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1.
Toxics ; 12(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38668473

RESUMO

The characterization of dissolved organic matter (DOM) is important for better understanding of the migration and transformation mechanisms of DOM in water bodies and its interaction with other contaminants. In this work, fluorescence characteristics and molecular compositions of the DOM samples collected from the mainstream, tributary, and sewage outfall of the Inner Mongolia section of the Yellow River (IMYR) were determined by using fluorescence spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). In addition, concentrations of potentially toxic elements (PTEs) in the relevant surface water and their potential relationships with DOM were investigated. The results showed that the abundance of tyrosine-like components increased significantly in downstream waters impacted by outfall effluents and was negatively correlated with the humification index (HIX). Compared to the mainstream, outfall and tributaries have a high number of molecular formulas and a higher proportion of CHOS molecular formulas. In particular, the O5S class has a relative intensity of 41.6% and the O5-7S class has more than 70%. Thirty-eight PTEs were measured in the surface water samples, and 12 found above their detective levels at all sampling sites. Protein-like components are positively correlated with Cu, which is likely indicating the source of Cu in the aquatic environment of the IMYR. Our results demonstrated that urban wastewater discharges significantly alter characteristics and compositions of DOM in the mainstream of IMYR with strongly anthropogenic features. These results and conclusions are important for understanding the role and sources of DOM in the Yellow River aquatic environment.

2.
BMC Womens Health ; 24(1): 239, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38616274

RESUMO

OBJECTIVE: To evaluate the surface electromyography (sEMG) of pelvic floor muscles (PFMs), compare between vaginal birth and cesarean section and correlate with maternity and obstetrics characteristics in primiparous 6-8 weeks postpartum. METHODS: PFMs surface electromyography screening data of primiparous postpartum women in our hospital at 6-8 weeks postpartum from 2018 to 2021 were selected and analyzed. The study collected data on delivery activities of 543 postpartum women totally. RESULTS: In general, the abnormal incidence of pelvic floor electromyography in postpartum women mainly occurred in slow muscle (type I fiber) stage and endurance testing stage. Compared to vaginal birth postpartum women, the incidence of abnormal pelvic floor electromyography in cesarean section postpartum women is lower. There were statistical differences in measurement values of pelvic floor electromyography in several different stages between cesarean section and vaginal birth (P < 0.005). Regarding the influence on pelvic floor electromyography, there were more influencing factors on vaginal birth postpartum women including age, height, weight, weight gain during pregnancy, gestational week, and first and second stage of labor than on cesarean section postpartum women whose influencing factors included age, weight gain during pregnancy, and newborn weight. CONCLUSION: Effects on surface electromyography (sEMG) of pelvic floor muscles (PFMs) at 6-8 weeks postpartum differed based on the different modes of delivery. The high-risk obstetric factors closely related to abnormal surface electromyography (sEMG) of pelvic floor muscles (PFMs) were maternal age, height, weight, and second stage of labor.


Assuntos
Cesárea , Diafragma da Pelve , Gravidez , Recém-Nascido , Feminino , Humanos , Estudos Transversais , Eletromiografia , Período Pós-Parto , Aumento de Peso
3.
J Nanobiotechnology ; 22(1): 131, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532389

RESUMO

Effective intracellular DNA transfection is imperative for cell-based therapy and gene therapy. Conventional gene transfection methods, including biochemical carriers, physical electroporation and microinjection, face challenges such as cell type dependency, low efficiency, safety concerns, and technical complexity. Nanoneedle arrays have emerged as a promising avenue for improving cellular nucleic acid delivery through direct penetration of the cell membrane, bypassing endocytosis and endosome escape processes. Nanostraws (NS), characterized by their hollow tubular structure, offer the advantage of flexible solution delivery compared to solid nanoneedles. However, NS struggle to stably self-penetrate the cell membrane, resulting in limited delivery efficiency. Coupling with extra physiochemical perforation strategies is a viable approach to improve their performance. This study systematically compared the efficiency of NS coupled with polyethylenimine (PEI) chemical modification, mechanical force, photothermal effect, and electric field on cell membrane perforation and DNA transfection. The results indicate that coupling NS with PEI modification, mechanical force, photothermal effects provide limited enhancement effects. In contrast, NS-electric field coupling significantly improves intracellular DNA transfection efficiency. This work demonstrates that NS serve as a versatile platform capable of integrating various physicochemical strategies, while electric field coupling stands out as a form worthy of primary consideration for efficient DNA transfection.


Assuntos
DNA , Eletroporação , Transfecção , Membrana Celular , Terapia Genética , Polietilenoimina/química
4.
Biomed Pharmacother ; 173: 116231, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38484561

RESUMO

Since December 2019, the infection caused by Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) has posed an enormous threat to human health security worldwide. Constant mutation of viral genome and varying therapeutic responses of patients infected with this virus prompted efforts to uncover more novel regulators in the pathogenesis. The involvement of N6-methyladenosine, a modified form of RNA, plays a crucial role in viral replication, viral pathogenicity, and intricate signaling pathways connected with immune responses. This review discusses research advances revealing the regulation of the life cycle of SARS-CoV-2 and antiviral responses of host cells by RNA m6A modification, highlights the biological functions of N6-methyladenosine components in SARS-CoV-2 infection and virus-host interactions, and outlines current challenges and future directions for exploring the potential clinical value of m6A modification in COVID-19.


Assuntos
COVID-19 , Humanos , Interações entre Hospedeiro e Microrganismos , SARS-CoV-2 , RNA
5.
Neuroscience ; 542: 21-32, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38340785

RESUMO

Neuroinflammation is an early event of brain injury after subarachnoid hemorrhage (SAH). Whether the macrophage mediators in resolving inflammation 1 (MaR1) is involved in SAH pathogenesis is unknown. In this study, 205 male Sprague-Dawley rats were subjected to SAH via endovascular perforation in the experimental and control groups. MaR1 was dosed intranasally at 1 h after SAH, with LGR6 siRNA and KG-501, GSK-J4 administered to determine the signaling pathway. Neurobehavioral, histological and biochemical data were obtained from the animal groups with designated treatments. The results showed: (i) The leucine-rich repeat containing G protein-coupled receptor 6 (LGR6) was decreased after SAH and reached to the lowest level at 24 h after SAH. Jumonji d3 (JMJD3) protein levels tended to increase and peaked at 24 h after SAH. LGR6 and JMJD3 expression were co-localized with microglia. (ii) MaR1 administration mitigated short-term neurological deficits, brain edema and long-term neurobehavioral performance after SAH, and attenuated microglial activation and neutrophil infiltration. (iii) Knockdown of LGR6, inhibition of CREB phosphorylation or JMJD3 activity abolished the anti-neuroinflammatory effect of MaR1 on the expression of CREB, CBP, JMJD3, IRF4, IRF5, IL-1ß, IL-6 and IL-10, thus prevented microglial activation and neutrophil infiltration. Together, the results show that MaR1 can activate LGR6 and affect CREB/JMJD3/IRF4 signaling to attenuate neuroinflammation after SAH, pointing to a potential pharmacological utility in this disorder.


Assuntos
Ácidos Docosa-Hexaenoicos , Doenças Neuroinflamatórias , Hemorragia Subaracnóidea , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/metabolismo , Transdução de Sinais
6.
Front Cell Infect Microbiol ; 14: 1289231, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318165

RESUMO

Background: Pulmonary trichomoniasis is considered a neglected disease due to failures in recognizing it, stemming from insensitive microbial methods and a lack of specific clinical features. This study aims to analyze the clinical implications of trichomonads detected in bronchoalveolar lavage fluid (BALF) by metagenomic next-generation sequencing (mNGS). Methods: This multicenter retrospective study included patients diagnosed with pneumonia, admitted to three tertiary hospitals in China from July 2018 to September 2022, with trichomonads detected in BALF through mNGS. The analysis covered demographics, comorbidities, symptoms, laboratory findings, mNGS results, clinical treatment, and outcomes of these patients. Results: A total of 17 patients were enrolled, comprising 14 males and 3 females. Trichomonas tenax and Trichomonas vaginalis were detected by mNGS in BALF samples of 15 and 2 patients, respectively. Patients were categorized into two groups based on the presence of risk factors for trichomonad infection, including immunocompromised conditions, uncontrolled diabetes mellitus, oral/periodontal diseases, and aspiration. Among 11 patients with risk factors (Case 1-11), 4 received nitromidazoles as part of comprehensive treatment, achieving a 100% treatment success rate. The remaining 7 patients, who did not receive nitromidazoles, had only one achieving relief after broad-spectrum antimicrobial therapy, resulting in a 14.3% treatment success rate. For the 6 patients without any risk factors for trichomonad infection (Case 12-17), none received nitromidazoles during hospitalization. However, 4 out of these 6 patients (66.7%) eventually recovered. Conclusion: mNGS proves to be an efficient tool for detecting trichomonads in BALF samples. Comprehensive analysis of clinical features and laboratory indicators is essential to distinguish between infection and colonization of trichomonads. Pulmonary trichomoniasis should not be overlooked when trichomonads are detected in BALF from patients with risk factors.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Tricomoníase , Feminino , Masculino , Humanos , Estudos Retrospectivos , Líquido da Lavagem Broncoalveolar , Fatores de Risco , Metagenômica , Tricomoníase/diagnóstico , Sensibilidade e Especificidade
7.
Acta Pharmacol Sin ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195693

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignancy, presenting a formidable challenge to the medical community owing to its intricate pathogenic mechanisms. Although current prevention, surveillance, early detection, diagnosis, and treatment have achieved some success in preventing HCC and controlling overall disease mortality, the imperative to explore novel treatment modalities for HCC remains increasingly urgent. Epigenetic modification has emerged as pivotal factors in the etiology of cancer. Among these, RNA N6-methyladenosine (m6A) modification stands out as one of the most prevalent, abundant, and evolutionarily conserved post-transcriptional alterations in eukaryotes. The literature underscores that the dynamic and reversible nature of m6A modifications orchestrates the intricate regulation of gene expression, thereby exerting a profound influence on cell destinies. Increasing evidence has substantiated conspicuous fluctuations in m6A modification levels throughout the progression of HCC. The deliberate modulation of m6A modification levels through molecular biology and pharmacological interventions has been demonstrated to exert a discernible impact on the pathogenesis of HCC. In this review, we elucidate the multifaceted biological functions of m6A modifications in HCC, and concurrently advancing novel therapeutic strategies for the management of this malignancy.

8.
Materials (Basel) ; 17(2)2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38255570

RESUMO

Highly transparent Ho:Y2O3 ceramics for laser diode lighting were prepared using the vacuum sintering method with 0.3 at.% Nb2O5 as a sintering additive. The microstructures, transmittance, and luminescence properties of the Ho:Y2O3 ceramic samples were investigated in detail. The transmittance levels of all samples with various Ho3+ concentrations reached ~81.5% (2 mm thick) at 1100 nm. Under the excitation of 363 nm (ultraviolet) or 448 nm (blue) light, Ho:Y2O3 transparent ceramic samples showed that green emission peaked at 550 nm. The emission intensity was strongly affected by the concentration of Ho3+ ions, reaching its highest level in the sample doped with 1 at.% Ho3+. The CIE coordinates of the luminescence were in the green region (i.e., the CIE coordinates of the sample doped with 1 at.% Ho3+ were [0.27, 0.53] and [0.30, 0.69], under the excitation of 363 nm and 448 nm light, respectively). The possibility of its application as laser diode lighting was reported. Under the excitation of 450 nm blue laser, the sample doped with 0.5 at.% Ho3+ had the best performance: the saturated luminous flux, lumen efficiency, and the luminescence saturation power densities were 800 lm, 57.7 lm/W, and 17.6 W/mm2, respectively. Furthermore, the materials have high thermal conductivity and mechanical strength due to their host of rare-earth sesquioxide. Thus, Ho:Y2O3 transparent ceramics are expected to be a promising candidate for green-light-emitting devices for solid-state lighting, such as laser diode lighting.

9.
Brachytherapy ; 23(2): 199-206, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38161082

RESUMO

PURPOSE: To investigate the feasibility of super-selectively endobronchial brachytherapy in the treatment of peripheral lung cancer guided by advanced navigation technology. METHODS AND MATERIALS: Six patients with peripheral lung tumors successfully underwent treatment with super-selectively endobronchial brachytherapy guided by advanced navigation technology following pathway planning and were subsequently followed up to assess survival and treatment-related toxicities. RESULTS: The endobronchial applicators were successfully placed inside the tumors of all patients using advanced navigation techniques according to the pretreatment plan, and brachytherapy was delivered at curative doses after evaluation using radiotherapy planning software. None of the patients showed local progression of the treated lesions during the follow-up for a duration ranging from 11 months to 35 months, with a median follow-up time of 23 months. The patient with the longest follow-up, nearly 3 years, exhibited a stable condition. After undergoing endobronchial brachytherapy, patients predominantly experienced localized fibrosis as indicated. No significant alterations in cardiopulmonary function were detected during the follow-up, and no other adverse effects were found. CONCLUSIONS: The use of endobronchial brachytherapy for the curative treatment of peripheral lung cancers is feasible. Furthermore, the development of novel bronchial navigation techniques has the potential to broaden the application of endobronchial brachytherapy.


Assuntos
Braquiterapia , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Braquiterapia/métodos , Dosagem Radioterapêutica , Brônquios/patologia
10.
Funct Integr Genomics ; 24(1): 3, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38091112

RESUMO

N6-methyladenosine (m6A) methylation is an extensive posttranscriptional RNA modification, and it is associated with various cellular responses, especially in tumor progression. An m6A "reader"-HNRNPA2B1 has been found oncogenic in multiple malignancies. As a key proliferation-related transcription factor, forkhead box protein M1 (FOXM1) is involved in tumorigenesis. Here, we elucidated the underlying mechanism by which HNRNPA2B1-mediated modification of FOXM1 promotes endometrial cancer (EC). The GSE115810 dataset was used to analyze the upregulated gene mRNA in late-stage EC tissues. The expression levels of HNRNPA2B1, FOXM1, and LCN2 in EC samples were shown by western blotting and qPCR. The interaction among HNRNPA2B1, FOXM1, and LCN2 in EC cells was detected using bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down, RNA decay analysis, and luciferase reporter experiments. Cisplatin (DDP)-resistant EC cells were constructed using HEC-1-A and HEC-1-B cells, named HEC-1-A/DDP and HEC-1-B/DDP, respectively. Proliferation, migration, and invasiveness in treated HEC-1-A/DDP and HEC-1-B/DDP cells were detected by EdU, wound healing, and transwell assays. Ferroptosis-resistant gene expression, MDA level, and ROS level were measured. The m6A modification level in EC tissues was elevated. HNRNPA2B1 and FOXM1 levels were upregulated in EC. HNRNPA2B1 expression was positively related to FOXM1 expression in EC samples, and HNRNPA2B1 bound to the 3'UTR of FOXM1 and stabilized FOXM1 mRNA via m6A modification. FOXM1 positively regulated LCN2 expression in EC cells by binding to the LCN2 promotor. Knockdown of FOXM1 downregulated ferroptosis-resistant gene expression and increased MDA and ROS levels in DDP-resistant EC cells. Rescue assays revealed that LCN2 overexpression eliminated the effects mediated by FOXM1 knockdown on the proliferation, migration, invasiveness, and ferroptosis in DDP-resistant EC cells. In conclusion, HNRNPA2B1-mediated mA modification of FOXM1 facilitates drug resistance and inhibits ferroptosis in EC cells by upregulating LCN2 expression.


Assuntos
Neoplasias do Endométrio , Ferroptose , Humanos , Feminino , Linhagem Celular Tumoral , Ferroptose/genética , Espécies Reativas de Oxigênio , Proliferação de Células/genética , Resistencia a Medicamentos Antineoplásicos/genética , RNA , Neoplasias do Endométrio/genética , RNA Mensageiro , Lipocalina-2/farmacologia , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/farmacologia
11.
Huan Jing Ke Xue ; 44(12): 6811-6822, 2023 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-38098406

RESUMO

NaHCO3-activated buckwheat biochar was studied, and an optimal biochar of 0.25N-BC [m(NaHCO3):m(buckwheat bark)=0.25:1]was selected. SEM, BET, XRD, Raman, FTIR, and XPS methods were applied to analyze the effects of NaHCO3 on the physicochemical properties of buckwheat biochar. The adsorption properties and mechanism of NaHCO3-activated buckwheat biochar for iopamidol(IPM), a nonionic iodol X-ray contrast agent, were also investigated. The results showed that compared with buckwheat skin biochar(BC), NaHCO3-activated biochar had higher structural defects(surface area and pore volume increased, respectively, from 480.40 m2·g-1 and 0.29 cm3·g-1 to 572.83 m2·g-1 and 0.40 cm3·g-1, with ID/IG being 1.22 times that of BC), the carbon and oxygen functional groups on the BC surface changed significantly, and the polarity increased [(N+O)/C from 0.15 to 0.24]. The maximum adsorption capacity of 0.25N-BC for IPM was 74.94 mg·g-1, which was 9.51 times that of BC(7.88 mg·g-1). The pseudo-second-order adsorption kinetics and Langmuir and Freundlich isotherm models could well fit the adsorption of 0.25N-BC for IPM. The adsorption processes were mainly chemical, monolayer, and heterogeneous multilayer adsorption. Pore filling, hydrogen bonding, π-π, and n-π interactions were the main mechanisms of 0.25N-BC adsorption for IPM. Comparing the activated buckwheat biochar by different bases [KOH, Na2CO3, NaHCO3, KHCO3, and Ca(HCO3)2], 0.25N-BC exhibited high adsorption capability and short equilibrium time and could effectively remove the IPM residue in the actual water(secondary sedimentation tank effluent and lake). The removal rate of IPM remained at 74.91% after three adsorption-desorption cycles. The results showed that NaHCO3-activated buckwheat biochar was a green, effective, and sustainable adsorbent for the removal of iodine-containing organic matter.


Assuntos
Fagopyrum , Poluentes Químicos da Água , Iopamidol , Adsorção , Poluentes Químicos da Água/análise , Carvão Vegetal/química , Cinética
12.
World J Gastrointest Surg ; 15(10): 2222-2233, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37969702

RESUMO

BACKGROUND: Patients with gastrointestinal tumors often suffer from poor nutritional status during treatment. Surgery is the main treatment for these patients, but the long postoperative recovery period is often accompanied by digestive and absorption dysfunction, leading to further deterioration of the nutritional status. Early enteral nutrition support is hypothesized to be helpful in improving this situation, but the exact effects have yet to be studied in depth. AIM: To observe the effect of early enteral nutritional support on postoperative recovery in patients with surgically treated gastrointestinal tract tumors, with the expectation that by improving the nutritional status of patients, the recovery process would be accelerated and the incidence of complications would be reduced, thus improving the quality of life. METHODS: A retrospective analysis of 121 patients with gastrointestinal tract tumors treated in our hospital from January 2020 to January 2023 was performed. Fifty-three of these patients received complete parenteral nutrition support as the control group for this study. The other 68 patients received early enteral nutritional support as the observation group of this study. The clinical indicators comparing the two groups included time to fever, time to recovery of postoperative bowel function, time to postoperative exhaustion, and length of hospital stay. The changes in immune function and nutritional indexes in the two groups were compared. Furthermore, we utilized the SF-36 scale to compare the changes in the quality of life between the two groups of patients. Finally, the occurrence of postoperative complications between the two patient groups was also compared. RESULTS: The postoperative fever time, postoperative bowel function recovery time, postoperative exhaustion time, and hospitalization time were all higher in the control group than in the observation group (P < 0.05). The levels of CD3+, CD4+, immunoglobulin (Ig) A, IgM, and IgG in the observation group were significantly higher than those in the control group at 1 d and 7 d postoperatively, while CD8+ was lower than in the control group (P < 0.05). Total protein, albumin, prealbumin, and transferrin levels were significantly higher in the observation group than in the control group at 7 d postoperatively (P < 0.05). The SF-36 scores of patients in the observation group were significantly higher than those in the control group (P < 0.0001). The overall incidence of adverse reactions after the intervention was significantly lower in the control group than in the observation group (P = 0.021). CONCLUSION: We found that patients with gastrointestinal tumors are nutritionally vulnerable, and early enteral nutrition support programs can improve the nutritional status of patients and speed up postoperative recovery. This program can not only improve the immune function of the patient and protect the intestinal function, but it can also help to improve the quality of life of the patient. However, this program will increase the incidence of complications in patients. Caution should be taken when adopting early enteral nutrition support measures for patients with gastric cancer. The patient's condition and physical condition should be comprehensively evaluated and closely monitored to prevent possible complications.

13.
Int J Mol Sci ; 24(22)2023 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-38003411

RESUMO

Bisphenol AF (BPAF) represents a common environmental estrogenic compound renowned for its capacity to induce endocrine disruptions. Notably, BPAF exhibits an enhanced binding affinity to estrogen receptors, which may have more potent estrogenic activity compared with its precursor bisphenol A (BPA). Notwithstanding, the existing studies on BPAF-induced prostate toxicity remain limited, with related toxicological research residing in the preliminary stage. Our previous studies have confirmed the role of BPAF in the induction of ventral prostatic hyperplasia, but its role in the dorsal lobe is not clear. In this study, BPAF (10, 90 µg/kg) and the inhibitor of nuclear transcription factor-κB (NF-κB), pyrrolidinedithiocarbamate (PDTC, 100 mg/kg), were administered intragastrically in rats for four weeks. Through comprehensive anatomical and pathological observations, as well as the assessment of PCNA over-expression, we asserted that BPAF at lower doses may foster dorsal prostatic hyperplasia in rats. The results of IHC and ELISA indicated that BPAF induced hyperplastic responses in the dorsal lobe of the prostate by interfering with a series of biomarkers in NF-κB signaling pathways, containing NF-κB p65, COX-2, TNF-α, and EGFR. These findings confirm the toxic effect of BPAF on prostate health and emphasize the potential corresponding mechanisms.


Assuntos
NF-kappa B , Hiperplasia Prostática , Humanos , Masculino , Ratos , Animais , NF-kappa B/metabolismo , Hiperplasia Prostática/induzido quimicamente , Hiperplasia , Próstata/metabolismo , Receptor alfa de Estrogênio/metabolismo , Transdução de Sinais , Compostos Benzidrílicos/toxicidade
14.
Plant Cell ; 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38036296

RESUMO

Genetic load refers to the accumulated and potentially life-threatening deleterious mutations in populations. Understanding the mechanisms underlying genetic load variation of transposable element (TE) insertion, a major large-effect mutation, during range expansion is an intriguing question in biology. Here, we used 1,115 global natural accessions of Arabidopsis (Arabidopsis thaliana) to study the driving forces of TE load variation during its range expansion. TE load increased with range expansion, especially in the recently established Yangtze River basin population. Effective population size, which explains 62.0% of the variance in TE load, high transposition rate, and selective sweeps contributed to TE accumulation in the expanded populations. We genetically mapped and identified multiple candidate causal genes and TEs, and revealed the genetic architecture of TE load variation. Overall, this study reveals the variation in TE genetic load during Arabidopsis expansion and highlights the causes of TE load variation from the perspectives of both population genetics and quantitative genetics.

15.
iScience ; 26(10): 108086, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37860767

RESUMO

The constant emergence of mutated pathogens poses great challenges to the existing vaccine system. A screening system is needed to screen for antigen designs and vaccination strategies capable of inducing cross-protective immunity. Herein, we report a screening system based on DNA vaccines and a micro-electroporation/electrophoresis system (MEES), which greatly improved the efficacy of DNA vaccines, elevating humoral and cellular immune responses by over 400- and 35-fold respectively. Eighteen vaccination strategies were screened simultaneously by sequential immunization with vaccines derived from wildtype (WT) SARS-CoV-2, Delta, or Omicron BA.1 variant. Sequential vaccination of BA.1-WT-Delta vaccines with MEES induced potent neutralizing antibodies against all three viral strains and BA.5 variant, demonstrating that cross-protective immunity against future mutants can be successfully induced by existing strain-derived vaccines when a proper combination and order of sequential vaccination are used. Our screening system could be used for fast-seeking vaccination strategies for emerging pathogens in the future.

16.
ACS Appl Mater Interfaces ; 15(43): 50015-50033, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37853502

RESUMO

Cell transfection plays a crucial role in the study of gene function and regulation of gene expression. The existing gene transfection methods, such as chemical carriers, viruses, electroporation, and microinjection, suffer from limitations, including cell type dependence, reliance on cellular endocytosis, low efficiency, safety concerns, and technical complexity. Nanopore-coupled electroporation offers a promising approach to localizing electric fields for efficient cell membrane perforation and nucleic acid transfection. However, the applicability of nanopore electroporation technology across different cell types lacks a systematic investigation. In this study, we explore the potential of nanopore electroporation for transfecting DNA plasmids into various cell types. Our nanopore electroporation device employs track-etched membranes as the core component. We find that nanopore electroporation efficiently transfects adherent cells, including well-spreading epithelial-like HeLa cells, cardiomyocyte-like HL-1 cells, and dendritic-cell-like DC2.4 cells. However, it shows a limited transfection efficiency in weakly spreading macrophages (RAW264.7) and suspension cells (Jurkat). To gain insights into these observations, we develop a COMSOL model, revealing that nanopore electroporation better localizes the electric field on adherent and well-spreading cells, promoting favorable membrane poration conditions. Our findings provide valuable references for advancing nanopore electroporation as a high-throughput, safe, and efficient gene transfection platform.


Assuntos
Nanoporos , Humanos , Células HeLa , Eletroporação/métodos , Transfecção , DNA/genética , DNA/metabolismo , Plasmídeos/genética
17.
Shanghai Kou Qiang Yi Xue ; 32(3): 241-245, 2023 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-37803976

RESUMO

PURPOSE: To investigate the effect of collagen sponge on early bone healing process of alveolar fossa after tooth extraction in rats. METHODS: A total of 16 healthy female SD rats were selected. Animal models with tooth extraction were established. The right alveolar fossa inserted with collagen sponge was as the experimental group, and the left alveolar fossa was as the control group with treatment. The rats were sacrificed 1, 2, 4 and 8 weeks after tooth extraction, and the osteogenesis of alveolar fossa was observed. Real-time quantitative PCR (qt-PCR) was used to detect the changes of osteogenesis related gene expression. SPSS 19.0 software package was used for statistical analysis. RESULTS: After surgery, alveolar cavity healing was significantly better in the experimental group than in the control group. Osterix, Runx2 and Vegf genes were expressed in the experimental group and the control group, and the expression levels of related genes in the experimental group were significantly higher than the control group 1, 2, 4 and 8 weeks after surgery(P<0.05). CONCLUSIONS: Collagen sponge could promote early alveolar bone healing, possibly related to the expression level of osteogenic genes regulated by collagen sponge.


Assuntos
Colágeno , Cicatrização , Ratos , Feminino , Animais , Ratos Sprague-Dawley , Colágeno/farmacologia , Alvéolo Dental/cirurgia , Extração Dentária , Osteogênese
18.
Cell Oncol (Dordr) ; 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37728859

RESUMO

PURPOSE: Tumor metastasis significantly impacts the prognosis of non-small cell lung cancer (NSCLC) patients, with lymph node (LN) metastasis being the most common and early form of spread. With the development of adjuvant immunotherapy, increasing attention has been paid to the tumor-draining lymph nodes(TDLN) in early-stage NSCLC, especially tumor-metastatic lymph nodes, which provides poor prognostic information but has potential benefits in adjuvant treatment. METHODS: We showed the remodeled immune environment in TDLNs through using TCR-seq to analyse 24 primary lung cancer tissues and 134 LNs from 24 lung cancer patients with or without LN metastasis. Additionally, we characterized the spatial profiling of immunocytes and tumor cells in TDLNs and primary tumor sites through using multi-IHC. RESULTS: We found the remodeled immune environment in TDLNs through analyzing primary lung cancer tissues and LNs from NSCLC patients with or without LN metastasis. Considering the intricate communication between tumor and immunocytes, we further subdivided TDLNs, revealing that metastasis-negative LNs from LN-metastatic patients (MNLN) exhibited greater immune activation, exhaustion, and memory in comparison to both metastasis-positive LNs (MPLN) and TDLNs from non-LN-metastatic patients (NMLN). CONCLUSIONS: Our data indicate that LN metastasis facilitated tumor-specific antigen presentation in TDLNs and induces T cell priming, while existing tumor cells generate an immune-suppressive environment in MPLNs through multiple mechanisms. These findings contribute to a comprehensive understanding of the immunological mechanisms through which LN metastasis influences tumor progression and plays a role in immunotherapy for NSCLC patients.

19.
Cell Cycle ; 22(17): 1865-1883, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37592763

RESUMO

Colorectal cancer is a common type of digestive tract cancer with a significant morbidity and death rate across the world, partially attributing to the metastasis-associated problems. In this study, integrative bioinformatics analyses were performed to identify genes that might contribute to colorectal cancer metastasis, and 293 genes were dramatically increased and 369 genes were decreased within colon cancer samples. Among up-regulated genes, top five genes correlated with colorectal cancer patient's prognosis were verified for expression in clinical samples and syntrophin beta 1 (SNTB1) was the most up-regulated. In vitro, SNTB1 knockdown suppresses the malignant behaviors of colorectal cancer cells, including cell viability, colony formation capacity, as well as the abilities to migrate and invade. Furthermore, SNTB1 knockdown decreased the levels of Wnt1, C-Jun, C-Myc, TCF7, and cyclin D1, and inhibited EMT in both cell lines. In vivo, SNTB1 knockdown inhibited tumor growth and metastasis in nude mice models. SNTB1 positively regulated Yes1 associated transcriptional regulator (YAP1) expression; YAP1 partially reversed the effects of SNTB1 on colorectal cancer cell phenotypes and the Wnt/ß-catenin/MYC signaling. In conclusion, SNTB1 knockdown inhibits colorectal cancer cell aggressiveness in vitro and tumor growth and metastasis in vivo through the Wnt/ß-catenin/MYC signaling; YAP1 might mediate SNTB1 functions on colorectal cancer.


Assuntos
Neoplasias Colorretais , beta Catenina , Animais , Humanos , Camundongos , beta Catenina/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Proteínas Proto-Oncogênicas c-myc/metabolismo , Via de Sinalização Wnt/genética
20.
Materials (Basel) ; 16(13)2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37444818

RESUMO

Highly transparent Er:Y2O3 ceramics (1-9 at.% Er) were fabricated by hot pressing sintering with ZrO2 as the sintering additive. The microstructures, transmittance, luminescent properties, thermal conductivity, and mechanical properties of the Er:Y2O3 ceramic samples were investigated in detail. The samples all exhibited dense and fine grain microstructures; the average grain sizes were about 0.8 µm. The transmittance levels of the samples with various Er concentrations (2 mm thick) at the wavelengths of 600 and 2700 nm were ~74 and ~83%, respectively. As the Er doping concentration increased from 1 to 9 at.%, the up-conversion luminescence of the samples gradually changed from green to red, with the intensity ratio of red/green light increasing from 0.28 to 2.01. Meanwhile, the down-conversion luminescence properties of the specimens were also studied. When the samples were under 980 nm excitation, the emission bands were detected at 1552, 1573, 1639, and 1661 nm. The thermal conductivity of the samples was found to decrease from 8.72 to 5.81 W/(m·K) with an increase of the Er concentration from 1 to 9 at.%. Moreover, the microhardness and fracture toughness of the samples with 1 at.% Er concentration were ~8.51 GPa and ~1.03 MPa·m1/2, respectively.

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