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1.
J Cell Mol Med ; 28(8): e18269, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38568056

RESUMO

Circular RNAs (circRNAs) play an important role in the progression of osteosarcoma. However, the precise function of circPVT1 in osteosarcoma remains elusive. This study aims to explore the molecular mechanism underlying the involvement of circPVT1 in osteosarcoma cells. We quantified circPVT1 expression using qRT-PCR in both control and osteosarcoma cell lines. To investigate the roles of circPVT1, miR-490-5p and HAVCR2 in vitro, we separately conducted overexpression and inhibition experiments for circPVT1, miR-490-5p and HAVCR2 in HOS and U2OS cells. Cell migration was assessed through wound healing and transwell migration assays, and invasion was measured via the Matrigel invasion assay. To elucidate the regulatory mechanism of circPVT1 in osteosarcoma, a comprehensive approach was employed, including fluorescence in situ hybridization, qRT-PCR, Western blot, bioinformatics, dual-luciferase reporter assay and rescue assay. CircPVT1 expression in osteosarcoma cell lines surpassed that in control cells. The depletion of circPVT1 resulted in a notable reduction in the in vitro migration and invasion of osteosarcoma cells. Mechanism experiments revealed that circPVT1 functioned as a miR-490-5p sequester, and directly targeted HAVCR2. Overexpression of miR-490-5p led to a significant attenuation of migration and invasion of osteosarcoma cells, whereas HAVCR2 overexpression had the opposite effect, promoting these abilities. Additionally, circPVT1 upregulated HAVCR2 expression via sequestering miR-490-5p, thereby orchestrating the migration and invasion in osteosarcoma cells. CircPVT1 orchestrates osteosarcoma migration and invasion by regulating the miR-490-5p/HAVCR2 axis, underscoring its potential as a promising therapeutic target for osteosarcoma.


Assuntos
Neoplasias Ósseas , MicroRNAs , Osteossarcoma , Humanos , Hibridização in Situ Fluorescente , Movimento Celular/genética , Osteossarcoma/genética , Neoplasias Ósseas/genética , MicroRNAs/genética , Receptor Celular 2 do Vírus da Hepatite A
2.
ACS Appl Mater Interfaces ; 16(14): 17954-17964, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38562008

RESUMO

Physical unclonable functions (PUFs) based on uncontrollable fabrication randomness are promising candidates for anticounterfeiting applications. Currently, the most popular optical PUFs are generally constructed from the scattering, fluorescent, or Raman phenomenon of nanomaterials. To further improve the security level of optical PUFs, advanced functions transparent to the above optical phenomenon have always been perused by researchers. Herein, we propose a new type of PUF based on the photothermal effect of gold nanoparticles, which shows negligible scattering, fluorescent, or Raman responses. The gold nanoparticles are randomly dispersed onto the surface of fused silica, which can enhance the photothermal effect and facilitate high contrast responses. By tuning the areal density of the gold nanoparticles, the optimized encoding capacity (2319) and the total authentication error probability (3.6428 × 10-24) are achieved from our PUF due to excellent bit uniformity (0.519) and inter Hamming distances (0.503). Moreover, the intra-Hamming distance (0.044) indicates the desired reliability. This advanced PUF with invisible features and high contrast responses provides a promising opportunity to implement authentication and identification with high security.

3.
Curr Med Sci ; 44(2): 450-461, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38639827

RESUMO

OBJECTIVE: Cymbopogon citratus (DC.) Stapf is a medicinal and edible herb that is widely used for the treatment of gastric, nervous and hypertensive disorders. In this study, we investigated the cardioprotective effects and mechanisms of the essential oil, the main active ingredient of Cymbopogon citratus, on isoproterenol (ISO)-induced cardiomyocyte hypertrophy. METHODS: The compositions of Cymbopogon citratus essential oil (CCEO) were determined by gas chromatography-mass spectrometry. Cardiomyocytes were pretreated with 16.9 µg/L CCEO for 1 h followed by 10 µmol/L ISO for 24 h. Cardiac hypertrophy-related indicators and NLRP3 inflammasome expression were evaluated. Subsequently, transcriptome sequencing (RNA-seq) and target verification were used to further explore the underlying mechanism. RESULTS: Our results showed that the CCEO mainly included citronellal (45.66%), geraniol (23.32%), and citronellol (10.37%). CCEO inhibited ISO-induced increases in cell surface area and protein content, as well as the upregulation of fetal gene expression. Moreover, CCEO inhibited ISO-induced NLRP3 inflammasome expression, as evidenced by decreased lactate dehydrogenase content and downregulated mRNA levels of NLRP3, ASC, CASP1, GSDMD, and IL-1ß, as well as reduced protein levels of NLRP3, ASC, pro-caspase-1, caspase-1 (p20), GSDMD-FL, GSDMD-N, and pro-IL-1ß. The RNA-seq results showed that CCEO inhibited the increase in the mRNA levels of 26 oxidative phosphorylation complex subunits in ISO-treated cardiomyocytes. Our further experiments confirmed that CCEO suppressed ISO-induced upregulation of mt-Nd1, Sdhd, mt-Cytb, Uqcrq, and mt-Atp6 but had no obvious effects on mt-Col expression. CONCLUSION: CCEO inhibits ISO-induced cardiomyocyte hypertrophy through the suppression of NLRP3 inflammasome expression and the regulation of several oxidative phosphorylation complex subunits.


Assuntos
Cymbopogon , Óleos Voláteis , Óleos Voláteis/farmacologia , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Cymbopogon/química , Cymbopogon/metabolismo , Isoproterenol , Miócitos Cardíacos/metabolismo , Fosforilação Oxidativa , RNA Mensageiro/metabolismo , Hipertrofia/induzido quimicamente , Hipertrofia/tratamento farmacológico , Hipertrofia/metabolismo
4.
Opt Express ; 32(6): 8986-8998, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571143

RESUMO

Starting from the Rayleigh-Rice perturbation theory, this paper derives the empirical Harvey scatter model and ABg scatter model applied extensively in optical analysis software packages and verifies the shift-invariant behavior of the scattered radiance in direction cosine space. Using data obtained from multi-wavelength laser scatterometer on carbon nanotube black coating and pineblack coating, we establish the polynomial model based on the sine of the scattering angle plus the sine of the specular reflection angle, i.e., sin θs+sin θ0 and the dual-Harvey model based on sin θs-sin θ0 , respectively. The models are in good accordance with the experimental data and further extend the valid range of empirical models.

5.
ACS Omega ; 9(15): 17204-17216, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38645319

RESUMO

The strong reservoir heterogeneity and complex microscopic pore structure in the Linxing area make it prone to water block damage during imbibition development. In order to explore the influence of reservoir microscopic characteristics on imbibition efficiency, taking the tight sandstone gas reservoir in the Linxing area of Ordos Basin as an example, the heterogeneity of the tight sandstone reservoir in the study area is characterized in terms of physical and chemical characteristics as well as the microscopic pore structure. Using nuclear magnetic resonance, high-pressure mercury pressure, and other testing methods, spontaneous seepage experiments in real sandstone were carried out to study the distribution law of different pore structures and seepage characteristics at different times and to systematically evaluate the microscopic pore characteristics of dense sandstone reservoirs and the factors affecting seepage and suction. The results show that due to the strong microscopic heterogeneity of tight sandstone, the macroscopic properties cannot directly reflect the microscopic characteristics, and the response to imbibition efficiency is stronger. The pore size is the main controlling factor affecting imbibition, and the contribution rate of the micropore and mesopore mainstream pore size spaces is higher than that of the macropore. Micropores provide imbibition power, and mesopores provide an imbibition interval. High-porosity and high permeability reservoirs are more conducive to imbibition replacement. The intercrystalline pores have a great influence on the imbibition efficiency, and the influence of intergranular pores and dissolution pores on the imbibition cannot be underestimated. The smaller the relative sorting coefficient, interfacial tension, and contact angle, the better the imbibition effect of fracturing fluid. Research results have theoretical guiding significance for spontaneous imbibition to improve oil recovery.

6.
Bioorg Chem ; 147: 107357, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38604020

RESUMO

Turmeric (Curcuma longa), a typical source with recognized anti-inflammatory activity, is one such medicine-food homology source, yet its anti-inflammatory mechanisms and specific component combinations remain unclear. In this study, a net fishing method combining bio-affinity ultrafiltration and ultra-high performance liquid chromatography-mass spectrometry (AUF-LC/MS) was employed and 13 potential COX-2 inhibitors were screened out from C. longa. 5 of them (C1, 17, 20, 22, 25) were accurately isolated and identified. Initially, their IC50 values were measured (IC50 of C1, 17, 20, 22 and 25 is 55.08, 48.26, 29.13, 111.28 and 150.48 µM, respectively), and their downregulation of COX-2 under safe concentrations (400, 40, 120, 50 and 400 µM for C1, 17, 20, 22 and 25, respectively) was confirmed on RAW 264.7 cells. Further, in transgenic zebrafish (Danio rerio), significant anti-inflammatory activity at safe concentrations (15, 3, 1.5, 1.5 and 3 µg/mL for C1, 17, 20, 22 and 25, respectively) were observed in a dose-dependent manner. More importantly, molecular docking analysis further revealed the mode of interaction between them and the key active site residues of COX-2. This study screened out and verified unreported COX-2 ligands, potentially accelerating the discovery of new bioactive compounds in other functional foods.

7.
ACS Appl Mater Interfaces ; 16(11): 14308-14320, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38456610

RESUMO

It is well known that low-silica SAPO-34, with an extra porosity (meso- and/or macropores) system, affords excellent catalytic performance in the methanol-to-olefins (MTO) reaction, while the direct synthesis of low-silica SAPO-34 with a hierarchical structure is difficult to achieve, principally because the crystal impurities are usually formed under a low silica content in a gel precursor. Herein, low-silica SAPO-34 nanocrystals were successfully fabricated for the first time by constructing an isomorphous core-shell structure in an epitaxial growth manner. In which, low-silica, ultrasmall nanosquare-shaped SAPO-34 crystals with the same growth orientation along the (100) crystal plane compactly grow on the monocrystal SAPO-34 cores. Crucially, the external surface acid properties of the core SAPO-34 with the Si-rich outer layer are effectively modified by the low-silica SAPO-34 shell. Furthermore, the growth process and Si-substitution mechanism of the shell zeolite were comprehensively investigated. It was found that with the prolonged crystallization time, more and more coordinated Si(4Al) and Si(3Al) structures via two substitution mechanisms (SM2 and SM3) are generated in the nanocrystalline SAPO-34 shell, which endow moderate acidity of the core-shell SAPO-34. Compared to the uncoated SAPO-34, the core-shell SAPO-34 performs a longer lifespan and a higher average selectivity of light olefins (ethylene plus propylene) when applied to the MTO reaction, which is attributed to the positive effects of the luxuriant interstitial pores offering a fast diffusion channel and the moderate acid density depressing the hydrogen transfer reaction of light olefins. This work provides new insights into the fabrication of low-silica SAPO-34 nanocrystals, which are based on the rational design of the isomorphous core-shell zeolite.

8.
Noncoding RNA Res ; 9(2): 341-349, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38505307

RESUMO

Circular RNAs (circRNAs) play a crucial role in cancer development and progression. This study aimed to identify potential circRNA biomarkers for osteosarcoma. Articles published from January 2010 to September 2023 were searched across eight databases to compare circRNA expression profiles in osteosarcoma and control samples (human, animal and cell lines). Meta-analysis was conducted under a random effects model. Subgroup analysis of circRNAs in different samples and tissues was performed. Diagnostic value was evaluated using receiver operator characteristic curves. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis explored functions of circRNA host genes. A circRNA-miRNA-mRNA axis depicted the regulatory mechanism in osteosarcoma. Among 1356 circRNAs with differential expression were identified across 226 original studies, only 74 were reported in at least three published sub-studies. Meta-analysis identified 58 dysregulated circRNAs (52 upregulated and 6 downregulated). Eleven circRNAs consistently showed dysregulation in tissues and cell lines, with hsa_circ_0005721 showing potential as a circulating biomarker in osteosarcoma. Sensitivity analysis demonstrated 97 % consistency. The overall area under the curve was 0.87 (95 % CI, 0.83-0.89). GO and KEGG enrichment analyses revealed host gene involvement in cancer. The circRNA-miRNA-mRNA axis revealed the regulatory axis and interactions within osteosarcoma specifically. This study demonstrates circRNAs as potential diagnostic biomarkers for osteosarcoma. Consistently reported dysregulated circRNAs are potential biomarkers in osteosarcoma pathogenesis, with hsa_circ_0005721 as a potential circulating biomarker for diagnosis and treatment.

9.
Sci Total Environ ; 924: 171700, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38490408

RESUMO

The speciation, bioaccumulation, and toxicity of the newly deposited atmospheric heavy metals in the soil-earthworm (Eisenia fetida) system were investigated by a fully factorial atmospheric exposure experiment using soils exposed to 0.8-year and 1.8-year atmospheric depositions. The results shown that the newly deposited metals (Cu, Cd, and Pb) primarily accumulated in the topsoil (0-6 cm) and were present as the highly bioavailable speciation. They can migrate further to increase the concentrations of Cu, Cd, and Pb in soil solution of the deeper layer (at 10 cm) by 12 %-436 %. Earthworms tended to preferentially accumulate the newly deposited metals, which contributed 10 %-61 % of Cu, Cd, and Pb in earthworms. Further, for the unpolluted and moderately polluted soils, the newly deposited metals induced the significant oxidative stress in earthworms, resulting in significant increases in antioxidant enzyme activities (SOD, CAT, and GSH-Px). No significant differences were observed in the levels of heavy metals in soil solutions, bioaccumulation, and enzyme activities in earthworms exposed to 0.8-year and 1.8-year depositions, indicating the bioavailability of atmospheric metals deposited into soils was rapidly decreased with time. This study highlights the high bioaccumulation and toxicity of heavy metals to earthworm from the new atmospheric deposition during the earthworm growing period.


Assuntos
Metais Pesados , Oligoquetos , Poluentes do Solo , Animais , Cobre/toxicidade , Cobre/análise , Cádmio , Solo , Bioacumulação , Chumbo , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , Metais Pesados/toxicidade , Metais Pesados/análise
10.
J Environ Manage ; 356: 120592, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38508009

RESUMO

Chicken manure (CM) can pose a serious threat to environmental and human health, and need to be managed properly. The compost can effectively treat CM. However, there is limited research on the heavy metals and antibiotic resistance genes (ARGs) during compost CM. In this study, the combined application of reactor and static composting (RSC) was used to produce organic fertilizer of CM (OCM), and heavy metals, ARGs and bacterial community structure was investigated. The results show that RSC could be used to produce OCM, and OCM meet the National organic fertilizer standard (NY/T525-2021). Compared to the initial CM, DTPA-Cu, DTPA-Zn, DTPA-Pb, DTPA-Cr, DTPA-Ni and DTPA-As in OCM decreased by 40.83%, 23.73%, 34.27%, 38.62%, 16.26%, and 43.35%, respectively. RSC decreased the relative abundance of ARGs in CM by 84.06%, while the relative abundance of sul1 and ermC increased. In addition, the relative abundance and diversity of ARGs were mainly influenced by the bacterial community, with Actinobacteria, Firmicutes, and Proteobacteria becoming the dominant phyla during composting, and probably being the main carriers and dispersers of most of the ARGs. Network analyses confirmed that Gracilibacillus, Lactobacillus, Nocardiopsis, Mesorhizobium and Salinicoccus were the main potential hosts of ARGs, with the main potential hosts of sul1 and ermC being Mesorhizobium and Salinicoccus. The passivation and physicochemical properties of heavy metals contribute to the removal of ARGs, with sul1 and ermC being affected by the toal heavy metals. Application of RSC allows CM to produce mature, safe organic fertilizer after 32 d and reduces the risk of rebound from ARGs, but the issues of sul1 and ermC gene removal cannot be ignored.


Assuntos
Compostagem , Metais Pesados , Animais , Humanos , Genes Bacterianos , Esterco/análise , Galinhas , Antibacterianos/farmacologia , Fertilizantes , Resistência Microbiana a Medicamentos/genética , Bactérias/genética , Metais Pesados/análise , Ácido Pentético
11.
Front Endocrinol (Lausanne) ; 15: 1359655, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487344

RESUMO

Objective: There is currently no non-invasive examination that can fully determine the diagnosis of osteomyelitis. SPECT/CT tomographic fusion imaging can provide both local metabolic activity and anatomical information to determine the condition and location. This study evaluates the diagnostic efficacy of 99mTc-MDP SPECT/CT in bone infections, compared to MRI. Methods: In this multicenter retrospective study, 363 patients with suspected bone and joint infections or osteomyelitis were included. Participants underwent 99mTc-MDP SPECT/CT and/or MRI examinations, supplemented by pathogenic bacterial cultures and histopathological analysis. Results: Only SPECT/CT was tested in 169 patients, and only MRI was used in 116. 78 people have implemented both inspections and have detailed information. The diagnostic sensitivity and specificity of SPECT/CT for infection were 96% and 92% respectively, with an accuracy of 96%. For MRI, these figures were 88%, 84%, and 87% respectively. Conclusion: This represents the largest global study to date evaluating osteomyelitis and bone infection diagnosis using 99mTc-MDP SPECT/CT tomographic fusion imaging. The findings indicate that 99mTc-MDP SPECT/CT fusion imaging offers superior diagnostic accuracy compared to MRI. This is particularly evident in cases involving metallic implants and chronic infections. 99mTc-MDP SPECT/CT fusion imaging emerges as a highly suitable non-invasive diagnostic modality, facilitating enhanced clinical follow-up and treatment.


Assuntos
Difosfatos , Osteomielite , Humanos , Estudos Retrospectivos , Medronato de Tecnécio Tc 99m , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tomografia Computadorizada de Emissão de Fóton Único , Imageamento por Ressonância Magnética , Osteomielite/diagnóstico por imagem
12.
ACS Pharmacol Transl Sci ; 7(3): 614-629, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38481692

RESUMO

Although groundbreaking biotechnological techniques such as gene editing have significantly progressed, the effective and targeted transport of therapeutic agents into host cells remains a major obstacle to the development of biotherapeutics. Confronting the unique challenge posed by large macromolecules such as proteins, peptides, and nucleic acids adds complexity to this issue. Recent findings reveal that the supercharging of proteins and peptides not only enables control over critical properties, such as temperature resistance and catalytic activity, but also holds promise as a viable strategy for their use in drug delivery. This review provides a concise summary of the attributes of supercharged proteins and peptides, encompassing both their natural occurrence and engineered variants. Furthermore, it sheds light on the present status and future possibilities of supercharged proteins and peptides as carriers for significant biomolecules in the realms of medical research and therapeutic applications.

13.
Cell Death Discov ; 10(1): 123, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461207

RESUMO

Solute carrier family 26 member 9 (SLC26A9) is a member of the Slc26a family of multifunctional anion transporters that functions as a Cl- channel in parietal cells during acid secretion. We explored the role of SLC26A9 in colorectal cancer (CRC) and its related mechanisms through clinical samples from CRC patients, CRC cell lines and mouse models. We observed that SLC26A9 was expressed at low levels in the cytoplasm of adjacent tissues, polyps and adenomas but was significantly increased in colorectal adenocarcinoma. Moreover, increased levels of SLC26A9 were associated with a high risk of disease and poor prognosis. In addition, downregulation of SLC26A9 in CRC cells induced cell cycle arrest and apoptosis but inhibited cell proliferation and xenograft tumor growth both in vitro and in vivo. Mechanistic analysis revealed that SLC26A9 was colocalized with ß-catenin in the nucleus of CRC cells. The translocation of these two proteins from the cytoplasm to the nucleus reflected the activation of Wnt/ß-catenin signaling, and promoted the transcription of downstream target proteins, including CyclinD1, c-Myc and Snail, but inhibited the expression of cytochrome C (Cyt-c), cleaved Caspase9, cleaved Caspase3 and apoptosis-inducing factor (AIF). CRC is accompanied by alteration of epithelial mesenchymal transition (EMT) markers. Meanwhile, further studies showed that in SW48 cells, overexpressing SLC26A9 was cocultured with the ß-catenin inhibitor XAV-939, ß-catenin was downregulated, and EMT was reversed. Our study demonstrated SLC26A9 may be responsible for alterations in the proliferative ability and aggressive potential of CRC by regulating the Wnt/ß-catenin signaling pathway.

14.
ACS Appl Mater Interfaces ; 16(8): 10344-10351, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38350064

RESUMO

The outstanding photoelectric properties of perovskites demonstrate extreme promise for application in X-ray detection. However, the soft lattice of the perovskite results in severe ionic migration for three-dimensional materials, limiting the operation stability of perovskite X-ray detectors. Although ligand-decorated nanocrystals (NCs) exhibit significantly higher stability than three-dimensional perovskites, defects remaining on the interface of NCs could still trigger halide migration under a high bias due to the incomplete ligand decoration. Furthermore, it is still challenging to realize sufficient thickness of absorption layers based on NCs for X-ray detectors through traditional methods. Herein, we develop a centimeter-size and millimeter-thick wafer based on CsPbBr3 NCs through isostatic pressing for X-ray detectors, in which the interfacial defects of NCs are remedied by CsPb2Br5 during aging of wafer in ambient humidity. The wafer shows outstanding sensitivity (200 µC Gyair-1 cm-2) and ultralow dark current drift (1.78 × 10-8 nA cm-1 s-1 V-1 @ 400 V cm-1). Moreover, it shows storage stability with negligible performance degradation for 60 days in ambient humidity. Thus, aging perovskite NC wafers for X-ray detection holds huge potential for next-generation X-ray imaging plates.

15.
Adv Sci (Weinh) ; 11(16): e2303775, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38327094

RESUMO

The spread of prion-like protein aggregates is a common driver of pathogenesis in various neurodegenerative diseases, including Alzheimer's disease (AD) and related Tauopathies. Tau pathologies exhibit a clear progressive spreading pattern that correlates with disease severity. Clinical observation combined with complementary experimental studies has shown that Tau preformed fibrils (PFF) are prion-like seeds that propagate pathology by entering cells and templating misfolding and aggregation of endogenous Tau. While several cell surface receptors of Tau are known, they are not specific to the fibrillar form of Tau. Moreover, the underlying cellular mechanisms of Tau PFF spreading remain poorly understood. Here, it is shown that the lymphocyte-activation gene 3 (Lag3) is a cell surface receptor that binds to PFF but not the monomer of Tau. Deletion of Lag3 or inhibition of Lag3 in primary cortical neurons significantly reduces the internalization of Tau PFF and subsequent Tau propagation and neuron-to-neuron transmission. Propagation of Tau pathology and behavioral deficits induced by injection of Tau PFF in the hippocampus and overlying cortex are attenuated in mice lacking Lag3 selectively in neurons. These results identify neuronal Lag3 as a receptor of pathologic Tau in the brain,and for AD and related Tauopathies, a therapeutic target.


Assuntos
Proteína do Gene 3 de Ativação de Linfócitos , Neurônios , Tauopatias , Proteínas tau , Animais , Proteínas tau/metabolismo , Proteínas tau/genética , Camundongos , Neurônios/metabolismo , Tauopatias/metabolismo , Tauopatias/genética , Tauopatias/patologia , Modelos Animais de Doenças , Doença de Alzheimer/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Humanos , Antígenos CD/metabolismo , Antígenos CD/genética
16.
Emerg Microbes Infect ; 13(1): 2321994, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38377136

RESUMO

Vaccines utilizing modified messenger RNA (mRNA) technology have shown robust protective efficacy against SARS-CoV-2 in humans. As the virus continues to evolve in both human and non-human hosts, risk remains that the performance of the vaccines can be compromised by new variants with strong immune escape abilities. Here we present preclinical characterizations of a novel bivalent mRNA vaccine RQ3025 for its safety and effectiveness in animal models. The mRNA sequence of the vaccine is designed to incorporate common mutations on the SARS-CoV-2 spike protein that have been discovered along the evolutionary paths of different variants. Broad-spectrum, high-titer neutralizing antibodies against multiple variants were induced in mice (BALB/c and K18-hACE2), hamsters and rats upon injections of RQ3025, demonstrating advantages over the monovalent mRNA vaccines. Effectiveness in protection against several newly emerged variants is also evident in RQ3025-vaccinated rats. Analysis of splenocytes derived cytokines in BALB/c mice suggested that a Th1-biased cellular immune response was induced by RQ3025. Histological analysis of multiple organs in rats following injection of a high dose of RQ3025 showed no evidence of pathological changes. This study proves the safety and effectiveness of RQ3025 as a broad-spectrum vaccine against SARS-CoV-2 variants in animal models and lays the foundation for its potential clinical application in the future.


Assuntos
COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Cricetinae , Humanos , Camundongos , Ratos , Animais , Vacinas Combinadas , SARS-CoV-2/genética , Vacinas de mRNA , Vacinas contra COVID-19/genética , COVID-19/prevenção & controle , Anticorpos Amplamente Neutralizantes , Camundongos Endogâmicos BALB C , RNA Mensageiro/genética
17.
Artigo em Inglês | MEDLINE | ID: mdl-38401095

RESUMO

Background: Intraperitoneal chemotherapy is an effective way to kill free tumor cells in the abdominal cavity. The safety and efficacy of raltitrexed perfusion during radical surgery for elderly patients with colorectal cancer are still unclear. Methods: In accordance with computer-generated random allocation sequences, 116 elderly patients with colorectal cancer who received radical surgery were randomly grouped into the raltitrexed intraperitoneal perfusion group or the saline intraperitoneal perfusion group from January 2020 to December 2021 in the First Affiliated Hospital of Bengbu Medical University. t tests and χ2 tests were used to analyze the difference between the two groups of the clinical characteristics, pathological features, perioperative parameters, and carcinoembryonic antigen mRNA in the peritoneal lavage fluid. Results: No statistically significant differences in postoperative complications after radical surgery were observed between the two groups. No statistically significant differences in peripheral blood indexes were observed between the two groups before surgery or on the first and third days after surgery. One day after radical surgery, the alanine transaminase (54.33 ± 4.93 vs 51.01 ± 5.56) and aspartate transaminase (49.28 ± 4.30 vs 50.99 ± 3.88) in the peripheral blood were higher in the raltitrexed intraperitoneal perfusion group than in the saline intraperitoneal perfusion group. At the same time, no significant difference was found on the third day after surgery. No significant differences in side effects of chemotherapy were observed between the two groups. The positive rate of carcinoembryonic antigen mRNA in the raltitrexed intraperitoneal perfusion group (8.47%) was significantly lower than that in the saline intraperitoneal perfusion group (22.81%) after surgery. Conclusion: Raltitrexed perfusion during radical surgery is safe and feasible for elderly patients with CRC and can reduce the positive rate of carcinoembryonic antigen mRNA in peritoneal lavage fluid, so it can be explored as a treatment option.

18.
ACS Appl Mater Interfaces ; 16(10): 12844-12852, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38416069

RESUMO

High-energy radiation detectors with a good imaging resolution, fast response, and high sensitivity are desired to operate at a high electric field. However, strong ion migration triggered by electrochemical reactions at the interface between a high-potential electrode and an organic-inorganic hybrid perovskite limits the stability of radiation detectors under a high electric field. Herein, we demonstrate that such ion migration could be effectively suppressed in devices with a Ti cathode, even at a high electric field of 50 V mm-1, through time-of-flight secondary-ion mass spectrometry. X-ray photoelectron spectroscopy illustrates that Ti-N bonds formed at the interface of MAPbBr3 perovskite single crystals/Ti electrode effectively inhibit the electrochemical reaction in organic-inorganic hybrid perovskite devices and ultimately improve the operating stability under a high electric field. The device with a Ti electrode reaches a high sensitivity of 96 ± 1 mC Gyair-1 cm-2 and a low detection limit of 2.8 ± 0.3 nGy s-1 under hard X-ray energy.

19.
Plant Genome ; 17(1): e20431, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38263612

RESUMO

Effects of individual single-nucleotide polymorphism (SNP) markers and the size of "training" and "test" populations affect prediction accuracy in genomic selection (GS). This study evaluated 11 subsets of 4932 SNPs using six genetic additive methods to understand marker density in GS prediction in alfalfa (Medicago sativa L.). In the GS methods, the effect of "training" to "test" population size was also evaluated. Fourteen alfalfa populations sampled from long-term grazing sites were genotyped using genotyping by sequencing for the identification of SNPs. These populations were also phenotyped for six agromorphological and three nutritive traits from 2018 to 2020. The accuracy of GS prediction improved across six GS methods when the ratio of "training" to "test" population size increased. However, the prediction accuracy of the six GS methods reduced to a range of -0.27 to 0.11 when random, uninformative SNPs were used. In this study, five Bayesian methods and ridge-regression best linear unbiased prediction (rrBLUP) method had similar GS accuracies for "training" sets, but rrBLUP tended to outperform Bayesian methods in independent "test" sets when SNP subsets with high mean-squared-estimated-marker effect were used. These findings can enhance the application of GS in alfalfa genetic improvement.


Assuntos
Medicago sativa , Polimorfismo de Nucleotídeo Único , Medicago sativa/genética , Densidade Demográfica , Teorema de Bayes , Locos de Características Quantitativas , Seleção Genética , Genômica/métodos
20.
ACS Pharmacol Transl Sci ; 7(1): 72-96, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38230285

RESUMO

Osteogenesis imperfecta (OI) is an uncommon genetic disorder characterized by shortness of stature, hearing loss, poor bone mass, recurrent fractures, and skeletal abnormalities. Pathogenic variations have been found in over 20 distinct genes that are involved in the pathophysiology of OI, contributing to the disorder's clinical and genetic variability. Although medications, surgical procedures, and other interventions can partially alleviate certain symptoms, there is still no known cure for OI. In this Review, we provide a comprehensive overview of genetic pathogenesis, existing treatment modalities, and new developments in biotechnologies such as gene editing, stem cell reprogramming, functional differentiation, and transplantation for potential future OI therapy.

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