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piRNAs (Piwi-interacting small RNAs) engage Piwi Argonautes to silence transposons and promote fertility in animal germlines. Genetic and computational studies have suggested that C. elegans piRNAs tolerate mismatched pairing and in principle could target every transcript. Here we employ in vivo cross-linking to identify transcriptome-wide interactions between piRNAs and target RNAs. We show that piRNAs engage all germline mRNAs and that piRNA binding follows microRNA-like pairing rules. Targeting correlates better with binding energy than with piRNA abundance, suggesting that piRNA concentration does not limit targeting. In mRNAs silenced by piRNAs, secondary small RNAs accumulate at the center and ends of piRNA binding sites. In germline-expressed mRNAs, however, targeting by the CSR-1 Argonaute correlates with reduced piRNA binding density and suppression of piRNA-associated secondary small RNAs. Our findings reveal physiologically important and nuanced regulation of individual piRNA targets and provide evidence for a comprehensive post-transcriptional regulatory step in germline gene expression.
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Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Células Germinativas/metabolismo , RNA Interferente Pequeno/metabolismo , Sequência de Aminoácidos , Animais , Pareamento de Bases , Sequência de Bases , Sítios de Ligação , Proteínas de Caenorhabditis elegans/química , Quimera/metabolismo , Inativação Gênica , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Splicing quantitative trait loci (sQTLs) have been demonstrated to contribute to disease etiology by affecting alternative splicing. However, the role of sQTLs in the development of non-small-cell lung cancer (NSCLC) remains unknown. Thus, we performed a genome-wide sQTL study to identify genetic variants that affect alternative splicing in lung tissues from 116 individuals of Chinese ancestry, which resulted in the identification of 1,385 sQTL-harboring genes (sGenes) containing 378,210 significant variant-intron pairs. A comprehensive characterization of these sQTLs showed that they were enriched in actively transcribed regions, genetic regulatory elements, and splicing-factor-binding sites. Moreover, sQTLs were largely distinct from expression quantitative trait loci (eQTLs) and showed significant enrichment in potential risk loci of NSCLC. We also integrated sQTLs into NSCLC GWAS datasets (13,327 affected individuals and 13,328 control individuals) by using splice-transcriptome-wide association study (spTWAS) and identified alternative splicing events in 19 genes that were significantly associated with NSCLC risk. By using functional annotation and experiments, we confirmed an sQTL variant, rs35861926, that reduced the risk of lung adenocarcinoma (rs35861926-T, OR = 0.88, 95% confidence interval [CI]: 0.82-0.93, p = 1.87 × 10-5) by promoting FARP1 exon 20 skipping to downregulate the expression level of the long transcript FARP1-011. Transcript FARP1-011 promoted the migration and proliferation of lung adenocarcinoma cells. Overall, our study provided informative lung sQTL resources and insights into the molecular mechanisms linking sQTL variants to NSCLC risk.
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Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Locos de Características Quantitativas/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Estudo de Associação Genômica Ampla/métodos , Neoplasias Pulmonares/genética , Processamento Alternativo/genética , Adenocarcinoma de Pulmão/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
BACKGROUND AND AIMS: An imbalance in lipid metabolism is the main cause of NAFLD. While the pathogenesis of lipid accumulation mediated by extrahepatic regulators has been extensively studied, the intrahepatic regulators modulating lipid homeostasis remain unclear. Previous studies have shown that systemic administration of IL-22 protects against NAFLD; however, the role of IL-22/IL22RA1 signaling in modulating hepatic lipid metabolism remains uncertain. APPROACH AND RESULTS: This study shows that hepatic IL22RA1 is vital in hepatic lipid regulation. IL22RA1 is downregulated in palmitic acid-treated mouse primary hepatocytes, as well as in the livers of NAFLD model mice and patients. Hepatocyte-specific Il22ra1 knockout mice display diet-induced hepatic steatosis, insulin resistance, impaired glucose tolerance, increased inflammation, and fibrosis compared with flox/flox mice. This is attributed to increased lipogenesis mediated by the accumulation of hepatic oxysterols, particularly 3 beta-hydroxy-5-cholestenoic acid (3ß HCA). Mechanistically, hepatic IL22RA1 deficiency facilitates 3ß HCA deposition through the activating transcription factor 3/oxysterol 7 alpha-hydroxylase axis. Notably, 3ß HCA facilitates lipogenesis in mouse primary hepatocytes and human liver organoids by activating liver X receptor-alpha signaling, but IL-22 treatment attenuates this effect. Additionally, restoring oxysterol 7 alpha-hydroxylase or silencing hepatic activating transcription factor 3 reduces both hepatic 3ß HCA and lipid contents in hepatocyte-specific Il22ra1 knockout mice. CONCLUSIONS: These findings indicate that IL22RA1 plays a crucial role in maintaining hepatic lipid homeostasis in an activating transcription factor 3/oxysterol 7 alpha-hydroxylase-dependent manner and establish a link between 3ß HCA and hepatic lipid homeostasis.
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Myeloid-derived suppressor cells (MDSCs) increase in number and gain immunosuppressive functions in tumours and many other pathological conditions. MDSCs are characterized by their strong T-cell immunosuppressive capacity. The effects that MDSCs may have on B cells, especially within the tumour microenvironment, are less well understood. Here, we report that either monocytic MDSCs or polymorphonuclear MDSCs can promote increases in interleukin (IL)-10-expressing CD19hiFcγRIIbhi regulatory B cells in vitro and in vivo. Splenic transitional-1, -2, and -3 cells and marginal zone B cells, but not follicular B cells, differentiate into IL-10-expressing CD19hiFcγRIIbhi regulatory B cells. The adoptive transfer of CD19hiFcγRIIbhi regulatory B cells via tail vein injection can promote subcutaneous 3LL tumour growth in mice. The expression of programmed death-ligand 1 on MDSCs was found to be strongly associated with CD19hiFcγRIIbhi regulatory B cell population expansion. Furthermore, the frequency of circulating CD19+FcγRIIhi regulatory B cells was significantly increased in advanced-stage lung cancer patients. Our results unveil a critical role of MDSCs in regulatory B-cell differentiation and population expansion in lung cancer patients.
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Linfócitos B Reguladores , Neoplasias Pulmonares , Células Supressoras Mieloides , Camundongos , Humanos , Animais , Linfócitos B Reguladores/metabolismo , Células Supressoras Mieloides/metabolismo , Antígeno B7-H1/metabolismo , Diferenciação Celular , Camundongos Endogâmicos C57BL , Microambiente TumoralRESUMO
Acinetobacter baumannii is a low-GC-content Gram-negative opportunistic pathogen that poses a serious global public health threat. Convenient and rapid genetic manipulation is beneficial for elucidating its pathogenic mechanisms and developing novel therapeutic methods. In this study, we report a new CRISPR-FnCpf1-based two-plasmid system for versatile and precise genome editing in A. baumannii. After identification, this new system prefers to recognize the 5'-TTN-3' (N = A, T, C or G) and the 5'-CTV-3' (V = A, C or G) protospacer-adjacent motif (PAM) sequence and utilize the spacer with lengths ranging from 19 to 25 nt. In direct comparison with the existing CRISPR-Cas9 system, it exhibits approximately four times the targetable range in A. baumannii. Moreover, by employing a tandem dual crRNA expression cassette, the new system can perform large-fragment deletion and simultaneous multiple gene editing, which is difficult to achieve via CRISPR-Cas9. Therefore, the new system is valuable and can greatly expand the genome editing toolbox of A. baumannii.
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N6 -methyladenosine (m6 A) modification has been identified as one of the most important epigenetic regulation mechanisms in the development of human cancers. However, the association between m6 A-associated single-nucleotide polymorphisms (m6 A-SNPs) and lung cancer risk remains largely unknown. Here, we identified m6 A-SNPs and examined the association of these m6 A-SNPs with lung cancer risk in 13,793 lung cancer cases and 14,027 controls. In silico functional annotation was used to identify causal m6 A-SNPs and target genes. Furthermore, methylated RNA immunoprecipitation and quantitative real-time polymerase chain reaction (MeRIP-qPCR) assay was performed to assess the m6 A modification level of different genotypes of the causal SNP. In vitro assays were performed to validate the potential role of the target gene in lung cancer. A total of 8794 m6 A-SNPs were detected, among which 397 SNPs in nine susceptibility loci were associated with lung cancer risk, including six novel loci. Bioinformatics analyses indicated that rs1321328 in 6q21 was located around the m6 A modification site of AK9 and significantly reduced AK9 expression (ß = -0.15, p = 2.78 × 10-8 ). Moreover, AK9 was significantly downregulated in lung cancer tissues than that in adjacent normal tissues of samples from the Cancer Genome Atlas and Nanjing Lung Cancer Cohort. MeRIP-qPCR assay suggested that C allele of rs1321328 could significantly decrease the m6 A modification level of AK9 compared with G allele. In vitro assays verified the tumor-suppressing role of AK9 in lung cancer. These findings shed light on the pathogenic mechanism of lung cancer susceptibility loci linked with m6 A modification.
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Adenina , Neoplasias Pulmonares , Polimorfismo de Nucleotídeo Único , Humanos , Adenina/análogos & derivados , Epigênese Genética , Genes Supressores de Tumor , Neoplasias Pulmonares/genética , Adenilato Quinase/metabolismoRESUMO
MAIN CONCLUSION: The post-transcriptional gene regulatory pathway and small RNA pathway play important roles in regulating the rapid and long-term response of Rhododendron moulmainense to high-temperature stress. The Rhododendron plays an important role in maintaining ecological balance. However, it is difficult to domesticate for use in urban ecosystems due to their strict optimum growth temperature condition, and its evolution and adaptation are little known. Here, we combined transcriptome and small RNAome to reveal the rapid response and long-term adaptability regulation strategies in Rhododendron moulmainense under high-temperature stress. The post-transcriptional gene regulatory pathway plays important roles in stress response, in which the protein folding pathway is rapidly induced at 4 h after heat stress, and alternative splicing plays an important role in regulating gene expression at 7 days after heat stress. The chloroplasts oxidative damage is the main factor inhibiting photosynthesis efficiency. Through WGCNA analysis, we identified gene association patterns and potential key regulatory genes responsible for maintaining the ROS steady-state under heat stress. Finally, we found that the sRNA synthesis pathway is induced under heat stress. Combined with small RNAome, we found that more miRNAs are significantly changed under long-term heat stress. Furthermore, MYBs might play a central role in target gene interaction network of differentially expressed miRNAs in R. moulmainense under heat stress. MYBs are closely related to ABA, consistently, ABA synthesis and signaling pathways are significantly inhibited, and the change in stomatal aperture is not obvious under heat stress. Taken together, we gained valuable insights into the transplantation and long-term conservation domestication of Rhododendron, and provide genetic resources for genetic modification and molecular breeding to improve heat resistance in Rhododendron.
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MicroRNAs , Rhododendron , Transcriptoma/genética , Rhododendron/genética , Rhododendron/metabolismo , Ecossistema , Resposta ao Choque Térmico/genética , MicroRNAs/genética , Perfilação da Expressão GênicaRESUMO
BACKGROUND: Ovarian cancer (OC) is distinguished by its aggressive nature and the limited efficacy of current treatment strategies. Recent studies have emphasized the significant role of cancer-associated fibroblasts (CAFs) in OC development and progression. METHODS: Employing sophisticated machine learning techniques on bulk transcriptomic datasets, we identified fibroblast growth factor 7 (FGF7), derived from CAFs, as a potential oncogenic factor. We investigated the relationship between FGF7 expression and various clinical parameters. A series of in vitro experiments were undertaken to evaluate the effect of CAFs-derived FGF7 on OC cell activities, such as proliferation, migration, and invasion. Single-cell transcriptomic analysis was also conducted to elucidate the interaction between FGF7 and its receptor. Detailed mechanistic investigations sought to clarify the pathways through which FGF7 fosters OC progression. RESULTS: Our findings indicate that higher FGF7 levels correlate with advanced tumor stages, increased vascular invasion, and poorer prognosis. CAFs-derived FGF7 significantly enhanced OC cell proliferation, migration, and invasion. Single-cell analysis and in vitro studies revealed that CAFs-derived FGF7 inhibits the ubiquitination and degradation of hypoxia-inducible factor 1 alpha (HIF-1α) via FGFR2 interaction. Activation of the FGF7/HIF-1α pathway resulted in the upregulation of mesenchymal markers and downregulation of epithelial markers. Importantly, in vivo treatment with neutralizing antibodies targeting CAFs-derived FGF7 substantially reduced tumor growth. CONCLUSION: Neutralizing FGF7 in the medium or inhibiting HIF-1α signaling reversed the effects of FGF7-mediated EMT, emphasizing the dependence of FGF7-mediated EMT on HIF-1α activation. These findings suggest that targeting the FGF7/HIF-1α/EMT axis may offer new therapeutic opportunities to intervene in OC progression.
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Fibroblastos Associados a Câncer , Neoplasias Ovarianas , Humanos , Feminino , Fibroblastos Associados a Câncer/metabolismo , Fator 7 de Crescimento de Fibroblastos/metabolismo , Fator 7 de Crescimento de Fibroblastos/farmacologia , Linhagem Celular Tumoral , Transdução de Sinais , Neoplasias Ovarianas/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Transição Epitelial-Mesenquimal/genética , Movimento Celular/genéticaRESUMO
Electrode materials are essential in the electrochemical process of storing charge in supercapacitors and have a significant impact on the cost and capacitive performance of the final product. Hence, it is imperative to make precise predictions regarding the capacitance of electrode materials in order to further the development of supercapacitors. MgCo2O4, with a theoretical capacitance of up to 3122 F g-1, holds immense research value as an electrode material. The objective of this study is to predict the capacitance of MgCo2O4 with high accuracy. This will be achieved by extracting numerous data from published papers and using some parameters as input features. The Recursive Feature Elimination (RFE) method was employed, using Random Forest (RF), Extreme Gradient Boosting (XGBoost) and Regression Tree (RT) as selectors to identify the optimal feature subset. Then, combining them with these three regression models to construct nine machine learning (ML) models. After performance evaluation and outlier analysis, the XGB-RFE-XGB model achieved R-squared (R²), root mean squared error (RMSE), and mean absolute error (MAE) of 0.95, 111.83 F g-1 and 68.25 F g-1, respectively, demonstrating its stability and reliability. Therefore, the XGB-RFE-XGB model can be used as a reliable predictive tool in subsequent experimental designs.
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Strategies based on nanomaterials for sterilization address the problem of antibiotic resistance faced by conventional antimicrobials, with the contribution of photocatalytic compounds being particularly prominent. Herein, to integrate multiple bactericidal techniques into a system for generating synergistic antibacterial effects, a novel photo-triggered AuAg@g-C3N4 composite nanoplatform was constructed by anchoring AuAg on the surface of a g-C3N4 layer. As the composite nanoplatform had a lower bandgap and superior visible light utilization efficiency, it could facilitate free electron transfer better and exhibit superior photocatalytic activity under light conditions. Moreover, the AuAg@g-C3N4 composite nanoplatform integrated the bactericidal modes of silver ion toxicity, physical disruption of bacterial cell membranes by the multilayer structure, and excellent photocatalytic activity, exhibiting extremely superior bactericidal effects against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis, with a bactericidal efficiency of up to 100%.
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A viscosity-sensitive, lysosome-targeted near-infrared fluorescent probe (PYATT) was reported in this paper. The fluorescent spectra of PYATT are strongly dependent on viscosity, resulting in a Stokes shift of about 190 nm. Given its photostability, low cytotoxicity, and high fluorescence quantum yield, PYATT is expected to be used in cell imaging. Due to the higher viscosity of tumor cells than normal cells, the fluorescence intensity of PYATT in tumor cells is higher than normal cells, which can realize the visualization of tumors. The near-infrared probe (PYATT) is viscosity-dependent in lysosomes, which is valuable in early diagnosis and treatment of tumor.
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Corantes Fluorescentes , Neoplasias , Humanos , Viscosidade , Diagnóstico por Imagem , Neoplasias/diagnóstico por imagem , Lisossomos , Células HeLa , Imagem ÓpticaRESUMO
Given the escalating incidence of bacterial diseases and the challenge posed by pathogenic bacterial resistance, it is imperative to identify appropriate methodologies for conducting proteomic investigations on bacteria, and thereby promoting the target-based drug/pesticide discovery. Interestingly, a novel technology termed "activity-based protein profiling" (ABPP) has been developed to identify the target proteins of active molecules. However, few studies have summarized advancements in ABPP for identifying the target proteins in antibacterial-active compounds. In order to accelerate the discovery and development of new drug/agrochemical discovery, we provide a concise overview of ABPP and its recent applications in antibacterial agent discovery. Diversiform cases were cited to demonstrate the potential of ABPP for target identification though highlighting the design strategies and summarizing the reported target protein of antibacterial compounds. Overall, this review is an excellent reference for probe design towards antibacterial compounds, and offers a new perspective of ABPP in bactericide development.
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Antibacterianos , Descoberta de Drogas , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Estrutura Molecular , Proteômica , HumanosRESUMO
PURPOSE: The current biomechanical research on the application of Kinesio taping (KT) to patients with chronic ankle instability (CAI) has focused on testing the expected movements. However, unexpected movements are more common in actual sports. Therefore, the present study aimed to investigate the effects of KT on the biomechanical characteristics of the knee and ankle joints during unexpected jumping movements. METHODS: Twenty-one patients with unilateral CAI were recruited to capture the biomechanical parameters during unexpected jumping movements under different interventions: no taping (NT), placebo taping (PT), and KT. A one-way repeated measures analysis of variance was used to compare the differences in knee and ankle biomechanical characteristics among patients with CAI between the three intervention conditions. RESULTS: At initial contact, the KT group demonstrated a significant decrease in ankle plantarflexion and knee flexion angles compared to the NT group (p < 0.05). At the early landing phase, the KT group had a significant increase in peak ankle dorsiflexion angle, peak ankle eversion angle, peak ankle dorsiflexion moment, and peak ankle eversion moment compared to the NT and PT groups (p < 0.05). Furthermore, the KT group had a significantly reduced peak knee flexion angle, peak knee eversion angle, and peak vertical ground reaction force (p < 0.05) compared to the NT and PT groups. CONCLUSION: KT significantly improves the sprain-prone touchdown posture of patients with CAI. And reducing the risk of ankle sprains during the early landing phase by promoting ankle dorsiflexion and eversion angles and moments.
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Traumatismos do Tornozelo , Instabilidade Articular , Humanos , Tornozelo , Extremidade Inferior , Articulação do Tornozelo , Traumatismos do Tornozelo/terapia , Articulação do Joelho , Instabilidade Articular/terapiaRESUMO
Ferroptosis has emerged as a potential mechanism for enhancing the efficacy of chemotherapy in cancer treatment. By suppressing nuclear factor erythroid 2-related factor 2 (Nrf2), cancer cells may lose their ability to counteract the oxidative stress induced by chemotherapy, thereby becoming more susceptible to ferroptosis. In this study, we investigate the potential of penexanthone A (PXA), a xanthone dimer component derived from the endophytic fungus Diaporthe goulteri, obtained from mangrove plant Acanthus ilicifolius, to enhance the therapeutic effect of cisplatin (CDDP) on colorectal cancer (CRC) by inhibiting Nrf2. The present study reported that PXA significantly improved the ability of CDDP to inhibit the activity of and induce apoptosis in CRC cells. Moreover, PXA was found to increase the level of oxidative stress and DNA damage caused by CDDP. In addition, the overexpression of Nrf2 reversed the DNA damage and ferroptosis induced by the combination of PXA and CDDP. In vivo experiments using zebrafish xenograft models demonstrated that PXA enhanced the therapeutic effect of CDDP on CRC. These studies suggest that PXA enhanced the sensitivity of CRC to CDDP and induce ferroptosis by targeting Nrf2 inhibition, indicating that PXA might serve as a novel anticancer drug in combination chemotherapy.
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Antineoplásicos , Neoplasias Colorretais , Ferroptose , Fator 2 Relacionado a NF-E2 , Xantonas , Peixe-Zebra , Fator 2 Relacionado a NF-E2/metabolismo , Humanos , Ferroptose/efeitos dos fármacos , Animais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Xantonas/farmacologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Estresse Oxidativo/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Apoptose/efeitos dos fármacosRESUMO
Humans have an extraordinary ability to recognize and differentiate voices. It is yet unclear whether voices are uniquely processed in the human brain. To explore the underlying neural mechanisms of voice processing, we recorded electrocorticographic signals from intracranial electrodes in epilepsy patients while they listened to six different categories of voice and nonvoice sounds. Subregions in the temporal lobe exhibited preferences for distinct voice stimuli, which were defined as "voice patches." Latency analyses suggested a dual hierarchical organization of the voice patches. We also found that voice patches were functionally connected under both task-engaged and resting states. Furthermore, the left motor areas were coactivated and correlated with the temporal voice patches during the sound-listening task. Taken together, this work reveals hierarchical cortical networks in the human brain for processing human voices.
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Percepção Auditiva/fisiologia , Encéfalo/fisiologia , Vias Neurais/fisiologia , Voz/fisiologia , Adulto , Eletrocorticografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Social anxiety disorder (SAD) is one of the most common psychiatric disorders in adolescents. The heterogeneity of both symptoms and etiology is an essential source of difficulties in the treatment and prevention of SAD. The study aimed to identify subtypes of adolescent SAD based on etiology-related phenotype dimensions and examine symptom and brain associations of the subtypes. We used a deeply phenotyped sample (47 phenotype subscales from 13 measures) of adolescents with SAD (n = 196) and healthy controls (n = 109) to extract etiology-relevant risk factors, based on which we identified subtypes of SAD. We compared the subtypes on clinical characteristics and brain morphometrics and functional connectivity, and examined subtype-specific links between risk factors, brain aberrance, and clinical characteristics. We identified six etiology-relevant risk factors and two subtypes of adolescent SAD. One subtype showed mainly elevated negative emotionality trait and coping style and diminished positive emotionality trait and coping style, while the other additionally had significantly high environmental risk factors, more severe impairments in social functioning, and significant abnormalities in brain structure and function. There were subtype-specific links between the risk factor profiles, brain aberrance, and clinical characteristics. The finding suggests two etiology-based subtypes of adolescent SAD, providing novel insights to the diversity of pathological pathways and precise intervention strategies.
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Enhancing the phototherapy efficacy of organic photosensitizers through molecular design is a fascinating but challenging task. Herein, we propose a simple design strategy to first realize the generation of superoxide anion radical (O2â¢-) by A-D-A fused-ring photosensitizers. Through replacing one cyano group of traditional end group with an ester group, we designed a novel nonplanar end group (A unit) to synthesize a novel A-D-A photosensitizer F8CA. In a comparison with its counterpart F8CN with the traditional end group, F8CA displays more loose packing and larger spin-orbit coupling constants. The F8CA nanoparticles showed higher photodynamic activities with the generation capability of singlet oxygen (1O2), hydroxyl radical (â¢OH), and O2â¢-, while F8CN nanoparticles could only generate 1O2 and â¢OH. In addition, F8CA nanoparticles still remain high photothermal conversion efficiency (61%). As a result, F8CA nanoparticles perform well in hypoxia-tolerant tumor phototherapy. This study brings an effective design thought for A-D-A photosensitizers.
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Nanopartículas , Neoplasias , Humanos , Fármacos Fotossensibilizantes , Fototerapia , Neoplasias/patologia , Oxigênio SingleteRESUMO
Phlorizin, as a flavonoid from a wide range of sources, is gradually becoming known for its biological activity. Phlorizin can exert antioxidant effects by regulating the IL-1ß/IKB-α/NF-KB signaling pathway. At the same time, it exerts its antibacterial activity by reducing intracellular DNA agglutination, reducing intracellular protein and energy synthesis, and destroying intracellular metabolism. In addition, phlorizin also has various pharmacological effects such as antiviral, antidiabetic, antitumor, and hepatoprotective effects. Based on domestic and foreign research reports, this article reviews the plant sources, extraction, and biological activities of phlorizin, providing a reference for improving the clinical application of phlorizin.
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Glucosídeos , Florizina , Florizina/farmacologia , Florizina/metabolismo , Antioxidantes/farmacologia , Flavonoides , Hipoglicemiantes/farmacologiaRESUMO
OBJECTIVES: To investigate the risk factors for bronchopulmonary dysplasia (BPD) in twin preterm infants with a gestational age of <34 weeks, and to provide a basis for early identification of BPD in twin preterm infants in clinical practice. METHODS: A retrospective analysis was performed for the twin preterm infants with a gestational age of <34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020. According to their conditions, they were divided into group A (both twins had BPD), group B (only one twin had BPD), and group C (neither twin had BPD). The risk factors for BPD in twin preterm infants were analyzed. Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins. RESULTS: A total of 904 pairs of twins with a gestational age of <34 weeks were included in this study. The multivariate logistic regression analysis showed that compared with group C, birth weight discordance of >25% between the twins was an independent risk factor for BPD in one of the twins (OR=3.370, 95%CI: 1.500-7.568, P<0.05), and high gestational age at birth was a protective factor against BPD (P<0.05). The conditional logistic regression analysis of group B showed that small-for-gestational-age (SGA) birth was an independent risk factor for BPD in individual twins (OR=5.017, 95%CI: 1.040-24.190, P<0.05). CONCLUSIONS: The development of BPD in twin preterm infants is associated with gestational age, birth weight discordance between the twins, and SGA birth.
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Displasia Broncopulmonar , Recém-Nascido Prematuro , Gêmeos , Humanos , Displasia Broncopulmonar/etiologia , Displasia Broncopulmonar/epidemiologia , Fatores de Risco , Recém-Nascido , Feminino , Estudos Retrospectivos , Masculino , Idade Gestacional , Peso ao Nascer , Modelos LogísticosRESUMO
Macrophage (MΦ) infection models are important tools for studying host-mycobacterial interactions. Although the multiplicity of infection (MOI) is an important experimental variable, the selection of MOI in mycobacterial infection experiments is largely empirical, without reference to solid experimental data. To provide relevant data, we used RNA-seq to analyze the gene expression profiles of MΦs 4 or 24 h after infection with Mycobacterium marinum (M. m) at MOIs ranging from 0.1 to 50. Analysis of differentially expressed genes (DEGs) showed that different MOIs are linked to distinct transcriptomic changes and only 10% of DEGs were shared by MΦ infected at all MOIs. KEGG pathway enrichment analysis revealed that type I interferon (IFN)-related pathways were inoculant dose-dependent and enriched only at high MOIs, whereas TNF pathways were inoculant dose-independent and enriched at all MOIs. Protein-protein interaction (PPI) network alignment showed that different MOIs had distinct key node genes. By fluorescence-activated cell sorting and follow-up RT-PCR analysis, we could separate infected MΦs from uninfected MΦs and found phagocytosis of mycobacteria to be the determinant factor for type I IFN production. The distinct transcriptional regulation of RAW264.7 MΦ genes at different MOIs was also seen with Mycobacterium tuberculosis (M.tb) infections and primary MΦ infection models. In summary, transcriptional profiling of mycobacterial infected MΦs revealed that different MOIs activate distinct immune pathways and the type I IFN pathway is activated only at high MOIs. This study should provide guidance for selecting the MOI most appropriate for different research questions.