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1.
Langmuir ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38920295

RESUMEN

Pickering double emulsions exhibit higher stability and biocompatibility compared with surfactant-stabilized double emulsions. However, tailored synthesis of particle stabilizers with appropriate wettability is time consuming and complicated and usually limits their large-scale adoption. Using binary stabilizers may be a simple and scalable strategy for Pickering double emulsion formation. Herein, commercially available hydrophobic silica nanoparticles (SNPs) and sodium alginate (SA) as binary stabilizers are used to prepare O/W/O Pickering double emulsions in one-step emulsification. The influence of system composition on double emulsion preparation is identified by optical microscopy, confocal laser scanning microscopy, and interfacial tension and water contact angle analyses. The formation of the O/W/O Pickering double emulsion depends critically on the aqueous phase viscosity and occurrence of emulsion inversion. Both hydrophobic SNPs and SA adsorb at the droplet surface to provide a steric barrier, while SA also reduces interfacial tension and increases aqueous phase viscosity, giving double emulsion long-term stability. Their microstructure and stability are controlled by adjusting the SA concentration, water-oil volume ratio, concentration and wettability of the particle stabilizer, and oil type. As a demonstration, the middle layer of the as-prepared O/W/O Pickering double emulsions can be cross-linked in situ with calcium ions to produce calcium alginate porous microspheres. We believe that our strategy for double emulsion formation holds great potential for practical applications in food, cosmetics, or pharmaceuticals.

2.
Int J Geriatr Psychiatry ; 38(10): e6010, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37794769

RESUMEN

OBJECTIVES: The proportion of older people with dementia in China is gradually increasing with the increase in the aging population over recent years. Hypertension and diabetes are common non-communicable diseases among rural populations in China. However, it remains unclear whether these conditions affect the occurrence and development of cognitive impairment as there is limited research on cognitive status and its risk factors among residents of rural areas. METHODS: A multi-stage stratified cluster random sampling method was used to select 5400 participants from rural permanent residents. A self-designed structured questionnaire was used to investigate demographic data of the participants. Cognitive function was assessed using the Montreal Cognitive Function Assessment Scale (MoCA). The results were analyzed using chi-square test, ANOVA and multiple linear regression analysis. RESULTS: A total of 5028 participants returned the survey, giving a response rate of 93.1%. Higher education (odds ratio (OR) = 3.2, 95% confidence interval (CI) 2.87-3.54, p < 0.001), higher income (OR = 1.61, 95% CI 1.16-2.07, p < 0.001), and dietary control (OR = 0.66, 95%CI 0.34-0.98, p < 0.001) were protective factors. A visual representation of the relationship between annual income and MoCA score showed an inverted U-curve, the group with an annual income of 6000-7999 RMB had a maximum OR of 1.93 (95%CI 0.12-2.74, p < 0.001). While difficulty in maintaining sleep were risk factors for cognitive impairment (OR = -2.28, 95% CI-4.18-0.39, p = 0.018). CONCLUSIONS: Participants with middle incomes had better cognitive status than those with the highest incomes. Higher education, proper diet control and good sleep are beneficial to the cognitive status of residents in rural areas.


Asunto(s)
Diabetes Mellitus , Hipertensión , Humanos , Anciano , Estudios Transversales , Población Rural , Factores de Riesgo , Hipertensión/epidemiología , Cognición , China/epidemiología
3.
J Cell Mol Med ; 26(23): 5820-5831, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36317420

RESUMEN

Glioma is a highly invasive primary brain tumour, making it challenging to accurately predict prognosis for glioma patients. Cuproptosis is a recently discovered cell death attracting significant attention in the tumour field. Whether cuproptosis-related genes have prognostic predictive value has not been clarified. In this study, uni-/multi-variate Cox and Lasso regression analyses were applied to construct a risk model based on cuproptosis-related lncRNAs using TCGA and CGGA cohorts. A nomogram was constructed to quantify individual risk, including clinical and genic characteristics and risk. GO and KEGG analyses were used to define functional enrichment of DEGs. Tumour mutation burden (TMB) and immune checkpoint analyses were performed to evaluate potential responses to ICI therapy. Ten prognostic lncRNAs were obtained from Cox regression. Based on the median risk score, patients were divided into high- and low-risk groups. Either for grade 2-3 or for grade 4, glioma patients with high-risk exhibited significant poorer prognoses. The risk was an independent risk factor associated with overall survival. The high-risk group was functionally associated with immune responses and cancer-related pathways. The high-risk group was associated with higher TMB scores. The expression levels of many immune checkpoints in the high-risk group were significantly higher than those in the low-risk group. Differentiated immune pathways were primarily enriched in the IFN response, immune checkpoint and T-cell co-stimulation pathways. In conclusion, we established a risk model based on cuproptosis-related lncRNAs showing excellent prognostic prediction ability but also indicating the immuno-microenvironment status of glioma.


Asunto(s)
Apoptosis , Glioma , ARN Largo no Codificante , Humanos , Glioma/genética , Glioma/terapia , Factores Inmunológicos , Inmunoterapia , Nomogramas , ARN Largo no Codificante/genética , Cobre
4.
Crit Rev Eukaryot Gene Expr ; 31(5): 33-40, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34591388

RESUMEN

The microRNA MiR-24-3p suppresses cancer progression by targeting TRIM11. The long noncoding RNA LUADT1 has been reported to promote lung adenocarcinoma proliferation. We found LUADT1 may form base pairing with miR-24-3p. This study aimed to explore the interactions among LUADT1, miR-24-3p, and TRIM11 in mantle cell lymphoma (MCL). Our study recruited 40 MCL patients and 40 healthy volunteers. Tumor tissues were collected from 40 newly diagnosed MCL patients and embedded in paraffin wax. B lymphocytes were isolated from all tissue samples by using CD19+ magnetic beads and DETACHaBEAD CD19. Human MCL cell line Grante-519 and JeKo-1 were transfected with LUADT1 and TRIM11 expression vectors, microRNA mimics or inhibitors. Then, quantitative polymerase chain reaction and Western blot were used to detect the level of relative messenger RNA and protein expression, respectively. Flow cytometry was performed to detect the apoptosis rate. LUADT1 and miR-24-3p were upregulated while TRIM11 was downregulated in MCL both in tissues and cell lines compared with hyperplastic lymphadenitis and peripheral lymphocyte cells. Bioinformatics analysis showed that LUADT1 may bind miR-24-3p, which can target TRIM11. Correlation analysis showed that LUADT1 was not significantly correlated with miR-24-3p. However, it was positively and significantly correlated with TRIM11. In MCL cells, LUADT1 overexpression led to upregulated TRIM11, whereas miR-24-3p overexpression led to downregulated TRIM11. Cell apoptosis analysis showed that LU-ADT1, miR-24-3p inhibitor and TRIM11 overexpression led to decreased apoptotic rate of MCL cells, whereas miR-24-3p overexpression led to an increased apoptotic rate of MCL cells. In addition, miR-24-3p overexpression attenuated the effects of LUADT1 overexpression. Therefore, LUADT1 was upregulated in MCL and could modulate TRIM11 by sponging miR-24-3p to inhibit cancer cell apoptosis.


Asunto(s)
Apoptosis , Linfocitos B/metabolismo , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/metabolismo , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Anciano , Línea Celular Tumoral , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , ARN Largo no Codificante/genética
5.
J Am Chem Soc ; 142(50): 21004-21016, 2020 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-33284628

RESUMEN

Aqueous liquids can be charged effectively by a number of methods for many important applications. Organic liquids, however, cannot be charged effectively by existing methods due to their low conductivities, especially the insulating nonpolar organic liquids; hence, there has not been any significant application developed based on charged organic liquids. This study describes an effective fundamental strategy for charging organic liquids, including nonpolar organic liquids: static charge is simply mixed into the liquid. Analyses suggested that the charged species are molecular ions that reside in the bulk of the liquid after charging. This method is simple and general, and the amount and polarity of charge can be flexibly tunable. The effectiveness of this method gives rise to opportunities for the development of novel applications. Charged organic droplets are manipulated for the first time by an electric field for controlling organic reactions. Particles with charge embedded in their bulk matrices are fabricated for the first time (i.e., via polymerizing the liquid monomers mixed with static charge). The charge in this novel class of bulk-charged particles is stable and permanent, especially when compared to the typical surface-charged particles. Simultaneous bulk-charged and bulk-magnetic particles are fabricated for the first time via simply mixing both the static charge and magnetic nanoparticles into the liquid monomers. These highly versatile particles are responsive to both electric and magnetic fields for practical applications.

6.
Acta Biochim Biophys Sin (Shanghai) ; 52(6): 675-682, 2020 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-32445466

RESUMEN

In this study, we aimed to explore the effect of TrkB-PLC/IP3 pathway on intestinal inflammatory factors and enterocyte apoptosis in mice with colitis. The mouse model of ulcerative colitis was established by medication, and 40 SPF C57BL/6J mice (8 weeks old) were randomly divided into normal group (healthy mice, n = 10), control group (sham-operated mice, n = 10), model group (model mice without any treatment, n = 10), and K252a group (model mice treated with 100 µmol/kg TrkB-PLC/IP3 pathway inhibitor for 5 days before clysis, n = 10). The results showed that mice in the model and K252a groups, as compared with normal and control groups, had no significant changes in the levels and protein expressions of serum tumor necrosis factor-α (TNF-α) and TNF-γ in the colon tissues (P>0.05), and had a significant increase in disease activity index, colon mucosa damage index, tissue damage index scores, and levels and protein expressions of serum interleukin-4 (IL-4) and IL-8, but had a significant decrease in the level and protein expression of serum IL-10 (P<0.05). Mice in the model and K252a groups showed blocked enterocyte cycle progression, elevated apoptosis ratio, and significantly increased mRNA and protein expressions of Caspase3, Bax, FasL, and Fas, but significantly reduced mRNA and protein expressions of p-TrkB, PLC-γ1, IP3, and Bcl-2 (P<0.05). Moreover, intestinal inflammation and apoptosis induced by colitis in the K252a group became more aggravated by inhibiting the activity of TrkB-PLC/IP3 pathway. In conclusion, inhibition of TrkB-PLC/IP3 pathway can increase the expression of intestinal inflammatory factors and promote enterocyte apoptosis in mice with colitis.


Asunto(s)
Apoptosis , Colitis Ulcerosa/metabolismo , Enterocitos/metabolismo , Mediadores de Inflamación/metabolismo , Fosfatos de Inositol/metabolismo , Glicoproteínas de Membrana/metabolismo , Fosfoinositido Fosfolipasa C/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Transducción de Señal , Animales , Colitis Ulcerosa/patología , Modelos Animales de Enfermedad , Enterocitos/patología , Ratones
7.
Mol Cell Biochem ; 450(1-2): 167-174, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29926321

RESUMEN

The basic helix-loop-helix (bHLH) superfamily of transcription factors have been implicated in a wide range of cellular functions such as proliferation, differentiation, tumorigenesis, and circadian rhythms. In a previous siRNA-based screen, bHLH family member e41 (BHLHE41) had been identified as a putative regulator of neuronal differentiation; however, its function remains largely elusive. To this end, using the CRISPR-Cas9 system, we established an isogenic Neuro2a (N2a) cell line with biallelic targeting of Bhlhe41 gene (Bhlhe41-/-). In undifferentiated N2a cells, complete knockout of Bhlhe41 resulted in marked proliferation inhibition, together with accumulation of apoptotic cells. Furthermore, retinoic acid (RA)-induced neurite outgrowth and expression of neuronal markers are significantly weakened in Bhlhe41-/- cells. We also showed that the activity of ERK1/2 signaling, a key regulator of neuronal differentiation, is likewise impaired in knockout cells. Together, these results suggest that Bhlhe41 plays critical roles in regulating cell death and neurite outgrowth in N2a cells.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Diferenciación Celular , Proliferación Celular , Sistema de Señalización de MAP Quinasas , Neuritas/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Sistemas CRISPR-Cas , Muerte Celular/efectos de los fármacos , Muerte Celular/genética , Línea Celular , Eliminación de Gen , Ratones , Tretinoina/farmacología
8.
BMC Neurol ; 19(1): 157, 2019 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-31291898

RESUMEN

BACKGROUND: Hereditary ataxia is a group of neurodegenerative diseases with progressive cerebellar ataxia of the gait and limbs as the main symptoms. The genetic patterns of the disease are diverse but it is mainly divided into autosomal dominant cerebellar ataxia (ADCA) and autosomal recessive cerebellar ataxia (ARCA), and about 45 pathogenic loci have been found in ADCA. The purpose of this study was to explore the genetic defect in a Chinese family with ADCA. METHODS: A three-generation Chinese family with ADCA was enrolled in this study, Exome sequencing was conducted in four family members, including the proband, and verified by Sanger sequencing. RESULTS: The rs779393130 mutation of the CACNA1C gene co-segregated with the ataxia phenotype in this family. The mutation was not detected in 50 unaffected controls. CONCLUSIONS: The rs779393130 mutation of CACNA1C may be associated with the phenotype of the disease. The CACNA1C gene encodes the Cav1.2 (alpha-1) subunit of an L-type calcium channel and this subunit may be related to the ADCA phenotype. These findings may have implications for family clinical monitoring and genetic counseling and may also help in understanding pathogenesis of this disease.


Asunto(s)
Canales de Calcio Tipo L/genética , Ataxia Cerebelosa/genética , Degeneraciones Espinocerebelosas/genética , Adulto , Pueblo Asiatico , Estudios de Casos y Controles , Femenino , Genes Dominantes , Humanos , Masculino , Mutación , Linaje , Fenotipo , Adulto Joven
9.
Cell Physiol Biochem ; 51(2): 681-691, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30463061

RESUMEN

BACKGROUND/AIMS: We aimed to explore the protective role of curcumin (Cur) in a cell model of Parkinson's disease (PD) and its underlying mechanism. METHODS: In this study, genes concerned with PD-related keywords were screened within DiGSeE database. The association network between Cur and selected genes was downloaded from STITCH, with the interactions analyzed by STRING. We built a mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+)-induced SH-SY5Y cell model of PD. Cell morphology was observed under an electron microscope. MTT assay was applied to detect cell proliferation rate. Western blot assay was conducted to determine the level of apoptotic markers, including cleaved caspase 3, Bcl-2-associated X protein (Bax) and B-cell lymphoma-extra-large (Bcl-xl). Tyrosine hydroxylase (TH), dopamine transporter (DAT) protein levels and dopamine (DA) concentration were identified as dopaminergic neuron markers and measured by western blotting or Enzyme-linked immunosorbent assay (ELISA). RESULTS: Cur rescued the toxicity effects of MPP+ on SH-SY5Y cells, by controlling morphological change, promoting cell proliferation and inhibiting apoptosis. Of all PD-related genes, HSP90 played an important role in Cur-gene network. HSP90 protein level was elevated by MPP+, whereas Cur could reverse this effect. Silencing of HSP90 significantly attenuated the curative effect introduced by Cur, while HSP90 overexpression enhanced the impact of Cur on PD. CONCLUSION: Cur can effectively inhibit the toxic effect of MPP+ on SH-SY5Y cells and significantly reduce the adverse effects of MPP+ on dopaminergic neurons via up-regulation of HSP90.


Asunto(s)
Apoptosis/efectos de los fármacos , Curcumina/farmacología , Proteínas HSP90 de Choque Térmico/metabolismo , 1-Metil-4-fenilpiridinio/toxicidad , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Dopamina/análisis , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Redes Reguladoras de Genes , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Proteínas HSP90 de Choque Térmico/genética , Humanos , Modelos Biológicos , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Proteína bcl-X/metabolismo
10.
Eur Neurol ; 78(3-4): 143-153, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28813703

RESUMEN

AIMS: To assess the efficacy and safety of adjuvant treatment with entacapone in the treatment of later Parkinson's disease (PD) patients with motor fluctuation. METHODS: We conducted a systematic review of relevant studies from 8 databases to June 23, 2016. RESULTS: Fourteen studies were included in this review (n = 2,804). The results showed that compared with placebo, adjuvant therapy with entacapone significantly increased on time (p < 0.01) and reduced off time (p < 0.01), the required levodopa (LD) dose (p < 0.01) and improved Parkinson's Disease Rating Scale (UPDRS) scores (activities of daily living score: p < 0.01; motor score: p < 0.01; UPDRS I-III score: p > 0.05). However, the withdrawal (OR 1.44, 95% CI 1.10-1.89, p < 0.01) due to adverse events and adverse events rates including nausea (OR 2.23, 95% CI 1.56-3.20, p < 0.01), urine discoloration (OR 14.99, 95% CI 7.63-29.44, p < 0.01), gastrointestinal disorder (OR 2.6, 95% CI 1.89-3.57, p < 0.01) and dyskinesia (OR 2.00, 95% CI 1.56-2.58, p < 0.01) increased in patients with entacapone compared with those given a placebo . CONCLUSIONS: This meta-analysis suggests that the entacapone used as adjuvant therapy to LD is effective in the management of later PD with fluctuation. However, patients on entacapone had a higher frequency of adverse events than those on placebo but no occurrence of severe adverse reactions.


Asunto(s)
Antiparkinsonianos/administración & dosificación , Catecoles/administración & dosificación , Nitrilos/administración & dosificación , Enfermedad de Parkinson/tratamiento farmacológico , Actividades Cotidianas , Anciano , Antiparkinsonianos/efectos adversos , Catecoles/efectos adversos , Quimioterapia Combinada , Discinesias , Femenino , Humanos , Levodopa/administración & dosificación , Masculino , Persona de Mediana Edad , Nitrilos/efectos adversos
11.
Angew Chem Int Ed Engl ; 55(34): 9956-60, 2016 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-27417888

RESUMEN

Charged liquid droplets are typically generated by a high-voltage power supply. Herein, a previously unreported method is used for charging liquid droplets: by transferring charge from an insulating solid surface charged by contact electrification to the droplets. Charging the solid surface by contact electrification involves bringing it into contact with another solid surface for generating static charge. Subsequently, water droplets that flow across the surface are found to be charged-thus, the charge is readily transferred from solid to liquid. The charge of the droplets can be tuned continuously from positive to negative by varying the way the solid surface is charged. The amount of charge generated is sufficient for manipulating, coalescing, and sorting the water droplets by solid surfaces charged by contact electrification. This method of generating charged droplets is general, simple, inexpensive, and does not need any additional equipment or power supply.

12.
Polymers (Basel) ; 16(5)2024 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-38475375

RESUMEN

A dual biofunctional hydrogel (HQCS-SP) wound dressing, offering antibacterial properties and a biological response, was innovatively designed and developed to repair full-layer skin defects. The HQCS-SP hydrogel creates an artificial matrix that facilitates cell recruitment, extracellular matrix deposition, exhibiting exceptional tissue affinity, robust self-healing, effective hemostatic capabilities and accelerates wound healing. It is synthesized by crosslinking modified chitosan (HQCS) with spirulina protein (SP) and Fe3+. The HQCS provides antibacterial, antioxidant, good tissue affinity and excellent hemostasis performance. The incorporation of SP not only reinforces the antioxidant, antibacterial, anti-inflammatory, and pro-angiogenesis effects but also participates in the regulation of signal pathways and promotes wound healing. Therefore, this study offers a new visual angle for the design of advanced functional trauma dressings with great application potential in the bio-medical field.

13.
RSC Adv ; 14(23): 16194-16206, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38769952

RESUMEN

The rapid emergence and spread of multidrug-resistant bacteria pose a serious challenge to human life and health, necessitating the development of novel antibacterial agents. Herein, to address this challenge, three iridium-based antibacterial agents were prepared and their antimicrobial activity were explored. Importantly, the three complexes all showed robust potency against S. aureus with MIC values in the range of 1.9-7.9 µg mL-1. Notably, the most active complex Ir3 also exhibited relative stability in mammalian fluids and a significant antibacterial effect on clinically isolated drug-resistant bacteria. Mechanism studies further demonstrated that the complex Ir3 can kill S. aureus by disrupting the integrity of the bacterial membrane and inducing ROS production. This multi-target advantage allows Ir3 to not only effectively combat bacterial resistance but also efficiently clear the bacterial biofilm. In addition, when used together, complex Ir3 could enhance the antibacterial potency of some clinical antibiotics against S. aureus. Moreover, both G. mellonella wax worms and mouse infection model demonstrated that Ir3 has low toxicity and robust anti-infective efficacy in vivo. Overall, complex Ir3 can serve as a new antibacterial agent for combating Gram-positive bacterial infections.

14.
Gels ; 10(5)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38786252

RESUMEN

Herein, the starch nanocrystal/tannic acid (ST) complex particles, which were prepared based on the hydrogen bond between starch nanocrystal (SNC) and tannic acid (TA), were successfully used to stabilize the HIPPE gels. The optimal TA concentration of the ST complex particles resulted in better water dispersibility, surface wettability, and interfacial activity as compared to SNC. The hydrogen bond responsible for the formation of ST complex particles and subsequent stable emulsions was demonstrated by varying the pH and ionic strength of the aqueous phase. Notably, the HIPPE gels stabilized via the ST complex particles can maintain long-term stability for up to three months. The HIPPEs stabilized via the ST complex particles all displayed gel-like features and had smaller droplets and denser droplet networks than the SNC-stabilized HIPPEs. The rheological behavior of HIPPE gels stabilized via the ST complex particles can be readily changed by tuning the mass ratio of SNC and TA as well as pH. Finally, the prepared HIPPE gels used to effectively protect encapsulated ß-carotene against high temperatures and ultraviolet radiation and its controllable release at room temperature were demonstrated. It is anticipated that the aforementioned findings will provide new perspectives on the preparation of Pickering emulsion for delivery systems.

15.
Nat Commun ; 15(1): 1986, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443343

RESUMEN

What is static charge? Despite the long history of research, the identity of static charge and mechanism by which static is generated by contact electrification are still unknown. Investigations are challenging due to the complexity of surfaces. This study involves the molecular-scale analysis of contact electrification using highly well-defined surfaces functionalized with a self-assembled monolayer of alkylsilanes. Analyses show the elementary molecular steps of contact electrification: the exact location of heterolytic cleavage of covalent bonds (i.e., Si-C bond), exact charged species generated (i.e., alkyl carbocation), and transfer of molecular fragments. The strong correlation between charge generation and molecular fragments due to their signature odd-even effects further shows that contact electrification is based on cleavage of covalent bonds and transfer of ionic molecular fragments. Static charge is thus an alkyl carbocation; in general, it is an ionic molecular fragment. This mechanism based on cleavage of covalent bonds is applicable to general types of insulating materials, such as covalently bonded polymers. The odd-even effect of charging caused by the difference of only one atom explains the highly sensitive nature of contact electrification.

16.
RSC Adv ; 14(28): 20130-20144, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38915333

RESUMEN

Multidrug-resistant bacteria resulting from the abuse and overuse of antibiotics have become a huge crisis in global public health security. Therefore, it is urgently needed to develop new antibacterial drugs with unique mechanisms of action. As a versatile moiety, morpholine has been widely employed to enhance the potency of numerous bioactive molecules. In this study, a series of ruthenium-based antibacterial agents modified with the morpholine moiety were designed and characterized, aiming to obtain a promising metalloantibiotic with a multitarget mechanism. Antibacterial activity screening demonstrated that the most active complex Ru(ii)-3 exhibited the strongest potency against Staphylococcus aureus (S. aureus) with an MIC value of only 0.78 µg mL-1, which is better than most clinically used antibiotics. Notably, Ru(ii)-3 not only possessed excellent bactericidal efficacy, but could also overcome bacterial resistance. Importantly, Ru(ii)-3 very efficiently removed biofilms produced by bacteria, inhibited the secretion of bacterial exotoxins, and enhanced the activity of many existing antibiotics. The results of mechanism studies confirmed that Ru(ii)-3 could destroy the bacterial membrane and induce ROS production in bacteria. Furthermore, animal infection models confirmed that Ru(ii)-3 showed significant anti-infective activity in vivo. Overall, this work demonstrated that a morpholine-modified ruthenium-based agent is a promising antibiotic candidate in tackling the crisis of drug-resistant bacteria.

17.
J Gastrointest Surg ; 27(12): 2787-2796, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37932596

RESUMEN

BACKGROUND: Tumor morphology links to early recurrence of hepatocellular carcinoma. Controversy exists regarding the recurrence risk of Liver Imaging Reporting and Data System morphologic Type II hepatocellular carcinoma. This study aims to explore risk factors for early recurrence of Type II hepatocellular carcinoma. METHODS: Retrospective analysis of hepatocellular carcinoma patients who underwent curative resection and preoperative contrast-enhanced MRI from June 2016 to June 2020. Our patients formed the development set, and hepatocellular carcinoma patients from the TCIA database served as validation. Univariable and multivariable Cox regression identified independent risk factors for early recurrence. A risk scoring system was established for risk stratification, and an early recurrence prediction model was developed and validated. RESULTS: 95 Type II hepatocellular carcinoma patients were in the development set, and 29 cases were in the validation set. Early recurrence rates were 33.7% and 37.9%, respectively. Multivariate analysis revealed age, histological grade, AFP, and intratumoral hemorrhage as independent risk factors for early recurrence. The model's diagnostic performance for early recurrence was AUC = 0.817 in the development set. A scoring system classified patients into low-risk (scores ≤ 3) and high-risk (scores > 3) groups. The high-risk group had significantly lower recurrence-free survival (40.0% vs 73.2%, P = 0.001), consistent with the validation set (25.0% vs 73.3%, P = 0.028). CONCLUSIONS: The risk scoring system demonstrated excellent discrimination and predictive ability, aiding clinicians in assessing early recurrence risk and identifying high-risk individuals effectively.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Estudios Retrospectivos , Factores de Riesgo , Imagen por Resonancia Magnética
18.
Ann Clin Lab Sci ; 53(5): 719-725, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37945010

RESUMEN

OBJECTIVE: To investigate the expression of lncRNA UCA1 in serum of patients with acute cerebral infarction (ACI) and its relationship with prognosis. METHODS: The serum lncRNA UCA1 level in participants was detected, and the correlation between the neurological function score (NIHSS score) of ACI patients and lncRNA UCA1 expression was analyzed. Patients were followed up at 3 months after discharge and were divided into favorable and unfavorable prognostic groups according to the modified Rankin scale (mRs). The risk factors of ACI patients with poor prognosis were analyzed, and the predictive value of each index for ACI prognosis was evaluated by ROC curve. RESULTS: The level of lncRNA UCA1 in ACI group was increased (P<0.001). ROC analysis showed that high lncRNA UCA1 expression had clinical significance for the diagnosis of ACI. Spearman correlation analysis revealed that NIHSS score was positively correlated with lncRNA UCA1 expression level in ACI group (r=0.6537, P<0.001). Hcy level and NIHSS score in poor prognosis group (n=63) were higher than those in good prognosis group (n=84), and lncRNA UCA1 level in serum in poor prognosis group was increased in comparison to good prognosis group (P<0.05). Logistic regression analysis investigated that admission NIHSS score, infarct size, and increased lncRNA UCA1 were the risk factors affecting the prognosis of ACI. CONCLUSION: Serum lncRNA UCA1 is abnormally elevated in ACI patients, and the elevated lncRNA UCA1 not only shows high accuracy in the diagnosis of ACI, but also has a certain predictive value for poor prognosis of ACI.


Asunto(s)
Isquemia Encefálica , ARN Largo no Codificante , Accidente Cerebrovascular , Humanos , Infarto Cerebral/genética , Infarto Cerebral/diagnóstico , Relevancia Clínica , Pronóstico , ARN Largo no Codificante/genética
19.
Front Neurol ; 14: 1029370, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36970514

RESUMEN

Objective: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are collectively known as Lewy body dementia (LBD). Considering the heterogeneous nature of LBD and the different constellations of symptoms with which patients can present, the exact molecular mechanism underlying the differences between these two isoforms is still unknown. Therefore, this study aimed to explore the biomarkers and potential mechanisms that distinguish between PDD and DLB. Methods: The mRNA expression profile dataset of GSE150696 was acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between 12 DLB and 12 PDD were identified from Brodmann area 9 of human postmortem brains using GEO2R. A series of bioinformatics methods were applied to identify the potential signaling pathways involved, and a protein-protein interaction (PPI) network was constructed. Weighted gene co-expression network analysis (WGCNA) was used to further investigate the relationship between gene co-expression and different LBD subtypes. Hub genes that are strongly associated with PDD and DLB were obtained from the intersection of DEGs and selected modules by WGCNA. Results: A total of 1,864 DEGs between PDD and DLB were filtered by the online analysis tool GEO2R. We found that the most significant GO- and KEGG-enriched terms are involved in the establishment of the vesicle localization and pathways of neurodegeneration-multiple diseases. Glycerolipid metabolism and viral myocarditis were enriched in the PDD group. A B-cell receptor signaling pathway and one carbon pool by folate correlated with DLB in the results obtained from the GSEA. We found several clusters of co-expressed genes which we designated by colors in our WGCNA analysis. Furthermore, we identified seven upregulated genes, namely, SNAP25, GRIN2A, GABRG2, GABRA1, GRIA1, SLC17A6, and SYN1, which are significantly correlated with PDD. Conclusion: The seven hub genes and the signaling pathways we identified may be involved in the heterogeneous pathogenesis of PDD and DLB.

20.
Nucl Med Commun ; 43(2): 177-185, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-34864810

RESUMEN

OBJECTIVE: To develop an 18F-fluorodeoxyglucose PET/computed tomography (CT) scoring model based on metabolic and radiologic findings of the pleura and fluid to identify malignant pleural effusion. METHODS: The PET and CT findings from patients with pleural effusion in the derivation dataset were used to develop a scoring model. Then, the diagnostic accuracy of the predictive score was verified by the validation dataset. RESULTS: Eight parameters independently predicting malignancy were retained in the scoring model, including pleural nodules or masses (4 points), focal pleural thickening (2 points), absence of pleural loculation (2 points), thickness of mediastinal pleura involvement ≥0.5 cm (2 points), maximum standardized uptake value (SUVmax) of mediastinal pleura involvement ≥2.3 (2 points), thickness of nonmediastinal pleura involvement ≥0.5 cm (1 point), SUVmax of nonmediastinal pleura involvement ≥3.0 (1 point) and fluid SUVmax ≥1.6 (1 point). The operating characteristics of the PET/CT score were 0.958 area under the curve (AUC), 88.6% sensitivity, 91.2% specificity, 10.09 positive likelihood ratio and 0.13 negative likelihood ratio, with 6 points as the threshold. These values in the validation dataset were 0.947, 91.7%, 88.4%, 7.91 and 0.094, respectively. No difference was found in AUCs between the derivation and validation datasets (z = 0.517, P = 0.697). The negative predictive value was 99.4% in the score from 0 to 2, and the positive predictive value was 98.3% for patients with score between 9 and 15. CONCLUSIONS: The PET/CT scoring model is a valuable strategy to help physicians to distinguish malignant-benign pleural effusion and stratify patients who will benefit from invasive procedures.


Asunto(s)
Fluorodesoxiglucosa F18
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