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1.
Chem Commun (Camb) ; 60(32): 4266-4274, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38572569

RESUMO

Sodium-ion batteries (SIBs), which have ample reserves and low production costs, are receiving more and more attention. As promising cathode candidates, layered transition metal oxides (LTMOs) have attracted intensive interest for their nontoxicity, high theoretical capacities, ease of manufacture, suitable voltage, abundant resources, and potential low cost. However, the commercial implementation of LTMOs is still hampered by their low rate capability, low energy density, insufficient cycling stability, and air instability. Therefore, this review comprehensively summarizes the research progress and modification strategies for LTMOs to enhance the stability of SIBs from microscopic heterostructure regulation to macroscale interface engineering modification. With the aim of realizing commercial applications of SIBs, more attention and research for improving the coulombic efficiency of LTMOS and close communication between academic and industrial organizations are also needed. It is expected that we will be able to provide unique perspectives for the design of powerful LTMOs in SIBs and guide the development of commercial application.

2.
J Fungi (Basel) ; 10(4)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38667920

RESUMO

Penicillium digitatum is a major postharvest pathogen that threatens the global citrus fruit industry and causes great economic losses annually. In the present study, inhibitory properties of cinnamon bark oil (CBO) against P. digitatum in vitro were investigated. Results indicated that 0.03% CBO could efficiently inhibit the spore germination, germ tube elongation, mycelial growth, colonial expansion and conidial accumulation of P. digitatum. The results of fluorescein diacetate (FDA) and MitoTraker Orange (MTO) staining also proved the suppression effects of CBO against P. digitatum. Meanwhile, CBO could inhibit green mold rots induced by P. digitatum in citrus fruit when the working concentration of CBO exceeded 0.06%. In addition, the expressions of 12 genes critical for the growth and virulence of P. digitatum were also significantly regulated under CBO stress. Through a transcriptomic analysis, a total of 1802 common differentially expressed genes (DEGs) were detected in P. digitatum after 4 h and 8 h of CBO treatment. Most of the DEG products were associated with carbohydrate, amino acid and lipid metabolism. They directly or indirectly led to the disturbance of the membrane and the generation of reactive oxygen species (ROS). Our results may deepen the understanding of antifungal properties of CBO against P. digitatum and provide the theoretical foundation to uncover the antifungal mechanism of CBO at the molecular level.

3.
Heliyon ; 10(3): e24507, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38314308

RESUMO

Background: Tuberculosis continues to be a significant public health concern in China, particularly among the elderly population. This study aimed to assess the risk factors of tuberculosis among elderly individuals in China through a cohort study, focusing on this high-risk population. Methods: The population-based census was strategically designed to cover diverse regions and demographics across the city. The survey captured demographic and lifestyle information, as well as a clinical examination. Participants were prospectively followed up over a specified duration to monitor the incidence of tuberculosis cases. Results: After a follow-up period of more than 7 years, 246 individuals developed tuberculosis, resulting in an incidence rate of 92.21 per 100,000 person-years (95 % CI 81.2-104.3). In multivariate analysis, the following factors were found to have significant associations with active tuberculosis. Increasing age correlated with a higher risk of active tuberculosis (AHR = 1.03 per 1-year increase in age, 95%CI: 1.01, 1.04, P < 0.001). Males continued to have a higher risk compared to females (HR = 2.73, 95%CI: 2.08, 3.58, P < 0.001). Individuals with a normal Body Mass Index (BMI) faced nearly three times higher risk compared to their obese counterparts (HR = 2.87, 95 % CI: 1.51, 5.46, P = 0.001). Conversely, those with an underweight BMI had a ten-fold higher risk compared to the obese group (HR = 9.89, 95 % CI: 4.92, 19.85, P < 0.001). Elderly individuals who quit smoking had a 1.35-fold increased risk compared to non-smokers (HR = 1.35, 95%CI: 1.12, 1.64, P < 0.001). Conclusions: Tuberculosis incidence among the elderly population in China remained alarmingly high. This finding emphasizes the urgent need for implementing proactive case detection measures specifically tailored to address the specific needs of this vulnerable demographic, particularly in individuals who are male, have a history of former or current smoking, and have a low BMI. Moreover, we must not underestimate the influence of former smoking on tuberculosis risk.

4.
Brain Res ; 1827: 148761, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38211826

RESUMO

As an extremely dangerous environmental contaminant, methylmercury (MeHg) results in detrimental health effects in human brain nervous system, one of its main targets. However, as a developmental toxicant, the brain of offspring is vulnerable to MeHg during pregnancy and lactation exposure. Unfortunately, mechanisms of neurodevelopmental injuries induced by MeHg have not been fully elucidated. N-acetylcysteine (NAC) has been used for several decades as an antioxidant to antagonize oxidative stress. However, the molecular mechanisms of NAC alleviating MeHg-induced neurodevelopmental toxicity are not clear. Here, for evaluation of the dose-dependent effects of MeHg exposure on neurodevelopmental injuries of offspring, and the possible protective effects of NAC, the pregnant female mice were exposed to MeHg (4, 8, 12 mg/L, respectively) and NAC (50, 100, 150 mg/kg, respectively) from gestational day 1 (GD1) to postnatal day 21 (PND21). Our results indicated that administering MeHg caused behavioral impairment and neuronal injuries in the cerebral cortex of newborn mice. MeHg dose-dependently caused reactive oxygen species (ROS) overproduction and oxidative stress aggravation, together with expression of Nrf2, HO-1, Notch1, and p21 up-regulation, and CDK2 inhibition. NAC treatment dose-dependently antagonized MeHg-induced oxidative stress that may contribute to alleviating neurobehavioral and neurodevelopmental impairments. These results give insight into that NAC can protect against MeHg-induced neurodevelopmental toxicity by its antioxidation capacity.


Assuntos
Acetilcisteína , Compostos de Metilmercúrio , Humanos , Gravidez , Feminino , Animais , Camundongos , Acetilcisteína/farmacologia , Compostos de Metilmercúrio/toxicidade , Lactação , Antioxidantes/farmacologia , Encéfalo
6.
J Fungi (Basel) ; 9(10)2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37888255

RESUMO

Penicillium expansum is the most popular post-harvest pathogen and causes blue mold disease in pome fruit and leads to significant economic losses worldwide every year. However, the fundamental regulation mechanisms of growth in P. expansum are unclear. Recently, non-coding RNAs (ncRNAs) have attracted more attention due to critical roles in normalizing gene expression and maintaining cellular genotypes in organisms. However, the research related to ncRNAs in P. expansum have not been reported. Therefore, to provide an overview of ncRNAs on composition, distribution, expression changes, and potential targets in the growth process, a comparative transcriptomic analysis was performed on spores and mycelia of P. expansum in the present study. A total of 2595 novel mRNAs, 3362 long non-coding RNAs (lncRNAs), 10 novel microRNAs (miRNAs), 86 novel small interfering RNAs (siRNAs), and 11,238 circular RNAs (circRNAs) were predicted and quantified. Of these, 1482 novel mRNAs, 5987 known mRNAs, 2047 lncRNAs, 40 miRNAs, 38 novel siRNAs, and 9235 circRNAs were differentially expressed (DE) in response to the different development stages. Afterward, the involved functions and pathways of DE RNAs were revealed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database enrichment analysis. The interaction networks between mRNAs, lncRNAs, and miRNAs were also predicted based on their correlation coefficient of expression profiles. Among them, it was found that miR168 family members may play important roles in fungal growth due to their central location in the network. These findings will contribute to a better understanding on regulation machinery at the RNA level on fungal growth and provide a theoretical basis to develop novel control strategies against P. expansum.

7.
Carcinogenesis ; 44(12): 847-858, 2023 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-37787763

RESUMO

OBJECTIVES: To explore the regulatory networks that underlie the development of chemoresistance in bladder cancer. METHODS: We analyzed profiles of differentially expressed long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs) and messenger RNA (mRNAs) in gemcitabine-resistant/sensitive bladder cancer cells using next-generation sequencing data. RESULTS: Hundreds of differentially expressed lncRNAs and miRNAs and thousands of circRNAs and mRNAs were identified. Bioinformatics analysis revealed the chromosomal localizations, classification and coexpression of mRNAs, as well as candidates for cis and trans regulation by lncRNAs. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of differentially expressed mRNAs and circRNAs indicated important functional roles of coregulated RNAs, thus establishing competing endogenous RNA (ceRNA) and protein-protein interactions networks that may underlie chemoresistance in bladder cancer. We demonstrated that lncRNA LINP1 can act as a ceRNA by inhibiting miR-193a-5p to increase TP73 expression; and that lncRNA ESRG and hsa_circ_0075881 can simultaneously bind miR-324-3p to increase ST6GAL1 expression. Modulation of ceRNA network components using ablation and overexpression approaches contributed to gemcitabine resistance in bladder cancer cells. CONCLUSIONS: These results elucidate mechanisms by which lncRNAs and circRNAs coregulate the development of bladder cancer cell resistance to gemcitabine, thus laying the foundation for future research to identify biomarkers and disease targets.


Assuntos
Carcinoma , MicroRNAs , RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Humanos , RNA Circular/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Gencitabina , RNA Endógeno Competitivo , Bexiga Urinária/metabolismo , Redes Reguladoras de Genes , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética
8.
BMC Pulm Med ; 23(1): 303, 2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37592285

RESUMO

BACKGROUND: A high mortality rate has always been observed in patients with severe community-acquired pneumonia (SCAP) admitted to the intensive care unit (ICU); however, there are few reported predictive models regarding the prognosis of this group of patients. This study aimed to screen for risk factors and assign a useful nomogram to predict mortality in these patients. METHODS: As a developmental cohort, we used 455 patients with SCAP admitted to ICU. Logistic regression analyses were used to identify independent risk factors for death. A mortality prediction model was built based on statistically significant risk factors. Furthermore, the model was visualized using a nomogram. As a validation cohort, we used 88 patients with SCAP admitted to ICU of another hospital. The performance of the nomogram was evaluated by analysis of the area under the receiver operating characteristic (ROC) curve (AUC), calibration curve analysis, and decision curve analysis (DCA). RESULTS: Lymphocytes, PaO2/FiO2, shock, and APACHE II score were independent risk factors for in-hospital mortality in the development cohort. External validation results showed a C-index of 0.903 (95% CI 0.838-0.968). The AUC of model for the development cohort was 0.85, which was better than APACHE II score 0.795 and SOFA score 0.69. The AUC for the validation cohort was 0.893, which was better than APACHE II score 0.746 and SOFA score 0.742. Calibration curves for both cohorts showed agreement between predicted and actual probabilities. The results of the DCA curves for both cohorts indicated that the model had a high clinical application in comparison to APACHE II and SOFA scoring systems. CONCLUSIONS: We developed a predictive model based on lymphocytes, PaO2/FiO2, shock, and APACHE II scores to predict in-hospital mortality in patients with SCAP admitted to the ICU. The model has the potential to help physicians assess the prognosis of this group of patients.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Síndrome do Desconforto Respiratório , Humanos , Mortalidade Hospitalar , Hospitais , Unidades de Terapia Intensiva , Fatores de Risco
9.
Int J Gen Med ; 16: 3373-3381, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37576915

RESUMO

Background: Depressive symptoms are common among perimenopausal women with breast cancer having modified radical mastectomy. Esketamine exerts antidepressant effects. This study aims to assess whether an intraoperative sub-anesthetic dose of esketamine prevents postoperative depressive symptoms in these patients. Methods: In this randomized, triple-blinded, placebo-controlled trial, we will enroll 130 perimenopausal women (aged 45-60 years) with breast cancer undergoing unilateral modified radical mastectomy. Patients will be randomly assigned with a 1:1 ratio to receive either esketamine (0.25 mg/kg i.v.) or normal saline after anesthesia induction and before skin incision. The primary outcome is the incidence of depressive symptoms at day 30 postoperatively, assessed using the Beck's Depression Inventory (BDI). Secondary outcomes include incidence of depressive symptoms and BDI scores at day 1, 3, and 180 postoperatively, anxiety symptoms and scores at day 1, 3, 30, and 180 postoperatively, pain intensity and quality of recovery at day 1 and 2 postoperatively, nausea and vomiting within 48 hours postoperatively, length of postoperative hospital stay, and cancer-specific outcomes. Data will be analyzed in the modified intention-to-treat population. Discussion: This is the first trial to evaluate the effects of a sub-anesthetic dose of esketamine on depressive symptoms in perimenopausal women after modified radical mastectomy. The results of this study will help to improve their mental health and recovery after breast cancer surgery. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200064348).

10.
Biochem Biophys Res Commun ; 674: 170-182, 2023 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-37423037

RESUMO

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with a poor prognosis. The growth of GBM cells depends on the core transcriptional apparatus, thus rendering RNA polymerase (RNA pol) complex as a candidate therapeutic target. The RNA pol II subunit B (POLR2B) gene encodes the second largest subunit of the RNA pol II (RPB2); however, its genomic status and function in GBM remain unclear. Certain GBM data sets in cBioPortal were used for investigating the genomic status and expression of POLR2B in GBM. The function of RPB2 was analyzed following knockdown of POLR2B expression by shRNA in GBM cells. The cell counting kit-8 assay and PI staining were used for cell proliferation and cell cycle analysis. A xenograft mouse model was established to analyze the function of RPB2 in vivo. RNA sequencing was performed to analyze the RPB2-regulated genes. GO and GSEA analyses were applied to investigate the RPB2-regulated gene function and associated pathways. In the present study, the genomic alteration and overexpression of the POLR2B gene was described in glioblastoma. The data indicated that knockdown of POLR2B expression suppressed tumor cell growth of glioblastoma in vitro and in vivo. The analysis further demonstrated the identification of the RPB2-regulated gene sets and highlighted the DNA damage-inducible transcript 4 gene as the downstream target of the POLR2B gene. The present study provides evidence indicating that RPB2 functions as a growth regulator in glioblastoma and could be used as a potential therapeutic target for the treatment of this disease.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Animais , Camundongos , Glioblastoma/patologia , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , Proliferação de Células/genética , Neoplasias Encefálicas/patologia , RNA Interferente Pequeno/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
11.
Neuroreport ; 34(13): 677-684, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37506308

RESUMO

The exosomes of mesenchymal stem cells have immunoregulatory properties and can effectively mitigate secondary neuroinflammation due to traumatic brain injury (TBI). In this study, we found that adipose-derived stem cell exosomes (ADSCs-Exo) could reduce the inflammatory response after traumatic brain injury by reducing NLRP3 inflammasome secretion by microglial. ADSCs-Exo were monitored by Western blot and electron microscopy. An in-vitro lipopolysaccharide (LPS)-caused primary microglia model and a TBI rat model were constructed. Functional recovery was examined using the modified neurological severity score and foot fault tests. Inflammasome inactivation in LPS-stimulated microglial, ADSCs-Exo can reduce the secretion of interleukin (IL)-1ß, IL-6 and tumor necrosis factor α. Compared with PBS-processed controls, the sensorimotor functional recovery was significantly improved by exosome treatment after injury at 14-35 days. Additionally, NLRP3 inflammasome was stimulated within 24 h after TBI. ADSCs-Exo application led to remarkable down-expression of NLRP3 and caspase-1. ADSCs-Exo can ameliorate LPS-induced inflammatory activation by reducing microglial pro-inflammatory cytokines. Moreover, the neuroprotective effect of ADSCs-Exo may be partially attributed to the inhibition thereof on the formation of NLRP3-mediated inflammasome. Such findings imply a potential function of ADSCs-Exo in treating TBI.


Assuntos
Lesões Encefálicas Traumáticas , Exossomos , Células-Tronco Mesenquimais , Ratos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Exossomos/metabolismo , Lipopolissacarídeos/toxicidade , Lesões Encefálicas Traumáticas/metabolismo , Transdução de Sinais , Células-Tronco Mesenquimais/metabolismo
12.
J Matern Fetal Neonatal Med ; 36(1): 2206941, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37121909

RESUMO

OBJECTIVE: To evaluate the association between pulmonary hemorrhage and bronchopulmonary dysplasia (BPD) in very low birth weight infants (VLBWIs). METHODS: The study participants were all VLBW newborns admitted from January 1, 2019 to December 31, 2021. The BPD subjects finally included were VLBWIs who survived until the diagnosis was established. This study was divided into pulmonary hemorrhage group (PH group, n = 35) and non-pulmonary hemorrhage group (Non-PH group, n = 190). RESULTS: By univariate analysis it was found that premature rupture of membranes, tracheal intubation in the delivery room, duration of mechanical ventilation, course of invasive ventilation (≥3 courses), pulmonary surfactant (>1 dose), medically and surgically treated patent ductus arteriosus, grade III-IV RDS, early onset sepsis, BPD and moderate to severe BPD showed significant differences between groups (p < .05). By Multivariate analysis, pulmonary hemorrhage did not increase the risks of BPD and moderate to severe BPD (adjusted OR for BPD = 1.710, 95% CI 0.581-5.039; adjusted OR for moderate to severe BPD = 2.401, 95% CI 0.736-7.834). CONCLUSION: It suggests that pulmonary hemorrhage is not associated with the development of BPD and moderate to severe BPD in VLBWIs.


Assuntos
Displasia Broncopulmonar , Permeabilidade do Canal Arterial , Lactente , Feminino , Recém-Nascido , Humanos , Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/epidemiologia , Recém-Nascido de muito Baixo Peso , Peso ao Nascer , Respiração Artificial , Permeabilidade do Canal Arterial/complicações , Idade Gestacional
13.
Int J Immunopathol Pharmacol ; 37: 3946320231152993, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36744872

RESUMO

This pilot study aimed to explore the effectiveness and safety of dexibuprofen suppository in the treatment of PDA in preterm infants. Preterm infants with gestational age <34 weeks and color Doppler echocardiographic evidence of hemodynamically significant PDA (hs PDA) with systemic hypoperfusion was intended to be included into this study since January 2020. As of January 1, 2021, this trial had recruited 87 preterm infants who met the inclusion criteria. Neonates were admitted into hospital within 1 hour after birth and were randomly assigned into two groups. Group one included 44 preterm newborns administered with oral ibuprofen. Group two included 43 preterm newborns administered with dexibuprofen suppository. This preliminary study showed that rectal dexibuprofen and oral ibuprofen were both effective for the closure of PDA, and the closure rate of dexibuprofen suppository was comparable to that of oral ibuprofen after the 1st and 2nd courses of treatment. In addition, rectal dexibuprofen did not increase the incidence of adverse outcomes, including bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and necrotising enterocolitis. This pilot study showed dexibuprofen suppository is as effective and safe as oral ibuprofen; yet, better designed, muticenter controlled studies are still needed.


Assuntos
Permeabilidade do Canal Arterial , Recém-Nascido Prematuro , Humanos , Lactente , Recém-Nascido , Permeabilidade do Canal Arterial/tratamento farmacológico , Permeabilidade do Canal Arterial/induzido quimicamente , Idade Gestacional , Ibuprofeno/efeitos adversos , Recém-Nascido de Baixo Peso , Projetos Piloto
14.
Kaohsiung J Med Sci ; 39(4): 337-344, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36655871

RESUMO

As one kind of novel noncoding RNA, circular RNAs (circRNAs) are involved in different biological processes. Although growing evidences have supported the important role of circRNAs in renal diseases, the mechanism remains unclear in neonatal acute kidney injury (AKI). High-throughput sequencing analysis was used to investigate the expression of circRNAs between hypoxia-induced AKI neonates and controls. Bioinformatics analysis was conducted to predict the function of differentially expressed circRNAs. Finally, the differentially expressed circRNAs were screened and determined by quantitative real-time PCR (qPCR). (1) A total of 296 differentially expressed circRNAs were identified (Fold change >2 and p < 0.05). Of them, 184 circRNAs were markedly upregulated, and 112 were significantly downregulated in the AKI group. (2) The pathway analysis showed that ubiquitin-mediated proteolysis, renal cell carcinoma, Jak-STAT, and HIF-1 signaling pathways participated in AKI. (3) Top five upregulated and five downregulated circRNAs with higher fold changes were selected for qPCR validation. Hsa_circ_0008898 (Fold Change = 5.48, p = 0.0376) and hsa_circ_0005519 (Fold Change = 4.65, p = 0.0071) were significantly upregulated, while hsa_circ_0132279 (Fold Change = -4.47, p = 0.0008), hsa_circ_0112327 (Fold Change = -4.26, p = 0.0048), and hsa_circ_0017647 (Fold Change = -4.15, p = 0.0313) were significantly downregulated in asphyxia-induced AKI group compared with the control group. This study could contribute to future research on neonatal AKI and facilitate the identification of novel therapeutic targets.


Assuntos
Injúria Renal Aguda , MicroRNAs , Recém-Nascido , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Análise de Sequência de RNA , Injúria Renal Aguda/genética , Biologia Computacional , Sequência de Bases , MicroRNAs/genética , MicroRNAs/metabolismo
15.
Environ Sci Pollut Res Int ; 30(7): 18312-18324, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36207637

RESUMO

Microbial electrolysis cells (MECs) have rapidly developed into a promising technology to treat sulfate-rich wastewater that lacks electron donors. Hence, a better understanding of the effect on the microbial community structure caused by different sources in bioelectrochemical systems is required. This study sought to investigate the effect of different carbon sources (NaHCO3, ethanol, and acetate were employed as sole carbon source respectively) on the performance of sulfate-reducing biocathodes. The sulfate reduction efficiency enhanced by the bioelectrochemical systems was 8.09 - 11.57% higher than that of open-circuit reference experiments. Furthermore, the optimum carbon source was ethanol with a maximum sulfate reduction rate of 170 mg L-1 d-1 in the bioelectrochemical systems. The different carbon sources induced significant differences in sulfate reduction efficiency as demonstrated by the application of a micro-electrical field. Microbial community structure and network analysis revealed that all three kinds of carbon source systems enriched large proportions of sulfate-reducing bacteria and electroactive bacteria but were significantly distinct in composition. The dominant sulfate-reducing bacteria that use NaHCO3 and acetate as carbon sources were Desulfobacter and Desulfobulbus, whereas those that use ethanol as carbon source were Desulfomicrobium and Desulfovibrio. Our results suggest that ethanol is a more suitable carbon source for sulfate reduction in bioelectrochemical systems.


Assuntos
Fontes de Energia Bioelétrica , Microbiota , Carbono , Sulfatos/química , Etanol , Acetatos
17.
Neurotoxicol Teratol ; 95: 107137, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36403891

RESUMO

Methylmercury (MeHg) is a potent neurotoxicant that could induce oxidative stress and autophagy. However, the underlying mechanisms through which MeHg affects the central nervous system have not been fully elucidated, and little has been known of the interaction between oxidative stress and autophagy. Therefore, rats were administrated with different MeHg concentrations to evaluate the neurotoxic effects and autophagy in cerebral cortex. Moreover, we have investigated the neuroprotective role of N-acetyl-L-cysteine (NAC) against MeHg-induced neurotoxicity in order to estimate the regulation effects of oxidative stress on autophagy. A total of 64 rats, 40 of which were randomly divided into control and MeHg-treated (4, 8 and 12 µ mol/kg) groups. The remaining 24 rats were divided into control, NAC control (1 mmol/kg), 12 µ mol/kg MeHg, and NAC pretreatment. Administration of 12 µ mol/kg MeHg significantly increased behavioral and pathological abnormalities, and autophagy levels. In addition, the oxidative stress levels increased, together with abnormal expression of autophagy-related molecules. Pretreatment with NAC significantly prevented MeHg-induced oxidative stress and PI3K/AKT/mTOR or AMPK/TSC2/mTOR-mediated autophagy. In conclusion, the present study suggested that oxidative stress can regulate autophagy through PI3K/AKT/mTOR or AMPK/TSC2/mTOR pathways. This study provides a theoretical basis for the study and treatment of MeHg-induced neurotoxicity.


Assuntos
Acetilcisteína , Compostos de Metilmercúrio , Animais , Ratos , Acetilcisteína/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/farmacologia , Autofagia , Córtex Cerebral , Compostos de Metilmercúrio/toxicidade , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR
18.
Front Cell Dev Biol ; 10: 1073688, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36531956

RESUMO

Stomach adenocarcinoma (STAD) is always characterized by high mortality and poor prognosis with drug resistance and recrudescence due to individual genetic heterogeneity. Adenosine-to-Inosine RNA editing (ATIRE) has been reported associated with multiple tumors but the potential connection between ATIRE-related signatures and STAD remains unclear. In this study, we comprehensively elevated the genetic characteristics of ATIRE in STAD patients and first screened five vital survival-related ATIRE sites to identify a novel ATIRE-Risk score. Based on the risk scores, we further divided the patients into two different subtypes with diverse clinical characteristics and immune landscapes including immune cell infiltration (ICI), tumor microenvironment (TME), and immune checkpoint expression analysis. The low-risk subgroups, associated with better survival prognosis, were characterized by activated immune-cells, higher immune scores in TME, and down-expression of immunotherapy checkpoints. Moreover, different expressional genes (DEGs) between the above subtypes were further identified and the activation of immune-related pathways were found in low-risk patients. The stratified survival analysis further indicated patients with low-risk and high-tumor mutation burden (TMB) exhibited the best prognosis outcomes, implying the role of TMB and ATIRE-Risk scores was synergistic for the prognosis of STAD. Interestingly, anti-tumor chemotherapeutic drugs all exhibited lower IC50 values in low-risk subgroups, suggesting these patients might obtain a better curative response from the combined chemotherapy of STAD. Finally, combined with classical clinical features and ATIRE-Risk scores, we successfully established a promising nomogram system to accurately predict the 1/3/5-years survival ratio of STAD and this model was also estimated with high diagnostic efficiency and stable C-index with calibration curves. These significant ATIRE sites are promising to be further explored and might serve as a novel therapeutic target for STAD treatment.

19.
Plants (Basel) ; 11(24)2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36559681

RESUMO

SlSPL-CNR is a multifunctional transcription factor gene that plays important roles in regulating tomato fruit ripening. However, the molecular basis of SlSPL-CNR in the regulatory networks is not exactly clear. In the present study, the biochemical characteristics and expression levels of genes involved in ethylene biosynthesis in Colorless nonripening (Cnr) natural mutant were determined. The proteomic changes during the ripening stage were also uncovered by isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic analysis. Results indicated that both the lycopene content and soluble solid content (SSC) in Cnr fruit were lower than those in wild-type AC fruit. Meanwhile, pH, flavonoid content, and chlorophyll content were higher in Cnr fruit. Expressions of genes involved in ethylene biosynthesis were also downregulated or delayed in Cnr fruit. Furthermore, 1024 and 1234 differentially expressed proteins (DEPs) were respectively identified for the breaker and 10 days postbreaker stages. Among them, a total of 512 proteins were differentially expressed at both stages. In addition, the functions of DEPs were classified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Results would lay the groundwork for wider explorations of the regulatory mechanism of SlSPL-CNR on tomato fruit ripening.

20.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 51(5): 603-612, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36581578

RESUMO

OBJECTIVE: To develop a Chinese version of Functional Status Scale (FSS) and to test its reliability and validity in very low birth weight infants (VLBWIs). METHODS: The FSS was translated into Chinese and the content was modified in accordance with relevant guidelines and specifications. The Chinese version of FSS was applied to evaluate VLBWIs admitted from January 2018 to June 2020 at 7th day after birth and 34 weeks of postmenstrual age, respectively. The scores were analyzed by descriptive statistics (coefficient of variation method, critical ratio method and answer distribution analysis method), and the reliability and the validity were analyzed. The internal consistency reliability was analyzed using Cronbach's α coefficient, the inter rater reliability was analyzed using Spearman correlation coefficient. The content validity was analyzed using correlation coefficient method and expert scoring method; the structural validity was analyzed using exploratory and confirmatory factor analysis method; the known group validity was analyzed using area under the curve (AUC) value and Pearson correlation coefficient. The preliminary response of the initial and re-evaluation scales was calculated. RESULTS: After screening by inclusion and exclusion criteria, 548 and 523 VLBWIs were included for initial evaluation and re-evaluation, respectively. Descriptive statistics showed that the mean was close to the median, the maximum and minimum values were close to or equal to the values at both ends, and the coefficient of variation was >0.15. The critical ratio method showed that the | t| value of all items in the initial evaluation and re-evaluation was >3 ( P<0.01). The answer distribution analysis method showed that the answer selection rate of different levels of each item was <80%. Internal consistency test showed that the general Cronbach's α was 0.803 and the re-evaluation Cronbach's α was 0.708, with a good internal consistency. According to the inter-rater reliability, the Spearman correlation coefficient was 0.968 in the initial evaluation and 0.989 in the re-evaluation ( P<0.01). The correlation coefficient of the items in the scale by the correlation coefficient method was more than 0.4. The item-level content validity index (I-CVI) was greater than 0.78, universal agreement of scale of content validity index was 0.83, the average of scale of content validity index was 0.97 and the Kappa was greater than 0.74. Exploratory factor analysis showed that the initial Kaiser-Meyer-Olkin (KMO) value was 0.846, the re-evaluated KMO value was 0.843 ( P<0.01). There was one factor with extracted eigenvalue>1, which could explain 54.221% and 53.403% of the total variation respectively, suggesting that there was a common factor in the initial evaluation and re-evaluation scales, which was consistent with the original scale design. Confirmatory factor analysis showed that the items in the initial and re-evaluation were significant ( P<0.01), and the value of standard load coefficient was greater than 0.5. The known group validity showed that FSS had a good predictive and discriminative ability for short-term outcomes. The items of mental status, motor function, sensory and communication in the re-evaluation scale had a good correlation with gross motor and fine motor energy areas in Gesell developmental schedule. The Pearson correlation coefficient between initial evaluation and re-evaluation was 0.609 ( P<0.01). CONCLUSION: The Chinese version FSS scale has good reliability and validity, the included items are simple and easy to be applied in clinical practice.


Assuntos
Estado Funcional , Humanos , China , Análise Fatorial , Reprodutibilidade dos Testes , Inquéritos e Questionários
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