on single metal atoms was demonstrated to be effective by anchoring isolated calcium (Ca) atoms on a composite of nitrogen-doped carbon and polyvinylidene fluoride (PVDF). The addition of Ca-atom-anchored carbon nanoparticles not only promotes the formation of the ß phase (from 29.8 to 56.3%), the most piezoelectrically active phase, in PVDF, but also introduces much higher porosity and hydrophilicity. Under ultrasonic excitation, the fabricated catalyst membrane demonstrates a record-high and stable dye decomposing rate of 0.11 min-1 and antibacterial efficiencies of 99.8%. Density functional theory calculations reveal that the primary contribution to catalytic activity arises from single-atom Ca doping and that a possible synergistic effect between PVDF and Ca atoms can improve the catalytic performance. It is shown that O2 molecules can be easily hydrogenated to produce ·OH on Ca-PVDF, and the local electric field provided by the ß-phase-PVDF might enhance the production of ·O2-. The proposed polymer membrane is expected to inspire the rational design of piezocatalysts and pave the way for the application of piezocatalysis technology for practical environmental remediation.

9.
Cancer Cell Int ; 24(1): 191, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822350

RESUMO

Mitogen-activated protein kinase inhibitors (MAPKi) were the first line drugs for advanced melanoma patients with BRAF mutation. Targeted therapies have significant therapeutic effects; however, drug resistance hinders their long-term efficacy. Therefore, the development of new therapeutic strategies against MAPKi resistance is critical. Our previous results showed that MAPKi promote feedback activation of STAT3 signaling in BRAF-mutated cancer cells. Studies have shown that alantolactone inhibited the activation of STAT3 in a variety of tumor cells. Our results confirmed that alantolactone suppressed cell proliferation and promoted apoptosis by inhibiting STAT3 feedback activation induced by MAPKi and downregulating the expression of downstream Oct4 and Sox2. The inhibitory effect of alantolactone combined with a MAPKi on melanoma cells was significantly stronger than that on normal cells. In vivo and in vitro experiments showed that combination treatment was effective against drug-resistant melanomas. Our research indicates a potential novel combination therapy (alantolactone and MAPKi) for patients with BRAF-mutated melanoma.

11.
Int J Biol Macromol ; 273(Pt 1): 133067, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38866287

RESUMO

Adjuvants, as the essential component of vaccines, are crucial in enhancing the magnitude, breadth and durability of immune responses. Unfortunately, commonly used Alum adjuvants predominantly provoke humoral immune response, but fail to evoke cellular immune response, which is crucial for the prevention of various chronic infectious diseases and cancers. Thus, it is necessary to develop effective adjuvants to simultaneously induce humoral and cellular immune response. In this work, we obtained a water soluble polysaccharide isolated and purified from Poria cocos, named as PCP, and explored the possibility of PCP as a vaccine adjuvant. The PCP, with Mw of 20.112 kDa, primarily consisted of →6)-α-D-Galp-(1→, with a small amount of →3)-ß-D-Glcp-(1 â†’ and →4)-ß-D-Glcp-(1→. Our results demonstrated that the PCP promoted the activation of dendritic cells (DCs) and macrophages in vitro. As the adjuvant to ovalbumin, the PCP facilitated the activation of DCs in lymph nodes, and evoked strong antibody response with a combination of Th1 and Th2 immune responses. Moreover, compared to Alum adjuvant, the PCP markedly induced a potent cellular response, especially the cytotoxic T lymphocytes response. Therefore, we confirmed that the PCP has great potential to be an available adjuvant for simultaneously inducing humoral and cellular immune responses.

12.
Cancer Med ; 13(12): e7423, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38899854

RESUMO

BACKGROUND: To investigate the sex-based heterogeneity of immune microenvironmental feature and its impact on the response to first-line PD-1 blockade plus chemotherapy in patients with driver-negative advanced or metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 439 patients with advanced NSCLC treated with first-line PD-1 blockade plus chemotherapy or chemotherapy were identified. Differences in clinical outcomes between female and male patients were determined using Kaplan-Meier curves. Neoantigen burden and five immune microenvironmental markers expression including PD-L1, CD4, CD8, FOXP3, and CD68 were compared between two groups. RESULTS: Of 175 eligible patients, 89 received PD-1 blockade plus chemotherapy and 86 received first-line chemotherapy. Forty five were women (25.7%) and 130 were men (74.3%). Female patients received first-line PD-1 blockade in combination with chemotherapy had dramatically better ORR (85.2% vs. 53.2%; p = 0.009), PFS (23.7 vs. 7.3 months; p = 0.013), and OS (46.2 vs. 20.0 months; p = 0.004) than males. Treatment outcomes were similar between females and males in chemotherapy group. Multivariate analyses showed that sex was the independent prognostic factor for patients received PD-1 blockade combined with chemotherapy. Although female patients had significantly lower tumor mutational and neoantigen burden than males, pretreatment tumor tissues of female patients had markedly higher CD4, CD4/FOXP3, and CD4/FOXP3/PD-L1 expression level than male patients. CONCLUSIONS: Female patients with untreated advanced or metastatic NSCLC would derive a larger benefit from PD-1 blockade in combination with chemotherapy than males. The biological significances of heterogeneity of tumor immune microenvironmental features between them need further investigation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Microambiente Tumoral , Humanos , Masculino , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Microambiente Tumoral/imunologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Idoso , Inibidores de Checkpoint Imunológico/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fatores Sexuais , Adulto , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Estudos Retrospectivos , Fatores de Transcrição Forkhead
13.
Artigo em Inglês | MEDLINE | ID: mdl-38904983

RESUMO

Metal organic frameworks (MOFs) constructed with bismuth metal have not been widely reported, especially multifunctional Bi-MOFs. Therefore, developing multifunctional MOFs is of great significance due to the increasing requirements of materials. In this work, a 3D Bi-MOF (Bi-TCPE) with multifunctionality was successfully constructed, demonstrating high thermal stability, water stability, a porous structure, and strong blue fluorescence emission. We evaluated the properties of Bi-TCPE in detecting anions (S2-, Cr2O72-, and CrO42-) in aqueous solution, along with the rapid visual detection of H2S gas and proton conduction. In terms of anion detection, Bi-TCPE achieved the rapid detection of trace S2- in aqueous solutions, while the Ksv value was 1.224 × 104 M-1 with a limit of detection (LOD) value of 1.93 µM through titration experiments. Furthermore, Bi-TCPE could sensitively detect Cr2O72- and CrO42-, with Ksv values of 1.144 × 104 and 1.066 × 104 M-1, respectively, while LOD reached 2.07 and 2.18 µM. Subsequently, we conducted H2S gas detection experiments, and the results indicated that Bi-TCPE could selectively detect H2S gas at extremely low concentrations (2.08 ppm) and with a fast response time (<10 s). We also observed significant color changes under both UV light and sunlight. Therefore, we developed a H2S detection test paper for the rapid visual detection of H2S gas. Finally, we evaluated the proton conductivity of Bi-TCPE, and the experimental results showed that the proton conductivity of Bi-TCPE reached 4.77 × 10-2 S·cm-1 at 98% RH and 90 °C, achieving an excellent value for unmodified and encapsulated MOFs. In addition, Bi-TCPE showed high stability in proton conduction experiments (it remained stable after 21 consecutive days of testing and 12 cycles of testing), demonstrating relatively high application value. These results indicate that Bi-TCPE is a multifunctional MOF material with great application potential.

14.
Sci Rep ; 14(1): 14300, 2024 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-38906967

RESUMO

We aim to explore the alterations of objective ocular torsion after unilateral lateral rectus recession-medial rectus resection (R&R) for intermittent exotropia (IXT). Seventy-two IXT patients undergoing R&R between March and June 2023 were enrolled. Ophthalmological examinations were performed before surgery and at 1 week and 1 month after surgery, mainly including prism and alternate cover test and optical coherence tomography. The mean disc-foveal angle of eyes showing intorsion significantly increased from - 1.5 ± 0.9° preoperatively to 2.0 ± 2.0° at 1 week (P = 0.0227) and 2.2 ± 1.6° at 1 month postoperatively (P = 0.0054). The mean disc-foveal angle of eyes exhibiting extorsion significantly reduced from 12.8 ± 1.9° preoperatively to 9.8 ± 3.1° at 1 week (P < 0.0001) and 9.7 ± 2.7° at 1 month postoperatively (P < 0.0001). The improvement of ocular extorsion at postoperative 1 month was more pronounced in patients with extorsion in operative eye compared to those with extorsion in inoperative eye (P = 0.0101). The improvement of ocular torsion was observed following R&R for IXT, with a greater effect noted in cases where the surgery was performed on the eye exhibiting extorsion.


Assuntos
Exotropia , Músculos Oculomotores , Procedimentos Cirúrgicos Oftalmológicos , Humanos , Exotropia/cirurgia , Masculino , Feminino , Músculos Oculomotores/cirurgia , Criança , Procedimentos Cirúrgicos Oftalmológicos/métodos , Procedimentos Cirúrgicos Oftalmológicos/efeitos adversos , Pré-Escolar , Adolescente , Tomografia de Coerência Óptica , Adulto , Anormalidade Torcional/cirurgia , Anormalidade Torcional/etiologia , Adulto Jovem , Resultado do Tratamento
16.
Int J Biol Sci ; 20(8): 3028-3045, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38904022

RESUMO

Following the identification of specific epidermal growth factor receptor (EGFR)-activating mutations, gefitinib, one of the first-generation tyrosine kinase inhibitors (TKIs), has proven efficacious in targeting NSCLC that is driven by specific EGFR-activating mutations. However, most patients who initially respond to gefitinib, develop acquired resistance. In the current study, we devised a novel strategy to enhance the efficacy of gefitinib. We developed a simple and effective, nano-interrupter termed zeolitic imidazolate framework-8@Gefitinib@hyaluraonic nanoparticle (ZIF-8@G@HA NP). This nanoparticle was prepared by loading gefitinib onto a ZIF-8 nanoplatform followed by coating with hyaluronic acid (HA). The burst of Zn2+ release triggered by pH-sensitive degradation of ZIF-8@G@HA NPs was shown to enhance the efficacy of gefitinib in parental lung carcinoma HCC827 cells and overcame acquired gefitinib resistance in gefitinib drug resistant (GDR) HCC827 cells. We found that when treated with ZIF-8@G@HA NPs, Zn2+ acts synergistically with gefitinib via increased apoptosis in both parental and GDR HCC827 cells. Consistently, this in vitro activity was correlated with in vivo tumor growth inhibition. Interestingly, GDR cells were more sensitive to Zn2+ when compared with parental cells. We further found that ZIF-8 NPs overcame gefitinib resistance by triggering reactive oxygen species (ROS) generation and consequent cell cycle arrest at the G2/M phase, resulting in cancer cell apoptosis. Zn2+ was also found to block P-gp activity, facilitating the accumulation of gefitinib in GDR cells, thus enhancing the anti-tumor efficacy of gefitinib resulting in reversal of gefitinib resistance. Thus, this study offers a novel and promising strategy to surmount acquired gefitinib resistance via cell cycle arrest at the G2/M phase by facilitating gefitinib accumulation in GDR cells.


Assuntos
Apoptose , Resistencia a Medicamentos Antineoplásicos , Gefitinibe , Neoplasias Pulmonares , Zinco , Gefitinibe/farmacologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linhagem Celular Tumoral , Animais , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Camundongos , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , Nanopartículas/química , Camundongos Nus , Espécies Reativas de Oxigênio/metabolismo , Zeolitas/química , Camundongos Endogâmicos BALB C
17.
Mol Ther ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822526

RESUMO

Vagus nerve regulates viral infection and inflammation via the alpha 7 nicotinic acetylcholine receptor (α7 nAChR); however, the role of α7 nAChR in ZIKA virus (ZIKV) infection, which can cause severe neurological diseases such as microcephaly and Guillain-Barré syndrome, remains unknown. Here, we first examined the role of α7 nAChR in ZIKV infection in vitro. A broad effect of α7 nAChR activation was identified in limiting ZIKV infection in multiple cell lines. Combined with transcriptomics analysis, we further demonstrated that α7 nAChR activation promoted autophagy and ferroptosis pathways to limit cellular ZIKV viral loads. Additionally, activation of α7 nAChR prevented ZIKV-induced p62 nucleus accumulation, which mediated an enhanced autophagy pathway. By regulating proteasome complex and an E3 ligase NEDD4, activation of α7 nAChR resulted in increased amount of cellular p62, which further enhanced the ferroptosis pathway to reduce ZIKV infection. Moreover, utilizing in vivo neonatal mouse models, we showed that α7 nAChR is essential in controlling the disease severity of ZIKV infection. Taken together, our findings identify an α7 nAChR-mediated effect that critically contributes to limiting ZIKV infection, and α7 nAChR activation offers a novel strategy for combating ZIKV infection and its complications.

18.
Nutr Diabetes ; 14(1): 36, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824142

RESUMO

BACKGROUND: Blood homocysteine (Hcy) level has become a sensitive indicator in predicting the development of cardiovascular disease. Studies have shown an association between individual mineral intake and blood Hcy levels. The effect of mixed minerals' intake on blood Hcy levels is unknown. METHODS: Data were obtained from the baseline survey data of the Shanghai Suburban Adult Cohort and Biobank(SSACB) in 2016. A total of 38273 participants aged 20-74 years met our inclusion and exclusion criteria. Food frequency questionnaire (FFQ) was used to calculate the intake of 10 minerals (calcium, potassium, magnesium, sodium, iron, zinc, selenium, phosphorus, copper and manganese). Measuring the concentration of Hcy in the morning fasting blood sample. Traditional regression models were used to assess the relationship between individual minerals' intake and blood Hcy levels. Three machine learning models (WQS, Qg-comp, and BKMR) were used to the relationship between mixed minerals' intake and blood Hcy levels, distinguishing the individual effects of each mineral and determining their respective weights in the joint effect. RESULTS: Traditional regression model showed that higher intake of calcium, phosphorus, potassium, magnesium, iron, zinc, copper, and manganese was associated with lower blood Hcy levels. Both Qg-comp and BKMR results consistently indicate that higher intake of mixed minerals is associated with lower blood Hcy levels. Calcium exhibits the highest weight in the joint effect in the WQS model. In Qg-comp, iron has the highest positive weight, while manganese has the highest negative weight. The BKMR results of the subsample after 10,000 iterations showed that except for sodium, all nine minerals had the high weights in the joint effect on the effect of blood Hcy levels. CONCLUSION: Overall, higher mixed mineral's intake was associated with lower blood Hcy levels, and each mineral contributed differently to the joint effect. Future studies are available to further explore the mechanisms underlying this association, and the potential impact of mixed minerals' intake on other health indicators needs to be further investigated. These efforts will help provide additional insights to deepen our understanding of mixed minerals and their potential role in health maintenance.


Assuntos
Homocisteína , Aprendizado de Máquina , Minerais , Humanos , Pessoa de Meia-Idade , Adulto , Feminino , Estudos Transversais , Masculino , Minerais/sangue , Minerais/administração & dosagem , Homocisteína/sangue , Idoso , Adulto Jovem , China , Dieta
19.
J Adv Res ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38844122

RESUMO

INTRODUCTION: With the escalating menace of organic compounds in environmental pollution imperiling the survival of aquatic organisms, the investigation of organic compound toxicity across diverse aquatic species assumes paramount significance for environmental protection. Understanding how different species respond to these compounds helps assess the potential ecological impact of pollution on aquatic ecosystems as a whole. Compared with traditional experimental methods, deep learning methods have higher accuracy in predicting aquatic toxicity, faster data processing speed and better generalization ability. OBJECTIVES: This article presents ATFPGT-multi, an advanced multi-task deep neural network prediction model for organic toxicity. METHODS: The model integrates molecular fingerprints and molecule graphs to characterize molecules, enabling the simultaneous prediction of acute toxicity for the same organic compound across four distinct fish species. Furthermore, to validate the advantages of multi-task learning, we independently construct prediction models, named ATFPGT-single, for each fish species. We employ cross-validation in our experiments to assess the performance and generalization ability of ATFPGT-multi. RESULTS: The experimental results indicate, first, that ATFPGT-multi outperforms ATFPGT-single on four fish datasets with AUC improvements of 9.8%, 4%, 4.8%, and 8.2%, respectively, demonstrating the superiority of multi-task learning over single-task learning. Furthermore, in comparison with previous algorithms, ATFPGT-multi outperforms comparative methods, emphasizing that our approach exhibits higher accuracy and reliability in predicting aquatic toxicity. Moreover, ATFPGT-multi utilizes attention scores to identify molecular fragments associated with fish toxicity in organic molecules, as demonstrated by two organic molecule examples in the main text, demonstrating the interpretability of ATFPGT-multi. CONCLUSION: In summary, ATFPGT-multi provides important support and reference for the further development of aquatic toxicity assessment. All of codes and datasets are freely available online at https://github.com/zhaoqi106/ATFPGT-multi.

20.
Biomed Opt Express ; 15(5): 3076-3091, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38855692

RESUMO

This research presents a novel approach for the dynamic monitoring of onion-like carbon nanoparticles inside colorectal cancer cells. Onion-like carbon nanoparticles are widely used in photothermal cancer therapy, and precise 3D tracking of their distribution is crucial. We proposed a limited-angle digital holographic tomography technique with unsupervised learning to achieve rapid and accurate monitoring. A key innovation is our internal learning neural network. This network addresses the information limitations of limited-angle measurements by directly mapping coordinates to measured data and reconstructing phase information at unmeasured angles without external training data. We validated the network using standard SiO2 microspheres. Subsequently, we reconstructed the 3D refractive index of onion-like carbon nanoparticles within cancer cells at various time points. Morphological parameters of the nanoparticles were quantitatively analyzed to understand their temporal evolution, offering initial insights into the underlying mechanisms. This methodology provides a new perspective for efficiently tracking nanoparticles within cancer cells.

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