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1.
Analyst ; 148(8): 1732-1742, 2023 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-36938870

RESUMEN

Dopamine (DA) plays an essential role in dopaminergic neuronal behavior and disease. However, current detection methods for discriminating the secretion of DA are hampered by the limitations of the requirement for bulky instrumentation and non-intuitive signals. Herein, we have controllably and proportionately integrated molybdenum disulfide (MoS2) with titanium dioxide (TiO2) to prepare MoS2@TiO2 nanocomposites (MoS2@TiO2 NCs) via a facile synthesis method. MoS2@TiO2 NCs with a certain reactant mass ratio have shown a significant enhancement in peroxidase-like activity with superiority of the nanocomposite structure compared to single MoS2 or natural enzyme. The method for catalyzing the decomposition of H2O2 by MoS2@TiO2 NCs and competition for hydroxyl radicals (˙OH) between the chromogenic agent and DA enable a sensitive, specific, and colorimetric DA analysis with a low detection limit of 0.194 µM and a wide linear detection range (0.8 to 100 µM). Because of the favorable detection performance, we were encouraged to explore and finally realize the visual detection of cellular DA secretion that is stimulated in a High-K+ neurocyte environment. Collectively, this method will provide a promising strategy for basic research in neuroscience with its portable, sensitive, and naked-eye detectable performance.


Asunto(s)
Dopamina , Nanocompuestos , Molibdeno/química , Peróxido de Hidrógeno/química , Nanocompuestos/química
2.
Small ; 18(12): e2105019, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34910848

RESUMEN

Light stimuli have notable advantages over other environmental stimuli, such as more precise spatial and temporal regulation, and the ability to serve as an energy source to power the system. In nature, photoresponsive nanochannels are important components of organisms, with examples including the rhodopsin channels in optic nerve cells and photoresponsive protein channels in the photosynthesis system of plants. Inspired by biological channels, scientists have constructed various photoresponsive, smart solid-state nanochannels membranes for a range of applications. In this review, the methods and applications of photosensitive nanochannels membranes are summarized. The authors believe that this review will inspire researchers to further develop multifunctional artificial nanochannels for applications in the fields of biosensors, stimuli-responsive smart devices, and nanofluidic devices, among others.


Asunto(s)
Técnicas Biosensibles
3.
Inorg Chem ; 61(6): 2883-2891, 2022 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-35108490

RESUMEN

The development of supramolecular coordination complexes (SCCs) with a bright aggregate state or mechanical-stimuli-responsive luminescence is very significant and challenging. Herein, we report the synthesis of three different supramolecular platinum(II) metallacycles via coordination-driven self-assembly of a diplatinum(II) acceptor and organic donors with a triphenylamine, carbazole, or tetraphenylethylene moiety. The triphenylamine-modified SCC exhibits aggregation-induced emission enhancement (AIEE) but no mechanofluorochromism. The carbazole and tetraphenylethylene-based SCCs exhibit changes in aggregate fluorescence and also exhibit reversible mechanofluorochromism. This work not only reports three rare metallacycles with AIEE, aggregate fluorescence change, or mechanofluorochromic nature but also explores their potential applications in cell imaging and solid-state lighting.

4.
Angew Chem Int Ed Engl ; 61(14): e202200482, 2022 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-35099850

RESUMEN

Discharge of antibiotic-containing wastewater causes environmental pollution and threatens biological and human health. An efficient treatment method for this wastewater is urgently required. We prepared inorganic-organic hybrid MXene-pillararene nanosheets with a large lateral size (5-8 µm). The hybrid nanosheets were stacked on supports via vacuum-assisted filtration to prepare membranes with regular parallel slits and an interlayer spacing of 1.36 nm, which were used to purify antibiotic-containing water. Permeance through the membrane increased 100-fold compared with most polymeric and other two-dimensional nanofiltration membranes with similar rejection. This high permeance and rejection was attributed to the large lateral size of the nanosheets, regular interlayer spacing, and electrostatic interaction between the membrane and antibiotics. These membranes will broaden the applications of lamellar materials for the separation of high-value-added drugs in academia and industry.


Asunto(s)
Aguas Residuales , Purificación del Agua , Antibacterianos , Humanos , Membranas Artificiales , Titanio
5.
Mol Cancer ; 18(1): 108, 2019 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-31221150

RESUMEN

BACKGROUND: Changes in glycogen metabolism is an essential feature among the various metabolic adaptations used by cancer cells to adjust to the conditions imposed by the tumor microenvironment. Our previous study showed that glycogen branching enzyme (GBE1) is downstream of the HIF1 pathway in hypoxia-conditioned lung cancer cells. In the present study, we investigated whether GBE1 is involved in the immune regulation of the tumor microenvironment in lung adenocarcinoma (LUAD). METHODS: We used RNA-sequencing analysis and the multiplex assay to determine changes in GBE1 knockdown cells. The role of GBE1 in LUAD was evaluated both in vitro and in vivo. RESULTS: GBE1 knockdown increased the expression of chemokines CCL5 and CXCL10 in A549 cells. CD8 expression correlated positively with CCL5 and CXCL10 expression in LUAD. The supernatants from the GBE1 knockdown cells increased recruitment of CD8+ T lymphocytes. However, the neutralizing antibodies of CCL5 or CXCL10 significantly inhibited cell migration induced by shGBE1 cell supernatants. STING/IFN-I pathway mediated the effect of GBE1 knockdown for CCL5 and CXCL10 upregulation. Moreover, PD-L1 increased significantly in shGBE1 A549 cells compared to those in control cells. Additionally, in LUAD tumor tissues, a negative link between PD-L1 and GBE1 was observed. Lastly, blockade of GBE1 signaling combined with anti-PD-L1 antibody significantly inhibited tumor growth in vivo. CONCLUSIONS: GBE1 blockade promotes the secretion of CCL5 and CXCL10 to recruit CD8+ T lymphocytes to the tumor microenvironment via the IFN-I/STING signaling pathway, accompanied by upregulation of PD-L1 in LUAD cells, suggesting that GBE1 could be a promising target for achieving tumor regression through cancer immunotherapy in LUAD.


Asunto(s)
Adenocarcinoma del Pulmón/patología , Perfilación de la Expresión Génica/métodos , Sistema de la Enzima Desramificadora del Glucógeno/genética , Neoplasias Pulmonares/patología , Análisis de Secuencia de ARN/métodos , Células A549 , Adenocarcinoma del Pulmón/genética , Antígeno B7-H1/metabolismo , Linfocitos T CD8-positivos/metabolismo , Línea Celular Tumoral , Quimiocina CCL5/genética , Quimiocina CXCL10/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Neoplasias Pulmonares/genética , Proteínas de la Membrana/metabolismo , Trasplante de Neoplasias , Transducción de Señal
6.
J Neuroinflammation ; 14(1): 167, 2017 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-28835272

RESUMEN

BACKGROUND: Neuroinflammation is an important secondary injury mechanism that has dual beneficial and detrimental roles in the pathophysiology of traumatic brain injury (TBI). Compelling data indicate that statins, a group of lipid-lowering drugs, also have extensive immunomodulatory and anti-inflammatory properties. Among statins, atorvastatin has been demonstrated as a neuroprotective agent in experimental TBI; however, there is a lack of evidence regarding its effects on neuroinflammation during the acute phase of TBI. The current study aimed to evaluate the effects of atorvastatin therapy on modulating the immune reaction, and to explore the possible involvement of peripheral leukocyte invasion and microglia/macrophage polarization in the acute period post-TBI. METHODS: C57BL/6 mice were subjected to TBI using a controlled cortical impact (CCI) device. Either atorvastatin or vehicle saline was administered orally starting 1 h post-TBI for three consecutive days. Short-term neurological deficits were evaluated using the modified neurological severity score (mNSS) and Rota-rod. Brain-invading leukocyte subpopulations were analyzed by flow cytometry and immunohistochemistry. Pro- and anti-inflammatory cytokines and chemokines were examined using enzyme-linked immunosorbent assay (ELISA). Markers of classically activated (M1) and alternatively activated (M2) microglia/macrophages were then determined by quantitative real-time PCR (qRT-PCR) and flow cytometry. Neuronal apoptosis was identified by double staining of terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL) staining and immunofluorescence labeling for neuronal nuclei (NeuN). RESULTS: Acute treatment with atorvastatin at doses of 1 mg/kg/day significantly reduced neuronal apoptosis and improved behavioral deficits. Invasions of T cells, neutrophils and natural killer (NK) cells were attenuated profoundly after atorvastatin therapy, as was the production of pro-inflammatory cytokines (IFN-γ and IL-6) and chemokines (RANTES and IP-10). Notably, atorvastatin treatment significantly increased the proportion of regulatory T cells (Tregs) in both the peripheral spleen and brain, and at the same time, increased their main effector cytokines IL-10 and TGF-ß1. We also found that atorvastatin significantly attenuated total microglia/macrophage activation but augmented the M2/M1 ratio by both inhibiting M1 polarization and enhancing M2 polarization. CONCLUSIONS: Our data demonstrated that acute atorvastatin administration could modulate post-TBI neuroinflammation effectively, via a mechanism that involves altering peripheral leukocyte invasion and the alternative polarization of microglia/macrophages.


Asunto(s)
Antiinflamatorios/uso terapéutico , Atorvastatina/uso terapéutico , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Modelos Animales de Enfermedad , Factores Inmunológicos/uso terapéutico , Mediadores de Inflamación/antagonistas & inhibidores , Animales , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/patología , Mediadores de Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL
7.
Membranes (Basel) ; 14(5)2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38786934

RESUMEN

The phenomenon of melting in metal-organic frameworks (MOFs) has recently garnered attention. Crystalline MOF materials can be transformed into an amorphous glassy state through melt-quenching treatment. The resulting MOF glass structure eliminates grain boundaries and retains short-range order while exhibiting long-range disorder. Based on these properties, it emerges as a promising candidate for high-performance separation membranes. MOF glass membranes exhibit permanent and accessible porosity, allowing for selective adsorption of different gas species. This review summarizes the melting mechanism of MOFs and explores the impact of ligands and metal ions on glassy MOFs. Additionally, it presents an analysis of the diverse classes of MOF glass composites, outlining their structures and properties, which are conducive to gas adsorption and separation. The absence of inter-crystalline defects in the structures, coupled with their distinctive mechanical properties, renders them highly promising for industrial gas separation applications. Furthermore, this review provides a summary of recent research on MOF glass composite membranes for gas adsorption and separation. It also addresses the challenges associated with membrane production and suggests future research directions.

8.
Int J Antimicrob Agents ; 63(5): 107120, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38417705

RESUMEN

OBJECTIVES: This study aimed to appraise clinical practice guidelines (CPGs) for the treatment of carbapenem-resistant Gram-negative Bacilli (CRGNB) infections and to summarise the recommendations. METHODS: A systematic search of the literature published from January 2012 to March 2023 was undertaken to identify CPGs related to CRGNB infections treatment. The methodological and reporting quality of eligible CPGs were assessed using six domains of the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool and seven domains of the Reporting Items for practice Guidelines in HealThcare (RIGHT) checklist. Basic information and recommendations of included CPGs were extracted and compared. RESULTS: A total of 21 CPGs from 7953 relevant articles were included. The mean overall AGREE II score was 62.7%, and was highest for "clarity of presentation" (90.2%) and lowest for "stakeholder involvement" (44.8%). The overall reporting quality of all of the CPGs was suboptimal, with the proportion of eligible items ranging from 45.7 to 85.7%. The treatment of CRGNB infections is related to the type of pathogen, the sensitivity of antimicrobial agents, and the site of infection. In general, the recommended options mainly included novel ß-lactam/ ß-lactamase inhibitors, cefiderocol, ampicillin-sulbactam (mainly for carbapenem-resistant Acinetobacter baumannii [CRAB]), and combination therapy, involving polymyxin B/colistin, tigecycline (except for carbapenem-resistant Pseudomonas aeruginosa), aminoglycosides, carbapenems, fosfomycin, and sulbactam (mainly for CRAB). CONCLUSIONS: The methodological and reporting quality of CPGs for the treatment of CRGNB infections are generally suboptimal and need further improvement. Both monotherapy with novel drugs and combination therapy play important roles in the treatment.


Asunto(s)
Antibacterianos , Carbapenémicos , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas , Guías de Práctica Clínica como Asunto , Humanos , Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Carbapenémicos/uso terapéutico , Carbapenémicos/farmacología , Cefiderocol , Fosfomicina/uso terapéutico , Fosfomicina/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Pruebas de Sensibilidad Microbiana/normas , Sulbactam/uso terapéutico , Sulbactam/farmacología , Tigeciclina/uso terapéutico , Tigeciclina/farmacología
9.
Diabetol Metab Syndr ; 16(1): 1, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38173012

RESUMEN

BACKGROUND: Triglyceride glucose (TyG) is associated with stroke, atherosclerosis, and adverse clinical outcomes. However, its correlation with cerebrovascular disease (CVD) mortality remains unclear. This study aimed to investigate the relationship between TyG index and mortality in patients with CVD. METHODS: Patient data sourced from the Medical Information Mart for Intensive Care -IV database were categorized based on TyG quartiles. Kaplan-Meier survival analysis was used to estimate survival disparities among the TyG subgroups. Cox proportional risk modeling was used to examine the association between the TyG index and mortality. Generalized summation models were applied to fit the smoothed curves. log-likelihood ratio test were used to analyze the non-linear relationship. RESULTS: The study comprised 1,965 patients (50.18% were male). The 28-day and 90-day mortality rates were 20.10% and 24.48%, respectively. The TyG index exhibited a linear relationship with the 28-day mortality (Hazards ratio (HR), 1.16; 95% confidence interval (CI), 0.99-1.36) and the 90-day mortality (HR, 1.18; 95% CI, 1.02-1.37). In the TyG Q4 group, each 1 mg/dl increase was linked to a 35% rise in the risk of 28-day mortality and a 38% increase in the risk of 90-day mortality. Subgroup analyses highlighted a more substantial association between TyG index and 90-day mortality in the diabetic group. CONCLUSION: Our findings underscore the positive association between TyG and the 28- and 90-day mortality rates in patients with CVD. This insight may prove pivotal for identifying at-risk populations and enhancing risk prediction in the clinical management of CVD.

10.
Transplantation ; 108(4): 1021-1032, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38049935

RESUMEN

BACKGROUND: Cytomegalovirus (CMV) infection is associated with higher non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). But the preferred drug for preventing cytomegalovirus infection is still controversial. We evaluate the efficacy, safety, and cost-effectiveness of antiviral agents based on the most recent studies. METHODS: A pairwise and network meta-analysis was conducted to obtain direct and indirect evidence of antivirals. The cost of allo-HSCT recipients in a teaching hospital was collected, and a cost-effectiveness analysis using a decision tree combined with Markov model was completed from the perspective of allo-HSCT recipients over a lifetime horizon. RESULTS: A total of 19 RCTs involving 3565 patients (8 antivirals) were included. In the network meta-analysis, relative to placebo, letermovir, valacyclovir, and ganciclovir significantly reduced CMV infection incidence; ganciclovir significantly reduced CMV disease incidence; ganciclovir significantly increased the incidence of serious adverse event; none of antivirals significantly reduced all-cause mortality. Based on meta-analysis and Chinese medical data, the incremental cost-effectiveness ratios (ICER) per quality-adjusted life year (QALY) saved for maribavir, acyclovir, valacyclovir, ganciclovir, and letermovir relative to placebo corresponded to US$216 635.70, US$11 590.20, US$11 816.40, US$13 049.90, and US$12 189.40, respectively. One-way sensitivity analysis showed the most influential parameter was discount rate. The probabilistic sensitivity analysis indicated a 53.0% probability of letermovir producing an ICER below the willingness-to-pay threshold of US$38 824.23/QALY. The scenario analysis demonstrated prophylaxis with letermovir is considered cost-effective in the United States. CONCLUSIONS: Currently, letermovir is an effective and well-tolerated treatment for preventing CMV infection, and it might be a cost-effective choice in allo-HSCT recipients in China.


Asunto(s)
Acetatos , Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Quinazolinas , Humanos , Citomegalovirus , Valaciclovir/farmacología , Antivirales/efectos adversos , Análisis de Costo-Efectividad , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/prevención & control , Infecciones por Citomegalovirus/epidemiología , Ganciclovir/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos
11.
J Neurotrauma ; 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38818807

RESUMEN

The kallikrein-kinin system is one of the first inflammatory pathways to be activated following traumatic brain injury (TBI) and has been shown to exacerbate brain edema formation in the acute phase through activation of bradykinin 2 receptors (B2R). However, the influence of B2R on chronic post-traumatic damage and outcome is unclear. In the current study, we assessed long-term effects of B2R-knockout (KO) after experimental TBI. B2R KO mice (heterozygous, homozygous) and wild-type (WT) littermates (n = 10/group) were subjected to controlled cortical impact (CCI) TBI. Lesion size was evaluated by magnetic resonance imaging up to 90 days after CCI. Motor and memory function were regularly assessed by Neurological Severity Score, Beam Walk, and Barnes maze test. Ninety days after TBI, brains were harvested for immunohistochemical analysis. There was no difference in cortical lesion size between B2R-deficient and WT animals 3 months after injury; however, hippocampal damage was reduced in B2R KO mice (p = 0.03). Protection of hippocampal tissue was accompanied by a significant improvement of learning and memory function 3 months after TBI (p = 0.02 WT vs. KO), whereas motor function was not influenced. Scar formation and astrogliosis were unaffected, but B2R deficiency led to a gene-dose-dependent attenuation of microglial activation and a reduction of CD45+ cells 3 months after TBI in cortex (p = 0.0003) and hippocampus (p < 0.0001). These results suggest that chronic hippocampal neurodegeneration and subsequent cognitive impairment are mediated by prolonged neuroinflammation and B2R. Inhibition of B2R may therefore represent a novel strategy to reduce long-term neurocognitive deficits after TBI.

12.
Aging (Albany NY) ; 16(1): 431-444, 2024 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-38189823

RESUMEN

BACKGROUND: Glioma is one of the most aggressive malignant brain tumors and is characterized by invasive growth and poor prognosis. TBC1D1, a member of the TBC family, is associated with the development of various malignancies. However, the role of TBC1D1 in glioma-genesis remains unclear. METHODS: The effect of TBC1D1 on the prognosis of glioma patients and related influencing factors were analyzed in the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. Expression of TBC1D1 in glioma cell lines was detected by western blotting. Cell viability and proliferation were measured by EdU and Colony formation assays, respectively. Transwell and wound healing assays were performed to determine the cell migration and invasion capacities. Immunofluorescence was used to observe actin morphology in the cytoskeleton. RESULTS: We discovered that high TBC1D1 expression in gliomas led to poor prognosis. Downregulation of TBC1D1 in glioma cells significantly inhibited multiple important functions, such as proliferation, migration, and invasion. We further demonstrated that the tumor-inhibitory effect of TBC1D1 might occur through the P-LIMK/cofilin pathway, destroying the cytoskeletal structure and affecting the depolymerization of F-actin, thereby inhibiting glioma migration. CONCLUSION: TBC1D1 affects the balance and integrity of the actin cytoskeleton via cofilin, thereby altering the morphology and aggressiveness of glioma cells. This study provides a new perspective on its role in tumorigenesis, thereby identifying a potential therapeutic target for the treatment of gliomas.


Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Proliferación Celular/genética , Línea Celular Tumoral , Glioma/patología , Neoplasias Encefálicas/patología , Movimiento Celular/genética , Actinas , Citoesqueleto de Actina/metabolismo , Factores Despolimerizantes de la Actina/metabolismo , Factores Despolimerizantes de la Actina/farmacología , Proteínas Activadoras de GTPasa/genética
13.
Int J Surg ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38896856

RESUMEN

INTRODUCTION: The triglyceride glucose index (TyG) is associated with cardiovascular diseases; however, its association with stroke remains unclear. This study aimed to elucidate this relationship by examining two extensive cohort studies using two-sample Mendelian randomization (MR). METHODS: Using data from the 1999-2018 National Health and Nutrition Examination Survey (NHANES) and the Medical Information Mart for Intensive Care (MIMIC)-IV, the correlation between TyG (continuous and quartile) and stroke was examined using multivariate Cox regression models and sensitivity analyses. Two-sample MR was employed to establish causality between TyG and stroke using the inverse variance weighting method. Genome-wide association study catalog queries were performed for single nucleotide polymorphism-mapped genes, and the STRING platform used to assess protein interactions. Functional annotation and enrichment analyses were also conducted. RESULTS: From the NHANES and MIMIC-IV cohorts, we included 740 and 589 participants with stroke, respectively. After adjusting for covariates, TyG was linearly associated with the risk of stroke death (NHANES: hazard ratio [HR] 0.64, 95% confidence interval [CI]: 0.41-0.99, P=0.047; Q3 vs. Q1, HR 0.62, 95%CI: 0.40-0.96, P=0.033; MIMIC-IV: HR 0.46, 95%CI: 0.27-0.80, P=0.006; Q3 vs. Q1, HR 0.32, 95%CI: 0.12-0.86; Q4 vs. Q1, HR 0.30, 95%CI: 0.10-0.89, P=0.030, P for trend=0.017). Two-sample MR analysis showed genetic prediction supported a causal association between a higher TyG and a reduced risk of stroke (odds ratio 0.711, 95%CI: 0.641-0.788, P=7.64e-11). CONCLUSIONS: TyG was causally associated with a reduced risk of stroke. TyG is a critical factor for stroke risk management.

14.
J Pharm Sci ; 113(9): 2904-2914, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38996917

RESUMEN

The optimal method for administering meropenem remains controversial. This study was conducted to explore the optimal two-step infusion strategy (TIT), and to investigate whether TIT is superior to intermittent infusion therapy (IIT) and prolonged infusion therapy (PIT). A physiologically based pharmacokinetics model for critically ill patients was established and evaluated. The validated model was utilized to evaluate the pharmacokinetics/pharmacodynamics (PK/PD) target attainment of meropenem. The PK/PD target attainment of different TITs varied greatly, and the total infusion duration and the first-step dose greatly affected these values. The optimal TIT was 0.25 g (30 min) + 0.75 g (150 min) at MICs of ≤2 mg/L, and 0.25 g (45 min) + 0.75 g (255 min) at MICs of 4-8 mg/L. The PK/PD target attainment of optimal TIT, PIT, and IIT were 100 % at MICs of ≤1 mg/L. When MIC increased to 2-8 mg/L, the PK/PD target attainment of optimal TIT was similar to that of PIT and higher than IIT. In conclusion, TIT did not significantly improve the PK/PD target attainment of meropenem compared with PIT. IIT is adequate at MICs of ≤1 mg/L, and PIT may be the optimal meropenem infusion method in critically ill patients with MICs of 2-8 mg/L.


Asunto(s)
Antibacterianos , Enfermedad Crítica , Meropenem , Pruebas de Sensibilidad Microbiana , Meropenem/farmacocinética , Meropenem/administración & dosificación , Meropenem/farmacología , Humanos , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Infusiones Intravenosas , Masculino , Modelos Biológicos , Persona de Mediana Edad , Femenino , Anciano
15.
Anal Methods ; 15(33): 4142-4148, 2023 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-37575050

RESUMEN

A 3D reduced graphene oxide (3DrGO) composite loaded with cauliflower-like MoS2 was prepared. Benefiting from the synergistic effects of 3DrGO and cauliflower-like MoS2, a glassy carbon electrode (GCE) modified with the 3DrGO-MoS2 composite (3DrGO-MoS2/GCE) displays high sensing performance for sunset yellow (SY) and tartrazine (TZ) at working potentials of 0.795 and 1.034 V. Furthermore, a well separated oxidation peak potential can achieve simultaneous detection of the two analytes. Under selected conditions, the peak current exhibits a piecewise linear relationship with the SY concentration in the range of 0.05-10 µmol L-1 and 10-60 µmol L-1, and the plot of peak current versus the TZ concentration also exhibits two linear segments in the range of 0.1-6.0 µmol L-1 and 6.0-60 µmol L-1. The detection limits of SY and TZ are as low as 17.6 and 37.4 nmol L-1, respectively. The prepared 3DrGO-MoS2/GCE was applied for the determination of SY and TZ in food samples with excellent recoveries of 95.1-105.4%.

16.
RSC Adv ; 13(15): 9918-9923, 2023 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-36998518

RESUMEN

A CeO2-Co3O4 nanocomposite (NC) was prepared and characterized by scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy and X-ray diffraction. The obtained CeO2-Co3O4 NC displayed biomimicking oxidase-like activity, which can catalytically oxidize the 3, 3', 5, 5'-tetramethylbenzidine (TMB) substrate from colorless to the blue oxidized TMB (ox-TMB) product with a characteristic absorption peak at 652 nm. When ascorbic acid (AA) was present, ox-TMB would be reduced, resulting in a lighter blue and lower absorbance. On the basis of these facts, a simple colorimetric method for detection of AA was established with a linear relationship ranging from 1.0 to 500 µM and a detection limit of 0.25 µM. When this method was used to detect AA in human serum and commercially available vitamin C tablet samples, a good recovery of 92.0% to 109.0% was obtained. Besides, the catalytic oxidation mechanism was investigated, and the possible catalytic mechanism of CeO2-Co3O4 NC can be described as follows. TMB is adsorbed on the CeO2-Co3O4 NC surface and provides lone-pair electrons to the CeO2-Co3O4 NC, leading to an increase in electron density of the CeO2-Co3O4 NC. An increased electron density can improve the electron transfer rate between TMB and the oxygen absorbed on its surface to generate O2˙- and ˙O2, which further oxidize TMB.

17.
Aging (Albany NY) ; 15(15): 7451-7475, 2023 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-37566748

RESUMEN

Solute carrier family 1 member 5 (SLC1A5) is a member of the solute carrier (SLC) superfamily of transporters and plays an important role in tumors as a key transporter of glutamine into cells. However, the relationship between SLC1A5, which is involved in immune regulation, and immune cell infiltration in the tumor microenvironment has not been elucidated, and the relationship between SLC1A5 and ferroptosis is rarely reported. Therefore, we comprehensively analyzed the expression level of SLC1A5 across cancers and compared it with that in normal tissues. Then, the relationship between SLC1A5 expression and the tumor immune microenvironment was analyzed by single-cell analysis, gene set enrichment analysis (GSEA), and Tumor Immune Estimation Resource (TIMER). Next, the correlations of the SLC1A5 expression level with immunotherapy response, immunomodulator expression, tumor mutation burden (TMB) and microsatellite instability (MSI) were evaluated. Finally, in vitro experiments verified that SLC1A5 participates in ferroptosis of glioma cells to regulate tumor progression. Our results indicated that SLC1A5 is aberrantly expressed in most cancer types and closely associated with prognosis. The GSEA results showed that SLC1A5 is involved in immune activation processes and closely related to the infiltration levels of different immune cells in different cancer types. Upon further investigation, we found that SLC1A5 is a suppressor of ferroptosis in glioma, and SLC1A5 knockdown inhibited the proliferation and migration of glioma cells in vitro. In conclusion, we conducted a pancancer analysis of SLC1A5, demonstrated its role as a prognostic biomarker in cancer patients and explored its potential biological functions.


Asunto(s)
Ferroptosis , Glioma , Humanos , Ferroptosis/genética , Biomarcadores , Adyuvantes Inmunológicos , Glutamina , Proteínas de Transporte de Membrana , Microambiente Tumoral/genética , Antígenos de Histocompatibilidad Menor , Sistema de Transporte de Aminoácidos ASC/genética
18.
BMJ Open ; 13(3): e068045, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36858471

RESUMEN

OBJECTIVES: The purpose of this study was to use easily obtained and directly observable clinical features to establish predictive models to identify patients at increased risk of stroke. SETTING AND PARTICIPANTS: A total of 46 240 valid records were obtained from 8 research centres and 14 communities in Jiangxi province, China, between February and September 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: The area under the receiver operating characteristic curve (AUC), sensitivity, specificity and accuracy were calculated to test the performance of the five models (logistic regression (LR), random forest (RF), decision tree (DT), extreme gradient boosting (XGBoost) and gradient boosting DT). The calibration curve was used to show calibration performance. RESULTS: The results indicated that XGBoost (AUC: 0.924, accuracy: 0.873, sensitivity: 0.776, specificity: 0.916) and RF (AUC: 0.924, accuracy: 0.872, sensitivity: 0.778, specificity: 0.913) demonstrated excellent performance in predicting stroke. Physical inactivity, hypertension, meat-based diet and high salt intake were important prediction features of stroke. CONCLUSION: The five machine learning models all had good predictive and discriminatory performance for stroke. The performance of RF and XGBoost was slightly better than that of LR, which was easier to interpret and less prone to overfitting. This work provides a rapid and accurate tool for stroke risk assessment, which can help to improve the efficiency of stroke screening medical services and the management of high-risk groups.


Asunto(s)
Accidente Cerebrovascular , Humanos , Calibración , Estudios Transversales , Pueblos del Este de Asia , Accidente Cerebrovascular/diagnóstico
19.
Front Surg ; 10: 1008605, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36865629

RESUMEN

Most spinal meningiomas (SM) are benign lesions of the thoracic spine and are usually treated surgically. This study aimed to explore treatment strategies and construct a nomogram for SM. Data on patients with SM from 2000 to 2019 were extracted from the Surveillance, Epidemiology, and End Results database. First, the distributional properties and characteristics of the patients were descriptively evaluated, and the patients were randomly divided into training and testing groups in a 6:4 ratio. Least absolute shrinkage and selection operator (LASSO) regression was used to screen the survival predictors. Kaplan-Meier curves explained survival probability by different variables. The nomogram was constructed based on the results of LASSO regression. The predictive power of the nomogram was identified using the concordance index, time-receiver operating characteristics, decision curve analysis, and calibration curves. We recruited 1,148 patients with SM. LASSO results for the training group showed that sex (coefficient, 0.004), age (coefficient, 0.034), surgery (coefficient, -0.474), tumor size (coefficient, 0.008), and marital status (coefficient, 0.335) were prognostic factors. The nomogram prognostic model showed good diagnostic ability in both the training and testing groups, with a C-index of 0.726, 95% (0.679, 0.773); 0.827, 95% (0.777, 0.877). The calibration and decision curves suggested that the prognostic model had better diagnostic performance and good clinical benefit. In the training and testing groups, the time-receiver operating characteristic curve showed that SM had moderate diagnostic ability at different times, and the survival rate of the high-risk group was significantly lower than that of the low-risk group (training group: p = 0.0071; testing group: p = 0.00013). Our nomogram prognostic model may have a crucial role in predicting the six-month, one-year, and two-year survival outcomes of patients with SM and may be useful for surgical clinicians to formulate treatment plans.

20.
Cancer Med ; 12(14): 15054-15064, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37255381

RESUMEN

BACKGROUND: The clinical effect of postoperative radiotherapy (PORT) in non-malignant meningioma (NMM) has not been well explored. METHODS: A total of 8629 patients with NMM (surgery alone group: n = 7716, postoperative radiotherapy group: n = 913) were obtained from the Surveillance, Epidemiology, and End Results database. Patient profiles were matched by 1:1 propensity score matching (PSM). Logistic regression analysis was performed to identify factors associated with PORT versus surgery alone (SA). Univariate and multivariate Cox regression analyses determined prognostic variables with overall survival (OS) in NMM. Subgroup analyses were performed with Cox proportional hazards regression models. RESULTS: All the SA (n = 7716) and PORT (n = 913) groups were included. Women with PORT (66.3%) and SA (70.9%) were almost twice as likely as men, and tumors with benign behaviors in the SA group were almost seven times more frequent than those with malignant characteristics. We explored the demographic, clinical characteristics, and prognostic factors in NMM. Laterality, surgery, tumor size, diagnosis year, age, and tumor behavior were associated with PORT versus SA. Patients treated with PORT had better OS than those treated with SA (p = 0.03). After PSM, PORT remained comparable to SA (hazard ratio 0.56, 95% confidence interval 0.35-0.88, p = 0.013). In the subgroup analysis of PORT treatment, borderline malignant behavior increased the death risk by 23%, while other variables did not have a significant clinical benefit (p > 0.05). CONCLUSIONS: Borderline malignant behavior should be considered seriously, and the PORT regimen should be actively implemented for patients with benign meningiomas.


Asunto(s)
Neoplasias Meníngeas , Meningioma , Masculino , Humanos , Femenino , Meningioma/epidemiología , Meningioma/radioterapia , Meningioma/cirugía , Puntaje de Propensión , Estudios Retrospectivos , Radioterapia Adyuvante , Programa de VERF , Neoplasias Meníngeas/epidemiología , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirugía
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