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1.
Front Neurol ; 15: 1349710, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562424

RESUMO

Background: An association between prognosis and high sodium levels in Traumatic Brain Injury (TBI) patients in Intensive Care Units (ICUs) has been noted, but limited research exists on the ideal sodium level in these patients or the impact on early mortality, using the MIMIC-IV database. Methods: A retrospective survey was conducted on TBI patients from the MIMIC-IV database. Patients were divided into two categories based on their highest serum sodium level within 24 h of admission exceeding 145 mmol/L: those with hypernatremia, and those with moderate-to-low sodium levels. Collected covariates encompasses demographic, clinical, laboratory, and intervention variables. A multivariate logistic regression model was implemented to forecast in-hospital mortality. Results: The study included 1749 TBI patients, with 209 (11.5%) experiencing in-hospital deaths. A non-linear test exposed an L-shaped correlation between sodium level and in-hospital mortality, with mortality rates increasing after a turning point at 144.1 mmol/L. Compared to the moderate-to-low group's 9.3% mortality rate, the hypernatremia group had a significantly higher mortality rate of 25.3% (crude odds ratio = 3.32, 95% confidence interval: 2.37 ~ 4.64, p < 0.001). After adjusting for all covariates, the hypernatremia group continued to show a significant correlation with higher mortality risk (adjusted odds ratio = 2.19, 95% confidence interval: 1.38 ~ 3.47, p = 0.001). This trend remained consistent regardless of the analyses stratification. Conclusion: The study reveals an L-shaped relationship between sodium levels and in-hospital deaths, with a pivotal point at 144.1 mmol/L. TBI patients displaying hypernatremia were independently linked to higher in-hospital mortality, underlining the need for further studies into targeted management of sodium levels in these patients.

2.
Perfusion ; : 2676591241244983, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565217

RESUMO

INTRODUCTION: We set out to investigate whether the use of Histidine-Tryptophan-Ketoglutarate (HTK) solution or del Nido cardioplegia is linked to an increased incidence of postoperative acute kidney injury (AKI) in patients undergoing coronary artery bypass surgery (CABG). METHODS: A retrospective study was carried out at our center, with a total of 478 patients included in the analysis. Among them, 268 patients were administered the del Nido solution (DN) while 210 patients received the HTK solution. The primary focus of this study was to assess the occurrence of postoperative AKI and the need for renal replacement therapy (RRT). Multivariable logistic regression was used to examine the relationship between the type of cardioplegia used and adverse kidney outcomes. Additionally, serum levels of sodium, potassium, and ionized calcium were monitored during cardiopulmonary bypass (CPB). RESULTS: The incidence of AKI was significantly higher in the HTK group compared to the DN group [(48/220 (21.81%) vs. 24/186 (12.90%), p = .049], although the rate of RRT did not show a statistically significant difference (9/48, 18.75% vs. 6/24, 25%, p = .538). Multivariate logistic regression analysis revealed that HTK was a significant risk factor for AKI. Furthermore, serum sodium and calcium levels were found to decrease following HTK cardioplegic infusion. Conclusion: Our study provides compelling evidence of the impact of cardioplegic solutions on postoperative AKI rates. It underscores the importance of optimizing cardiac arrest protocols. These findings warrant further prospective investigations into the influence of cardioplegic solutions on electrolyte imbalances and postoperative AKI rates.

3.
J Am Chem Soc ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38593469

RESUMO

Hydrolytically stable materials exhibiting a wide range of programmable water sorption behaviors are crucial for on-demand water sorption systems. While notable advancements in employing metal-organic frameworks (MOFs) as promising water adsorbents have been made, developing a robust yet easily tailorable MOF scaffold for specific operational conditions remains a challenge. To address this demand, we employed a topology-guided linker installation strategy using NU-600, which is a zirconium-based MOF (Zr-MOF) that contains three vacant crystallographically defined coordination sites. Through a judicious selection of three N-heterocyclic auxiliary linkers of specific lengths, we installed them into designated sites, giving rise to six new MOFs bearing different combinations of linkers in predetermined positions. The resulting MOFs, denoted as NU-606 to NU-611, demonstrate enhanced structural stability against capillary force-driven channel collapse during water desorption due to the increased connectivity of the Zr6 clusters in the resulting MOFs. Furthermore, incorporating these auxiliary linkers with various hydrophilic N sites enables the systematic modulation of the pore-filling pressure from about 55% relative humidity (RH) for the parent NU-600 down to below 40% RH. This topology-driven linker installation strategy offers precise control of water sorption properties for MOFs, highlighting a facile route to design MOF adsorbents for use in water sorption applications.

4.
Materials (Basel) ; 17(3)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38591540

RESUMO

The control of the solidification structure of a casting billet is directly correlated with the quality of steel. Variations in superheat can influence the transition from columnar crystals to equiaxed crystals during the solidification process, subsequently impacting the final solidification structure of the billet. In this study, a model of microstructure evolution during billet solidification was established by combining simulation and experiment, and the dendrite growth microstructure evolution during billet solidification under different superheat was studied. The results show that when the superheat is 60 K, the complete solidification time of the casting billet from the end of the 50 mm section is 252 s, when the superheat is 40 K, the complete solidification time of the casting billet is 250 s, and when the superheat is 20 K, the complete solidification time of the casting billet is 245 s. When the superheat is 20 K, the proportion of the equiaxed crystal region is higher-the highest value is 53.35%-and the average grain radius is 0.84556 mm. The proportion of the equiaxed crystal region decreases with the increase of superheat. When the superheat is 60 K, the proportion of the equiaxed crystal region is the lowest-the lowest value is 46.27%-and the average grain radius is 1.07653 mm. Proper reduction of superheat can obviously reduce the size of equiaxed crystal, expand the area of equiaxed crystal and improve the quality of casting billet.

5.
Opt Lett ; 49(8): 1892-1895, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38621032

RESUMO

We experimentally demonstrate the highly-efficient nonlocal erasing and writing of ferroelectric domains using a femtosecond laser in lithium niobate. Based on the induction of a focused infrared femtosecond laser without any relative displacement or additional treatment, the original multiple ferroelectric domains can be either erased (erasing operation) or elongated (writing operation) simultaneously in the crystal, depending on the laser focusing depth and the laser pulse energy. In the erasing operation, the original multiple ferroelectric domains can be cleared completely by just one laser induction, while in the writing operation, the average length of the ferroelectric domains can be elongated up to 235 µm by three laser inductions. A model has been proposed in which a thermoelectric field and a space charge field are used cooperatively to successfully explain the mechanism of nonlocal erasing and writing. This method greatly improves the efficiency and flexibility of tailoring ferroelectric domain structures, paving the way to large-scale all-optical industrial production for nonlinear photonic crystals and nonvolatile ferroelectric domain wall memories.

6.
Adv Sci (Weinh) ; : e2310295, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38626370

RESUMO

Neuropathic pain can occur during the prediabetic stage, even in the absence of hyperglycemia. The presence of prediabetic neuropathic pain (PDNP) poses challenges to the management of individuals with prediabetes. However, the mechanisms underlying this pain remain unclear. This study aims to investigate the underlying mechanism and identify potential therapeutic targets of PDNP. A prediabetic animal model induced by a high-energy diet exhibits both mechanical allodynia and thermal hyperalgesia. Furthermore, hyperexcitability and decreased potassium currents are observed in the dorsal root ganglion (DRG) neurons of these rats. TREK1 and TREK2 channels, which belong to the two-pore-domain K+ channel (K2P) family and play an important role in controlling cellular excitability, are downregulated in DRG neurons. Moreover, this alteration is modulated by Sortilin, a molecular partner that modulates the expression of TREK1. The overexpression of Sortilin negatively affects the expression of TREK1 and TREK2, leading to increased neuronal excitability in the DRG and enhanced peripheral pain sensitivity in rats. Moreover, the downregulation of Sortilin or activation of TREK1 and TREK2 channels by genetic or pharmacological approaches can alleviate PDNP. Therefore, targeting the Sortilin-mediated TREK1/2 pathway may provide a therapeutic approach for ameliorating PDNP.

7.
BMC Med Genomics ; 17(1): 102, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654378

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is on the rise globally, and past research suggests a significant association with various blood cell components. Our goal is to explore the potential correlation between whole blood cell indices and NAFLD risk using Mendelian randomization (MR). METHODS: We analyzed data from 4,198 participants in the 2017-2018 National Health and Nutrition Examination Survey to investigate the link between blood cell indicators and NAFLD. Using various methods like weighted quantile sum and multivariate logistic regression, we assessed the association. Additionally, two-sample Mendelian randomization were employed to infer causality for 36 blood cell indicators and NAFLD. RESULTS: Multivariate logistic regression identified 10 NAFLD risk factors. Weighted quantile sum revealed a positive correlation (p = 6.03e-07) between total blood cell indices and NAFLD, with hemoglobin and lymphocyte counts as key contributors. Restricted cubic spline analysis found five indicators with significant nonlinear correlations to NAFLD. Mendelian randomization showed a notable association between reticulocyte counts and NAFLD using the inverse-variance weighted method. CONCLUSIONS: Hematological markers pose an independent NAFLD risk, with a positive causal link found for reticulocyte count. These results emphasize the importance of monitoring NAFLD and investigating specific underlying mechanisms further.


Assuntos
Análise da Randomização Mendeliana , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/sangue , Masculino , Fatores de Risco , Feminino , Pessoa de Meia-Idade , Células Sanguíneas/metabolismo , Adulto , Inquéritos Nutricionais
8.
Eur J Med Res ; 29(1): 177, 2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38494503

RESUMO

BACKGROUND: Phosducin-like 3 (PDCL3) is a member of the photoreceptor family, characterized by a thioredoxin-like structural domain and evolutionary conservation. It plays roles in angiogenesis and apoptosis. Despite its significance, research on the biological role of PDCL3 in liver hepatocellular carcinoma (LIHC) remains limited. This study aims to explore the prognostic value and potential mechanisms of PDCL3 in cancer, particularly in LIHC, through bioinformatics analysis. METHODS: RNA-seq data and corresponding clinical information for pan-cancer and LIHC were extracted from the TCGA database to analyze PDCL3 expression and survival prognosis. Differential expression of PDCL3 was analyzed using the HPA database. GO and KEGG enrichment analysis were performed for PDCL3-associated genes. The relationship between PDCL3 expression and various immune cell types was examined using the TIMER website. Clinical samples were collected, and immunohistochemistry and immunofluorescence experiments were conducted to validate the differential expression of PDCL3 in LIHC and normal tissues. In vitro assays, including CCK-8, wound healing, Transwell, and colony formation experiments, were employed to determine the biological functions of PDCL3 in LIHC cells. RESULTS: Analysis from TIMER, GEPIA, UALCAN, and HPA databases revealed differential expression of PDCL3 in various tumors. Prognostic analysis from GEPIA and TCGA databases indicated that high PDCL3 expression was associated with poorer clinical staging and prognosis in LIHC. Enrichment analysis of PDCL3-associated genes revealed its involvement in various immune responses. TCGA and TIMER databases showed that high PDCL3 expression in LIHC decreased tumor immune activity by reducing macrophage infiltration. PDCL3 exhibited positive correlations with multiple immune checkpoint genes. Immunohistochemistry (IHC) and immunofluorescence (IF) experiments confirmed elevated PDCL3 expression in LIHC tissues compared to adjacent normal tissues. In vitro experiments demonstrated that PDCL3 promoted LIHC cell proliferation, migration, invasion, and colony-forming ability. CONCLUSION: PDCL3 is highly expressed in various cancer types. Our study suggests that elevated PDCL3 expression in hepatocellular carcinoma is associated with poorer prognosis and may serve as a potential diagnostic biomarker for LIHC. PDCL3 may regulate the biological functions of LIHC by modulating immune infiltration. However, the precise regulatory mechanisms of PDCL3 in cancer warrant further investigation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Prognóstico , Neoplasias Hepáticas/genética , Biomarcadores , Proteínas de Transporte , Proteínas do Tecido Nervoso
9.
J Colloid Interface Sci ; 664: 946-959, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38508030

RESUMO

Three-dimensional interconnected nickel-cobalt layered double hydroxides (NiCo-LDHs) were prepared on nickel foam by ion exchange using a cobalt-based metal-organic framework (Co-MOF) as a template at different temperatures. The effects of the Co-MOF preparation temperature on the growth, mass, morphology, and electrochemical properties of the Co-MOF and derived NiCo-LDH samples were studied. The synthesis temperature from 30 to 50 °C gradually increased the mass of the active material and the thickness of the Co-MOF sheets grown on the nickel foam. The higher the temperature is, the larger the proportion of Co3+. ß-Cobalt hydroxide (ß-Co(OH)2) sheets were generated above 60 °C. The morphology and mass loading pattern of the derived flocculent layer clusters of NiCo-LDH were inherited from metal-organic frameworks (MOFs). The areal capacitance of NiCo-LDH shows an inverted U-shaped curve trend with increasing temperature. The electrode material synthesized at 50 °C had a tremendous specific capacitance of 7631 mF·cm-2 at a current density of 2 mA·cm-2. The asymmetric supercapacitor assembled with the sample and active carbon (AC) achieved an energy density of 55.0 Wh·kg-1 at a power density of 800.0 W·kg-1, demonstrating the great potential of the NiCo-LDH material for energy storage. This work presents a new strategy for designing and fabricating advanced green supercapacitor materials with large power and energy densities.

10.
Blood Cancer J ; 14(1): 52, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519476

RESUMO

Induction regimens for multiple myeloma (MM) commonly include bortezomib, which has typically been administered twice weekly despite studies demonstrating comparable efficacy and less peripheral neuropathy (PN) with once-weekly bortezomib. We aimed to analyze the real-world prevalence and efficacy of once-weekly versus twice-weekly bortezomib regimens in newly diagnosed MM. We analyzed 2497 US patients aged 18-70 years treated with commercial first-line bortezomib using nationwide Flatiron Health electronic health record-derived data, including 910 (36.4%) patients who received twice-weekly and 1522 (63.2%) who received once-weekly bortezomib. Once-weekly bortezomib use increased over time, from 57.7% in 2017 to 73.1% in 2022. Multivariate analysis identified worsened performance status and more recent year of diagnosis with higher odds of receiving once-weekly bortezomib. Real-world progression-free survival (median 37.2 months with once-weekly versus 39.6 months with twice-weekly, p = 0.906) and overall survival (medians not reached in either cohort, p = 0.800) were comparable. PN rates were higher in patients receiving twice-weekly bortezomib (34.7% versus 18.5%, p < 0.001). In conclusion, once-weekly bortezomib is clearly associated with similar efficacy and fewer toxicities compared to twice-weekly bortezomib. Our findings support once-weekly bortezomib as a standard-of-care regimen for newly diagnosed patients with MM.


Assuntos
Mieloma Múltiplo , Humanos , Bortezomib/efeitos adversos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/etiologia , Esquema de Medicação , Resultado do Tratamento , Intervalo Livre de Doença , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/uso terapêutico
11.
Acta Biochim Biophys Sin (Shanghai) ; 56(2): 162-173, 2024 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-38298056

RESUMO

Voltage-dependent anion channel 1 (VDAC1) is a pore protein located in the outer mitochondrial membrane. Its channel gating mediates mitochondrial respiration and cell metabolism, and it has been identified as a critical modulator of mitochondria-mediated apoptosis. In many diseases characterized by mitochondrial dysfunction, such as cancer and neurodegenerative diseases, VDAC1 is considered a promising potential therapeutic target. However, there is limited research on the regulatory factors involved in VDAC1 protein expression in both normal and pathological states. In this study, we find that VDAC1 protein expression is up-regulated in various neuronal cell lines in response to intracellular metabolic and oxidative stress. We further demonstrate that VDAC1 expression is modulated by intracellular ATP level. Through the use of pharmacological agonists and inhibitors and small interfering RNA (siRNA), we reveal that the AMPK/PGC-1α signaling pathway is involved in regulating VDAC1 expression. Additionally, based on bioinformatics predictions and biochemical verification, we identify p53 as a potential transcription factor that regulates VDAC1 promoter activity during metabolic oxidative stress. Our findings suggest that VDAC1 expression is regulated by the AMPK/PGC-1α and p53 pathways, which contributes to the maintenance of stress adaptation and apoptotic homeostasis in neuronal cells.


Assuntos
Proteína Supressora de Tumor p53 , Canal de Ânion 1 Dependente de Voltagem , Canal de Ânion 1 Dependente de Voltagem/genética , Canal de Ânion 1 Dependente de Voltagem/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Estresse Oxidativo , Apoptose/genética , Trifosfato de Adenosina/metabolismo
12.
J Am Chem Soc ; 146(8): 5108-5117, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38367279

RESUMO

Enzymes are natural catalysts for a wide range of metabolic chemical transformations, including selective hydrolysis, oxidation, and phosphorylation. Herein, we demonstrate a strategy for the encapsulation of enzymes within a highly stable zirconium-based metal-organic framework. UiO-66-F4 was synthesized under mild conditions using an enzyme-compatible amino acid modulator, serine, at a modest temperature in an aqueous solution. Enzyme@UiO-66-F4 biocomposites were then formed by an in situ encapsulation route in which UiO-66-F4 grows around the enzymes and, consequently, provides protection for the enzymes. A range of enzymes, namely, lysozyme, horseradish peroxidase, and amano lipase, were successfully encapsulated within UiO-66-F4. We further demonstrate that the resulting biocomposites are stable under conditions that could denature many enzymes. Horseradish peroxidase encapsulated within UiO-66-F4 maintained its biological activity even after being treated with the proteolytic enzyme pepsin and heated at 60 °C. This strategy expands the toolbox of potential metal-organic frameworks with different topologies or functionalities that can be used as enzyme encapsulation hosts. We also demonstrate that this versatile process of in situ encapsulation of enzymes under mild conditions (i.e., submerged in water and at a modest temperature) can be generalized to encapsulate enzymes of various sizes within UiO-66-F4 while protecting them from harsh conditions (i.e., high temperatures, contact with denaturants or organic solvents).


Assuntos
Estruturas Metalorgânicas , Compostos Organometálicos , Ácidos Ftálicos , Estruturas Metalorgânicas/química , Zircônio/química , Biomimética , Compostos Organometálicos/química , Peroxidase do Rábano Silvestre
13.
Acta Pharm Sin B ; 14(2): 653-666, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38322337

RESUMO

Stress and illness connection is complex and involves multiple physiological systems. Panax ginsengs, reputed for their broad-spectrum "cure-all" effect, are widely prescribed to treat stress and related illnesses. However, the identity of ginseng's "cure-all" medicinal compounds that relieve stress remains unresolved. Here, we identify ginsentides as the principal bioactives that coordinate multiple systems to restore homeostasis in response to stress. Ginsentides are disulfide-rich, cell-penetrating and proteolytic-stable microproteins. Using affinity-enrichment mass spectrometry target identification together with in vitro, ex vivo and in vivo validations, we show that highly purified or synthetic ginsentides promote vasorelaxation by producing nitric oxide through endothelial cells via intracellular PI3K/Akt signaling pathway, alleviate α1-adrenergic receptor overactivity by reversing phenylephrine-induced constriction of aorta, decrease monocyte adhesion to endothelial cells via CD166/ESAM/CD40 and inhibit P2Y12 receptors to reduce platelet aggregation. Orally administered ginsentides were effective in animal models to reduce ADP-induced platelet aggregation, to prevent collagen and adrenaline-induced pulmonary thrombosis as well as anti-stress behavior of tail suspension and forced swimming tests in mice. Together, these results strongly suggest that ginsentides are the principal panacea compounds of ginsengs because of their ability to target multiple extra- and intra-cellular proteins to reverse stress-induced damages.

14.
Opt Lett ; 49(4): 1097-1100, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38359262

RESUMO

We experimentally extend the nonlinear Gaussian to flat-top beam shaping from one to two dimensions through a three-dimensional nonlinear photonic crystal. Employing a near-infrared femtosecond laser, we induce a modification inside lithium niobate to achieve a second-order nonlinear optical coefficient modulation in three dimensions. The flat-topped truncation of wavefront has been adjusted in a mutual perpendicular coordinate separately. Among the generated flat-topped beams, the optimal flatness is 97.1%, and the nonlinear conversion efficiency is 10-2 at the peak power of 37 kW with the interaction length of 630 µm. By adding an extra dimension, our work simultaneously enables full-wavefront flat-top distribution and nonlinear frequency conversion.

15.
Adv Mater ; 36(16): e2312249, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38193634

RESUMO

Ionic thermocells convert heat into electricity and are promising power sources for electronic devices. However, discontinuous and small electricity output limits practical use under varying environmental conditions. Here, a thermogalvanic ionogel with a high Seebeck coefficient (32.4 mV K-1) is designed. Thermocells that combine thermogalvanic ionogel-based thermocells, which realize all-weather power generation via passive radiative cooling, are also developed. These thermocells generate electricity continuously under varying weather conditions and over a wide temperature range (-40 to 90 °C), with a normalized power density of 25.84 mW m-2 K-2. Advanced characterization shows that the chaotropic effect enhances the Seebeck coefficient, while the self-supplying temperature difference given the radiative cooling structure enables all-weather power generation. These results provide an effective strategy for developing practical thermocells suitable for diverse daily and seasonal variations.

16.
J Am Chem Soc ; 146(6): 3943-3954, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38295342

RESUMO

CALF-20, a Zn-triazolate-based metal-organic framework (MOF), is one of the most promising adsorbent materials for CO2 capture. However, competitive adsorption of water severely limits its performance when the relative humidity (RH) exceeds 40%, limiting the potential implementation of CALF-20 in practical settings where CO2 is saturated with moisture, such as postcombustion flue gas. In this work, three newly designed MOFs related to CALF-20, denoted as NU-220, CALF-20M-w, and CALF-20M-e that feature hydrophobic methyltriazolate linkers, are presented. Inclusion of methyl groups in the linker is proposed as a strategy to improve the uptake of CO2 in the presence of water. Notably, both CALF-20M-w and CALF-20M-e retain over 20% of their initial CO2 capture efficiency at 70% RH─a threshold at which CALF-20 shows negligible CO2 uptake. Grand canonical Monte Carlo simulations reveal that the methyl group hinders water network formation in the pores of CALF-20M-w and CALF-20M-e and enhances their CO2 selectivity over N2 in the presence of a high moisture content. Moreover, calculated radial distribution functions indicate that introducing the methyl group into the triazolate linker increases the distance between water molecules and Zn coordination bonds, offering insights into the origin of the enhanced moisture stability observed for CALF-20M-w and CALF-20M-e relative to CALF-20. Overall, this straightforward design strategy has afforded more robust sorbents that can potentially meet the challenge of effectively capturing CO2 in practical industrial applications.

17.
Small ; : e2305838, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38258379

RESUMO

Interstitial fluid (ISF) is an attractive alternative to regular blood sampling for health checks and disease diagnosis. Porous microneedles (MNs) are well suited for collecting ISF in a minimally invasive manner. However, traditional methods of molding MNs from microfabricated templates involve prohibitive fabrication costs and fixed designs. To overcome these limitations, this study presents a facile and economical additive manufacturing approach to create porous MNs. Compared to traditional layerwise build sequences, direct ink drawing with nanocomposite inks can define sharp MNs with tailored shapes and achieve vastly improved fabrication efficiency. The key to this fabrication strategy is the yield-stress fluid ink that is easily formulated by dispersing silica nanoparticles into the cellulose acetate polymer solution. As-printed MNs are solidified into interconnected porous microstructure inside a coagulation bath of deionized water. The resulting MNs exhibit high mechanical strength and high porosity. This approach also allows porous MNs to be easily integrated on various substrates. In particular, MNs on filter paper substrates are highly flexible to rapidly collect ISF on non-flat skin sites. The extracted ISF is used for quantitative analysis of biomarkers, including glucose, = calcium ions, and calcium ions. Overall, the developments allow facile fabrication of porous MNs for transdermal diagnosis and therapy.

18.
Medicine (Baltimore) ; 103(3): e34342, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38241554

RESUMO

E2F transcription factors (E2Fs) are a family of transcription factors critical regulators of the cell cycle, apoptosis, and differentiation, thus influencing tumorigenesis. However, the specific roles of E2Fs in lung adenocarcinoma (LUAD) remain unclear. Data from The Cancer Genome Atlas (TCGA) were used. R version. 4.0.3 and multiple databases (TIMER, cBioportal, gene expression profile interaction analysis [GEPIA], LinkedOmics, and CancerSEA) were utilized to investigate mRNA expression, mutational analysis, prognosis, clinical correlations, co-expressed gene, pathway and network, and single-cell analyses. Immunohistochemistry (IHC) confirmed that E2F transcription factor 7 (E2F7) correlated with LUAD. Among the E2Fs, E2F7 was identified by constructing a prognostic model most significantly associated with overall survival (OS) in LUAD patients. The univariate and multivariate Cox regression analyses showed that E2F7, p-T stage, and p-TNM stage were closely related to OS and progression-free survival (PFS) (P < .05) in LUAD. E2F 7/8 were also identified as significantly associated with tumor stage in the GEPIA database. Compared with paracancerous tissues, E2F7 was up-regulated in LUAD by IHC, and E2F7 might be positively correlated with larger tumors and higher TNM stages. E2F7 may primarily regulate DNA repair, damage, and cell cycle processes and thus affect LUAD tumorigenesis, invasion, and metastasis by LinkedOmics and CancerSEA. E2F7 serves as a potential prognostic biomarker for LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Prognóstico , Adenocarcinoma de Pulmão/genética , Carcinogênese , Transformação Celular Neoplásica , Neoplasias Pulmonares/genética , Biomarcadores , Fator de Transcrição E2F7
19.
ACS Appl Mater Interfaces ; 16(4): 5093-5102, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38236238

RESUMO

Metal-organic frameworks (MOFs) have demonstrated their versatility in a wide range of applications, including chemical separation, gas capture, and storage. In industrial adsorption processes, MOFs are integral to the creation of selective gas adsorption fixed beds. In this context, the assessment of their separation performance under relevant conditions often relies on breakthrough experiments. One aspect frequently overlooked in these experiments is the shaping of MOF powders, which can significantly impact the accuracy of breakthrough results. In this study, we present an approach for immobilizing MOF particles on the surface of glass beads (GBs) utilizing trimethylolpropane triglycidyl ether (TMPTGE) as a binder, leading to the creation of MOF@GB materials. We successfully synthesized five targeted MOF composites, namely, SIFSIX-3-Ni@GB, CALF-20@GB, UiO-66@GB, HKUST-1@GB, and MOF-808@GB, each possessing distinct pore sizes and structural topologies. Characterization studies employing powder X-ray diffraction and adsorption isotherm analyses demonstrated that MOFs@GB retained their crystallinity and 73-90% of the Brunauer-Emmett-Teller area of their parent MOFs. Dynamic breakthrough experiments revealed that, in comparison to their parent MOFs, MOF@GB configurations enhanced the accuracy of breakthrough measurements by mitigating pressure buildup and minimizing reductions in the gas flow rate. This work underscores the significance of meticulous experimental design, specifically in shaping MOF powders, to optimize the efficacy of breakthrough experiments. Our proposed strategy aims to provide a versatile platform for MOF powder processing, thereby facilitating more reliable breakthrough experiments.

20.
Cancer Immunol Res ; 12(3): 363-376, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38289255

RESUMO

Extensive infiltration by tumor-associated macrophages (TAM) in combination with myeloid-derived suppressor cells constitute the immunosuppressive microenvironment and promote the malignant phenotype of gliomas. The aggressive mesenchymal (MES)-subtype glioma stem cells (GSC) are prominent in the immunosuppressive microenvironment of gliomas. However, the underlying immune-suppressive mechanisms are still unknown. The current study showed that the antitumor immune microenvironment was activated in glioma in Nfat1-/- mice, suggesting induction of the immune-suppressive microenvironment by nuclear factor of activated T cells-1 (NFAT1). In TAMs, NFAT1 could upregulate the transcriptional activity of complement 3 (C3) and increase the secretion of C3a, which could then bind to C3aR and promote M2-like macrophage polarization by activating TIM-3. Simultaneously, C3a/C3aR activated the Ca2+-NFAT1 pathway, forming a positive feedback loop for the M2-like polarization of TAMs, which further promoted the MES transition of GSCs. Finally, disruption of this feedback loop using a C3aR inhibitor significantly inhibited glioma growth both in vitro and in vivo. The current study demonstrated that a NFAT1-C3a-C3aR positive feedback loop induces M2-like TAMs and further promotes the malignant phenotype of GSCs, which might be the potential therapeutic target for glioma.


Assuntos
Glioma , Macrófagos , Animais , Camundongos , Macrófagos Associados a Tumor/metabolismo , Retroalimentação , Glioma/genética , Fenótipo , Células-Tronco Neoplásicas/metabolismo , Microambiente Tumoral , Linhagem Celular Tumoral
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