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1.
Infect Drug Resist ; 17: 1215-1228, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562405

RESUMO

Objective: To examine the risk factors linked with occupational blood exposure (OBE) among nursing staff (NS), we pinpoint deficiencies in the compliance with policies of infection prevention and control, and assess the expenditures associated with infection prevention and control. Methods: Healthcare workers that completed an "Occupational Blood Exposure Report Form" were divided into NS (observation) group and non-NS (control) group. Univariate and multivariable analyses were conducted to compare both groups in various aspects. We also explored design patents intended to minimize occupational exposure. Results: The highest incidence of OBE was observed in the department of neurosurgery. Among NS, OBE incidence was found to be influenced by independent risk factors, such as gender, age, occupational title, work location, and incidence of sharps injuries. Protective factors against OBEs included the use of arterial blood gas needles and suture needles. Personal protective equipment (PPE) usage rates were low in both groups prior to OBEs (0.74% vs 0.00%, P > 0.05). Correct emergency management could be improved promptly by both groups following an OBE (P > 0.05). However, the observation group exhibited a higher proportion of blood expression after a sharps injury and a higher re-evaluation rate at 6 months post-exposure compared to the control group (P < 0.05). In 2018, the per capita costs of infection prevention and control for NS were the Chinese Yuan (RMB) 339.43 per individual. In response to these findings, two utility model patents have been authorized. Conclusion: The risk and protective factors related to the occurrence of OBEs were investigated in this study, suggesting that there is a need for improvement in the rate of PPE usage and the re-evaluation rate of OBEs among NS. Additionally, focused training on emergency blood expression and compliance with policies among non-NS personnel is deemed necessary.

2.
World J Diabetes ; 15(3): 502-518, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38591083

RESUMO

BACKGROUND: Jianpi Gushen Huayu Decoction (JPGS) has been used to clinically treat diabetic nephropathy (DN) for many years. However, the protective mechanism of JPGS in treating DN remains unclear. AIM: To evaluate the therapeutic effects and the possible mechanism of JPGS on DN. METHODS: We first evaluated the therapeutic potential of JPGS on a DN mouse model. We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics. Furthermore, we examined the effects of JPGS on c-Jun N-terminal kinase (JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3). RESULTS: The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress. Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice. A total of 51 differential metabolites were screened. Pathway analysis results indicated that nine pathways significantly changed between the control and model groups, while six pathways significantly altered between the model and JPGS groups. Pathways related to cysteine and methionine metabolism; alanine, tryptophan metabolism; aspartate and glutamate metabolism; and riboflavin metabolism were identified as the key pathways through which JPGS affects DN. Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors. CONCLUSION: JPGS could markedly treat mice with streptozotocin (STZ)-induced DN, which is possibly related to the regulation of several metabolic pathways found in kidneys. Furthermore, JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathway-mediated apoptosis in DN mice.

3.
Adv Sci (Weinh) ; 11(14): e2308496, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38308190

RESUMO

During maternal-to-zygotic transition (MZT) in the embryo, mRNA undergoes complex post-transcriptional regulatory processes. However, it is unclear whether and how alternative splicing plays a functional role in MZT. By analyzing transcriptome changes in mouse and human early embryos, dynamic changes in alternative splicing during MZT are observed and a previously unnoticed process of zygotic splicing activation (ZSA) following embryonic transcriptional activation is described. As the underlying mechanism of RNA splicing, splicing factors undergo dramatic maternal-to-zygotic conversion. This conversion relies on the key maternal factors BTG4 and PABPN1L and is zygotic-transcription-dependent. CDK11-dependent phosphorylation of the key splicing factor, SF3B1, and its aggregation with SRSF2 in the subnuclear domains of 2-cell embryos are prerequisites for ZSA. Isoforms generated by erroneous splicing, such as full-length Dppa4, hinder normal embryonic development. Moreover, alternative splicing regulates the conversion of early embryonic blastomeres from totipotency to pluripotency, thereby affecting embryonic lineage differentiation. ZSA is an essential post-transcriptional process of MZT and has physiological significance in generating new life. In addition to transcriptional activation, appropriate expression of transcript isoforms is also necessary for preimplantation embryonic development.


Assuntos
Transcriptoma , Zigoto , Humanos , Animais , Camundongos , Transcriptoma/genética , Zigoto/metabolismo , Desenvolvimento Embrionário/genética , Splicing de RNA , Isoformas de Proteínas/genética , Proteínas de Ligação a Poli(A)/genética , Proteínas de Ligação a Poli(A)/metabolismo , Proteínas Nucleares/genética
4.
Protoplasma ; 261(3): 571-579, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38170395

RESUMO

Our experiments explored the effects of far-red (FR) light on cucumber (Cucumis sativus L. 'Zhongnong No. 26') seedling growth. Our results indicated that FR light significantly promoted the growth of cucumber seedlings. Specifically, it promoted the accumulation of shoot biomass and the elongation of internodes and leaves (except the first leaf at the bottom). Further analysis showed that FR light had no effect on the accumulation contents of abscisic acid (ABA) and auxin (IAA) in seedling leaves. Still, it significantly caused the increase of the gibberellin (GA3, GA4, and GA7) contents and the decrease of GA1 content, which suggested that the leaf expansion progress under FR light may be primarily related to GA. Therefore, the cucumber seedling leaf expansion response to GA was evaluated under different light sources. The exogenous spraying of different GA4/7 contents significantly promoted the leaf expansion of cucumber seedlings under white light, while the GA biosynthesis inhibitor paclobutrazol (PAC) significantly promoted the expression of GA hydrolytic genes (GA2ox2 and GA2ox4) and decreased the content of endogenous active GA, which inhibited the leaf expansion induced by FR light. As expected, the combination of exogenous GA4/7 and PAC restored the growth promotion effect of FR light on cucumber seedling leaves. It increased the contents of endogenous active GA (GA1, GA3, GA4, and GA7), and the expression trend in GA synthetic/hydrolytic-related genes was the opposite of that of PAC was applied alone. All of the above results indicated that FR light regulates leaf expansion progress in cucumber seedlings through GA.


Assuntos
Cucumis sativus , Giberelinas , Giberelinas/farmacologia , Giberelinas/metabolismo , Plântula/metabolismo , Cucumis sativus/genética , Luz Vermelha , Folhas de Planta/metabolismo
5.
Adv Mater ; 36(16): e2311327, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38221508

RESUMO

Severe capacity decay under subzero temperatures remains a significant challenge for lithium-ion batteries (LIBs) due to the sluggish interfacial kinetics. Current efforts to mitigate this deteriorating interfacial behavior rely on high-solubility lithium salts (e.g., Lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), Lithium bis(fluorosulfonyl)imide (LiFSI))-based electrolytes to construct anion participated solvation structures. However, such electrolytes bring issues of corrosion on the current collector and increased costs. Herein, the most commonly used Lithium hexafluorophosphate (LiPF6) instead, to establish a peculiar solvation structure with a high ratio of ion pairs and aggregates by introducing a deshielding NO3 - additive for low-temperature LIBs is utilized. The deshielding anion significantly reduces the energy barrier for interfacial behavior at low temperatures. Benefiting from this, the graphite (Gr) anode retains a high capacity of ≈72.3% at -20 °C, which is far superior to the 32.3% and 19.4% capacity retention of counterpart electrolytes. Moreover, the LiCoO2/Gr full cell exhibits a stable cycling performance of 100 cycles at -20 °C due to the inhibited lithium plating. This work heralds a new paradigm in LiPF6-based electrolyte design for LIBs operating at subzero temperatures.

6.
EMBO Mol Med ; 16(2): 294-318, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38297099

RESUMO

Diabetic retinopathy (DR) is a leading cause of irreversible vision loss in working-age populations. Fat mass and obesity-associated protein (FTO) is an N6-methyladenosine (m6A) demethylase that demethylates RNAs involved in energy homeostasis, though its influence on DR is not well studied. Herein, we detected elevated FTO expression in vitreous fibrovascular membranes of patients with proliferative DR. FTO promoted cell cycle progression and tip cell formation of endothelial cells (ECs) to facilitate angiogenesis in vitro, in mice, and in zebrafish. FTO also regulated EC-pericyte crosstalk to trigger diabetic microvascular leakage, and mediated EC-microglia interactions to induce retinal inflammation and neurodegeneration in vivo and in vitro. Mechanistically, FTO affected EC features via modulating CDK2 mRNA stability in an m6A-YTHDF2-dependent manner. FTO up-regulation under diabetic conditions was driven by lactate-mediated histone lactylation. FB23-2, an inhibitor to FTO's m6A demethylase activity, suppressed angiogenic phenotypes in vitro. To allow for systemic administration, we developed a nanoplatform encapsulating FB23-2 and confirmed its targeting and therapeutic efficiency in mice. Collectively, our study demonstrates that FTO is important for EC function and retinal homeostasis in DR, and warrants further investigation as a therapeutic target for DR patients.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato , Quinase 2 Dependente de Ciclina , Diabetes Mellitus , Retinopatia Diabética , Animais , Camundongos , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Quinase 2 Dependente de Ciclina/genética , Quinase 2 Dependente de Ciclina/metabolismo , Células Endoteliais/metabolismo , Retina/metabolismo , RNA , Peixe-Zebra/genética
7.
Angew Chem Int Ed Engl ; 63(12): e202318369, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38179853

RESUMO

Thermal safety issues of batteries have hindered their large-scale applications. Nonflammable electrolytes improved safety but solvent evaporation above 100 °C limited thermal tolerance, lacking reliability. Herein, fire-tolerant metal-air batteries were realized by introducing solute-in-air electrolytes whose hygroscopic solutes could spontaneously reabsorb the evaporated water solvent. Using Zn/CaCl2 -in-air/carbon batteries as a proof-of-concept, they failed upon burning at 631.8 °C but self-recovered then by reabsorbing water from the air at room temperature. Different from conventional aqueous electrolytes whose irreversible thermal transformation is determined by the boiling points of solvents, solute-in-air electrolytes make this transformation determined by the much higher decomposition temperature of solutes. It was found that stronger intramolecular bonds instead of intermolecular (van der Waals) interactions were strongly correlated to ultra-high tolerance temperatures of our solute-in-air electrolytes, inspiring a concept of non-van der Waals electrolytes. Our study would improve the understanding of the thermal properties of electrolytes, guide the design of solute-in-air electrolytes, and enhance battery safety.

8.
Adv Mater ; 36(4): e2304900, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37549425

RESUMO

An initial Coulombic efficiency (ICE) higher than 90% is crucial for industrial lithium-ion batteries, but numerous electrode materials are not standards compliant. Lithium trapping, due to i) incomplete solid-state reaction of Li+ generation and ii) sluggish Li+ diffusion, undermines ICE in high-capacity electrodes (e.g., conversion-type electrodes). Current approaches mitigating lithium trapping emphasize ii) nanoscaling (<50 nm) to minimize Li+ diffusion distance, followed by severe solid electrolyte interphase formation and inferior volumetric energy density. Herein, this work accentuates i) instead, to demonstrate that the lithium trapping can be mitigated by boosting the solid-state reaction reactivity. As a proof-of-concept, ternary LiFeO2 anodes, whose discharged products contain highly reactive vacancy-rich Fe nanoparticles, can alleviate lithium trapping and enable a remarkable average ICE of ≈92.77%, much higher than binary Fe2 O3 anodes (≈75.19%). Synchrotron-based techniques and theoretical simulations reveal that the solid-state reconversion reaction for Li+ generation between Fe and Li2 O can be effectively promoted by the Fe-vacancy-rich local chemical environment. The superior ICE is further demonstrated by assembled pouch cells. This work proposes a novel paradigm of regulating intrinsic solid-state chemistry to ameliorate electrochemical performance and facilitate industrial applications of various advanced electrode materials.

9.
Biomed Chromatogr ; 38(1): e5763, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37858975

RESUMO

Alisol B 23-acetate (AB23A) has been demonstrated to have beneficial effects on nonalcoholic steatohepatitis (NASH). However, the mechanisms of AB23A on NASH remain unclear. This study aimed to investigate the mechanisms underlying the metabolic regulatory effects of AB23A on NASH. We used AB23A to treat mice with NASH, which was induced by a methionine and choline deficient (MCD) diet. We initially investigated therapeutic effect and resistance to oxidation and inflammation of AB23A on NASH. Subsequently, we performed untargeted metabolomic analyses and relative validation assessments to evaluate the metabolic regulatory effects of AB23A. AB23A reduced lipid accumulation, ameliorated oxidative stress and decreased pro-inflammatory cytokines in the liver. Untargeted metabolomic analysis found that AB23A altered the metabolites of liver. A total of 55 differential metabolites and three common changed pathways were screened among the control, model and AB23A treatment groups. Further tests validated the effects of AB23A on modulating common changed pathway-involved factors. AB23A treatment can ameliorate NASH by inhibiting oxidative stress and inflammation. The mechanism of AB23A on NASH may be related to the regulation of alanine, aspartate and glutamate metabolism, d-glutamine and d-glutamate metabolism, and arginine biosynthesis pathways.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Metionina/metabolismo , Metionina/farmacologia , Colina , Fígado/metabolismo , Racemetionina/metabolismo , Racemetionina/farmacologia , Dieta , Inflamação/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
10.
J Multidiscip Healthc ; 16: 4091-4097, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38111827

RESUMO

Objective: The objective of this study is to examine the qualification rate of hand disinfection in the surgical department wards and analyze the influencing factors. Methods: A surprise assessment was carried out to evaluate the daily adherence to hand hygiene protocols in the surgical department wards. We aimed to investigate the factors that impact the qualification rate of hand disinfection. Results: In this study, the qualification rate of hand disinfection was determined to be 64.38%. Notably, this rate exhibited significant variations based on gender, age, surgical site, and department category. Specifically, the qualification rate of hand disinfection among female participants stood at 82.35%, surpassing the qualification rate observed among male counterparts of 52.83%. Furthermore, doctors in the age group of 41-50 years demonstrated the highest qualification rate, and the abdominal surgical site exhibited the most noteworthy qualification rate, reaching 79.49%. The outcomes of the multiple logistic regression analysis highlighted the significance of age and gender as influential factors impacting the qualification rate. Specifically, doctors aged 51 years or older exhibited the lowest hand hygiene compliance, whereas female doctors demonstrated a notably higher qualification rate compared to their male counterparts. Conclusion: The disheartening qualification rate of hand disinfection highlights a concerning lack of awareness regarding hand hygiene among surgeons in their professional duties. Consequently, targeted interventions are imperative, focusing on intensified training, educational initiatives, enhanced supervision, and internal performance evaluations for key groups. The findings not only serve as a valuable database but also offer a viable roadmap for similar hospitals to reinforce the management of nosocomial infections.

11.
Langmuir ; 39(46): 16606-16617, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37934508

RESUMO

Chemo-mechanical grinding (CMG) is a valid processing method to achieve a low-damage surface of silicon. However, the atomic interfacial mechanism during the CMG is still unclear. Herein, the CMG process of silicon was investigated using first principles and frictional wear tests in which the effects of pressure and speed on the interfacial reaction were comprehensively analyzed. Simulations showed that the formation and breakage of chemical bonds occurred at the CeO2/silicon interface during CMG, and the newly formed chemical bonds were stronger than those on the silicon surface. Also, it was found that the pressure and speed improved the materials removal rate by means of accelerating the interfacial chemical reactions, which is also verified by frictional wear tests. This study provides new insights into the atomic interfacial mechanism during silicon CMG.

12.
Violence Vict ; 38(5): 754-784, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37827579

RESUMO

There has been limited study of the link between victimization and the criminal offense in the correctional context, despite the extensive literature supporting the overlap of victims and offenders in the general population. In this study, 2,880 inmates in 12 institutional correction facilities in Taiwan were examined to explore the common factors of the victim-offender overlap, guided by the importation, deprivation, and low self-control theories. The results of bivariate probit regression analysis revealed the presence of the victim-offender phenomenon in Taiwanese inmates. Specifically, the inmates who had experienced violent victimization in childhood and those who held negative perceptions of corrections staff and management tended to be both victims and offenders as measured by various types of prison misconduct and victimization. The results also showed that importation and deprivation factors have similar explanatory power for both misconduct and victimization, and low self-control has greater explanatory power for misconduct than for victimization.


Assuntos
Vítimas de Crime , Criminosos , Prisioneiros , Autocontrole , Humanos , Prisões
13.
Huan Jing Ke Xue ; 44(9): 4985-4995, 2023 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-37699816

RESUMO

The Miyun Reservoir is the major source of surface drinking water in Beijing. However, the total nitrogen (TN) concentrations in the Miyun Reservoir and inflowing rivers have recently been increasing. In this study, the Mangniu River, a typical inflow river in the upper reaches of the Miyun Reservoir, was selected as the study area to investigate the spatial distribution and transformation of various nitrogen forms from the perspective of microbial community composition and predicting function, aimimg at providing a scientific reference for nitrogen pollution control of the Miyun Reservoir. The results indicated that except for TN, all the other physical and chemical water quality indicators in the upper reaches of the Miyun Reservoir met the Class II criteria of the environmental quality standards for surface water in China (GB 3838-2002). Additionally, NO3--N was the primary constituent of TN, ranging from 77.7% to 92.9%. Banchengzi Reservoir has a certain self-purification ability because its high C/N ratio promotes denitrification. Significant differences in microbial community structure were observed between the water and sediments of Mangniu River along with spatial distribution. High NO3--N concentration was the major environmental factor affecting the succession of microbial community structure. Many nitrification and denitrification microorganisms existed in Mengniu River, and the relative abundance of denitrification bacteria (DNB) was higher than that of nitrification bacteria, and that in the sediments was slightly higher than that in the water. Nitrosopumilus and Pseudomonas were the dominant nitrification and denitrification bacteria in Mengniuhe River, respectively. The results of phylogenetic investigation of communities by the reconstruction of unobserved states (PICRUSt2) showed that NO3--N reduction module was the major nitrogen metabolism module, which primarily occurred in water. The abundance of the functional genes for nitrification (i.e., narGH) was the highest in water, and the major functional gene involved in NO3--N reduction was nirBD of DNRA, which was primarily present in the sediments; however, the main functional gene involved in denitrification was nirK.


Assuntos
Microbiota , Rios , Filogenia , Nitrogênio , Qualidade da Água
14.
Ultrasonics ; 135: 107131, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37556915

RESUMO

Compared with conventional drilling (CD), ultrasonic vibration-assisted drilling(UVAD) is experimentally proven a promising method to reduce the cutting temperature. But sometimes cutting temperature also becomes higher in UVAD than in CD. To further make clear the cutting temperature mechanisms in UVAD, this study aims to study the effect of tool's ultrasonic vibration on the cutting heat generation and heat dissipation at a relatively micro level. Firstly, drilling experiments are designed to explore the variations of cutting heat under different ultrasonic vibrations. Then, to analyze the influence of ultrasonic vibration on the cutting heat theoretically, a kinematic model is developed to describe the dynamic contact between the cutting edge and workpiece in UVAD. Besides, a cutting heat analysis model based on the contact characteristics in UVAD is proposed to study and compare the variations of cutting heat generation. The effect of ultrasonic vibration on the cutting heat generation, heat dispassion, and the resultant cutting temperature under different machining in UVAD conditions are discussed. It is indicated from the theoretical analysis that more cutting heat tends to be produced due to the significantly increased sliding velocity on the cutting edge-workpiece interface when the ultrasonic vibration is applied. The analysis agrees with the experimental results that the cutting temperature in dry UVAD is higher than in dry CD. But on the other hand, ultrasonic vibration can also improve the lubrication and cooling effect under appropriate machining conditions, which is beneficial to the reduction in cutting temperature. The investigation shows the multifaceted influences of ultrasonic vibration on the cutting temperature in the drilling process in detail, which provides a reference for UVAD parameter optimization.

15.
JACC Asia ; 3(3): 446-454, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37396422

RESUMO

Background: Although current guidelines recommend beta-blockers (BBs) after acute myocardial infarction (AMI), the role of calcium-channel blockers (CCBs) has not been well investigated, especially nondihydropyridine. Objectives: This study aimed to compare the effects of CCBs on cardiovascular outcomes compared with BBs in AMI because patients from East Asia have a higher incidence of a vasospastic angina component compared with Western countries. Methods: Among 15,628 patients enrolled in the KAMIR-V (Korean Acute Myocardial Infarction Registry-V), we evaluated 10,650 in-hospital survivors who were treated with either CCBs or BBs. We applied a propensity score for 1:4 pair matching of baseline covariates and Cox regression to compare CCBs and BBs. The primary endpoint was all-cause death at 1 year. The secondary endpoints were 1-year major adverse cardiac and cerebrovascular events, which was the composite of cardiac death, myocardial infarction, revascularization, and readmission due to heart failure and stroke. Results: There was a significant interaction with the treatment arm with left ventricular ejection fraction (LVEF) (P for interaction = 0.011). CCB groups at discharge had higher 1-year cardiac death and major adverse cardiac and cerebrovascular events for patients with LVEF <50% (HR: 4.950; 95% CI: 1.329-18.435; P = 0.017; and HR: 1.810; 95% CI: 1.038-3.158; P = 0.037, respectively) but not for patients with LVEF ≥50% (HR: 0.699; 95% CI: 0.435-1.124; P = 0.140). Conclusions: CCB therapy did not increase adverse cardiovascular events for patients after AMI with preserved LVEF. CCBs can be considered as an alternative for BBs in East Asian patients after AMI with preserved LVEF.

16.
Cell Rep ; 42(7): 112779, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37436898

RESUMO

Retinal pigment epithelium (RPE) dysfunction and choroidal neovascularization (CNV) are predominant features of age-related macular degeneration (AMD), with an unclear mechanism. Herein, we show that RNA demethylase α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) is up-regulated in AMD. In RPE cells, ALKBH5 overexpression associates with depolarization, oxidative stress, disturbed autophagy, irregular lipid homeostasis, and elevated VEGF-A secretion, which subsequently promotes proliferation, migration, and tube formation of vascular endothelial cells. Consistently, ALKBH5 overexpression in mice RPE correlates with various pathological phenotypes, including visual impairments, RPE anomalies, choroidal neovascularization (CNV), and interrupted retinal homeostasis. Mechanistically, ALKBH5 regulates retinal features through its demethylation activity. It targets PIK3C2B and regulates the AKT/mTOR signaling pathway with YTHDF2 as the N6-methyladenosine reader. IOX1, an ALKBH5 inhibitor, suppresses hypoxia-induced RPE dysfunction and CNV progression. Collectively, we demonstrate that ALKBH5 induces RPE dysfunction and CNV progression in AMD via PIK3C2B-mediated activation of the AKT/mTOR pathway. Pharmacological inhibitors of ALKBH5, like IOX1, are promising therapeutic options for AMD.


Assuntos
Homólogo AlkB 5 da RNA Desmetilase , Neovascularização de Coroide , Degeneração Macular , Animais , Camundongos , Neovascularização de Coroide/metabolismo , Células Endoteliais/metabolismo , Degeneração Macular/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/metabolismo
17.
Genes Dis ; 10(5): 1857-1869, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37492708

RESUMO

Hepatocellular carcinoma (HCC) has a very high incidence and fatality rate, and in most cases, it is already at an advanced stage when diagnosed. Therefore, early prevention and detection of HCC are two of the most effective strategies. However, the methods recommended in the practice guidelines for the detection of HCC cannot guarantee high sensitivity and specificity except for the liver biopsy, which is known as the "gold standard". In this review, we divided the detection of HCC into pre-treatment diagnosis and post-treatment monitoring, and found that in addition to the traditional imaging detection and liver biopsy, alpha fetoprotein (AFP), lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), protein induced by vitamin K absence or antagonist-II (PIVKA-II) and other biomarkers are excellent biomarkers for HCC, especially when they are combined together. Most notably, the emerging liquid biopsy shows great promise in detecting HCC. In addition, lactic dehydrogenase (LDH), suppressor of cytokine signaling (SOCS) and other relevant biomarkers may become promising biomarkers for HCC post-treatment monitoring. Through the detailed introduction of the diagnostic technology of HCC, we can have a detailed understanding of its development process and then obtain some enlightenment from the diagnosis, to improve the diagnostic rate of HCC and reduce its mortality.

18.
Food Chem ; 426: 136611, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37356237

RESUMO

Herein, we proposed surface engineering of magnetic peroxidase mimic using bacteriophage by electrostatic interaction to prepare bacteriophage SapYZU15 modified Fe3O4 (SapYZU15@Fe3O4) for colorimetric determination of S. aureus in food. SapYZU15@Fe3O4 exhibits peroxidase-like activity, catalyzing 3,3',5,5'-tetramethylbenzidine (TMB) chromogenic reaction. After introducing S. aureus, peroxidase-like activity of SapYZU15@Fe3O4 was specifically inhibited, resulting in deceleration of TMB chromogenic reaction. This phenomenon benefits from the presence of unique tail protein gene in the bacteriophage SapYZU15 genome, leading to a specific biological interaction between S. aureus and SapYZU15. On basis of this principle, SapYZU15@Fe3O4 can be employed for colorimetric determination of S. aureus with a limiting detection (LOD), calculated as low as 1.2 × 102 CFU mL-1. With this proposed method, colorimetric detection of S. aureus in food was successfully achieved. This portends that surface engineering of nanozymes using bacteriophage has great potential in the field of colorimetric detection of pathogenic bacterium in food.


Assuntos
Bacteriófagos , Peroxidase , Peroxidase/genética , Peroxidase/metabolismo , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Bacteriófagos/genética , Bacteriófagos/metabolismo , Colorimetria/métodos , Peroxidases , Fenômenos Magnéticos , Peróxido de Hidrogênio
19.
Eur Heart J Cardiovasc Pharmacother ; 9(5): 421-426, 2023 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-37291702

RESUMO

AIMS: Atrial fibrillation (AF) is linked to an increased risk of dementia, even in stroke-free patients. The impact of statin therapy on dementia risk is unclear in AF patients receiving oral anticoagulant (OAC) (vitamin K antagonist and direct-acting OAC). We sought to investigate the impact of statin therapy on dementia risk in AF patients receiving OAC. METHODS AND RESULTS: Using the Korean National Health Insurance Service database, 91 018 non-valvular AF (NVAF) patients from January 2013 to December 2017 were included in the analysis. Of the total, 17 700 patients (19.4%) were in the statin therapy group, and 73 318 patients (80.6%) were in the non-statin therapy group. The primary endpoint was the occurrence of dementia. The median duration of follow-up was 2.1 years. Statin therapy was associated with a significantly lower dementia risk than non-statin therapy for CHA2DS2-VASc scores ≥2 (hazard ratio = 0.77, 95% confidence interval 0.64-0.90, P = 0.026) in NVAF patients receiving OAC. The statin therapy group had a significantly lower dementia risk in a dose-dependent relationship compared with the non-statin therapy group (P for trend <0.001). CONCLUSION: In NVAF patients who received OAC, statin therapy lowered the dementia risk compared with no statin therapy. Furthermore, statin therapy is associated with a dose-dependent reduction in dementia risk.


Assuntos
Fibrilação Atrial , Demência , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/complicações , Anticoagulantes/efeitos adversos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Inibidores do Fator Xa , Demência/diagnóstico , Demência/epidemiologia , Demência/prevenção & controle
20.
J Agric Food Chem ; 71(22): 8332-8344, 2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37216206

RESUMO

The broad-spectrum UV filter oxybenzone is toxic to plants at environmentally relevant concentrations. Lysine acetylation (LysAc) is one of the essential post-translational modifications (PTMs) in plant signaling responses. The goal of this study was to uncover the LysAc regulatory mechanism in response to toxic exposures to oxybenzone as a first step in elucidating xenobiotic acclimatory reactions by using the model Brassica rapa L. ssp. chinensis. A total of 6124 sites on 2497 proteins were acetylated, 63 proteins were differentially abundant, and 162 proteins were differentially acetylated under oxybenzone treatment. Bioinformatics analysis showed that a large number of antioxidant proteins were significantly acetylated under oxybenzone treatment, implying that LysAc alleviated the adverse effects of reactive oxygen species (ROS) by inducing antioxidant systems and stress-related proteins; the significant changes in acetylation modification of enzymes involved in different branches of carbon metabolism in plants under oxybenzone treatment mean that plants can change the direction of carbon flow allocation by regulating the activities of carbon metabolism-related enzymes. Our results profile the protein LysAc under oxybenzone treatment and propose an adaptive mechanism at the post-translational level of vascular plants in response to pollutants, providing a dataset reference for future related research.


Assuntos
Brassica rapa , Lisina , Lisina/metabolismo , Brassica rapa/metabolismo , Acetilação , Proteômica , Antioxidantes/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas/metabolismo
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