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1.
BMC Plant Biol ; 24(1): 649, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38977989

RESUMO

BACKGROUND: The cold tolerance of rice is closely related to its production and geographic distribution. The identification of cold tolerance-related genes is of important significance for developing cold-tolerant rice. Dongxiang wild rice (Oryza rufipogon Griff.) (DXWR) is well-adapted to the cold climate of northernmost-latitude habitats ever found in the world, and is one of the most valuable rice germplasms for cold tolerance improvement. RESULTS: Transcriptome analysis revealed genes differentially expressed between Xieqingzao B (XB; a cold sensitive variety) and 19H19 (derived from an interspecific cross between DXWR and XB) in the room temperature (RT), low temperature (LT), and recovery treatments. The results demonstrated that chloroplast genes might be involved in the regulation of cold tolerance in rice. A high-resolution SNP genetic map was constructed using 120 BC5F2 lines derived from a cross between 19H19 and XB based on the genotyping-by-sequencing (GBS) technique. Two quantitative trait loci (QTLs) for cold tolerance at the early seedling stage (CTS), qCTS12 and qCTS8, were detected. Moreover, a total of 112 candidate genes associated with cold tolerance were identified based on bulked segregant analysis sequencing (BSA-seq). These candidate genes were divided into eight functional categories, and the expression trend of candidate genes related to 'oxidation-reduction process' and 'response to stress' differed between XB and 19H19 in the RT, LT and recovery treatments. Among these candidate genes, the expression level of LOC_Os12g18729 in 19H19 (related to 'response to stress') decreased in the LT treatment but restored and enhanced during the recovery treatment whereas the expression level of LOC_Os12g18729 in XB declined during recovery treatment. Additionally, XB contained a 42-bp deletion in the third exon of LOC_Os12g18729, and the genotype of BC5F2 individuals with a survival percentage (SP) lower than 15% was consistent with that of XB. Weighted gene coexpression network analysis (WGCNA) and modular regulatory network learning with per gene information (MERLIN) algorithm revealed a gene interaction/coexpression network regulating cold tolerance in rice. In the network, differentially expressed genes (DEGs) related to 'oxidation-reduction process', 'response to stress' and 'protein phosphorylation' interacted with LOC_Os12g18729. Moreover, the knockout mutant of LOC_Os12g18729 decreased cold tolerance in early rice seedling stage signifcantly compared with that of wild type. CONCLUSIONS: In general, study of the genetic basis of cold tolerance of rice is important for the development of cold-tolerant rice varieties. In the present study, QTL mapping, BSA-seq and RNA-seq were integrated to identify two CTS QTLs qCTS8 and qCTS12. Furthermore, qRT-PCR, genotype sequencing and knockout analysis indicated that LOC_Os12g18729 could be the candidate gene of qCTS12. These results are expected to further exploration of the genetic mechanism of CTS in rice and improve cold tolerance of cultivated rice by introducing the cold tolerant genes from DXWR through marker-assisted selection.


Assuntos
Temperatura Baixa , Oryza , Locos de Características Quantitativas , Plântula , Oryza/genética , Oryza/fisiologia , Locos de Características Quantitativas/genética , Plântula/genética , Plântula/fisiologia , Plântula/crescimento & desenvolvimento , Genes de Plantas , RNA-Seq , Mapeamento Cromossômico , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Resposta ao Choque Frio/genética
2.
Lab Chip ; 24(14): 3367-3376, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38845509

RESUMO

Point-of-care testing of "sample in, answer out" is urgently needed for communicable diseases. Recently, rapid nucleic acid tests for infectious diseases have been developed for use in resource-limited areas, but they require types of equipment in central laboratories and are poorly integrated. In this work, a portable centrifugal microfluidic testing system is developed, integrated with magnetic bead-based nucleic acid extraction, recombinase-assisted amplification and CRISPR-Cas13a detection. The system, with the advantage of its power-supplied active rotating chip and highly programable flow control through integrated addressable active thermally-triggered wax valves, has a rapid turnaround time within 45 min, requiring only one user step. All reagents are preloaded into the chip and can be automatically released. By exploiting a multichannel chip, it is capable of simultaneously detecting 10 infectious viruses with limits of detection of 1 copy per reaction and 5 copies per reaction in plasmid samples and mock plasma samples, respectively. The system was used to analyse clinical plasma samples with good consistency compared to laboratory-based molecular testing. Moreover, the generalizability of our device is reported by successfully testing nasopharyngeal swabs and whole blood samples. The portable device does not require the operation of professional technicians, making it an excellent assay for on-site testing.


Assuntos
Sistemas CRISPR-Cas , Dispositivos Lab-On-A-Chip , Humanos , Técnicas de Amplificação de Ácido Nucleico/instrumentação , Desenho de Equipamento , Técnicas Analíticas Microfluídicas/instrumentação , Limite de Detecção
3.
Nutrients ; 16(11)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38892575

RESUMO

Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate, prompting a growing demand for novel, safe, and effective therapies. Natural products (NPs) have emerged as promising candidates in drug development due to their diverse biological activities, low toxicity, and minimal side effects. This paper begins by reviewing existing treatment methods and drugs for liver cancer. It then summarizes the therapeutic effects of NPs sourced from various origins on liver cancer. Finally, we analyze the potential mechanisms of NPs in treating liver cancer, including inhibition of angiogenesis, migration, and invasion; regulation of the cell cycle; induction of apoptosis, autophagy, pyroptosis, and ferroptosis; influence on tumor metabolism; immune regulation; regulation of intestinal function; and regulation of key signaling pathways. This systematic review aims to provide a comprehensive overview of NPs research in liver cancer treatment, offering a foundation for further development and application in pharmaceuticals and functional foods.


Assuntos
Produtos Biológicos , Neoplasias Hepáticas , Humanos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Animais , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Autofagia/efeitos dos fármacos
4.
Burns Trauma ; 12: tkae017, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887221

RESUMO

Background: Due to vasculature injury and increased oxygen consumption, the early wound microenvironment is typically in a hypoxic state. We observed enhanced cell migration ability under early short-term hypoxia. CCL2 belongs to the CC chemokine family and was found to be increased in early hypoxic wounds and enriched in the extracellular signal-regulated kinase (ERK)1/2 pathway in our previous study. However, the underlying mechanism through which the CCL2-ERK1/2 pathway regulates wound healing under early short-term hypoxia remains unclear. Activation of epithelial-mesenchymal transition (EMT) is a key process in cancer cell metastasis, during which epithelial cells acquire the characteristics of mesenchymal cells and enhance cell motility and migration ability. However, the relationship between epithelial cell migration and EMT under early short-term hypoxia has yet to be explored. Methods: HaCaT cells were cultured to verify the effect of early short-term hypoxia on migration through cell scratch assays. Lentiviruses with silenced or overexpressed CCL2 were used to explore the relationship between CCL2 and migration under short-term hypoxia. An acute full-thickness cutaneous wound rat model was established with the application of an ERK inhibitor to reveal the hidden role of the ERK1/2 pathway in the early stage of wound healing. The EMT process was verified in all the above experiments through western blotting. Results: In our study, we found that short-term hypoxia promoted cell migration. Mechanistically, hypoxia promoted cell migration through mediating CCL2. Overexpression of CCL2 via lentivirus promoted cell migration, while silencing CCL2 via lentivirus inhibited cell migration and the production of related downstream proteins. In addition, we found that CCL2 was enriched in the ERK1/2 pathway, and the application of an ERK inhibitor in vivo and in vitro verified the upstream and downstream relationships between the CCL2 pathway and ERK1/2. Western blot results both in vivo and in vitro demonstrated that early short-term hypoxia promotes epidermal cell migration by activating the CCL2-ERK1/2 pathway and EMT during wound healing. Conclusions: Our work demonstrated that hypoxia in the early stage serves as a stimulus for triggering wound healing through activating the CCL2-ERK1/2 pathway and EMT, which promote epidermal cell migration and accelerate wound closure. These findings provide additional detailed insights into the mechanism of wound healing and new targets for clinical treatment.

5.
Surgery ; 176(2): 310-318, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38760234

RESUMO

BACKGROUND: The survival paradox (ie, the prognosis of the population at earlier tumor stages is worse than that of the population at later stages) has been observed in colorectal cancer based on the American Joint Committee on Cancer Tumor-Nodes-Metastases staging system. We aimed to clarify the reason for the survival paradox and its impact on patient treatment. METHODS: We conducted a retrospective study analyzing eligible patients with colorectal cancer from the Surveillance, Epidemiology, and End Results database and Zhejiang Cancer Hospital between 2010 and 2019. Adjusting for confounders using propensity score matching allowed confirmation of the effect of staging on the survival paradox. RESULTS: Based on the Surveillance, Epidemiology, and End Results database, the subgroups with survival paradox might be IIB/C versus IIIA, IIA versus IIIA, and T4N0 (IIB/C) versus T3N1 (IIIB). After propensity score matching, stage IIB/C still had a worse prognosis than stage IIIA (5-year overall survival: 69.3% vs 78.5%, P < .001). Interestingly, the proportion of stage IIIA people receiving chemotherapy was higher than that of stage IIB/C (P < .001), and logistic regression models showed that staging was the reason for deciding whether a patient receives chemotherapy or not. These phenomena between stage IIB/C and IIIA were verified in the local database. CONCLUSION: These results suggested that the survival paradox was mainly due to underestimation of stage T4 weights or overestimation of stage N1 weights, and the low proportion of chemotherapy in patients with T4N0M0 colorectal cancer (proven to be more malignant than stage IIIA) might be related to the assignment to earlier stages, resulting in a lack of attention and poor compliance to chemotherapy in these patients.


Assuntos
Neoplasias Colorretais , Estadiamento de Neoplasias , Pontuação de Propensão , Humanos , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Neoplasias Colorretais/tratamento farmacológico , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Prognóstico , Programa de SEER , Taxa de Sobrevida , China/epidemiologia , Adulto
7.
Toxics ; 12(5)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38787126

RESUMO

Red mud is an industrial solid waste rarely utilized and often disposed of in landfills, resulting in resource waste and environmental pollution. However, due to its high pH and abundance of iron and aluminum oxides and hydroxides, red mud has excellent adsorption properties which can effectively remove heavy metals through ion exchange, adsorption, and precipitation. Therefore, red mud is a valuable resource rather than a waste byproduct. In recent years, red mud has been increasingly studied for its potential in wastewater treatment and soil improvement. Red mud can effectively reduce the migration and impact of heavy metals in soils and water bodies. This paper reviews the research results from using red mud to mitigate cadmium pollution in water bodies and soils, discusses the environmental risks of red mud, and proposes key research directions for the future management of red mud in cadmium-contaminated environments.

8.
Braz J Cardiovasc Surg ; 39(3): e20230218, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748809

RESUMO

INTRODUCTION: This study aimed to investigate the predictive value of the vasoactive-inotropic score (VIS) at different time points for postoperative prolonged mechanical ventilation (PMV) in adult congenital heart disease patients undergoing surgical treatment combined with coronary artery bypass grafting. METHODS: Patients were divided into two groups that developed PMV or not. The propensity score matching method was applied to reduce the effects of confounding factors between the two groups. VIS at different time points (VIS at the end of surgery, VIS6h, VIS12h, and VIS12h max) after surgery were recorded and calculated. The value of VIS in predicting PMV was analyzed by the receiver operating characteristic (ROC) curve, and multivariate logistic regression was used to analyze independent risk factors. RESULTS: Among 250 patients, 52 were in the PMV group, and 198 were in the non-PMV group. PMV rate was 20.8%. After propensity score matching, 94 patients were matched in pairs. At each time point, the area under the ROC curve predicted by VIS for PMV was > 0.500, among which VIS at the end of surgery was the largest (0.805). The optimal cutoff point for VIS of 6.5 could predict PMV with 78.7% sensitivity and 72.3% specificity. VIS at the end of surgery was an independent risk factor for PMV (odds ratio=1.301, 95% confidence interval 1.091~1.551, P<0.01). CONCLUSION: VIS at the end of surgery is an independent predictor for PMV in patients with adult congenital heart disease surgical treatment combined with coronary artery bypass grafting.


Assuntos
Ponte de Artéria Coronária , Cardiopatias Congênitas , Pontuação de Propensão , Curva ROC , Respiração Artificial , Humanos , Ponte de Artéria Coronária/métodos , Feminino , Masculino , Cardiopatias Congênitas/cirurgia , Adulto , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo , Estudos Retrospectivos , Valor Preditivo dos Testes , Período Pós-Operatório , Modelos Logísticos
9.
Chem Biodivers ; 21(7): e202400635, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38687253

RESUMO

The phytochemical investigation of the fruits of Cornus officinalis yielded a new phenolic acid derivative, neophenolic acid A (1), and a novel flavonoid glycoside, (2R)-naringenin-7-O-ß-(6''-galloyl-glucopyranoside) (2 a), along with six known flavonoid glycosides (2 b-7). Their structures were determined by 1D, 2D NMR and HRESIMS data. The absolute configuration of 1 was established by ECD analysis. Compounds 1- 7 were evaluated for their neuroprotective activities against corticosterone (CORT)-induced injury in PC-12 cells. Compounds 1, 2 a, 2 b, 5, and 6 exhibited neuroprotective activities against CORT-induced neurotoxicity in PC-12 cells. The underlying mechanism study suggested that compounds 1, 2 a, 2 b, 5, and 6 were able to attenuate CORT-induced apoptosis and damage, increase the levels of MMP and decrease Ca2+ inward flow in PC-12 cells.


Assuntos
Apoptose , Cornus , Frutas , Fármacos Neuroprotetores , Cornus/química , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Animais , Frutas/química , Ratos , Células PC12 , Apoptose/efeitos dos fármacos , Corticosterona/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Estrutura Molecular , Flavonoides/farmacologia , Flavonoides/isolamento & purificação , Flavonoides/química , Relação Estrutura-Atividade , Cálcio/metabolismo
10.
Invest Ophthalmol Vis Sci ; 65(4): 15, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38587443

RESUMO

Purpose: The purpose of this study was to understand how monocular luminance reduction affects binocular balance and examine whether it differentially influences fusion and mixed perception in amblyopia. Methods: Twenty-three normally sighted observers and 12 adults with amblyopia participated in this study. A novel binocular rivalry task was used to measure the phase duration of four perceptual responses (right- and left-tilts, fusion, and mixed perception) before and after a neutral density (ND) filter was applied at various levels to the dominant eye (DE) of controls and the fellow eye (FE) of patients with amblyopia. Phase durations were analyzed to assess whether the duration of fusion or mixed perception shifted after monocular luminance reduction. Moreover, we quantified ocular dominance and adjusted monocular contrast and luminance separately to investigate the relationship between changes in ocular dominance induced by the two manipulations. Results: In line with previous studies, binocular balance shifted in favor of the brighter eye in both normal adults and patients with amblyopia. As a function of the ND filter's density, the duration of fusion and mixed perception decreased in normal controls, whereas that of fusion but not mixed perception increased significantly in patients with amblyopia. In addition, changes in binocular balance from luminance reduction were more significant in more balanced amblyopes or normal observers. Furthermore, shifts in binocular balance after contrast and luminance modulation were correlated in both normal and amblyopic observers. Conclusions: The duration of fusion but not mixed perception increased in amblyopia after monocular luminance reduction in the FE. Moreover, our findings demonstrate that changes in ocular dominance from contrast-modulation and luminance-modulation are correlated in both normal and amblyopic observers.


Assuntos
Ambliopia , Adulto , Humanos , Dominância Ocular , Percepção
11.
J Control Release ; 369: 687-695, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38575073

RESUMO

Extracts of the Chilean soapbark tree, Quillaja Saponaria (QS) are the source of potent immune-stimulatory saponin compounds. This study compared the adjuvanticity and toxicity of QS-18 and QS-21, assessing the potential to substitute QS-18 in place of QS-21 for vaccine development. QS-18, the most abundant QS saponin fraction, has been largely overlooked due to safety concerns. We found that QS-18 spontaneously inserted into liposomes, thereby neutralizing hemolytic activity, and following administration did not induce local reactogenicity in a footpad swelling test in mice. With high-dose intramuscular administration, transient weight loss was minor, and QS-18 did not induce significantly more weight loss compared to a liposome vaccine adjuvant system lacking it. Two days after administration, no elevation of inflammatory cytokines was detected in murine serum. In a formulation including cobalt-porphyrin-phospholipid (CoPoP) for short peptide sequestration, QS-18 did not impact the formation of peptide nanoparticles. With immunization, QS-18 peptide particles induced higher levels of cancer neoepitope-specific and tumor-associated antigen-specific CD8+ T cells compared to QS-21 particles, without indication of greater toxicity based on mouse body weight. T cell receptor sequencing of antigen-specific CD8+ T cells showed that QS-18 induced significantly more T cell transcripts. In two murine cancer models, vaccination with QS-18 peptide particles induced a similar therapeutic effect as QS-21 particles, without indication of increased toxicity. Antigen-specific CD8+ T cells in the tumor microenvironment were found to express the exhaustion marker PD-1, pointing to the rationale for exploring combination therapy. Taken together, these data demonstrate that QS-18, when formulated in liposomes, can be a safe and effective adjuvant to induce tumor-inhibiting cellular responses in murine models with potential to facilitate or diminish costs of production for vaccine adjuvant systems. Further studies are warranted to assess liposomal QS-18 immunogic, reactogenic and toxicological profiles in mice and other animal species.


Assuntos
Adjuvantes Imunológicos , Vacinas Anticâncer , Lipossomos , Quillaja , Animais , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Quillaja/química , Adjuvantes Imunológicos/administração & dosagem , Feminino , Camundongos Endogâmicos C57BL , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/imunologia , Camundongos , Saponinas de Quilaia , Citocinas , Saponinas/administração & dosagem , Saponinas/farmacologia , Linhagem Celular Tumoral , Vacinas de Subunidades Proteicas
12.
Diabetes Metab Syndr Obes ; 17: 1249-1265, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38496004

RESUMO

Purpose: The purpose of this study is to explore the independent-influencing factors from normal people to prediabetes and from prediabetes to diabetes and use different prediction models to build diabetes prediction models. Methods: The original data in this retrospective study are collected from the participants who took physical examinations in the Health Management Center of Peking University Shenzhen Hospital. Regression analysis is individually applied between the populations of normal and prediabetes, as well as the populations of prediabetes and diabetes, for feature selection. Afterward,the independent influencing factors mentioned above are used as predictive factors to construct a prediction model. Results: Selecting physical examination indicators for training different ML models through univariate and multivariate logistic regression, the study finds Age, PRO, TP, and ALT are four independent risk factors for normal people to develop prediabetes, and GLB and HDL.C are two independent protective factors, while logistic regression performs best on the testing set (Acc: 0.76, F-measure: 0.74, AUC: 0.78). We also find Age, Gender, BMI, SBP, U.GLU, PRO, ALT, and TG are independent risk factors for prediabetes people to diabetes, and AST is an independent protective factor, while logistic regression performs best on the testing set (Acc: 0.86, F-measure: 0.84, AUC: 0.74). Conclusion: The discussion of the clinical relationships between these indicators and diabetes supports the interpretability of our feature selection. Among four prediction models, the logistic regression model achieved the best performance on the testing set.

13.
Cancer Res Commun ; 4(4): 958-969, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38506662

RESUMO

Mimotopes of short CD8+ T-cell epitopes generally comprise one or more mutated residues, and can increase the immunogenicity and function of peptide cancer vaccines. We recently developed a two-step approach to generate enhanced mimotopes using positional peptide microlibraries and herein applied this strategy to the broadly used H-2Kb-restricted murine leukemia p15E tumor rejection epitope. The wild-type p15E epitope (sequence: KSPWFTTL) was poorly immunogenic in mice, even when combined with a potent peptide nanoparticle vaccine system and did not delay p15E-expressing MC38 tumor growth. Following positional microlibrary functional screening of over 150 mimotope candidates, two were identified, both with mutations at residue 3 (p15E-P3C; "3C," and p15E-P3M; "3M") that better induced p15E-specific CD8+ T cells and led to tumor rejection. Although 3M was more immunogenic, 3C effectively delayed tumor growth in a therapeutic setting relative to the wild-type p15E. As 3C had less H-2Kb affinity relative to both p15E and 3M, 15 additional mimotope candidates (all that incorporated the 3C mutation) were assessed that maintained or improved predicted MHC-I affinity. Valine substitution at position 2 (3C2V, sequence: KVCWFTTL) led to improved p15E-specific immunogenicity, tumor rejection, and subsequent long-term antitumor immunity. 3C, 3M, and 3C2V mimotopes were more effective than p15E in controlling MC38 and B16-F10 tumors. T-cell receptor (TCR) sequencing revealed unique TCR transcripts for mimotopes, but there were no major differences in clonality. These results provide new p15E mimotopes for further vaccine use and illustrate considerations for MHC-I affinity, immunogenicity, and functional efficacy in mimotope design. SIGNIFICANCE: The MHC-I-restricted p15E tumor rejection epitope is expressed in multiple murine cancer lines and is used as a marker of antitumor cellular immunity, but has seen limited success as a vaccine immunogen. An in vivo screening approach based on a positional peptide microlibraries is used to identify enhanced p15E mimotopes bearing amino acid mutations that induce significantly improved functional immunogenicity relative to vaccination with the wild-type epitope.


Assuntos
Neoplasias , Vacinas , Animais , Camundongos , Neoplasias/terapia , Peptídeos , Epitopos de Linfócito T/genética , Receptores de Antígenos de Linfócitos T
14.
Cell Rep Med ; 5(3): 101433, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38401547

RESUMO

Inclusion of defined quantities of the two major surface proteins of influenza virus, hemagglutinin (HA) and neuraminidase (NA), could benefit seasonal influenza vaccines. Recombinant HA and NA multimeric proteins derived from three influenza serotypes, H1N1, H3N2, and type B, are surface displayed on nanoliposomes co-loaded with immunostimulatory adjuvants, generating "hexaplex" particles that are used to immunize mice. Protective immune responses to hexaplex liposomes involve functional antibody elicitation against each included antigen, comparable to vaccination with monovalent antigen particles. When compared to contemporary recombinant or adjuvanted influenza virus vaccines, hexaplex liposomes perform favorably in many areas, including antibody production, T cell activation, protection from lethal virus challenge, and protection following passive sera transfer. Based on these results, hexaplex liposomes warrant further investigation as an adjuvanted recombinant influenza vaccine formulation.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Infecções por Orthomyxoviridae , Camundongos , Animais , Humanos , Hemaglutininas , Neuraminidase/genética , Vírus da Influenza A Subtipo H3N2 , Lipossomos , Adjuvantes Imunológicos , Vacinas Sintéticas
15.
J Nanobiotechnology ; 22(1): 54, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326903

RESUMO

The treatment of critical-size bone defects with irregular shapes remains a major challenge in the field of orthopedics. Bone implants with adaptability to complex morphological bone defects, bone-adhesive properties, and potent osteogenic capacity are necessary. Here, a shape-adaptive, highly bone-adhesive, and ultrasound-powered injectable nanocomposite hydrogel is developed via dynamic covalent crosslinking of amine-modified piezoelectric nanoparticles and biopolymer hydrogel networks for electrically accelerated bone healing. Depending on the inorganic-organic interaction between the amino-modified piezoelectric nanoparticles and the bio-adhesive hydrogel network, the bone adhesive strength of the prepared hydrogel exhibited an approximately 3-fold increase. In response to ultrasound radiation, the nanocomposite hydrogel could generate a controllable electrical output (-41.16 to 61.82 mV) to enhance the osteogenic effect in vitro and in vivo significantly. Rat critical-size calvarial defect repair validates accelerated bone healing. In addition, bioinformatics analysis reveals that the ultrasound-responsive nanocomposite hydrogel enhanced the osteogenic differentiation of bone mesenchymal stem cells by increasing calcium ion influx and up-regulating the PI3K/AKT and MEK/ERK signaling pathways. Overall, the present work reveals a novel wireless ultrasound-powered bone-adhesive nanocomposite hydrogel that broadens the therapeutic horizons for irregular bone defects.


Assuntos
Osteogênese , Fosfatidilinositol 3-Quinases , Ratos , Animais , Nanogéis , Osso e Ossos/diagnóstico por imagem , Hidrogéis/farmacologia
16.
Small ; 20(9): e2304534, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37849036

RESUMO

The receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) glycoprotein is an appealing immunogen, but associated vaccine approaches must overcome the hapten-like nature of the compact protein and adapt to emerging variants with evolving RBD sequences. Here, a vaccine manufacturing methodology is proposed comprising a sterile-filtered freeze-dried lipid cake formulation that can be reconstituted with liquid proteins to instantaneously form liposome-displayed protein nanoparticles. Mannitol is used as a bulking agent and a small amount of Tween-80 surfactant is required to achieve reconstituted submicron particles that do not precipitate prior to usage. The lipid particles include an E. coli-derived monophosphoryl lipid A (EcML) for immunogenicity, and cobalt porphyrin-phospholipid (CoPoP) for antigen display. Reconstitution of the lipid cake with aqueous protein results in rapid conversion of the RBD into intact liposome-bound format prior to injection. Protein particles can readily be formed with sequent-divergent RBD proteins derived from the ancestral or Omicron strains. Immunization of mice elicits antibodies that neutralize respective viral strains. When K18-hACE2 transgenic mice are immunized and challenged with ancestral SARS-CoV-2 or the Omicron BA.5 variant, both liquid liposomes displaying the RBD and rapid reconstituted particles protect mice from infection, as measured by the viral load in the lungs and nasal turbinates.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Animais , Camundongos , Nanovacinas , SARS-CoV-2 , Escherichia coli , Lipossomos , COVID-19/prevenção & controle , Lipídeos
17.
Rev. bras. cir. cardiovasc ; 39(3): e20230218, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1559391

RESUMO

ABSTRACT Introduction: This study aimed to investigate the predictive value of the vasoactive-inotropic score (VIS) at different time points for postoperative prolonged mechanical ventilation (PMV) in adult congenital heart disease patients undergoing surgical treatment combined with coronary artery bypass grafting. Methods: Patients were divided into two groups that developed PMV or not. The propensity score matching method was applied to reduce the effects of confounding factors between the two groups. VIS at different time points (VIS at the end of surgery, VIS6h, VIS12h, and VIS12h max) after surgery were recorded and calculated. The value of VIS in predicting PMV was analyzed by the receiver operating characteristic (ROC) curve, and multivariate logistic regression was used to analyze independent risk factors. Results: Among 250 patients, 52 were in the PMV group, and 198 were in the non-PMV group. PMV rate was 20.8%. After propensity score matching, 94 patients were matched in pairs. At each time point, the area under the ROC curve predicted by VIS for PMV was > 0.500, among which VIS at the end of surgery was the largest (0.805). The optimal cutoff point for VIS of 6.5 could predict PMV with 78.7% sensitivity and 72.3% specificity. VIS at the end of surgery was an independent risk factor for PMV (odds ratio=1.301, 95% confidence interval 1.091~1.551, P<0.01). Conclusion: VIS at the end of surgery is an independent predictor for PMV in patients with adult congenital heart disease surgical treatment combined with coronary artery bypass grafting.

18.
BMC Plant Biol ; 23(1): 553, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37940897

RESUMO

BACKGROUND: Rice (Oryza sativa L.) is one of the most widely cultivated grain crops in the world that meets the caloric needs of more than half the world's population. Salt stress seriously affects rice production and threatens food security. Therefore, mining salt tolerance genes in salt-tolerant germplasm and elucidating their molecular mechanisms in rice are necessary for the breeding of salt tolerant cultivars. RESULTS: In this study, a salt stress-responsive jacalin-related lectin (JRL) family gene, OsJRL45, was identified in the salt-tolerant rice variety 'sea rice 86' (SR86). OsJRL45 showed high expression level in leaves, and the corresponding protein mainly localized to the endoplasmic reticulum. The knockout mutant and overexpression lines of OsJRL45 revealed that OsJRL45 positively regulates the salt tolerance of rice plants at all growth stages. Compared with the wild type (WT), the OsJRL45 overexpression lines showed greater salt tolerance at the reproductive stage, and significantly higher seed setting rate and 1,000-grain weight. Moreover, OsJRL45 expression significantly improved the salt-resistant ability and yield of a salt-sensitive indica cultivar, L6-23. Furthermore, OsJRL45 enhanced the antioxidant capacity of rice plants and facilitated the maintenance of Na+-K+ homeostasis under salt stress conditions. Five proteins associated with OsJRL45 were screened by transcriptome and interaction network analysis, of which one, the transmembrane transporter Os10g0210500 affects the salt tolerance of rice by regulating ion transport-, salt stress-, and hormone-responsive proteins. CONCLUSIONS: The OsJRL45 gene isolated from SR86 positively regulated the salt tolerance of rice plants at all growth stages, and significantly increased the yield of salt-sensitive rice cultivar under NaCl treatment. OsJRL45 increased the activity of antioxidant enzyme of rice and regulated Na+/K+ dynamic equilibrium under salinity conditions. Our data suggest that OsJRL45 may improve the salt tolerance of rice by mediating the expression of ion transport-, salt stress response-, and hormone response-related genes.


Assuntos
Oryza , Plântula , Plântula/metabolismo , Tolerância ao Sal/genética , Oryza/metabolismo , Lectinas/metabolismo , Antioxidantes/metabolismo , Melhoramento Vegetal , Hormônios/metabolismo
19.
Expert Rev Vaccines ; 22(1): 1022-1040, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37878481

RESUMO

INTRODUCTION: Liposomes have been used as carriers for vaccine adjuvants and antigens due to their inherent biocompatibility and versatility as delivery vehicles. Two vial admixture of protein antigens with liposome-formulated immunostimulatory adjuvants has become a broadly used clinical vaccine preparation approach. Compared to freely soluble antigens, liposome-associated forms can enhance antigen delivery to antigen-presenting cells and co-deliver antigens with adjuvants, leading to improved vaccine efficacy. AREAS COVERED: Several antigen-capture strategies for liposomal vaccines have been developed for proteins, peptides, and nucleic acids. Specific antigen delivery methodologies are discussed, including electrostatic adsorption, encapsulation inside the liposome aqueous core, and covalent and non-covalent antigen capture. EXPERT OPINION: Several commercial vaccines include active lipid components, highlighting an increasingly prominent role of liposomes and lipid nanoparticles in vaccine development. Utilizing liposomes to associate antigens offers potential advantages, including antigen and adjuvant dose-sparing, co-delivery of antigen and adjuvant to immune cells, and enhanced immunogenicity. Antigen capture by liposomes has demonstrated feasibility in clinical testing. New antigen-capture techniques have been developed and appear to be of interest for vaccine development.


Assuntos
Lipossomos , Vacinas , Humanos , Antígenos , Adjuvantes Imunológicos , Células Apresentadoras de Antígenos
20.
Carbohydr Polym ; 320: 121200, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37659790

RESUMO

To investigate the influence of surface gelatinization on cold plasma (CP) modification of starch, this study used CaCl2 to modify maize starch by surface gelatinization, further combined with CP treatment and characterized its multi-scale structure and physicochemical properties. The results revealed that starch surface gelatinization causes roughness and fragmentation on the granule surface, and CP undergoes etching effects. The synergistic modification promotes starch degradation, as evidenced by molecular weight decrease and short-chain ratio increase. Although the growth rings, FT-IR patterns, and crystal types of starch remained unchanged, the synergistic modification induced a reduction in the short-range orderliness and crystallinity of starch, thus causing a decrease in the pasting properties and contributing to its solubility. Notably, the CP treatment improved the RDS and SDS contents of the gelatinized starch due to more active sites on the granule surface after gelatinization, and this finding may provide insight into the deep processing of starch.


Assuntos
Gases em Plasma , Cloreto de Cálcio , Espectroscopia de Infravermelho com Transformada de Fourier , Zea mays , Amido
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