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1.
Mil Med Res ; 11(1): 22, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622688

RESUMO

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.


Assuntos
Ferroptose , Traumatismo por Reperfusão , Animais , Camundongos , Diclorodifenil Dicloroetileno , Hepatócitos , Interferon-alfa , RNA , RNA Mensageiro
2.
Front Immunol ; 15: 1298749, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38440733

RESUMO

Since the leprosy cases have fallen dramatically, the incidence of leprosy has remained stable over the past years, indicating that multidrug therapy seems unable to eradicate leprosy. More seriously, the emergence of rifampicin-resistant strains also affects the effectiveness of treatment. Immunoprophylaxis was mainly carried out through vaccination with the BCG but also included vaccines such as LepVax and MiP. Meanwhile, it is well known that the infection and pathogenesis largely depend on the host's genetic background and immunity, with the onset of the disease being genetically regulated. The immune process heavily influences the clinical course of the disease. However, the impact of immune processes and genetic regulation of leprosy on pathogenesis and immunological levels is largely unknown. Therefore, we summarize the latest research progress in leprosy treatment, prevention, immunity and gene function. The comprehensive research in these areas will help elucidate the pathogenesis of leprosy and provide a basis for developing leprosy elimination strategies.


Assuntos
Hansenostáticos , Hanseníase , Humanos , Quimioterapia Combinada , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Hanseníase/genética , Hanseníase/prevenção & controle , Rifampina , Imunidade
3.
Viruses ; 16(2)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38399951

RESUMO

Two strains of viruses, JC13C644 and JC13C673, were isolated from Culicoides tainanus collected in Jiangcheng County, Yunnan Province, situated along the border area shared by China, Laos, and Vietnam. JC13C644 and JC13C673 viruses can cause cytopathic effect (CPE) in mammalian cells BHK21 and Vero cells, and cause morbidity and mortality in suckling mice 48 h after intracerebral inoculation. Whole-genome sequencing was performed, yielding complete sequences for all 10 segments from Seg-1 (3942nt) to Seg-10 (810nt). Phylogenetic analysis of the sub-core-shell (T2) showed that the JC13C644 and JC13C673 viruses clustered with the Epizootic Hemorrhagic Disease Virus (EHDV) isolated from Japan and Australia, with nucleotide and amino acid homology of 93.1% to 98.3% and 99.2% to 99.6%, respectively, suggesting that they were Eastern group EHDV. The phylogenetic analysis of outer capsid protein (OC1) and outer capsid protein (OC2) showed that the JC13C644 and JC13C673 viruses were clustered with the EHDV-10 isolated from Japan in 1998, with the nucleotide homology of 98.3% and 98.5%, and the amino acid homology of 99.6% and 99.6-99.8%, respectively, indicating that they belong to the EHDV-10. Seroepidemiological survey results demonstrated that JC13C644 virus-neutralizing antibodies were present in 29.02% (177/610) of locally collected cattle serum and 11.32% (89/786) of goat serum, implying the virus's presence in Jiangcheng, Yunnan Province. This finding suggests that EHDV-10 circulates not only among blood-sucking insects in nature but also infects local domestic animals in China. Notably, this marks the first-ever isolation of the virus in China and its discovery outside of Japan since its initial isolation from Japanese cattle. In light of these results, it is evident that EHDV Serotype 10 exists beyond Japan, notably in the natural vectors of southern Eurasia, with the capacity to infect local cattle and goats. Therefore, it is imperative to intensify the surveillance of EHDV infection in domestic animals, particularly focusing on the detection and monitoring of new virus serotypes that may emerge in the region and pose risks to animal health.


Assuntos
Ceratopogonidae , Vírus da Doença Hemorrágica Epizoótica , Infecções por Reoviridae , Chlorocebus aethiops , Bovinos , Animais , Camundongos , Vírus da Doença Hemorrágica Epizoótica/genética , Gado , Sorogrupo , China/epidemiologia , Filogenia , Infecções por Reoviridae/epidemiologia , Infecções por Reoviridae/veterinária , Proteínas do Capsídeo , Células Vero , Cabras , Aminoácidos , Nucleotídeos
4.
Front Microbiol ; 15: 1349746, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38389524

RESUMO

Bacterial ghosts (BGs) are promising vaccine platforms owing to their high adjuvant properties and delivery efficiency. Heterologous antigens can be anchored to different parts of BGs using genetic engineering strategies to prepare vaccines. However, several key issues need to be resolved, including the efficient preparation of BGs and determining the optimal anchoring position of exogenous antigens in the BGs. Here, we prepared an efficient temperature-controlled lysis system using lysis gene E of phage PhiX174 and used the major outer membrane protein (MOMP) of Chlamydia abortus (C. abortus) as a model antigen to explore the optimal display location of exogenous antigens in BGs. We demonstrated that the constructed recombinant temperature-controlled lysis plasmid can still stably inhibit E gene expression at 37°C, and the lysis efficiency of E. coli can reach above 99.9%. Four recombinant MOMP Escherichia coli (E. coli) ghost vaccines were constructed using different anchor sequences. These vaccines all induced strong specific antibody responses and secrete high levels of IFN-γ in immunized mice and significantly increased the clearance of C. abortus in a mouse infection model. Notably, the strongest immune effect was observed when MOMP was displayed on the surface of E. coli ghosts (rECG-InpN-M), which resulted in the clearance of C. abortus in mice 6 days earlier than that with the recombinant MOMP vaccine. Altogether, we constructed an efficient BG temperature-controlled lysis system and provided a feasible strategy for developing a BG delivery platform with enhanced immune effects.

5.
PLoS One ; 19(2): e0299113, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38422029

RESUMO

Saline-alkali soil significantly impairs crop growth. This research employs the impacts of the modifier and water-soluble fertilizer, as well as their interaction, on the root systems of alfalfa and leymus chinensis in saline-alkali soil. The results exhibit that the hydrochar source modifier effectively enhances the root growth of both forage species. There are certain improvements in the root growth indicators of both crops at a dosage of 20 g/kg. Root enzyme activity and rhizosphere soil enzyme activity are enhanced in alfalfa, showing significant improvements in the first planting compared to the second planting. The application of water-soluble fertilizers also promotes root growth and root dehydrogenase activity. The root dehydrogenase activity of alfalfa and leymus chinensis are enhanced 62.18% and 10.15% in first planting than that of blank, respectively. Additionally, the two-factor variance analysis revealed a correlation between rhizosphere soil enzyme activity and changes in root traits. Higher rhizosphere soil enzyme activity is observed in conjunction with better root growth. The combined application of a modifier and water-soluble fertilizer has demonstrated a significant interaction effect on various aspects of the first planting of alfalfa and leymus chinensis. Moreover, the combined application of the modifier and water-soluble fertilizer has yielded superior results when compared to the individual application of either the modifier or the water-soluble fertilizer alone. This combined approach has proven effective in improving saline-alkali soil conditions and promoting crop growth in such challenging environments.


Assuntos
Álcalis , Fertilizantes , Intoxicação por Metais Pesados , Medicago sativa , Poaceae , Solução Salina , Solo , Água , Oxirredutases
6.
Trials ; 25(1): 73, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254137

RESUMO

BACKGROUND: Maternal oxygen supplementation is usually used as an intrauterine resuscitation technique to prevent fetal hypoxia and acidemia during delivery. However, there has been a great deal of controversy regarding the effects of prophylactic maternal oxygen during cesarean section, during which the incidence of fetal acidemia seems to be higher compared with that during labor. High-flow nasal oxygen (HFNO) can improve oxygenation better in patients with high-flow oxygen airflow. The purpose of this study is to determine whether maternal oxygen supplementation with HFNO has a positive effect on fetal acidemia during cesarean section through umbilical arterial blood gas analysis. METHOD: This prospective, single-center, randomized, double-blinded trial will enroll 120 patients undergoing cesarean section. Participants will be randomly assigned to the HFNO group or air group at a 1:1 ratio. For parturients in the HFNO group, the flow rate is 40L/min, and the oxygen is heated to 37℃ with humidity 100% oxygen concentration through the Optiflow high-flow nasal oxygen system. And for the air group, the flow rate is 2 L/min with an air pattern through the same device. The primary outcome was umbilical artery (UA) lactate. Secondary outcomes include UA pH, PO2, PCO2, BE, the incidence of pH < 7.20 and pH < 7.10, Apgar scores at 1 and 5 min, and neonatal adverse outcomes. DISCUSSION: Our study is the first trial investigating whether maternal oxygen supplementation with HFNO can reduce the umbilical artery lactate levels and the incidence of fetal acidemia in cesarean section under combined spinal-epidural anesthesia. TRIAL REGISTRATION: ClinicalTrials.gov NCT05921955. Registered on 27 June 2023.


Assuntos
Acidose , Cesárea , Gravidez , Recém-Nascido , Humanos , Feminino , Cesárea/efeitos adversos , Estudos Prospectivos , Acidose/diagnóstico , Acidose/prevenção & controle , Ácido Láctico , Oxigênio , Oxigenoterapia/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
J Hazard Mater ; 466: 133545, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38244453

RESUMO

Caenorhabditis elegans was employed as model to compare reproductive toxicity between pristine and aged polylactic acid microplastics (PLA-MPs). Aged PLA-MPs induced by UV irradiation showed degradation reflected by decrease in size and alteration in morphological surface. Aged PLA-MPs also exhibited some certain changes of chemical properties compared to pristine PLA-MP. Compared with pristine PLA-MPs, more severe toxicity on reproductive capacity and gonad development was detected in 1-100 µg/L aged PLA-MPs. Meanwhile, aged PLA-MPs caused more severe enhancement in germline apoptosis and alterations in expressions of ced-9, ced-4, ced-3, and egl-1 governing cell apoptosis. In addition, aged PLA-MPs resulted in more severe increase in expression of DNA damage related genes (cep-1, mrt-2, hus-1, and clk-2) compared to pristine PLA-MPs, and the alterations in expression of ced-9, ced-4, ced-3, and egl-1 in pristine and aged PLA-MPs could be reversed by RNAi of cep-1, mrt-2, hus-1, and clk-2. Besides this, enhanced germline apoptosis in pristine and aged PLA-MPs exposed animals was also suppressed by RNAi of cep-1, mrt-2, hus-1, and clk-2. Therefore, our results suggested the more severe exposure risk of aged PLA-MPs than pristine PLA-MPs in causing reproductive toxicity, which was associated with the changed physicochemical properties and DNA damage induced germline apoptosis.


Assuntos
Caenorhabditis elegans , Microplásticos , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Microplásticos/metabolismo , Plásticos/metabolismo , Poliésteres
8.
Biosens Bioelectron ; 250: 116052, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38266616

RESUMO

Cell imaging technology is undoubtedly a powerful tool for studying single-cell heterogeneity due to its non-invasive and visual advantages. It covers microscope hardware, software, and image analysis techniques, which are hindered by low throughput owing to abundant hands-on time and expertise. Herein, a cellular nucleus image-based smarter microscope system for single-cell analysis is reported to achieve high-throughput analysis and high-content detection of cells. By combining the hardware of an automatic fluorescence microscope and multi-object recognition/acquisition software, we have achieved more advanced process automation with the assistance of Robotic Process Automation (RPA), which realizes a high-throughput collection of single-cell images. Automated acquisition of single-cell images has benefits beyond ease and throughout and can lead to uniform standard and higher quality images. We further constructed a single-cell image database-based convolutional neural network (Efficient Convolutional Neural Network, E-CNN) exceeding 20618 single-cell nucleus images. Computational analysis of large and complex data sets enhances the content and efficiency of single-cell analysis with the assistance of Artificial Intelligence (AI), which breaks through the super-resolution microscope's hardware limitation, such as specialized light sources with specific wavelengths, advanced optical components, and high-performance graphics cards. Our system can identify single-cell nucleus images that cannot be artificially distinguished with an accuracy of 95.3%. Overall, we build an ordinary microscope into a high-throughput analysis and high-content smarter microscope system, making it a candidate tool for Imaging cytology.


Assuntos
Inteligência Artificial , Técnicas Biossensoriais , Software , Processamento de Imagem Assistida por Computador/métodos , Microscopia de Fluorescência , Análise de Célula Única
10.
Natl Sci Rev ; 11(1): nwad172, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38116095

RESUMO

Wireless power transfer (WPT) technology based on magnetic resonance (a basic physical phenomenon) can directly transfer energy from the source to the load without wires and other physical contacts, and has been successfully applied to implantable medical devices, electric vehicles, robotic arms and other fields. However, due to the frequency splitting of near-field coupling, the resonant WPT system has some unique limitations, such as poor transmission stability and low efficiency. Here, we propose anti-resonance with level pinning for high-performance WPT. By introducing the anti-resonance mode into the basic WPT platform, we uncover the competition between dissipative coupling and coherent coupling to achieve novel level pinning, and construct an effective anti-parity-time (anti-PT)-symmetric non-Hermitian system that is superior to previous PT-symmetric WPT schemes. On the one hand, the eigenvalue of the anti-PT-symmetric system at resonance frequency is always pure real in both strong and weak coupling regions, and can be used to overcome the transmission efficiency decrease caused by weak coupling, as brought about by, for example, a large size ratio of the transmitter to receiver, or a long transmission distance. On the other hand, due to the level pinning effect of the two kinds of coupling mechanisms, the working frequency of the system is guaranteed to be locked, so frequency tracking is not required when the position and size of the receiver change. Even if the system deviates from the matching condition, an efficient WPT can be realized, thereby demonstrating the robustness of the level pinning. The experimental results show that when the size ratio of the transmitter coil to the receiver coil is 4.29 (which is in the weak coupling region), the transfer efficiency of the anti-PT-symmetric system is nearly 4.3 (3.2) times higher than that of the PT-symmetric system when the matching conditions are satisfied (deviated). With the miniaturization and integration of devices in mind, a synthetic anti-PT-symmetric system is used to realize a robust WPT. Anti-PT-symmetric WPT technology based on the synthetic dimension not only provides a good research platform for the study of abundant non-Hermitian physics, but also provides a means of going beyond traditional near-field applications with resonance mechanisms, such as resonance imaging, wireless sensing and photonic routing.

11.
Healthcare (Basel) ; 11(23)2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38063627

RESUMO

OBJECTIVES: The study explores the relationship between social support, self-care ability, and life quality of cured leprosy patients (CLPs), aiming to develop strategies to enhance their overall well-being. METHODS: From July to December 2021, we investigated the social support, self-care ability, and life quality of CLPs through three scales and analyzed the correlation between them. In addition, structural estimation modeling (SEM) was employed to analyze their correlation. RESULTS: A total of 9245 CLPs were recruited, with a male-to-female ratio of 2.19:1, and 94.04% of cured patients was 60 years or above, with predominantly home-cured patients. The scores of WHOQOL-BREF, SSRS, and ESCA were (51.39 ± 9.89), (31.87 ± 8.76), and (100.95 ± 19.75), respectively. The results indicate a poorer quality of life and social support for CLPs compared to the general population in China. Furthermore, the home group had higher scores on these scales than the leprosarium group. The correlation analysis showed significant interactions between life quality, social support, self-care ability, and various domains (p < 0.05). SEM results revealed that the direct effect of self-care ability on life quality was 0.13, and the indirect effect on quality of life through social support was 0.08. The mediating effect of social support accounted for 22.86% of the total effect in the home group. In the leprosarium group, the effect of self-care ability on quality of life was 0.14. CONCLUSIONS: Most CLPs in Jiangsu Province are concentrated in the central region, with a high disease burden. We found that CLPs have a poorer life quality than the general population, with the leprosarium group being worse than the home group. The government and society should pay more attention to and support these cured patients.

12.
Front Immunol ; 14: 1263389, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37885888

RESUMO

Objective: Recently, circulating donor-derive cell free DNA (dd-cfDNA) has gained growing attention in the field of solid organ transplantation. The aim of the study was to analyze circulating dd-cfDNA levels in graft rejection, ACR and AMR separately for each rejection type compared with non-rejection, and assessed the diagnostic potential of dd-cfDNA levels in predicting graft rejection after lung transplantation. Methods: A systematic search for relevant articles was conducted on Medline, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases without restriction of languages. The search date ended on June 1, 2023. STATA software was used to analyze the difference between graft rejection, ACR, AMR and stable controls, and evaluate the diagnostic performance of circulating dd-cfDNA in detecting graft rejection. Results: The results indicated that circulating dd-cfDNA levels in graft rejection, ACR, and AMR were significantly higher than non-rejection (graft rejection: SMD=1.78, 95% CI: 1.31-2.25, I2 = 88.6%, P< 0.001; ACR: SMD=1.03, 95% CI: 0.47-1.59, I2 = 89.0%, P < 0.001; AMR: SMD= 1.78, 95% CI: 1.20-2.35, I2 = 89.8%, P < 0.001). Circulating dd-cfDNA levels distinguished graft rejection from non-rejection with a pooled sensitivity of 0.87 (95% CI: 0.80-0.92) and a pooled specificity of 0.82 (95% CI: 0.76-0.86). The corresponding SROC yield an AUROC of 0.90 (95% CI: 0.87-0.93). Conclusion: Circulating dd-cfDNA could be used as a non-invasive biomarker to distinguish the patients with graft rejection from normal stable controls. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023440467.


Assuntos
Ácidos Nucleicos Livres , Transplante de Pulmão , Transplante de Órgãos , Humanos , Transplante de Pulmão/efeitos adversos , Biomarcadores , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/genética , Ácidos Nucleicos Livres/genética
13.
Acta Trop ; 248: 107050, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37875168

RESUMO

Chlamydiosis and brucellosis induced abortions have resulted in significant economic losses in the global livestock industry. Although there have been numerous reports on these two diseases in ruminants in China, limited information is available regarding the prevalence of Chlamydia abortus (C. abortus) and Brucella spp. infection in pigs. This study aimed to investigate the prevalence of C. abortus and Brucella spp. infections in pig serum using serology and to identify potential risk factors. In total, 2816 serum samples were collected from 12 provinces in China. The presence of C. abortus antibodies was determined using an enzyme-linked immunosorbent assay (ELISA), while the presence of Brucella spp. antibodies was examined using the Rose Bengal Plate Test (RBPT) and the Standard Agglutination Test (SAT). The seroprevalences of C. abortus and Brucella spp. were 8.38 % (236/2816) and 0.11 % (3/2816), respectively. Geographical location, season, and age were found to be risk factors associated with C. abortus infection in pig herds in China (p<0.01), and the seropositive rate for C. abortus in sow herds was strongly associated with the occurrence of abortion (p<0.01). Overall, in China, pigs exhibit a higher seroprevalence of C. abortus, whereas the prevalence of Brucella is limited. This study represents the first comprehensive survey of C. abortus and Brucella spp. in pig herds in China that established potential risk factors and provided data for the prevention and control of intraspecies and interspecies transmission of C. abortus to humans.


Assuntos
Brucella , Brucelose , Gravidez , Humanos , Suínos , Animais , Feminino , Estudos Soroepidemiológicos , Brucelose/epidemiologia , Brucelose/veterinária , Fatores de Risco , Anticorpos Antibacterianos , China/epidemiologia , Brucella abortus
14.
BMC Microbiol ; 23(1): 246, 2023 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-37660043

RESUMO

BACKGROUND: Zoonotic diseases pose a significant threat to public health. Chlamydia, as an intracellular pathogen, can colonize the intestinal tract of humans and animals, changing the gut microbiota. However, only a few studies have evaluated alterations in the gut microbiota of horses infected with Chlamydia. Therefore, this study aimed to investigate gut microbiota and serum biochemical indicators in horses with Chlamydial infection (IG) and healthy horses (HG). Fecal and blood samples were collected from 16 horses (IG: 10; HG: 6) before morning feeding for the determination of gut microbiota and serum biochemical parameters. RESULTS: The results showed that total globulin (GLB), alanine aminotransferase (ALT), and creatine kinase (CK) levels were significantly increased in IG compared with HG. Notably, the gut microbial diversity increased in IG compared with HG. Furthermore, Moraxellaceae and Akkermanisa abundance decreased in IG, while Streptococcus, Treponema, Prevotella, and Paraprevotella abundances (13 genera of bacterial species) increased. Compared with HG, carbohydrate metabolism increased in IG while amino acid metabolism decreased. In addition, the abundance of 18 genera of bacteria was associated with the level of five serum biochemical indicators. CONCLUSIONS: In summary, this study elucidated the influence of Chlamydia infection in horses on the gut microbiota, unraveling consequential alterations in its composition and metabolic profile. Therefore, this study improves the understanding of Chlamydia-induced intestinal infections.


Assuntos
Infecções por Chlamydia , Chlamydia , Microbioma Gastrointestinal , Humanos , Animais , Cavalos , Infecções por Chlamydia/veterinária , Zoonoses , Bacteroidetes
15.
Materials (Basel) ; 16(17)2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37687701

RESUMO

Wireless power transfer (WPT) is a technology that enables energy transmission without physical contact, utilizing magnetic and electric fields as soft media. While WPT has numerous applications, the increasing power transfer distance often results in a decrease in transmission efficiency, as well as the urgent need for addressing safety concerns. Metamaterials offer a promising way for improving efficiency and reducing the flux density in WPT systems. This paper provides an overview of the current status and technical challenges of metamaterial-based WPT systems. The basic principles of magnetic coupling resonant wireless power transfer (MCR-WPT) are presented, followed by a detailed description of the metamaterial design theory and its application in WPT. The paper then reviews the metamaterial-based wireless energy transmission system from three perspectives: transmission efficiency, misalignment tolerance, and electromagnetic shielding. Finally, the paper summarizes the development trends and technical challenges of metamaterial-based WPT systems.

16.
Cell Death Dis ; 14(9): 625, 2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37737207

RESUMO

Hepatocarcinogenesis is initiated by repeated hepatocyte death and liver damage, and the underlying mechanisms mediating cell death and the subsequent carcinogenesis remain to be fully investigated. Immunoresponsive gene 1 (IRG1) and its enzymatic metabolite itaconate are known to suppress inflammation in myeloid cells, and its expression in liver parenchymal hepatocytes is currently determined. However, the potential roles of IRG1 in hepatocarcinogenesis are still unknown. Here, using the diethylnitrosamine (DEN)-induced hepatocarcinogenesis mouse model, we found that IRG1 expression in hepatocytes was markedly induced upon DEN administration. The DEN-induced IRG1 was then determined to promote the intrinsic mitochondrial apoptosis of hepatocytes and liver damage, thus enhancing the subsequent hepatocarcinogenesis. Mechanistically, the mitochondrial IRG1 could associate and trap anti-apoptotic MCL-1 to inhibit the interaction between MCL-1 and pro-apoptotic Bim, thus promoting Bim activation and downstream Bax mitochondrial translocation, and then releasing cytochrome c and initiating apoptosis. Thus, the inducible mitochondrial IRG1 promotes hepatocyte apoptosis and the following hepatocarcinogenesis, which provides mechanistic insight and a potential target for preventing liver injury and HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteína de Sequência 1 de Leucemia de Células Mieloides , Animais , Camundongos , Apoptose , Carcinogênese , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/genética , Hepatócitos , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética
17.
Chemosphere ; 336: 139193, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37315859

RESUMO

Polylactic acid (PLA) accounts for approximately 45% of the global market of biodegradable plastics. Using Caenorhabditis elegans as an animal model, we examined the effect of long-term exposure to PLA microplastic (MP) on reproductive capacity and the underlying mechanism. Brood size, number of fertilized eggs in uterus, and number of hatched eggs were significantly reduced by exposure to 10 and 100 µg/L PLA MP. Number of mitotic cells per gonad, area of gonad arm, and length of gonad arm were further significantly decreased by exposure to 10 and 100 µg/L PLA MP. In addition, exposure to 10 and 100 µg/L PLA MP enhanced germline apoptosis in the gonad. Accompanied with the enhancement in germline apoptosis, exposure to 10 and 100 µg/L PLA MP decreased expression of ced-9 and increased expressions of ced-3, ced-4, and egl-1. Moreover, the induction of germline apoptosis in PLA MP exposed nematodes was suppressed by RNAi of ced-3, ced-4, and egl-1, and strengthened by RNAi of ced-9. Meanwhile, we did not detect the obvious effect of leachate of 10 and 100 µg/L PLA MPs on reproductive capacity, gonad development, germline apoptosis, and expression of apoptosis related genes. Therefore, exposure to 10 and 100 µg/L PLA MPs potentially reduces the reproductive capacity by influencing the gonad development and enhancing the germline apoptosis in nematodes.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Feminino , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Plásticos/metabolismo , Células Germinativas , Poliésteres/toxicidade , Poliésteres/metabolismo , Apoptose , Gônadas/metabolismo
18.
Nanomaterials (Basel) ; 13(11)2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37299682

RESUMO

Telomerase is constitutively overexpressed in the majority of human cancers and telomerase inhibition provides a promising broad-spectrum anticancer therapeutic strategy. BIBR 1532 is a well-known synthetic telomerase inhibitor that blocks the enzymatic activity of hTERT, the catalytic subunit of telomerase. However, water insolubility of BIBR 1532 leads to low cellular uptake and inadequate delivery and thus, limits its anti-tumor effects. Zeolitic imidazolate framework-8 (ZIF-8) is considered as an attractive drug delivery vehicle for improved transport, release and anti-tumor effects of BIBR 1532. Herein, ZIF-8 and BIBR 1532@ZIF-8 were synthesized, respectively, and the physicochemical characterizations confirmed the successful encapsulation of BIBR 1532 in ZIF-8 coupled with an improved stability of BIBR 1532. ZIF-8 could alter the permeability of lysosomal membrane probably by the imidazole ring-dependent protonation. Moreover, ZIF-8 encapsulation facilitated the cellular uptake and release of BIBR 1532 with more accumulation in the nucleus. BIBR 1532 encapsulation with ZIF-8 triggered a more obvious growth inhibition of cancer cells as compared with free BIBR 1532. A more potent inhibition on hTERT mRNA expression, aggravated G0/G1 arrest accompanied with an increased cellular senescence were detected in BIBR 1532@ZIF-8-treated cancer cells. Our work has provided preliminary information on improving the transport, release and efficacy of water-insoluble small molecule drugs by using ZIF-8 as a delivery vehicle.

20.
RSC Adv ; 13(15): 9998-10004, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37006374

RESUMO

A photoresponsive therapeutic antibacterial platform was designed and constructed using polydopamine-functionalized selenium nanoparticles as a carrier loaded with indocyanine green (Se@PDA-ICG). The therapeutic platform was confirmed by characterization and the antibacterial activity of Se@PDA-ICG against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) was investigated. Under 808 nm laser irradiation, the antibacterial rate of Se@PDA-ICG against E. coli and S. aureus was 100% at 125 µg mL-1. Furthermore, in a mouse wound infection model, the wound closure rate of the Se@PDA-ICG photoresponse group was 88.74% compared with 45.8% for the control group after 8 days of treatment, indicating that it could effectively kill bacteria and dramatically accelerate the wound healing process. These results suggested that Se@PDA-ICG could be a promising photo-activated antibacterial candidate material for biomedical applications.

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