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1.
Nano Lett ; 2024 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-39431642

RESUMEN

We study monolayer WSe2 using ultrafast electron diffraction. We introduce an approach to quantitatively extract atomic-site-specific information, providing an element-specific view of incoherent atomic vibrations following femtosecond excitation. Via differences between W and Se vibrations, we identify stages in the nonthermal evolution of the phonon population. Combined with a calculated phonon dispersion, this element specificity enables us to identify a long-lasting overpopulation of specific optical phonons and to interpret the stages as energy transfer processes between specific phonon groups. These results demonstrate the appeal of resolving element-specific vibrational information in the ultrafast time domain.

2.
Front Endocrinol (Lausanne) ; 15: 1411262, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39247915

RESUMEN

Background: Under the current pandemic of Corona Virus Disease 2019 (COVID-19), The relationship between fatigue and COVID-19 has been found. Infection with COVID-19 is associated with fatigue long after the acute phase of COVID-19. Understanding the association of thyroid hormones levels with post-COVID condition, such as fatigue, is necessary to improve quality of life. Methods: This population-based cohort study was conducted in Dalian, China, from December 2022, to March 2023, using a Yidu Core platform in the First Affiliated Hospital of Dalian Medical University, that integrates medical records, laboratory tests, and all diagnosis and treatment information based on patients in hospital. Eligible individuals were 40 patients with COVID-19, Divided them into fatigue group and non-fatigue group following up by telephone using the FS-14 scale after 6 months. The primary outcomes were the diagnoses of fatigue. The association between thyroid hormones levels and post-COVID condition, such as fatigue, was assessed using logistic regression analysis. Results: Compared with the non-fatigue group, the FT3 level in fatigue group was lower (p<0.05). FT3 was negatively correlated with fatigue after 6 months (OR 0.257, p<0.05). After adjusting for confounding factors such as age and gender, low FT3 was a risk factor for fatigue in patients with COVID-19, (OR 0.225, p<0.05). And the FT3 is less than 2.47 mol/L, it is the best critical value for predicting long-term fatigue, with a sensitivity of 92.3% and a specificity of 48.1%. Conclusions: Most people still have fatigue 6 months after COVID-19 infection. FT3 serves as the important index to predict fatigue in patients with COVID-19. it should be closely monitored during infection.


Asunto(s)
COVID-19 , Fatiga , Triyodotironina , Humanos , COVID-19/complicaciones , COVID-19/epidemiología , Fatiga/etiología , Fatiga/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Triyodotironina/sangre , Adulto , China/epidemiología , SARS-CoV-2 , Anciano , Estudios de Cohortes
3.
Eur J Radiol ; 180: 111688, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39182273

RESUMEN

PURPOSE: As a non-invasive coronary functional examination, coronary computed tomography angiography (CCTA)-derived fractional flow reserve (CT-FFR) showed predictive value in several non-cardiac surgeries. This study aimed to evaluate the predictive value of CT-FFR in lung cancer surgery. METHOD: We retrospectively collected 227 patients from January 2017 to June 2022 and used machine learning-based CT-FFR to evaluate the stable coronary artery disease (CAD) patients undergoing lung cancer surgery. The major adverse cardiac event (MACE) was defined as perioperative myocardial injury (PMI), myocardial infarction, heart failure, atrial and ventricular arrhythmia with hemodynamic disorder, cardiogenic shock and cardiac death. The multivariate logistic regression analysis was performed to identify risk factors for MACE and PMI. The discriminative capacity, goodness-of-fit, and reclassification improvement of prediction model were determined before and after the addition of CT-FFR≤0.8. RESULTS: The incidence of MACE was 20.7 % and PMI was 15.9 %. CT-FFR significantly outperformed CCTA in terms of accuracy for predicting MACE (0.737 vs 0.524). In the multivariate regression analysis, CT-FFR≤0.8 was an independent risk factor for both MACE [OR=10.77 (4.637, 25.016), P<0.001] and PMI [OR=8.255 (3.372, 20.207), P<0.001]. Additionally, we found that the performance of prediction model for both MACE and PMI improved after the addition of CT-FFR. CONCLUSIONS: CT-FFR can be used to assess the risk of perioperative MACE and PMI in patients with stable CAD undergoing lung cancer surgery. It adds prognostic information in the cardiac evaluation of patients undergoing lung cancer surgery.


Asunto(s)
Angiografía por Tomografía Computarizada , Enfermedad de la Arteria Coronaria , Reserva del Flujo Fraccional Miocárdico , Neoplasias Pulmonares , Valor Predictivo de las Pruebas , Humanos , Masculino , Femenino , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/diagnóstico por imagen , Angiografía por Tomografía Computarizada/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/cirugía , Complicaciones Posoperatorias/diagnóstico por imagen , Angiografía Coronaria/métodos , Factores de Riesgo , Aprendizaje Automático
4.
World J Diabetes ; 15(6): 1340-1352, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38983805

RESUMEN

BACKGROUND: The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass (DJB) surgery is not clear. AIM: To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model. METHODS: DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model. All adipose tissue was weighed and observed under microscope. Use inguinal fat to represent subcutaneous adipose tissue (SAT) and mesangial fat to represent visceral adipose tissue. RNA-sequencing was utilized to evaluate gene expression alterations adipocytes. The hematoxylin and eosin staining, reverse transcription-quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to study the changes. Insulin resistance was evaluated by immunofluorescence. RESULTS: After DJB, whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved. Fat cell volume in both visceral adipose tissue (VAT) and SAT increased. Compared to SAT, VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone (GH) pathway and downstream adiponectin secretion were involved in metabolic regulation. The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased. Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity. CONCLUSION: GH improves insulin resistance in VAT in male diabetic rats after receiving DJB, possibly by increasing adiponectin secretion.

5.
Sci Adv ; 10(26): eadk3897, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38941460

RESUMEN

The topology of the electronic band structure of solids can be described by its Berry curvature distribution across the Brillouin zone. We theoretically introduce and experimentally demonstrate a general methodology based on the measurement of energy- and momentum-resolved optical transition rates, allowing to reveal signatures of Berry curvature texture in reciprocal space. By performing time- and angle-resolved photoemission spectroscopy of atomically thin WSe2 using polarization-modulated excitations, we demonstrate that excitons become an asset in extracting the quantum geometrical properties of solids. We also investigate the resilience of our measurement protocol against ultrafast scattering processes following direct chiroptical transitions.

6.
Polymers (Basel) ; 16(2)2024 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-38276693

RESUMEN

Water scarcity and water pollution have become increasingly severe, and therefore, the purification of water resources has recently garnered increasing attention. Given its position as a major water resource, the efficient purification of drinking water is of crucial importance. In this study, we adopted a phase transition method to prepare ZrO2/BCM (bamboo cellulose membranes), after which we developed IP-ZrO2/BC-NFM (bamboo cellulose nanofiltration membranes) through interfacial polymerization using piperazine (PIP) and tricarbonyl chloride (TMC). Subsequently, we integrated these two membranes to create a combined "ultrafiltration + nanofiltration" membrane process for the treatment of drinking water. The membrane combination process was conducted at 25 °C, with ultrafiltration at 0.1 MPa and nanofiltration at 0.5 MPa. This membrane combination, featuring "ultrafiltration + nanofiltration," had a significant impact on reducing turbidity, consistently maintaining the post-filtration turbidity of drinking water at or below 0.1 NTU. Furthermore, the removal rates for CODMN and ammonia nitrogen reached 75% and 88.6%, respectively, aligning with the standards for high-quality drinking water. In a continuous 3 h experiment, the nanofiltration unit exhibited consistent retention rates for Na2SO4 and bovine serum protein (BSA), with variations of less than 5%, indicating exceptional separation performance. After 9 h of operation, the water flux of the nanofiltration unit began to stabilize, with a decrease rate of approximately 25%, demonstrating that the "ultrafiltration + nanofiltration" membrane combination can maintain consistent performance during extended use. In conclusion, the "ultrafiltration + nanofiltration" membrane combination exhibited remarkable performance in the treatment of drinking water, offering a viable solution to address issues related to water scarcity and water pollution.

8.
J Environ Sci (China) ; 138: 439-449, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38135409

RESUMEN

The booming development of rare earth industry and the extensive utilization of its products accompanied by urban development have led to the accelerated accumulation of rare earth elements (REEs) as emerging pollutants in atmospheric environment. In this study, the variation of REEs in PM2.5 with urban (a non-mining city) transformation was investigated through five consecutive years of sample collection. The compositional variability and provenance contribution of REEs in PM2.5 were characterized, and the REEs exposure risks of children and adults via inhalation, ingestion and dermal absorption were also evaluated. The results showed an increase in the total REEs concentration from 46.46 ± 35.16 mg/kg (2017) to 81.22 ± 38.98 mg/kg (2021) over the five-year period, with Ce and La making the largest contribution. The actual increment of industrial and traffic emission source among the three pollution sources was 1.34 ng/m3. Coal combustion source displayed a downward trend. Ingestion was the main exposure pathway for REEs in PM2.5 for both children and adults. Ce contributed the most to the total intake of REEs in PM2.5 among the population, followed by La and Nd. The exposure risks of REEs in PM2.5 in the region were relatively low, but the trend of change was of great concern. It was strongly recommended to strengthen the concern about traffic-related non-exhaust emissions of particulate matter.


Asunto(s)
Contaminantes Atmosféricos , Metales de Tierras Raras , Adulto , Niño , Humanos , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Ciudades , Monitoreo del Ambiente/métodos , Metales de Tierras Raras/análisis , China
9.
Int Immunopharmacol ; 127: 111423, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38141410

RESUMEN

AIM: Periodontitis is a prevalent oral immunoinflammatory condition that is distinguished by the compromised functionality of periodontal ligament stem cells (PDLSCs). Bomidin, a new recombinant antimicrobial peptide (AMP), exhibits antibacterial properties and modulates immune responses. Nevertheless, the precise anti-inflammatory impact of bomidin in periodontitis has yet to be fully elucidated. Thus, the study aimed to clarified the role of bomidin in modulating inflammation and its underlying mechanisms. METHODS: TNF-α was applied to treating PDLSCs for establishing a cell model of periodontitis. Bomidin, RSL3, ML385 and cycloheximide were also used to treat PDLSCs. Transcriptome sequencing, RT-qPCR, western blot, immunofluorescence, immunohistochemistry, Fe2+ detection probe, molecular docking, Co-IP assay, ubiquitination assay and murine models of periodontitis were used. RESULTS: Our study demonstrated that bomidin effectively suppressed inflammation in PDLSCs stimulated by TNF-α, through down-regulating the MAPK and NF-κB signaling pathways. Furthermore, bomidin exerted inhibitory effects on ferroptosis and activated the Keap1/Nrf2 pathway in the TNF-α group. There is a strong likelihood of bonding bomidin with Keap1 protein, which facilitated the degradation of Keap1 protein via the ubiquitin-proteasome pathway, leading to an enhanced translocation of Nrf2 protein to the nucleus. CONCLUSIONS: Bomidin can directly bond to Keap1 protein, resulting in the degradation of Keap1 through the ubiquitin-proteasome pathway, thereby further activating the Keap1/Nrf2 pathway. The upregulation of the Keap1/Nrf2 signaling pathway was found to contribute to the suppression of ferroptosis, ultimately alleviating inflammation in treatment of periodontitis.


Asunto(s)
Ferroptosis , Periodontitis , Ratones , Animales , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Ligamento Periodontal/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Simulación del Acoplamiento Molecular , Complejo de la Endopetidasa Proteasomal/metabolismo , Complejo de la Endopetidasa Proteasomal/farmacología , Osteogénesis , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Periodontitis/tratamiento farmacológico , Periodontitis/metabolismo , Células Madre/metabolismo , Ubiquitinas/metabolismo , Ubiquitinas/farmacología
10.
Sci Adv ; 9(47): eadi4661, 2023 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-38000022

RESUMEN

Metastable phases present a promising route to expand the functionality of complex materials. Of particular interest are light-induced metastable phases that are inaccessible under equilibrium conditions, as they often host new, emergent properties switchable on ultrafast timescales. However, the processes governing the trajectories to such hidden phases remain largely unexplored. Here, using time- and angle-resolved photoemission spectroscopy, we investigate the ultrafast dynamics of the formation of a hidden quantum state in the layered dichalcogenide 1T-TaS2 upon photoexcitation. Our results reveal the nonthermal character of the transition governed by a collective charge-density-wave excitation. Using a double-pulse excitation of the structural mode, we show vibrational coherent control of the phase-transition efficiency. Our demonstration of exceptional control, switching speed, and stability of the hidden state are key for device applications at the nexus of electronics and photonics.

11.
Mol Pharm ; 20(10): 4971-4983, 2023 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-37699256

RESUMEN

mRNA vaccines encoding a single spike protein effectively prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the emergence of SARS-CoV-2 variants leads to a wide range of immune evasion. Herein, a unique trivalent mRNA vaccine based on ancestral SARS-CoV-2, Delta, and Omicron variant spike receptor-binding domain (RBD) mRNAs was developed to tackle the immune evasion of the variants. First, three RBD mRNAs of SARS-CoV-2, Delta, and Omicron were coencapsulated into lipid nanoparticles (LNPs) by using microfluidic technology. After that, the physicochemical properties and time-dependent storage stability of the trivalent mRNA vaccine nanoformulation were tested by using dynamic light scattering (DLS). In vitro, the trivalent mRNA vaccine exhibited better lysosomal escape ability, transfection efficiency, and biocompatibility than did the commercial transfection reagent Lipo3000. In addition, Western blot analyses confirmed that the three RBD proteins can be detected in cells transfected with the trivalent mRNA vaccine. Furthermore, ex vivo imaging analysis indicated that the livers of BALB/c mice had the strongest protein expression levels after intramuscular (IM) injection. Using a prime-boost strategy, this trivalent vaccine elicited robust humoral and T-cell immune responses in both the high-dose and low-dose groups and showed no toxicity in BALB/c mice. Three specific IgG antibodies in the high-dose group against SARS-CoV-2, Delta, and Omicron variants approached ∼1/1,833,333, ∼1/1,866,667, and ∼1/925,000, respectively. Taken together, two doses of inoculation with the trivalent mRNA vaccine may provide broad and effective immunization responses against SARS-CoV-2 and variants.


Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Ratones , Humanos , SARS-CoV-2/genética , Vacunas contra la COVID-19 , COVID-19/prevención & control , Inmunización , Vacunas de ARNm , Anticuerpos Neutralizantes
12.
Int J Mol Sci ; 24(18)2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37762432

RESUMEN

Soybean (Glycine max (L.) Merr.) is an important source of plant protein, the nutritional quality of which is considerably affected by the content of the sulfur-containing amino acid, methionine (Met). To improve the quality of soybean protein and increase the Met content in seeds, soybean cystathionine γ-synthase 2 (GmCGS2), the first unique enzyme in Met biosynthesis, was overexpressed in the soybean cultivar "Jack", producing three transgenic lines (OE3, OE4, and OE10). We detected a considerable increase in the content of free Met and other free amino acids in the developing seeds of the three transgenic lines at the 15th and 75th days after flowering (15D and 75D). In addition, transcriptome analysis showed that the expression of genes related to Met biosynthesis from the aspartate-family pathway and S-methyl Met cycle was promoted in developing green seeds of OE10. Ultimately, the accumulation of total amino acids and soluble proteins in transgenic mature seeds was promoted. Altogether, these results indicated that GmCGS2 plays an important role in Met biosynthesis, by providing a basis for improving the nutritional quality of soybean seeds.


Asunto(s)
Aminoácidos , Glycine max , Glycine max/metabolismo , Aminoácidos/metabolismo , Proteínas de Soja/genética , Proteínas de Soja/metabolismo , Proteínas de Plantas/metabolismo , Semillas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Regulación de la Expresión Génica de las Plantas
13.
Phys Rev Lett ; 131(6): 066402, 2023 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-37625042

RESUMEN

We performed spin-, time- and angle-resolved extreme ultraviolet photoemission spectroscopy of excitons prepared by photoexcitation of inversion-symmetric 2H-WSe_{2} with circularly polarized light. The very short probing depth of XUV photoemission permits selective measurement of photoelectrons originating from the top-most WSe_{2} layer, allowing for direct measurement of hidden spin polarization of bright and momentum-forbidden dark excitons. Our results reveal efficient chiroptical control of bright excitons' hidden spin polarization. Following optical photoexcitation, intervalley scattering between nonequivalent K-K^{'} valleys leads to a decay of bright excitons' hidden spin polarization. Conversely, the ultrafast formation of momentum-forbidden dark excitons acts as a local spin polarization reservoir, which could be used for spin injection in van der Waals heterostructures involving multilayer transition metal dichalcogenides.

14.
Nat Commun ; 14(1): 5057, 2023 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-37598179

RESUMEN

Atomically thin layered van der Waals heterostructures feature exotic and emergent optoelectronic properties. With growing interest in these novel quantum materials, the microscopic understanding of fundamental interfacial coupling mechanisms is of capital importance. Here, using multidimensional photoemission spectroscopy, we provide a layer- and momentum-resolved view on ultrafast interlayer electron and energy transfer in a monolayer-WSe2/graphene heterostructure. Depending on the nature of the optically prepared state, we find the different dominating transfer mechanisms: while electron injection from graphene to WSe2 is observed after photoexcitation of quasi-free hot carriers in the graphene layer, we establish an interfacial Meitner-Auger energy transfer process following the excitation of excitons in WSe2. By analysing the time-energy-momentum distributions of excited-state carriers with a rate-equation model, we distinguish these two types of interfacial dynamics and identify the ultrafast conversion of excitons in WSe2 to valence band transitions in graphene. Microscopic calculations find interfacial dipole-monopole coupling underlying the Meitner-Auger energy transfer to dominate over conventional Förster- and Dexter-type interactions, in agreement with the experimental observations. The energy transfer mechanism revealed here might enable new hot-carrier-based device concepts with van der Waals heterostructures.

15.
Clin Chim Acta ; 548: 117522, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37598740

RESUMEN

BACKGROUND: Tetralogy of Fallot (TOF) is a common congenital heart disease with high mortality. However, the medical imageology and liquidbiopsy techniques present certain limitations. Thus, this study investigated the plasma metabolic profiles to distinguish key metabolites for early diagnosis of TOF. METHODS: In total, 69 patients with TOF and 43 normal controls were enrolled for targeted metabolomics based on liquid chromatography-tandem mass spectroscopy (LC-MS/MS). Absolute quantification of metabolites was performed using our standard database. The differentially expressed metabolites (DEMs) were screened by fold change (FC), VIP value and pearson correlation coefficient of OPLS-DA model. Receiver operating characteristic curve (ROC) was used to evaluate predictive ability of DEMs. RESULTS: Different metabolic profiles were presented between TOF and Normal.The pathway analysis showed that significantly changed metabolites were enriched in nicotinamide and purine metabolism. Many intermediatesproductof purine and amido acid were higher in TOF than in Normal group, while energy substrates and electron carriers were lower in TOF than in Normal group. ROC analysis revealed a high diagnostic value of plasma FAD for differentiating TOF from Normal (AUC = 1). CONCLUSION: Our study quantitatively characterized plasma metabolites in patients with TOF and may help to develop reliable biomarkers that contribute to the early TOF screening.


Asunto(s)
Tetralogía de Fallot , Humanos , Tetralogía de Fallot/diagnóstico , Cromatografía Liquida , Espectrometría de Masas en Tándem , Metabolómica , Purinas
16.
ACS Chem Neurosci ; 14(18): 3540-3550, 2023 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-37650601

RESUMEN

κ-Carrageenan is a linear sulfated polysaccharide extracted from the cell wall of marine red algae, and its enzymatically digested oligosaccharides (KOS) can inhibit microglial hyperactivation. Alzheimer's disease (AD) is a common chronic neurodegenerative disease, characterized by cognitive and memory impairment accompanied by nerve cell damage. Microglia activation causing enhancement of proinflammatory effects and neurotoxicity is one of the early events in AD disease. In this study, whether KOS have therapeutic or preventive effects in the AD model prepared from APP/PS1 transgenic mice was determined. Learning and memory of AD mice were detected by water maze experiments, and microglial activation-related protein expression and deposition of APP and Aß1-42 in the brain were examined. The effects of KOS on expressed inflammatory factors and inflammation-related proteins by microglia were tested by cell experiments. Transwell coculture was used to investigate the effect of microglia on neural cell activity after KOS treatment. The results showed that KOS could relieve the clinical symptoms in AD mice, and a decrease in the expression of inflammatory factors and inflammation-related proteins in brain tissue was detected. KOS alleviated nerve cell apoptosis by inhibiting the overactivation of microglia, thus exhibiting neuroprotective effects. Exploring the protective effect of KOS inhibition of microglia inflammation is expected to provide a theoretical basis for KOS as a therapeutic drug for neurodegenerative diseases.


Asunto(s)
Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Animales , Ratones , Microglía , Carragenina , Enfermedad de Alzheimer/tratamiento farmacológico , Oligosacáridos/farmacología , Autofagia , Inflamación/tratamiento farmacológico , Ratones Transgénicos
17.
J Mater Chem B ; 11(31): 7454-7465, 2023 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-37448376

RESUMEN

mRNA vaccines have emerged as a highly promising approach for preventing cancer and infectious diseases, attributed to their superior immunogenicity, rapid development speed, and quality-controlled scale production. While homologous mRNA vaccine administration is currently the most prevalent method employed in clinical settings, heterologous administration is a promising avenue worth exploring. In this report, two types of mRNA vaccine formulations for SARS-CoV-2 infection were developed based on different lipid nanoparticle (LNP) delivery systems, and heterologous and homologous mRNA vaccinations were administered to explore the levels of immune responses comparatively. First, five novel H-series ionizable lipids were synthesized and confirmed by NMR and MS. Subsequently, six SARS-CoV-2 receptor-binding domain (RBD) mRNA-encapsulated LNP formulations were prepared using a microfluidic mixer based on H-series and MC3 lipids. These formulations exhibited spherical structures with an average diameter ranging from 90-140 nm, as characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The safety of these formulations was confirmed in vitro by the cytotoxicity assay. Moreover, transfection assay, lysosomal escape test, and western blot, and in vivo biodistribution analyses collectively demonstrated that lipids H03 and MC3 exhibited superior in vitro and in vivo delivery efficacy in comparison to other H-series lipids. Notably, H03-Fluc mRNA exhibited an approximately 2.2-fold higher in vivo bioluminescence signal intensity than MC3-Fluc mRNA. Additionally, evaluation of humoral immunity demonstrated that homologous H03-mRNA vaccination elicited an immune response that was approximately 3-fold higher than that of homologous MC3-mRNA vaccination. More significantly, the heterologous H03-mRNA/MC3-mRNA vaccination elicited an immune response that was approximately 2-3-fold higher than that of homologous H03-mRNA vaccination and 6-9-fold higher than that of homologous MC3-mRNA vaccination, without any observable adverse effects. These results suggest that heterologous mRNA vaccination is superior to homologous mRNA vaccination and may be attributed to differences in LNP carriers. Therefore, our research may inspire further exploration of different delivery systems to enhance mRNA-based therapeutics.


Asunto(s)
COVID-19 , Humanos , COVID-19/prevención & control , SARS-CoV-2 , Distribución Tisular , Vacunas de ARNm , Lípidos
18.
Int J Pharm ; 642: 123155, 2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37402442

RESUMEN

Lipid nanoparticles (LNPs)-based mRNA vaccines have shown great potential in the fight against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. However, it remains still a challenge to improve the delivery efficiency of LNPs and the long-term stability of their mediated mRNA vaccines. Herein, a novel ionizable lipid 2-hexyldecyl 6-(ethyl(3-((2-hexyldecyl)oxy)-2-hydroxypropyl)amino)hexanoate (HEAH) derived LNPs were developed for delivering the receptor binding domain (RBD) mRNAs. In vitro cell assays confirmed that the ionizable lipid HEAH with one ether bond and one ester bond derived LNPs possessed higher mRNA delivery efficiency compared with the approved ALC-0315 with two ester bonds used in the BNT162b2 vaccine. Notably, the HEAH-derived LNPs powder lyophilized did not significantly change for 30 days after storage at 37 °C indicating good thermostability. After two RBD mRNAs of Delta and Omicron variants were encapsulated into the HEAH-derived LNPs, a bivalent mRNA vaccine was obtained as a nanoparticle formulation. Importantly, the bivalent mRNA vaccine not only resisted Delta and Omicron and also generated protective antibodies against ancestral SARS-CoV-2. The HEAH-mediated bivalent vaccine induced stronger humoral and cellular immunity than those of the ALC-0315 group. Taken together, the ionizable lipid HEAH-derived LNPs show outstanding potential in improving the delivery efficiency of mRNA and the stability of mRNA vaccine.


Asunto(s)
COVID-19 , Nanopartículas , Humanos , Vacunas Combinadas , Vacuna BNT162 , COVID-19/prevención & control , SARS-CoV-2/genética , Vacunas de ARNm , Decanoatos , Ésteres , Anticuerpos Antivirales
19.
ACS Biomater Sci Eng ; 9(8): 4720-4734, 2023 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-37491189

RESUMEN

Hyperglycemia in patients with diabetes affect osteoblast function, leading to abnormal bone metabolism and implant failure. Adequate bone volume surrounding an implant is essential for osseointegration, which can be improved by implant surface modifications. In this study, titanium surfaces were hydrothermally treated with a mixture of phytic acid (PA) and calcium hydroxide to produce a calcium-decorated surface. The control group comprised pure titanium with a sandblasted/acid-etched (SLA) surface. The elemental composition, hydrophilicity, surface roughness, and morphology of the titanium surfaces were examined. Evaluation of in vitro osteogenic differentiation ability in a high-glucose environment using alkaline phosphatase (ALP) staining, ALP activity assays, Alizarin Red S staining, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and immunofluorescence staining revealed that Ca-PA-modified SLA titanium surfaces can promote osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). Evaluation of oxidative stress and aging using reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and ß-galactosidase staining revealed that Ca-PA-modified SLA titanium surfaces can reduce ROS production and ameliorate oxidative stress damage in hBMSCs. In vivo assessment of osteogenesis in a diabetic rat model revealed that Ca-PA coating promotes peri-implant osseointegration. Ca-PA-modified SLA titanium surface is a candidate for improving implant osseointegration in patients with diabetes.


Asunto(s)
Diabetes Mellitus , Osteogénesis , Humanos , Ratas , Animales , Especies Reactivas de Oxígeno , Ácido Fítico/farmacología , Titanio/farmacología , Proliferación Celular , Senescencia Celular , Oseointegración , Glucosa
20.
Front Immunol ; 14: 1194662, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37261355

RESUMEN

Macrophages are an integral part of the innate immune response in periodontal tissue and play a crucial role in the progression of periodontitis. Here we reported that macrophages also provoke periodontitis-induced gingival destruction through Piezol-mediated collagen degradation. We discovered that the PIEZO1 expression was markedly elevated in patients with periodontitis through transcriptomic profiling. Moreover, Piezo1 promoted macrophage polarization toward the M1 type in response to lipopolysaccharide (LPS) and induced production of proinflammatory cytokines, which in turn stimulated production of matrix metalloproteinases (MMPs) leading to collagen degradation. Our study suggests that Piezol might be a potential therapeutic target for treating periodontitis-induced gingival destruction.


Asunto(s)
Encía , Periodontitis , Humanos , Encía/metabolismo , Periodontitis/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Colágeno/metabolismo , Macrófagos/metabolismo , Canales Iónicos/metabolismo
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