Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 225
Filtrar
1.
World J Urol ; 42(1): 321, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38744781

RESUMEN

PURPOSE: Utilize magnetic resonance defecography (MRD) to analyze the primary pelvic floor dysfunctions in patients with stress urinary incontinence (SUI) associated with pelvic organ prolapse (POP), and in SUI patients with asymptomatic POP. METHOD: We performed MRD in both SUI and POP subjects. As a primary analysis, the functional MR parameters were compared between the isolated POP and POP combined SUI groups. As a secondary analysis, the functional MR data were compared between the POP combined SUI and the SUI with asymptomatic POP (isolated SUI) groups. RESULTS: MRD noted the main characteristics of SUI combined moderate or severe POP, including the shorter closed urethra length (1.87 cm vs. 2.50 cm, p < 0.001), more prevalent urethral hypermobility (112.31° vs. 85.67°, p = 0.003), bladder neck funneling (48.28% vs. 20.51%, p = 0.020), lower position of vesicourethral junction (2.11 cm vs. 1.67 cm, p = 0.030), and more severe prolapse of the posterior bladder wall (6.26 cm vs. 4.35 cm, p = 0.008). The isolated SUI patients showed the shortest length of the closed urethra (1.56 cm vs. 1.87 cm, p = 0.029), a larger vesicourethral angle (153.80° vs. 107.58°, p < 0.001), the more positive bladder funneling (84.85% vs. 48.28%, p = 0.002) and a special urethral opening sign (45.45% vs. 3.45%, p < 0.001). CONCLUSIONS: Patients with SUI accompanying POP primarily exhibit excessive urethral mobility and a shortened urethral closure. SUI patients with asymptomatic POP mainly show dysfunction of the urethra and bladder neck, characterized by the opening of the urethra and bladder neck and a shortened urethral closure.


Asunto(s)
Defecografía , Imagen por Resonancia Magnética , Prolapso de Órgano Pélvico , Incontinencia Urinaria de Esfuerzo , Humanos , Incontinencia Urinaria de Esfuerzo/diagnóstico por imagen , Prolapso de Órgano Pélvico/diagnóstico por imagen , Prolapso de Órgano Pélvico/complicaciones , Femenino , Persona de Mediana Edad , Anciano , Adulto
2.
HIV Med ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38770643

RESUMEN

OBJECTIVE: The objective of this study was to gain insight into the barriers hindering the use of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) in five cities in China. METHODS: MSM were recruited via community-based organizations in an online "snowball" manner. Participants completed the questionnaire anonymously and shared it with key MSM peers (seeds) in five cities in China. Based on the results of univariate analysis, we used a structural equation model to analyse the role of PrEP knowledge awareness, PrEP counselling, and other behavioural variables on PrEP use. RESULTS: The study collected a total of 4223 valid questionnaires, and 18.2% of participants reported PrEP use. The results of the standardized total effects showed that the following paths were statistically significant (p < 0.05): from the age of first sex with men to PrEP knowledge awareness (ß = -0.113) and PrEP use (ß = 0.042); from high-risk sexual behaviour scores to PrEP counselling (ß = 0.039) and PrEP use (ß = 0.103); from the number of HIV tests in the last year to PrEP knowledge awareness (ß = 0.034), PrEP counselling (ß = 0.170), and PrEP use (ß = 0.197); from the level of self-perceived risk of HIV infection to PrEP counselling (ß = -0.115); from PrEP knowledge awareness to PrEP use (ß = -0.049); and from PrEP counselling to PrEP use (ß = 0.420). CONCLUSIONS: The proportion of PrEP use among MSM was relatively low. Age at first sex with men, number of HIV tests, high-risk sexual behaviour, and PrEP counselling had a positive effect on PrEP use, whereas PrEP knowledge awareness had an inverse effect on PrEP use.

3.
Environ Sci Ecotechnol ; 21: 100411, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38746776

RESUMEN

Recent advancements in constructed wetlands (CWs) have highlighted the imperative of enhancing nitrogen (N) removal efficiency. However, the variability in influent substrate concentrations presents a challenge in optimizing N removal strategies due to its impact on removal efficiency and mechanisms. Here we show the interplay between influent substrate concentration and N removal processes within integrated vertical-flow constructed wetlands (IVFCWs), using wastewaters enriched with NO3--N and NH4+-N at varying carbon to nitrogen (C/N) ratios (1, 3, and 6). In the NO3--N enriched systems, a positive correlation was observed between the C/N ratio and total nitrogen (TN) removal efficiency, which markedly increased from 13.46 ± 2.23% to 87.00 ± 2.37% as the C/N ratio escalated from 1 to 6. Conversely, in NH4+-N enriched systems, TN removal efficiencies in the A-6 setup (33.69 ± 4.83%) were marginally 1.25 to 1.29 times higher than those in A-3 and A-1 systems, attributed to constraints in dissolved oxygen (DO) levels and alkalinity. Microbial community analysis and metabolic pathway assessment revealed that anaerobic denitrification, microbial N assimilation, and dissimilatory nitrate reduction to ammonium (DNRA) predominated in NO3--N systems with higher C/N ratios (C/N ≥ 3). In contrast, aerobic denitrification and microbial N assimilation were the primary pathways in NH4+-N systems and low C/N NO3--N systems. A mass balance approach indicated denitrification and microbial N assimilation contributed 4.12-47.12% and 8.51-38.96% in NO3--N systems, respectively, and 0.55-17.35% and 7.83-33.55% in NH4+-N systems to TN removal. To enhance N removal, strategies for NO3--N dominated systems should address carbon source limitations and electron competition between denitrification and DNRA processes, while NH4+-N dominated systems require optimization of carbon utilization pathways, and ensuring adequate DO and alkalinity supply.

4.
Artículo en Inglés | MEDLINE | ID: mdl-38641052

RESUMEN

PURPOSE: To identify the predictors of infectious disease-specific health literacy (IDSHL), and establish an easy-to-apply nomogram to predict the IDSHL of older adults. METHODS: This cross-sectional study included 380 older adults who completed the IDSHL, self-rated health, sociodemographic and other questionnaires. Logistic regression was used to identify the IDSHL predictors. Nomogram was used to construct a predictive model. RESULTS: Up to 70.1% of older adults had limited IDSHL. Age, education, place of residence, self-rated health, and Internet access were the important influencing factors of IDSHL. The established nomogram model showed high accuracy (receiver operating characteristic curve: 0.848). CONCLUSIONS: The IDSHL of Chinese older adults was significantly deficient. The constructed nomogram is an intuitive tool for IDSHL prediction that can not only contribute towards rapid screening of high-risk older adults with limited IDSHL but also provide guidance for healthcare providers to develop prevention strategies for infectious diseases.

5.
J Hazard Mater ; 470: 134259, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38626687

RESUMEN

Seeking for a safe, efficient, inexpensive, and eco-friendly oxidizer is always a big challenge for in-situ chemical oxidation (ISCO) technology. This study adopted the potassium peroxoborate (PPB), a novel peroxide, for soil remediation for the first time. PPB based chemical oxidation system (PPB-CO) could efficiently degrade polycyclic aromatic hydrocarbons (PAHs) without other reagents added, reaching 72.1 %, 64.2 %, and 50.0 % removal rates for naphthalene, phenanthrene, and pyrene after 24 h reaction, respectively. The superior total PAHs removal efficiency (60.6 %) was 3.6-4.7 times higher than that of other commercial peroxides (2Na2CO3•3H2O, CaO2, and H2O2). Mechanism analysis revealed that varieties of reactive oxygen species (ROS) can be generated by PPB through Fenton-like or non-Fenton routines, including H2O2, perborates species, O2•-, •OH, and 1O2. The sustainable generation of H2O2 reduced the disproportionation effect of H2O2 by 86 %, significantly improving the utilization rate. Moreover, sandbox experiments and actual contaminated soil remediation experiments verified the feasibility of PPB-CO in a real polluted site. This work provides a novel strategy for effectively soil remediation, highlighting the selection and application of new oxidants.

6.
Nat Commun ; 15(1): 3061, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594238

RESUMEN

Radiation mapping has attracted widespread research attention and increased public concerns on environmental monitoring. Regarding materials and their configurations, radiation detectors have been developed to identify the position and strength of the radioactive sources. However, due to the complex mechanisms of radiation-matter interaction and data limitation, high-performance and low-cost radiation mapping is still challenging. Here, we present a radiation mapping framework using Tetris-inspired detector pixels. Applying inter-pixel padding for enhancing contrast between pixels and neural networks trained with Monte Carlo (MC) simulation data, a detector with as few as four pixels can achieve high-resolution directional prediction. A moving detector with Maximum a Posteriori (MAP) further achieved radiation position localization. Field testing with a simple detector has verified the capability of the MAP method for source localization. Our framework offers an avenue for high-quality radiation mapping with simple detector configurations and is anticipated to be deployed for real-world radiation detection.

7.
Int J Biol Macromol ; 268(Pt 1): 131583, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38621554

RESUMEN

This study evaluated the foaming properties, the dynamic adsorption behavior at the air/water (A/W) interface and the foam rheological characteristics of complexes formed by soy protein isolate (SPI) and different charged polysaccharides, including chitosan (CS), guar gum (GUG) and gellan gum (GEG). The results showed that the SPI/CS10 had the highest initial foam volume (26.67 mL), which were 3.89 %, 100.08 % and 70.19 % higher than that of single SPI, SPI/GUG and SPI/GEG complexes, respectively. Moreover, three charged polysaccharides could all significantly improve the foam stability of complexes. Among them, foams stabilized by SPI/GEG10 were the most stable that the foam volume slightly changed (approximately 1 mL) and no drainage occurred throughout the whole recording process. The interfacial behavior analysis showed that SPI/CS10 had higher diffusion (Kdiff) and rearrangement rate (KR) but lower penetration rate (KP) at the A/W interface compared with single SPI, while SPI/GUG10 and all SPI/GEG complexes showed higher KR and KP but lower Kdiff. In addition, SPI/CS10 was beneficial to concurrently enhance the elastic strength and solid-like behavior of foam system, while all SPI/GEG complexes could improve the elastic strength of foam system but was not conducive to the solid-like behavior.


Asunto(s)
Aire , Polisacáridos , Reología , Proteínas de Soja , Agua , Proteínas de Soja/química , Agua/química , Polisacáridos/química , Gomas de Plantas/química , Galactanos/química , Polisacáridos Bacterianos/química , Quitosano/química , Adsorción , Mananos/química
8.
Environ Sci Ecotechnol ; 21: 100418, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38638606

RESUMEN

Urban surface water pollution poses significant threats to aquatic ecosystems and human health. Conventional nitrogen removal technologies used in urban surface water exhibit drawbacks such as high consumption of carbon sources, high sludge production, and focus on dissolved oxygen (DO) concentration while neglecting the impact of DO gradients. Here, we show an ecological filter walls (EFW) that removes pollutants from urban surface water. We utilized a polymer-based three-dimensional matrix to enhance water permeability, and emergent plants were integrated into the EFW to facilitate biofilm formation. We observed that varying aeration intensities within the EFW's aerobic zone resulted in distinct DO gradients, with an optimal DO control at 3.19 ± 0.2 mg L-1 achieving superior nitrogen removal efficiencies. Specifically, the removal efficiencies of total organic carbon, total nitrogen, ammonia, and nitrate were 79.4%, 81.3%, 99.6%, and 79.1%, respectively. Microbial community analysis under a 3 mg L-1 DO condition revealed a shift in microbial composition and abundance, with genera such as Dechloromonas, Acinetobacter, unclassified_f__Comamonadaceae, SM1A02 and Pseudomonas playing pivotal roles in carbon and nitrogen elimination. Notably, the EFW facilitated shortcut nitrification-denitrification processes, predominantly contributing to nitrogen removal. Considering low manufacturing cost, flexible application, small artificial trace, and good pollutant removal ability, EFW has promising potential as an innovative approach to urban surface water treatment.

9.
J Sci Food Agric ; 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38591735

RESUMEN

BACKGROUND: Recently, peptides have been studied in Caenorhabditis elegans for anti-aging research. Due to the lack of sufficient evidence, we conducted this meta-analysis focusing on the anti-aging effect of peptides in C. elegans to provide more convincing evidence. RESULTS: A literature search in PubMed, SCOUPUS, and Web of Science databases yielded 2879 articles. After removing duplicates and based on inclusion criteria and STAIR checklist quality assessment, nine articles were selected. Data extraction and analysis showed that, compared to the control group without peptide intervention, peptide supplementation significantly reduced nematode mortality risk [hazard ratio = 0.54, 95% confidence interval (CI) = 0.47, 0.62; P < 0.05], significantly increased the pharyngeal pumping rate [standardized mean difference (SMD) = 1.64, 95% CI = 0.87, 2.41; P < 0.05], bending frequency (SMD = 1.67, 95% CI = 1.16, 2.18; P < 0.05), and significantly decreased the accumulation of lipofuscin levels within nematodes (SMD = -4.48, 95% CI = -6.85, -2.12; P < 0.05). Additionally, subgroup analysis showed that doses ranging from 0.1 to 1 mg/mL (HR = 0.50, 95% CI = 0.38, 0.65; P < 0.05) displayed better anti-aging effects compared to other dose ranges. CONCLUSION: The findings suggest that peptides can significantly extend the lifespan of C. elegans under normal circumstances and improve three indicators of healthy life. More importantly, subgroup analysis revealed that a dosage of 0.1-1 mg/mL demonstrated superior anti-aging effects. This meta-analysis provides more convincing evidence that peptides can play an anti-aging role in C. elegans. © 2024 Society of Chemical Industry.

10.
Front Immunol ; 15: 1334109, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38481996

RESUMEN

Background: As a damage-associated molecular pattern protein, high mobility group box 1 (HMGB1) is associated with kidney and systemic inflammation. The predictive and therapeutic value of HMGB1 as a biomarker has been confirmed in various diseases. However, its value in diabetic kidney disease (DKD) remains unclear. Therefore, this study aimed to investigate the correlation between serum and urine HMGB1 levels and DKD progression. Methods: We recruited 196 patients with type 2 diabetes mellitus (T2DM), including 109 with DKD and 87 T2DM patients without DKD. Additionally, 60 healthy participants without T2DM were also recruited as controls. Serum and urine samples were collected for HMGB1 analysis. Simultaneously, tumor necrosis factor receptor superfamily member 1A (TNFR-1) in serum and kidney injury molecule (KIM-1) in urine samples were evaluated for comparison. Results: Serum and urine HMGB1 levels were significantly higher in patients with DKD than in patients with T2DM and healthy controls. Additionally, serum HMGB1 levels significantly and positively correlated with serum TNFR-1 (R 2 = 0.567, p<0.001) and urine KIM-1 levels (R 2 = 0.440, p<0.001), and urine HMGB1 has a similar correlation. In the population with T2DM, the risk of DKD progression increased with an increase in serum HMGB1 levels. Multivariate logistic regression analysis showed that elevated serum HMGB1 level was an independent risk factor for renal function progression in patients with DKD, and regression analysis did not change in the model corrected for multiple variables. The restricted cubic spline depicted a nonlinear relationship between serum HMGB1 and renal function progression in patients with DKD (p-nonlinear=0.007, p<0.001), and this positive effect remained consistent across subgroups. Conclusion: Serum HMGB1 was significantly correlated with DKD and disease severity. When the HMGB1 level was ≥27 ng/ml, the risk of renal progression increased sharply, indicating that serum HMGB1 can be used as a potential biomarker for the diagnosis of DKD progression.


Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Proteína HMGB1 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Biomarcadores , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/metabolismo , Riñón/metabolismo
11.
Int J Biol Macromol ; 264(Pt 2): 130761, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38467213

RESUMEN

Diabetic vascular complications include diabetic macroangiopathy and diabetic microangiopathy. Diabetic microangiopathy is characterised by impaired microvascular endothelial function, basement membrane thickening, and microthrombosis, which may promote renal, ocular, cardiac, and peripheral system damage in diabetic patients. Therefore, new preventive and therapeutic strategies are urgently required. Sirt1, a member of the nicotinamide adenine dinucleotide-dependent histone deacetylase class III family, regulates different organ growth and development, oxidative stress, mitochondrial function, metabolism, inflammation, and aging. Sirt1 is downregulated in vascular injury and microangiopathy. Moreover, its expression and distribution in different organs correlate with age and play critical regulatory roles in oxidative stress and inflammation. This review introduces the background of diabetic microangiopathy and the main functions of Sirt1. Then, the relationship between Sirt1 and different diabetic microangiopathies and the regulatory roles mediated by different cells are described. Finally, we summarize the modulators that target Sirt1 to ameliorate diabetic microangiopathy as an essential preventive and therapeutic measure for diabetic microangiopathy. In conclusion, targeting Sirt1 may be a new therapeutic strategy for diabetic microangiopathy.


Asunto(s)
Diabetes Mellitus , Angiopatías Diabéticas , Humanos , Sirtuina 1/metabolismo , Diabetes Mellitus/metabolismo , Estrés Oxidativo/fisiología , Inflamación
12.
Front Pharmacol ; 15: 1362509, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38515835

RESUMEN

Silicosis is a chronic illness marked by diffuse fibrosis in lung tissue resulting from continuous exposure to SiO2-rich dust in the workplace. The onset and progression of silicosis is a complicated and poorly understood pathological process involving numerous cells and molecules. However, silicosis poses a severe threat to public health in developing countries, where it is the most prevalent occupational disease. There is convincing evidence supporting that innate and adaptive immune cells, as well as their cytokines, play a significant role in the development of silicosis. In this review, we describe the roles of immune cells and cytokines in silicosis, and summarize current knowledge on several important inflammatory signaling pathways associated with the disease, aiming to provide novel targets and strategies for the treatment of silicosis-related inflammation.

13.
J Stroke Cerebrovasc Dis ; 33(5): 107672, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38447783

RESUMEN

OBJECTIVES: The aim was to investigate whether the angiographic demonstration of a cutoff sign on the initial angiogram could predict recanalization and prognosis in acute ischemic stroke patients treated by endovascular thrombectomy. METHODS: The angiographic and clinical data of patients who underwent endovascular treatment from October 2018 to April 2023 were retrospectively reviewed. The pretreatment angiographic appearance of the thrombus's proximal part was assessed and classified as either the cutoff sign (+) or (-). Patients' baseline characteristics and angiographic and clinical outcomes between the two groups were analyzed using propensity score matching. Then, the two commonly used techniques, stent retrieval and contact aspiration, were compared in terms of successful reperfusion and clinical outcome in patients with the cutoff sign. RESULTS: The cutoff sign was observed in 77 (36.2%) of 213 patients. Patients with the cutoff sign were younger and were less likely to have involvement of the anterior circulation. Compared with the cutoff sign (-) group, the cutoff sign (+) group had a significantly longer procedure time (103 versus 80 min, P =0.002) and a lower percentage of 3-month good functional outcomes (18.2% versus 36%, P =0.006). After propensity score matching, the procedure time (100 versus 75 min, P =0.002) and the 3-month good outcome (19.2% versus 41.4%, P =0.004) remained significantly different. No significant differences were observed in the radiological (OR 0.758, 95% CI 0.157 to 3.658; P =0.730) and clinical (OR 0.747, 95% CI 0.147 to 3.787; P =0.725) outcomes between the two techniques. CONCLUSIONS: The cutoff sign might be an unfavorable prognostic indicator in patients undergoing mechanical thrombectomy, and the efficacy of mechanical thrombectomy techniques does not differ in patients positive for the cutoff sign.


Asunto(s)
Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Pronóstico , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/etiología , Estudios Retrospectivos , Resultado del Tratamiento , Angiografía , Trombectomía/efectos adversos , Trombectomía/métodos , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/terapia , Isquemia Encefálica/etiología
14.
J Exp Bot ; 75(8): 2574-2583, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38307018

RESUMEN

Transcriptional regulation is a crucial component of plant adaptation to numerous different stresses; however, its role in how plants adapt to low-boron (B) stress remains unclear. In this study, we show that the C2H2-type transcription factor SENSITIVE TO PROTON RHIZOTOXICITY1 (STOP1) in Arabidopsis is essential for improving plant growth under low-B conditions. STOP1 and the boric acid-channel protein NOD26-LIKE MAJOR INTRINSIC PROTEIN5;1 (NIP5;1) were found to co-localize in root epidermal cells, and STOP1 binds to the 5´-untranslated region of NIP5;1 to activate its expression and enhance B uptake by the roots. Overexpression of STOP1 increased tolerance to low-B stress by up-regulating NIP5;1 transcript levels. Further genetic analyses revealed that STOP1 and NIP5;1 function together in the same pathway to confer low-B tolerance. These results highlight the importance of the STOP1-NIP5;1 module in improving plant growth under low-B conditions.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Transporte Biológico , Boro , Regulación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Raíces de Plantas/genética , Factores de Transcripción/genética
15.
Cell Commun Signal ; 22(1): 114, 2024 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-38347622

RESUMEN

Sirtuins, which are NAD+-dependent class III histone deacetylases, are involved in various biological processes, including DNA damage repair, immune inflammation, oxidative stress, mitochondrial homeostasis, autophagy, and apoptosis. Sirtuins are essential regulators of cellular function and organismal health. Increasing evidence suggests that the development of age-related diseases, including kidney diseases, is associated with aberrant expression of sirtuins, and that regulation of sirtuins expression and activity can effectively improve kidney function and delay the progression of kidney disease. In this review, we summarise current studies highlighting the role of sirtuins in renal diseases. First, we discuss sirtuin family members and their main mechanisms of action. We then outline the possible roles of sirtuins in various cell types in kidney diseases. Finally, we summarise the compounds that activate or inhibit sirtuin activity and that consequently ameliorate renal diseases. In conclusion, targeted modulation of sirtuins is a potential therapeutic strategy for kidney diseases. Video Abstract.


Asunto(s)
Enfermedades Renales , Sirtuinas , Humanos , Sirtuinas/metabolismo , Enfermedades Renales/tratamiento farmacológico , Estrés Oxidativo , Reparación del ADN
16.
Cancer Gene Ther ; 31(4): 586-598, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38267623

RESUMEN

Glutamate-NMDAR receptors (GRINs) have been reported to influence cancer immunogenicity; however, the relationship between GRIN alterations and the response to immune checkpoint inhibitors (ICIs) has not been determined. This study combined clinical characteristics and mutational profiles from multiple cohorts to form a discovery cohort (n = 901). The aim of this study was to investigate the correlation between the mutation status of the GRIN gene and the response to ICI therapy. Additionally, an independent ICI-treated cohort from the Memorial Sloan Kettering Cancer Center (MSKCC, N = 1513) was used for validation. Furthermore, this study explored the associations between GRIN2A mutations and intrinsic and extrinsic immunity using multiomics analysis. In the discovery cohort, patients with GRIN2A-MUTs had improved clinical outcomes, as indicated by a higher objective response rate (ORR: 36.8% vs 25.8%, P = 0.020), durable clinical benefit (DCB: 55.2% vs 38.7%, P = 0.005), prolonged progression-free survival (PFS: HR = 0.65; 95% CI 0.49 to 0.87; P = 0.003), and increased overall survival (OS: HR = 0.67; 95% CI 0.50 to 0.89; P = 0.006). Similar results were observed in the validation cohort, in which GRIN2A-MUT patients exhibited a significant improvement in overall survival (HR = 0.66; 95% CI = 0.49 to 0.88; P = 0.005; adjusted P = 0.045). Moreover, patients with GRIN2A-MUTs exhibited an increase in tumor mutational burden, high expression of costimulatory molecules, increased activity of antigen-processing machinery, and infiltration of various immune cells. Additionally, gene sets associated with cell cycle regulation and the interferon response were enriched in GRIN2A-mutated tumors. In conclusion, GRIN2A mutation is a novel biomarker associated with a favorable response to ICIs in multiple cancers.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Neoplasias , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Interferones , Mutación , Biomarcadores de Tumor/genética
17.
Se Pu ; 42(1): 75-83, 2024 Jan 08.
Artículo en Chino | MEDLINE | ID: mdl-38197208

RESUMEN

Most preservatives are irritating and can easily induce skin sensitivities. Therefore, both domestic and international regulations impose clear restrictions on the use of preservatives in cosmetics. Herein, gas chromatography-tandem mass spectrometry (GC-MS/MS) was employed to simultaneously analyze the levels of 15 preservative allergens in cosmetics. Further, a precise identification approach based on a two-column retention index and mass spectrometry matching degree was developed. Cosmetic samples were extracted via acetonitrile vortex ultrasound extraction and then dehydrated with anhydrous MgSO4. The preservative allergens were separated on two columns, namely, DB-5MS and DB-WAX. Targets were identified using electron impact ionization (EI) source and the multiple reaction monitoring (MRM) mode and characterized using a retention index calibrated by a series of n-alkane standards. Following two tests, the LODs for the 15 preservative allergens on the DB-5MS column were in the range of 0.02-0.2 mg/kg, while those for 12 preservative allergens on the DB-WAX column were in the range of 0.01-20 mg/kg. The preservative allergens on the DB-5MS and DB-WAX columns demonstrated strong correlations, with all correlation coefficients exceeding 0.99. The recoveries for the 15 preservative allergens were in the range of 70.1%-129.8% at low, medium, and high levels, and the relative standard deviations (RSDs) were all below 15% (n=6) when using water, lotion, facial mask, and cream as the representative matrix. Next, 80 batches of genuine samples were tested using the established method. Isopropyl 4-hydroxybenzoate, a prohibited preservative, was detected in two sample batches using the DB-5MS and DB-WAX columns. Additionally, 11 and 10 restricted preservative allergens were identified on the DB-5MS and DB-WAX columns, respectively. The test results indicate that the double-column system approach offers excellent accuracy, effectively preventing false-positive and false-negative results, and can detect the 15 preservative allergens in cosmetics. The use of the retention index for the qualitative detection of these preservative allergens offers valuable options for non-targeted screening and meeting regulatory criteria.


Asunto(s)
Alérgenos , Cosméticos , Espectrometría de Masas en Tándem , Cromatografía de Gases y Espectrometría de Masas , Alcanos , Conservadores Farmacéuticos
18.
J Ethnopharmacol ; 324: 117721, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38199335

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease and currently there are no specific and effective drugs for its treatment. Podocyte injury is a detrimental feature and the major cause of albuminuria in DN. We previously reported Tangshen Formula (TSF), a Chinese herbal medicine, has shown therapeutic effects on DN. However, the underlying mechanisms remain obscure. AIM OF THE STUDY: This study aimed to explore the protective effect of TSF on podocyte apoptosis in DN and elucidate the potential mechanism. MATERIALS AND METHODS: The effects of TSF were assessed in a murine model using male KKAy diabetic mice, as well as in advanced glycation end products-stimulated primary mice podocytes. Transcription factor EB (TFEB) knockdown primary podocytes were employed for mechanistic studies. In vivo and in vitro studies were performed and results assessed using transmission electron microscopy, immunofluorescence staining, and western blotting. RESULTS: TSF treatment alleviated podocyte apoptosis and structural impairment, decreased albuminuria, and mitigated renal dysfunction in KKAy mice. Notably, TSF extracted twice showed a more significant reduction in proteinuria than TSF extracted three times. Accumulation of autophagic biomarkers p62 and LC3, and aberrant autophagic flux in podocytes of DN mice were significantly altered by TSF therapy. Consistent with the in vivo results, TSF prevented the apoptosis of primary podocytes exposed to AGEs and activated autophagy. However, the anti-apoptosis capacity of TSF was countered by the autophagy-lysosome inhibitor chloroquine. We found that TSF increased the nuclear translocation of TFEB in diabetic podocytes, and thus upregulated transcription of its several autophagic target genes. Pharmacological activation of TFEB by TSF accelerated the conversion of autophagosome to autolysosome and lysosomal biogenesis, further augmented autophagic flux. Conversely, TFEB knockdown negated the favorable effects of TSF on autophagy in AGEs-stimulated primary podocytes. CONCLUSIONS: These findings indicate TSF appears to attenuate podocyte apoptosis and promote autophagy in DN via the TFEB-mediated autophagy-lysosome system. Thus, TSF may be a therapeutic candidate for DN.


Asunto(s)
Diabetes Mellitus Experimental , Nefropatías Diabéticas , Medicamentos Herbarios Chinos , Podocitos , Ratones , Masculino , Animales , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/prevención & control , Nefropatías Diabéticas/metabolismo , Albuminuria/tratamiento farmacológico , Albuminuria/prevención & control , Albuminuria/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Autofagia , Apoptosis , Lisosomas/metabolismo
19.
Small ; : e2308748, 2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38282458

RESUMEN

The upconversion luminescence (UCL) in the second near-infrared window (NIR-II) is highly attractive due to its excellent performance in high-resolution bioimaging, anticounterfeiting, and temperature sensing. However, upconvertion nanoparticles (UCNPs) are normally emitted in visible light, potentially impacting the imaging quality. Here, a monochromatic Er3+ -rich (NaErF4 :x%Yb@NaYF4 ) nanoparticles with excitation at 1532 nm and emission at 978 nm is proposed, both situated in the NIR-II region. The proper proportion of Yb3+ ions doping has a positive effect on the NIR-II emission, by enhancing the cross relaxation efficiency and accelerating the energy transfer rate. Owing to the interaction between the Er3+ and Yb3+ is inhibited at low temperatures, the UCL emission intensities at visible and NIR-II regions show opposite trend with temperature changing, which establishes a fitting formula to derive temperature from the luminous intensity ratio, promoting the potential application of UCL in NIR-II regions for the temperature sensing.

20.
Int Urol Nephrol ; 56(1): 155-166, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37422767

RESUMEN

PURPOSE: To evaluate the key topics and emerging trends in the field of cardiorenal syndrome type 4 (CRS-4) by bibliometrics and visual analysis. METHODS: Citespace, VOSviewer, and Bibliometrix package were used to analyze the collected data from the Web of Science Core Collection, including publication trends, leading countries, active authors and institutions, co-cited references, journals, and keyword analysis. RESULTS: Finally, 2267 articles were obtained. From 2004 to 2022, the number of publications was increasing year by year. A total of 735 authors from 543 institutions in 94 countries/regions participated in the publication of CRS-4 field, which were mostly from North America and Europe. Most of the co-cited references were reviews or guidelines from kidney/heart specialist journals or top journals. The journals concerning nephrology had a higher academic influence in this field. Oxidative stress and inflammation remained hot topics in CRS-4 research, as well as uremic toxins. Fibroblast growth factor 23 and klotho were emerging trends in recent years. Sodium glucose cotransporter 2 (SGLT2) inhibitors were the latest frontier hot spots. Future research advances may pay more attention to the prevention and prognosis assessment of CRS-4. CONCLUSION: Our study provides some key information for scholars to determine the direction of future research.


Asunto(s)
Síndrome Cardiorrenal , Humanos , Síndrome Cardiorrenal/terapia , Bibliometría , Riñón , Corazón , Europa (Continente)
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...