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2.
J Phys Chem B ; 128(15): 3585-3597, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38593280

RESUMEN

Super-resolution and single-molecule microscopies have been increasingly applied to complex biological systems. A major challenge of these approaches is that fluorescent puncta must be detected in the low signal, high noise, heterogeneous background environments of cells and tissue. We present RASP, Radiality Analysis of Single Puncta, a bioimaging-segmentation method that solves this problem. RASP removes false-positive puncta that other analysis methods detect and detects features over a broad range of spatial scales: from single proteins to complex cell phenotypes. RASP outperforms the state-of-the-art methods in precision and speed using image gradients to separate Gaussian-shaped objects from the background. We demonstrate RASP's power by showing that it can extract spatial correlations between microglia, neurons, and α-synuclein oligomers in the human brain. This sensitive, computationally efficient approach enables fluorescent puncta and cellular features to be distinguished in cellular and tissue environments, with sensitivity down to the level of the single protein. Python and MATLAB codes, enabling users to perform this RASP analysis on their own data, are provided as Supporting Information and links to third-party repositories.


Asunto(s)
Encéfalo , Humanos
3.
Sci Total Environ ; 927: 172276, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38583634

RESUMEN

The increases in extent and frequency of extreme drought events and increased nitrogen (N) deposition due to global change are expected to have profound impacts on carbon cycling in semi-arid grasslands. However, how ecosystem CO2 exchange processes respond to different drought scenarios individually and interactively with N addition remains uncertain. In this study, we experimentally explored the effects of different drought scenarios (early season extreme drought, 50 % reduction in precipitation amount, and 50 % reduction in precipitation events) and N addition on net ecosystem CO2 exchange (NEE), ecosystem respiration (ER), and gross ecosystem productivity (GEP) over three growing seasons (2019-2021) in a semi-arid grassland in northern China. The growing-season ecosystem carbon fluxes in response to drought and N addition were influenced by inter-annual precipitation changes, with 2019 as a normal precipitation year, and 2020 and 2021 as wet years. Early season extreme drought stimulated NEE by reducing ER. 50 % reduction in precipitation amount decreased ER and GEP consistently in three years, but only significantly suppressed NEE in 2019. 50 % reduction in precipitation events stimulated NEE. Nitrogen addition stimulated NEE, ER, and GEP, but only significantly in wet years. The structural equation models showed that changes in carbon fluxes were regulated by soil moisture, soil temperature, microbial biomass nitrogen (MBN), and the key plant functional traits. Decreased community-weighted means of specific leaf area (CWMSLA) was closely related to the reduced ER and GEP under early season extreme drought and 50 % reduction in precipitation amount. While increased community-weighted means of plant height (CWMPH) largely accounted for the stimulated ER and GEP under 50 % reduction in precipitation events. Our study stresses the distinct effects of different drought scenarios and N enrichment on carbon fluxes, and highlights the importance of soil traits and the key plant traits in determining carbon exchange in this water-limited ecosystem.


Asunto(s)
Ciclo del Carbono , Sequías , Pradera , Nitrógeno , Nitrógeno/análisis , China , Lluvia , Cambio Climático , Ecosistema , Carbono/metabolismo , Estaciones del Año
4.
Ecol Appl ; : e2969, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38562107

RESUMEN

Drought and nitrogen enrichment could profoundly affect the productivity of semiarid ecosystems. However, how ecosystem productivity will respond to different drought scenarios, especially with a concurrent increase in nitrogen availability, is still poorly understood. Using data from a 4-year field experiment conducted in a semiarid temperate steppe, we explored the responses of aboveground net primary productivity (ANPP) to different drought scenarios and nitrogen addition, and the underlying mechanisms linking soil properties, plant species richness, functional diversity (community-weighted means of plant traits, functional dispersion) and phylogenetic diversity (net relatedness index) to ANPP. Our results showed that completely excluding precipitation in June (1-month intense drought) and reducing half the precipitation amount from June to August (season-long chronic drought) both significantly reduced ANPP, with the latter having a more negative impact on ANPP. However, reducing half of the precipitation frequency from June to August (precipitation redistribution) had no significant effect on ANPP. Nitrogen addition increased ANPP irrespective of drought scenarios. ANPP was primarily determined by soil moisture and nitrogen availability by regulating the community-weighted means of plant height, rather than other aspects of plant diversity. Our findings suggest that precipitation amount is more important than precipitation redistribution in influencing the productivity of temperate steppe, and nitrogen supply could alleviate the adverse impacts of drought on grassland productivity. Our study advances the mechanistic understanding of how the temperate grassland responds to drought stress, and implies that management strategies to protect tall species in the community would be beneficial for maintaining the productivity and carbon sequestration of grassland ecosystems under climate drought.

5.
Artículo en Inglés | MEDLINE | ID: mdl-38568771

RESUMEN

The pathogenesis of Alzheimer's disease (AD) is extremely intricate, which makes AD patients almost incurable. Recent studies have demonstrated that analyzing multi-modal data can offer a comprehensive perspective on the different stages of AD progression, which is beneficial for early diagnosis of AD. In this paper, we propose a deep self-reconstruction fusion similarity hashing (DS-FSH) method to effectively capture the AD-related biomarkers from the multi-modal data and leverage them to diagnose AD. Given that most existing methods ignore the topological structure of the data, a deep self-reconstruction model based on random walk graph regularization is designed to reconstruct the multi-modal data, thereby learning the nonlinear relationship between samples. Additionally, a fused similarity hash based on anchor graph is proposed to generate discriminative binary hash codes for multi-modal reconstructed data. This allows sample fused similarity to be effectively modeled by a fusion similarity matrix based on anchor graph while modal correlation can be approximated by Hamming distance. Especially, extracted features from the multi-modal data are classified using deep sparse autoencoders classifier. Finally, experiments conduct on the AD Neuroimaging Initiative database show that DS-FSH outperforms comparable methods of AD classification. To conclude, DS-FSH identifies multi-modal features closely associated with AD, which are expected to contribute significantly to understanding of the pathogenesis of AD.

6.
J Sep Sci ; 47(2): e2300788, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38286727

RESUMEN

Fufang Xiling Jiedu capsule (FXJC), a traditional Chinese medicine that evolved from "Yinqiao Powder", is widely used for the treatment of cold and influenza. However, due to a lack of in vivo metabolism research, the chemical components responsible for the therapeutic effects still remain unclear. Hence, this study aimed to describe the metabolic profiles of the FXJC in rat plasma, urine, and feces. A combined data mining strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was employed and 201 xenobiotics, including 117 prototype components and 84 metabolites were detected. Phenolic acids, flavonoids, triterpenes, and lignans were prominent ingredients absorbed in vivo, and the major metabolic pathways of the detected metabolites were glucuronidation, sulfation, methylation, and oxidation. This is the first systematic study on the metabolism of the FXJC in vivo, providing valuable information for future studies on the efficacy, toxicity, and mechanism of the FXJC.


Asunto(s)
Medicamentos Herbarios Chinos , Espectrometría de Masas en Tándem , Ratas , Animales , Espectrometría de Masas en Tándem/métodos , Ratas Sprague-Dawley , Cromatografía Líquida de Alta Presión/métodos , Administración Oral , Medicamentos Herbarios Chinos/análisis , Metaboloma
7.
Asian J Androl ; 2023 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-37788012

RESUMEN

ABSTRACT: The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining spermatogenesis. The single-cell RNA sequencing (scRNA-seq) analysis of the testis was performed to identify genes upregulated in spermatogonia. Using scRNA-seq analysis, we identified the spermatogonia upregulated gene origin recognition complex subunit 6 (Orc6), which is involved in DNA replication and cell cycle regulation; its protein expression in the human and mouse testis was detected by western blot and immunofluorescence. To explore the potential function of Orc6 in spermatogonia, the C18-4 cell line was transfected with control or Orc6 siRNA. Subsequently, 5-ethynyl-2-deoxyuridine (EdU) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, flow cytometry, and western blot were used to evaluate its effects on proliferation and apoptosis. It was revealed that ORC6 could promote proliferation and inhibit apoptosis of C18-4 cells. Bulk RNA sequencing and bioinformatics analysis indicated that Orc6 was involved in the activation of wingless/integrated (Wnt)/ ß-catenin signaling. Western blot revealed that the expression of ß-catenin protein and its phosphorylation (Ser675) were significantly decreased when silencing the expression of ORC6. Our findings indicated that Orc6 was upregulated in spermatogonia, whereby it regulated proliferation and apoptosis by activating Wnt/ß-catenin signaling.

8.
Chem Commun (Camb) ; 59(89): 13305-13308, 2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-37859456

RESUMEN

The high activity of the In2O3/In2S3 heterostructure can be activated into homogeneous In2OxS3-x nanodots, thereupon stabilizing the subsequent cycles. The In2O3/In2S3 can offer a high capacity of 1140 mA h g-1 at 0.1 A g-1 after 290 cycles, and even at 1 A g-1, it harvests a reversible capacity of 900 mA h g-1 after 600 cycles.

9.
Asian J Androl ; 25(6): 662-673, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37202929

RESUMEN

Klinefelter syndrome (KS) is the most common genetic cause of human male infertility. However, the effect of the extra X chromosome on different testicular cell types remains poorly understood. Here, we profiled testicular single-cell transcriptomes from three KS patients and normal karyotype control individuals. Among the different somatic cells, Sertoli cells showed the greatest transcriptome changes in KS patients. Further analysis showed that X-inactive-specific transcript ( XIST ), a key factor that inactivates one X chromosome in female mammals, was widely expressed in each testicular somatic cell type but not in Sertoli cells. The loss of XIST in Sertoli cells leads to an increased level of X chromosome genes, and further disrupts their transcription pattern and cellular function. This phenomenon was not detected in other somatic cells such as Leydig cells and vascular endothelial cells. These results proposed a new mechanism to explain why testicular atrophy in KS patients is heterogeneous with loss of seminiferous tubules but interstitial hyperplasia. Our study provides a theoretical basis for subsequent research and related treatment of KS by identifying Sertoli cell-specific X chromosome inactivation failure.


Asunto(s)
Síndrome de Klinefelter , Células de Sertoli , Animales , Humanos , Masculino , Femenino , Células de Sertoli/metabolismo , Síndrome de Klinefelter/genética , Células Endoteliales , Testículo/metabolismo , Cromosoma X/metabolismo , Mamíferos/genética
10.
Asian J Androl ; 25(6): 725-730, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37040217

RESUMEN

This study aimed to evaluate the ability of rete testis thickness (RTT) and testicular shear wave elastography (SWE) to differentiate obstructive azoospermia (OA) from nonobstructive azoospermia (NOA). We assessed 290 testes of 145 infertile males with azoospermia and 94 testes of 47 healthy volunteers at Shanghai General Hospital (Shanghai, China) between August 2019 and October 2021. The testicular volume (TV), SWE, and RTT were compared among patients with OA and NOA and healthy controls. The diagnostic performances of the three variables were evaluated using the receiver operating characteristic curve. The TV, SWE, and RTT in OA differed significantly from those in NOA (all P ≤ 0.001) but were similar to those in healthy controls. Males with OA and NOA were similar at TVs of 9-11 cm 3 ( P = 0.838), with sensitivity, specificity, Youden index, and area under the curve of 50.0%, 84.2%, 0.34, and 0.662 (95% confidence interval [CI]: 0.502-0.799), respectively, for SWE cut-off of 3.1 kPa; and 94.1%, 79.2%, 0.74, and 0.904 (95% CI: 0.811-0.996), respectively, for RTT cut-off of 1.6 mm. The results showed that RTT performed significantly better than SWE in differentiating OA from NOA in the TV overlap range. In conclusion, ultrasonographic RTT evaluation proved a promising diagnostic approach to differentiate OA from NOA, particularly in the TV overlap range.


Asunto(s)
Azoospermia , Masculino , Humanos , Red Testicular , China , Testículo
11.
Asian J Androl ; 2023 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-36861503

RESUMEN

Stepwise mini-incision microdissection testicular sperm extraction (mTESE) is a procedure that attempts to minimize testicular damage. However, the mini-incision approach may vary in patients with different etiologies. Here, we performed a retrospective analysis of 665 men with nonobstructive azoospermia (NOA) who underwent stepwise mini-incision mTESE (Group 1) and 365 men who underwent standard mTESE (Group 2). The results showed that the operation time (mean ± standard deviation) for patients with successful sperm retrieval in Group 1 (64.0 ± 26.6 min) was significantly shorter than that in Group 2 (80.2 ± 31.3 min), with P <0.001. The total sperm retrieval rate (SRR) was 23.1% in our study, and there was no significant difference between Group 1 and Group 2 ( P >0.05), even when the etiologies of NOA were taken into consideration. The results of consecutive multivariate logistic regression analysis (odds ratio [OR]: 0.57; 95% confidence interval [CI]: 0.38-0.87; P =0.009) and receiver operating characteristic (ROC) analysis (area under the ROC curve [AUC]=0.628) showed that preoperative anti-Müllerian hormone (AMH) level in idiopathic NOA patients was a potential predictor for surgical outcomes after initial three small incisions made in the equatorial region without sperm examined under an operating microscope (Steps 2-4). In conclusion, stepwise mini-incision mTESE is a useful technique for NOA patients, with comparable SRR, less surgical invasiveness, and shorter operation time compared with the standard approach. Low AMH levels may predict successful sperm retrieval in idiopathic patients even after a failed initial mini-incision procedure.

12.
Asian J Androl ; 25(1): 73-77, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35381699

RESUMEN

Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA. From December 2015 to December 2020, 33 patients were diagnosed as CUAVD with OA in Shanghai General Hospital (Shanghai, China). Patient information, ultrasound findings, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Of 33 patients, 29 patients were retrospectively analyzed. Vasoepididymostomy (VE) or cross VE was performed in 12 patients, the patency rate was 41.7% (5/12), and natural pregnancy was achieved in one of the patients. The other 17 patients underwent testicular sperm extraction as the distal vas deferens (contralateral side) was obstructed. These findings showed that VE or cross VE remains an alternative treatment for CUAVD patients with OA, even with a relatively low rate of patency and natural pregnancy.


Asunto(s)
Azoospermia , Conducto Deferente , Embarazo , Femenino , Humanos , Masculino , Conducto Deferente/cirugía , Conducto Deferente/anomalías , Azoospermia/cirugía , Epidídimo/cirugía , Estudios Retrospectivos , Centros de Atención Terciaria , China , Semen
13.
J Voice ; 2022 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-36460539

RESUMEN

OBJECTIVE: To investigate the consistency between the Reflux Symptom Score-12 (RSS-12) and Reflux Symptom Index (RSI) in Chinese people. METHODS: Patients with symptoms of LPR from the outpatient otorhinolaryngology-head and neck surgery clinic were included. All included patients completed the RSS-12 and RSI. The patient with RSS-12>11 or RSI>13 suggested possible LPR. For the patients with RSI >13 or RSS-12>11, they were treated using diet recommendations and were prescribed a twice-daily pantoprazole for 12 weeks. The consistency between the RSS-12 and RSI was compared with the weighted Cohen's kappa statistic. RESULTS: A total of 258 patients were included. The mean scores for RSS-12 and RSI were 13.21±17.31 and 12.86±6.15, respectively. The positive rate of LPR was 17.44% based on the RSI, and 24.42% based on the RSS-12. The kappa value between the RSS-12 and RSI was 0.736 (P < 0.001). Following 12 weeks of treatment, there was a significant reduction in both RSI and RSS-12. Based on the RSI, 73% of patients had a good treatment response, whereas according to the RSS-12, 85% of patients had a good treatment response. CONCLUSION: There is a good consistency between RSS-12 and RSI, meaning that the RSS-12 is a feasible LPR initial screening tool. The RSS-12 provides a more comprehensive evaluation of reflux symptoms and treatment effect than RSI in patients with LPR.

14.
J Org Chem ; 87(18): 12460-12469, 2022 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-36067376

RESUMEN

A high efficiency protocol was developed for the synthesis of 2,5-disubstituted oxazoles via iodine-promoted oxidative domino cyclization. These reactions were performed with readily available methyl azaarenes and α-amino ketones under metal-free conditions. This protocol is a simple method with high functional group compatibility, a wide range of substrates, and excellent yield, providing a new way to synthesize azaarene-attached oxazoles.


Asunto(s)
Yodo , Cetonas , Catálisis , Yoduros , Estructura Molecular , Oxazoles , Estrés Oxidativo
15.
Front Endocrinol (Lausanne) ; 13: 828162, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35418951

RESUMEN

The highly prevalent cognitive impairment in hemodialysis patients is associated with all-cause mortality; however, the role of different cognitive domain impairments in this association is still not clarified. Our objective was to determine the association between cognitive domain impairment and all-cause mortality in elderly adult patients undergoing hemodialysis. We conducted a prospective cohort study including patients from 11 hemodialysis centers in Beijing. Baseline data were collected, and a series of neuropsychological batteries covering 5 domains of cognitive function were included for the assessment of cognitive function. According to the fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria (DSM-V), the patients were classified as normal, mild, and major cognitive impairment for global and domain cognitive function, then followed up for 1 year. Kaplan-Meier survival analysis was used to compare the difference in the cumulative survival rate in different cognitive domains. A multivariate Cox proportional hazards regression analysis was used to determine the association between global or domain cognitive impairment and all-cause mortality. A total of 613 patients were enrolled, the mean age was 63.82 ± 7.14 years old, and 42.1% were women. After 49.53 ± 8.42 weeks of follow-up, 69 deaths occurred. Kaplan-Meier plots demonstrated a significant association of cognitive impairment in memory, executive function, attention, and language domains with all-cause death. Multivariate Cox regression analysis showed that mild and major impairment of global cognition (HR = 2.89 (95% CI, 1.01-8.34), p = 0.049 and HR = 4.35 (95% CI, 1.55-12.16), p = 0.005, respectively), executive cognitive domain (HR = 2.51 (95% CI, 1.20-5.24), p = 0.014; HR = 3.91 (95% CI, 1.70-9.03), p = 0.001, respectively), and memory cognitive domain (HR = 2.13 (95% CI, 1.07-4.24), p = 0.031; HR = 3.67 (95% CI, 1.71-7.92), p = 0.001, respectively) were associated with all-cause mortality. Combined impairment of 3, 4, and 5 cognitive domains was associated with all-cause mortality [HR = 5.75 (95% CI, 1.88-17.57), p = 0.002; HR = 12.42 (95% CI, 3.69-41.80), p < 0.001; HR = 13.48 (95% CI, 3.38-53.73), p < 0.001, respectively]. We demonstrate an association between the executive and memory cognitive domain impairment and all-cause mortality in hemodialysis patients. Our data suggest that the impairments in these cognitive domains might help in the early identification of hemodialysis patients at risk of death.


Asunto(s)
Disfunción Cognitiva , Adulto , Anciano , Cognición , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Función Ejecutiva , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Diálisis Renal/psicología
16.
Clin Interv Aging ; 17: 265-275, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35313671

RESUMEN

Purpose: The study aimed to determine the prevalence and risk factors of frailty among a Chinese cohort of hemodialysis patients and to assess the degree to which frailty was associated with all-cause mortality. Participants and Methods: We enrolled a group of older adults (≥60 years old) in a prospective cohort study of cognitive impairment in Chinese patients undergoing hemodialysis (registered in Clinical Trials.gov, ID: NCT03251573). We assessed the prevalence of frailty using Fried's definition in the Cardiovascular Health Study, then we evaluated the associated risk factors of frailty using multivariate logistic regression analysis. Finally, we assessed the association of frailty and all-cause mortality with multivariable Cox proportional hazard regression analyses. Results: The prevalence of frailty in these 204 enrolled hemodialysis patients was 72.1%. Patients with frailty were more inclined to have composite abnormal components that included poor physical functioning, exhaustion, low physical activity, and undernutrition. Multivariable logistic regression analysis suggested that increased age, female gender, history of diabetes, longer dialysis vintage, lower Kt/V, lower serum level of albumin concentrations, and increased serum iPTH concentrations were independently associated with frailty. Cox regression analysis indicated that frailty as a dichotomous construct was strongly associated with an increased risk of mortality (HR 6.092, 95% CI 1.886-19.677, P = 0.003) in unadjusted analyses. After adjusting (Model I = no adjusted; II = adjusted for age, gender; III = adjusted for age, gender, history of diabetes; IV = adjusted for all covariates associated at the p ≤ 0.10 level with death in unadjusted analyses, including age, history of diabetes, MoCA<26, single-pool Kt/V, and the levels of albumin and iPTH), the association was slightly affected but observed consistent as before. Conclusion: Frailty is extremely common and is associated with serious clinical outcomes among older hemodialysis patients. Based on those clinical features of frailty, future studies should focus on exploring effective interventions aimed to prevent or attenuate frailty in the older hemodialysis population.


Asunto(s)
Fragilidad , Diálisis Renal , Anciano , Femenino , Anciano Frágil , Fragilidad/epidemiología , Fragilidad/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
17.
Oncol Rep ; 47(3)2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35059740

RESUMEN

Lung cancer is a common cancer type, and has the highest mortality rate in the world. A genome­wide association study suggests that the genetic marker rs9390123 is significantly associated with DNA repair capacity (DRC) in lung cancer. Analysis of the data derived from the 1000 Genomes Project indicated that there is another single nucleotide polymorphism (SNP), rs9399451, in strong linkage disequilibrium with rs9390123 in Caucasian individuals, thus suggesting that this SNP could be associated with DRC. However, the causal SNP and mechanism of DRC remain unclear. In the present study, dual luciferase assay results indicated that both SNPs are functional in lung cells. Through chromosome conformation capture, an enhancer containing the two functional SNPs was observed to bind the promoter of peroxisomal biogenesis factor 3 and phosphatase and actin regulator 2 antisense RNA 1 (PHACTR2­AS1). Knockdown of PHACTR2­AS1 could significantly influence lung cell proliferation, colony formation, migration and wound healing, which verified that PHACTR2­AS1 is a novel oncogene for lung cancer. Through chromatin immunoprecipitation, the transcription factor POU class 2 homeobox 1 (POU2F1) was identified to bind to the surrounding segments of these two SNPs, and their interaction was investigated. The present study identified the mechanism via which rs9390123 and rs9399451 could influence DRC.


Asunto(s)
Reparación del ADN/genética , Lipoproteínas/genética , Neoplasias Pulmonares/genética , Proteínas de la Membrana/genética , Proteínas de Microfilamentos/genética , Proteínas del Tejido Nervioso/genética , Peroxinas/genética , Polimorfismo de Nucleótido Simple/genética , ARN sin Sentido/genética , Regulación Neoplásica de la Expresión Génica , Estudio de Asociación del Genoma Completo , Humanos , Oncogenes/genética
18.
Ocul Immunol Inflamm ; 30(6): 1449-1459, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33970759

RESUMEN

BACKGROUND: Immune checkpoint inhibitors (ICIs) -induced adverse events (AEs) have been reported affecting almost all human organs. However, studies about ocular AEs are few. A meta-analysis was performed to evaluate the risks of ICI-related ophthalmic AEs compare to chemotherapy.Methods: Eligible studies were selected from phase II/III randomized controlled trials investigating ICIs. The data were analyzed by R software and Stata. RESULTS: Odds ratio of treatment-related AE (trAEs) and nonspecific ophthalmic trAEs (NS-trAEs) were lower for PD-1/PD-L1 inhibitors than chemotherapy (OR 0.44, p < .05; OR 0.28, p < .001; OR 0.18, p < . 05; OR: 0.18, p < .001respectively). Compared with monotherapy, PD-1 plus CTLA-4 inhibitors increased the risks of immune-related AEs (irAEs) (OR 4.52, p < .01); ICIs plus chemotherapy increased the risks of trAEs and irAEs (OR 2.82, p < .001; OR 3.63, p < .05 respectively). CONCLUSIONS: PD-L1/PD-1 inhibitors had lower risks of trAEs and NS-trAEs than chemotherapy; Compared with monotherapy, combination therapy had higher risks of ophthalmic trAEs and irAEs. ABBREVIATION: PD-1: programmed cell death protein 1; PD-L1: programmed cell death protein ligand 1; CTLA-4: cytotoxic T-lymphocyte-associated protein 4; ICI: immune checkpoint inhibitor; AE: adverse event; trAE: treatment-related adverse event;irAE: immune-related adverse events; NS-trAE: nonspecific ophthalmic treatment-related adverse event; RCT: randomized controlled trials; PFS: progression-free survival; OS: overall survival; ORR: objective response rate; MM: melanoma; NSCLC: non-small cell lung cancer; SCLC: small cell lung cancer; HNSCC: head-neck squamous cell carcinoma; PICOL: patient, intervention, comparison, and outcome; Versus: VS; Chem: chemotherapy; 95%CI: 95% confidence interval; FEM: fixed-effects model; REM: random-effects model; NA: not applicable; MeSH: medical subject heading.


Asunto(s)
Antineoplásicos Inmunológicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Receptor de Muerte Celular Programada 1 , Antígeno B7-H1/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Antineoplásicos Inmunológicos/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico
19.
Environ Technol ; 43(20): 3121-3130, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33843481

RESUMEN

The cell membrane permeability, morphology, metabolomics, and gene expression of Microcystis aeruginosa under various concentrations of succinic acid (SA) were evaluated to clarify the mechanism of SA inhibition of M. aeruginosa. The results showed that SA caused intracellular protein and nucleic acid extravasation by increasing the cell membrane permeability. Scanning electron microscopy suggested that a high dose of SA (60 mg L-1) could damage the cell membrane and even cause lysis in some cells. Metabolomics result demonstrated that change in intracellular lipids content was the main reason for the increase of cell membrane permeability. In addition, SA could negatively affect amino acids metabolism, inhibit the biosynthesis of nucleotides, and interfere with the tricarboxylic acid (TCA) cycle of algal cells. Furthermore, SA also affected N assimilation and caused oxidative damage to Microcystis. In conclusion, SA inhibits the growth of M. aeruginosa through multisite action.


Asunto(s)
Microcystis , Expresión Génica , Microcystis/fisiología , Estrés Oxidativo , Ácido Succínico/farmacología
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