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Targeting telomere maintenance has emerged as a promising strategy for hepatocellular carcinoma (HCC) treatment. However, given the duality of the telomere-telomerase axis in telomere maintenance, a comprehensive strategy is urgently needed. Herein, we develop a poly(amino acid) (D-PAAs)-based strategy for spatiotemporal codelivery of telomerase inhibitor, BIBR1523, and AKT inhibitor, isobavachalcone. By leveraging D-PAAs' modifiability, we synthesize polymer-inhibitor conjugates (PB and PI) and a folic acid-decorated tumor-targeting vector (PF). These building blocks undergo micellization to fabricate a codelivery nanomedicine (P-BI@P-FA) by exploiting D-PAAs' noncovalent assembly. P-BI@P-FA improves the pharmacokinetics, tumor selectivity, and bioavailability of small molecule inhibitors and initiates a dual telomere-specific inhibition by combining telomerase deactivation with telomere disruption. Furthermore, a hybrid tumor-targeting magnetic nanosystem is designed using D-PAAs and manganese dioxide to showcase magnetic resonance imaging capacities. Our D-PAAs-based strategy addresses the pressing need for telomere-specific HCC treatment while allowing for diagnostic application, presenting a promising avenue for nanomedicine design.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Imagen por Resonancia Magnética , Nanomedicina , Telomerasa , Telómero , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Telomerasa/antagonistas & inhibidores , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Humanos , Nanomedicina/métodos , Telómero/metabolismo , Imagen por Resonancia Magnética/métodos , Animales , Ratones , Línea Celular Tumoral , Aminoácidos/química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéuticoRESUMEN
Dental caries is a chronic oral infectious disease, and Streptococcus mutans (S. mutans) plays an important role in the formation of dental caries. Trans-cinnamaldehyde (CA) exhibits broad-spectrum antibacterial activity; however, its target and mechanism of action of CA on S. mutans needs to be further explored. In this study, it was verified that CA could inhibit the growth and biofilm formation of S. mutans. Further proteomic analysis identified 33, 55, and 78 differentially expressed proteins (DEPs) in S. mutans treated with CA for 1, 2, and 4 h, respectively. Bioinformatics analysis showed that CA interfered with carbohydrate metabolism, glycolysis, pyruvate metabolism, and the TCA cycle, as well as amino acid metabolism of S. mutans. Protein interactions suggested that pyruvate dehydrogenase (PDH) plays an important role in the antibacterial effect of CA. Moreover, the upstream and downstream pathways related to PDH were verified by various assays, and the results proved that CA not only suppressed the glucose and sucrose consumption and inhibited glucosyltransferase (GTF) and lactate dehydrogenase (LDH) activities but also decreased the ATP production. Interestingly, the protein interaction, qRT-PCR, and molecular docking analysis showed that PDH might be the target of CA to fight S. mutans. In summary, the study shows that CA interferes with the carbohydrate metabolism of bacteria by inhibiting glycolysis and the tricarboxylic acid (TCA) cycle via binding to PDH, which verifies that PDH is a potential target for the development of new drugs against S. mutans.
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Acroleína , Metabolismo de los Hidratos de Carbono , Simulación del Acoplamiento Molecular , Complejo Piruvato Deshidrogenasa , Streptococcus mutans , Streptococcus mutans/efectos de los fármacos , Streptococcus mutans/genética , Streptococcus mutans/enzimología , Acroleína/farmacología , Acroleína/análogos & derivados , Acroleína/metabolismo , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Complejo Piruvato Deshidrogenasa/metabolismo , Complejo Piruvato Deshidrogenasa/antagonistas & inhibidores , Antibacterianos/farmacología , Glucólisis/efectos de los fármacos , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/antagonistas & inhibidores , Proteómica/métodos , Caries Dental/microbiología , Ciclo del Ácido Cítrico/efectos de los fármacos , Adenosina Trifosfato/metabolismoRESUMEN
HRS9432(A) is a long-acting echinocandin antifungal medication primarily used to treat invasive fungal infections, particularly invasive candidiasis. The safety, tolerability, and pharmacokinetic characteristics of HRS9432(A) injection were investigated in a randomized, double-blind, placebo-controlled, single- and multiple-ascending-dose Phase I study involving 56 healthy adult subjects. Doses ranging from 200 to 1200 mg were administered. Safety was continually monitored, including adverse events, clinical laboratory examinations, vital signs, 12-lead electrocardiograms, and physical examinations, while the pharmacokinetic profile within the body was evaluated. The results indicated that concentrations of HRS9432 peaked immediately after infusion, demonstrating essentially linear pharmacokinetic characteristics within the dosage range of 200-1,200 mg. It exhibited a low clearance rate and an extended half-life, with a clearance of approximately 0.2 L/h, a volume of distribution of around 40 L, and a half-life of approximately 140h following a single dose. The accumulation index for AUC0-τ after multiple doses ranged from 1.41 to 1.75. No severe adverse events occurred during the study, and the severity of all adverse events was mild or moderate. Therefore, the intravenous administration of HRS9432(A) in healthy Chinese adult subjects, either as multiple infusions of 200 to 600 mg (once a week, four doses) or as a single infusion of 900-1,200 mg, demonstrated overall good safety and tolerability. The pharmacokinetic exhibited essentially linear characteristics in the body, supporting a weekly dosing frequency for clinical applications and providing additional options for the treatment or prevention of invasive fungal infections. CLINICAL TRIALS: This study is registered with the International Clinical Trials Registry Platform as ChiCTR2300073525.
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Antifúngicos , Voluntarios Sanos , Humanos , Método Doble Ciego , Adulto , Masculino , Antifúngicos/farmacocinética , Antifúngicos/administración & dosificación , Antifúngicos/efectos adversos , Femenino , Adulto Joven , Semivida , Área Bajo la Curva , Micafungina/farmacocinética , Micafungina/administración & dosificación , Micafungina/efectos adversos , Persona de Mediana Edad , Pueblo Asiatico , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Phylogeographic studies have gained prominence in linking past geological events to the distribution patterns of biodiversity, primarily in mountainous regions. However, such studies often focus on plant taxa, neglecting the intricate biogeographical patterns of microbes, particularly soil microbial communities. This article explores the spatial distribution of the nematode-trapping fungus Arthrobotrys oligospora, a widespread microorganism, in a tectonically active region at the southeastern edge of the Qinghai-Tibetan Plateau. By analysing the genetic variation of this fungus alongside the historical structure of major river watersheds, we sought to uncover potential connections between the two. Our study involved sampling 149 strains from 116 sites across six major watersheds in the region. RESULTS: The resulting haplotype network revealed five distinct clusters, each corresponding closely to a specific watershed. These clusters exhibited high haplotype diversity and low nucleotide diversity, supporting the notion of watershed-based segregation. Further analysis of haplotypes shared across watersheds provided evidence for three proposed past river connections. In particular, we found numerous shared haplotypes between the Yangtze and Mekong basins, as well as between the Yangtze and the Red basins. Evidence for a Irrawaddy-Salween-Red and a Yangtze-Pearl-Red river connections were also portrayed in our mapping exercise. CONCLUSIONS: These findings emphasize the crucial role of historical geomorphological events in shaping the biogeography of microbial biodiversity, alongside contemporary biotic and abiotic factors. Watershed perimeters emerged as effective predictors of such patterns, suggesting their suitability as analytical units for regional-scale studies. Our study also demonstrates the potential of microorganisms and phylogeographic approaches to complement traditional geological analyses, providing a more comprehensive understanding of past landscape structure and its evolution.
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Variación Genética , Haplotipos , Filogenia , Filogeografía , Ríos , Microbiología del Suelo , China , Ríos/microbiología , Ascomicetos/genética , Ascomicetos/clasificación , Ascomicetos/aislamiento & purificación , Biodiversidad , ADN de Hongos/genéticaRESUMEN
Sodium thiosulfate has been used for decades in the treatment of calciphylaxis and cyanide detoxification, and has recently shown initial therapeutic promise in critical diseases such as neuronal ischemia, diabetes mellitus, heart failure and acute lung injury. However, the precise mechanism of sodium thiosulfate remains incompletely defined and sometimes contradictory. Although sodium thiosulfate has been widely accepted as a donor of hydrogen sulfide (H2S), emerging findings suggest that it is the executive signaling molecule for H2S and that its effects may not be dependent on H2S. This article presents an overview of the current understanding of sodium thiosulfate, including its synthesis, biological characteristics, and clinical applications of sodium thiosulfate, as well as the underlying mechanisms in vivo. We also discussed the interplay of sodium thiosulfate and H2S. Our review highlights sodium thiosulfate as a key player in sulfide signaling with the broad clinical potential for the future.
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Sulfuro de Hidrógeno , Transducción de Señal , Tiosulfatos , Tiosulfatos/química , Sulfuro de Hidrógeno/metabolismo , Sulfuro de Hidrógeno/química , Humanos , Animales , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Despite improved treatments for acute myocardial infarction (AMI), myocardial fibrosis remains a key driver of adverse left ventricular (LV) remodeling and increased mortality. Fibroblast activation and proliferation significantly contribute to this process by enhancing cardiac fibrosis, which can lead to detrimental changes in LV structure. This study evaluates the effectiveness of 99mTc-labeled fibroblast activation protein inhibitor (99mTc-HFAPi) SPECT imaging in predicting LV remodeling over 12 months in post-AMI patients. METHODS: A cohort of 58 AMI patients (46 males, median age 61 [53, 67] years) underwent baseline 99mTc-HFAPi imaging (5 ± 2 days post-MI), perfusion imaging (6 ± 2 days post-MI), and echocardiography (2 ± 2 days post-MI). Additionally, 15 patients had follow-up 99mTc-HFAPi and perfusion imaging, while 30 patients had follow-up echocardiography. Myocardial 99mTc-HFAPi activity was assessed at the patient level. LV remodeling was defined as a ≥10% increase in LV end-diastolic diameter (LVEDD) or LV end-systolic diameter (LVESD) from baseline to follow-up echocardiography. RESULTS: AMI patients displayed localized but non-uniform 99mTc-HFAPi uptake, exceeding perfusion defects. Baseline 99mTc-HFAPi activity exhibited significant correlations with BNPmax, LDHmax, cTNImax, and WBCmax, inversely correlating with LVEF. After 12 months, 11 patients (36.66%) experienced LV remodeling. Univariate regression analysis demonstrated an association between baseline 99mTc-HFAPi uptake extent and LV remodeling (OR = 2.14, 95%CI, 1.04, 4.39, P = 0.038). CONCLUSIONS: 99mTc-HFAPi SPECT imaging holds promise in predicting LV remodeling post-MI, providing valuable insights for patient management and prognosis.
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BACKGROUND: The effectiveness of post-exposure prophylaxis (PEP) depends on participants adherence, making it crucial to assess and compare regimen options to enhance human immunodeficiency virus (HIV) prophylaxis strategies. However, no prospective study in China has shown that the completion rate and adherence of single-tablet regimens in HIV PEP are higher than those of multi-tablet preparations. Therefore, this study aimed to assess the completion rate and adherence of two HIV PEP regimens. METHODS: In this single-center, prospective, open-label cohort study, we included 179 participants from May 2022 to March 2023 and analyzed the differences in the 28-day medication completion rate, adherence, safety, tolerance, and effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir disoproxil fumarate, emtricitabine, and dolutegravir (TDF/FTC + DTG). RESULTS: The PEP completion rate and adherence were higher in the BIC/FTC/TAF group than in the TDF/FTC + DTG group (completion rate: 97.8% vs. 82.6%, P = 0.009; adherence: 99.6 ± 2.82% vs. 90.2 ± 25.29%, P = 0.003). The incidence of adverse reactions in the BIC/FTC/TAF and TDF/FTC + DTG groups was 15.2% and 10.3% (P = 0.33), respectively. In the TDF/FTC + DTG group, one participant stopped PEP owing to adverse reactions (1.1%). No other participants stopped PEP due to adverse events. CONCLUSIONS: BIC/FTC/TAF and TDF/FTC + DTG have good safety and tolerance as PEP regimens. BIC/FTC/TAF has a higher completion rate and increased adherence, thus, is recommended as a PEP regimen. These findings emphasize the importance of regimen choice in optimizing PEP outcomes. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200059994(2022-05-14), https://www.chictr.org.cn/bin/project/edit?pid=167391 ).
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Amidas , Fármacos Anti-VIH , Combinación de Medicamentos , Emtricitabina , Infecciones por VIH , Compuestos Heterocíclicos con 3 Anillos , Profilaxis Posexposición , Piridonas , Tenofovir , Humanos , Infecciones por VIH/prevención & control , Estudios Prospectivos , Masculino , Emtricitabina/uso terapéutico , Emtricitabina/administración & dosificación , Tenofovir/uso terapéutico , Tenofovir/administración & dosificación , Tenofovir/análogos & derivados , China , Adulto , Femenino , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Amidas/uso terapéutico , Amidas/administración & dosificación , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Persona de Mediana Edad , Profilaxis Posexposición/métodos , Cumplimiento de la Medicación/estadística & datos numéricos , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/administración & dosificación , Alanina/uso terapéutico , Alanina/administración & dosificación , Adenina/análogos & derivados , Adenina/uso terapéutico , Adenina/administración & dosificación , Adulto Joven , PiperazinasRESUMEN
Metabolism is reprogrammed in a variety of cancer cells to ensure their rapid proliferation. Cancer cells prefer to utilize glycolysis to produce energy as well as to provide large amounts of precursors for their division. In this process, cancer cells inhibit the activity of pyruvate dehydrogenase complex (PDC) by upregulating the expression of pyruvate dehydrogenase kinases (PDKs). Inhibiting the activity of PDKs in cancer cells can effectively block this metabolic transition in cancer cells, while also activating mitochondrial oxidative metabolism and promoting apoptosis of cancer cells. To this day, the study of PDKs inhibitors has become one of the research hotspots in the field of medicinal chemistry. Novel structures targeting PDKs are constantly being discovered, and some inhibitors have entered the clinical research stage. Here, we reviewed the research progress of PDKs inhibitors in recent years and classified them according to the PDKs binding sites they acted on, aiming to summarize the structural characteristics of inhibitors acting on different binding sites and explore their clinical application value. Finally, the shortcomings of some PDKs inhibitors and the further development direction of PDKs inhibitors are discussed.
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Proteínas Serina-Treonina Quinasas , Complejo Piruvato Deshidrogenasa , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/metabolismo , Complejo Piruvato Deshidrogenasa/metabolismo , Glucólisis , Sitios de UniónRESUMEN
In recent years, tumor immunotherapy, aimed at increasing the activity of immune cells and reducing immunosuppressive effects, has attracted wide attention. Among them, immune checkpoint blocking (ICB) is the most commonly explored therapeutic approach. All approved immune checkpoint inhibitors (ICIs) are clinically effective monoclonal antibodies (mAbs). Compared with biological agents, small-molecule drugs have many unique advantages in tumor immunotherapy. Therefore, they also play an important role. Immunosuppressive signals such as PD-L1, IDO1, and TGF-ß, etc. overexpressed in tumor cells form the tumor immunosuppressive microenvironment. In addition, the efficacy of multi-pathway combined immunotherapy has also been reported and verified. Here, we mainly reviewed the mechanism of tumor immunotherapy, analyzed the research status of small-molecule modulators, and discussed drug candidates' structure-activity relationship (SAR). It provides more opportunities for further research to design more immune small-molecule modulators with novel structures.
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Inmunoterapia , Receptor de Muerte Celular Programada 1 , Anticuerpos Monoclonales , Factores Inmunológicos , Relación Estructura-Actividad , InmunosupresoresRESUMEN
PURPOSE: Family resilience helps cancer-affected families overcome challenges and may influence an individual's fear of cancer recurrence (FCR). Identifying distinct classes of family resilience among lung cancer patients is crucial for tailored interventions. This study aimed to identify latent classes of family resilience in lung cancer patients and explore their relationships with FCR. METHODS: Three hundred ten lung cancer patients from three hospitals in Fujian were recruited from June to September 2021. Clinical data were extracted from medical records, while sociodemographic details, family resilience, and FCR were self-reported. A latent class analysis was performed to identify family resilience classes. RESULTS: A 4-class solution showed the best fit. Compared to Class 1, the patients who had no comorbidities (ORs = 3.480-16.005) had an increased likelihood of belonging to Class 2 and 3, while those who were not family breadwinners (ORs = 0.118-0.176) had a decreased likelihood. Further, the patients who (1) did not lack interest/pleasure in doing things during the past 2-week period (OR = 7.057), (2) were never smokers (OR = 6.230), and (3) were urban residents (OR = 8.985) had an increased likelihood of belonging to Class 4, while those who were (1) male (OR = 0.167), (2) not the family breadwinner (OR = 0.152), and (3) had none or only one child (OR = 0.203) had a decreased likelihood of belonging to Class 4. The FCR level differed significantly among these four classes. CONCLUSION: Our study identified four distinct classes of family resilience among Chinese lung cancer patients. FCR severity decreased with increasing levels of family resilience.
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Neoplasias Pulmonares , Resiliencia Psicológica , Niño , Humanos , Masculino , Estudios Transversales , Análisis de Clases Latentes , Salud de la Familia , MiedoRESUMEN
BACKGROUND: Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphologic features, and PCOS is associated with infertility. PH domain Leucine-rich repeat Protein Phosphatase 1 (PHLPP1) has been shown to regulate AKT. The aim of present study is to investigate the role of PHLPP1 in PCOS. METHODS: The expression levels of PHLPP1 in dihydrotestosterone (DHT)-treated human ovarian granular KGN cells were determined by qRT-PCR and Western blot. PHLPP1 was silenced or overexpressed using lentivirus. Cell proliferation was detected by CCK-8. Apoptosis and ROS generation were analyzed by flow cytometry. Glycolysis was analyzed by measuring extracellular acidification rate (ECAR). RESULTS: DHT treatment suppressed proliferation, promoted apoptosis, enhanced ROS, and inhibited glycolysis in KGN cells. PHLPP1 silencing alleviated the DHT-induced suppression of proliferation and glycolysis, and promotion of apoptosis and ROS in KGN cells. PHLPP1 regulated cell proliferation and glycolysis in human KGN cells via the AKT signaling pathway. CONCLUSIONS: Our results showed that PHLPP1 mediates the proliferation and aerobic glycolysis activity of human ovarian granular cells through regulating AKT signaling.
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Síndrome del Ovario Poliquístico , Femenino , Humanos , Proteínas Proto-Oncogénicas c-akt , Especies Reactivas de Oxígeno , Glucólisis , Proteínas Nucleares , Fosfoproteínas Fosfatasas/genéticaRESUMEN
A new cladosporol derivative xylophilum A (1), together with 10 known compounds (2-11), were isolated from the rice fermentation of the fungus Cladosporium xylophilum. Their structures were established by extensive spectroscopic methods and comparison of their NMR data with literatures. The antimicrobial activity of compound 1 against 11 kinds of pathogenic microbial was evaluated, but no significant activity was found (MIC >100 µg/ml).
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Secondary lymphedema is caused by damage to the lymphatic system from surgery, cancer treatment, infection, trauma, or obesity. This damage induces stresses such as oxidative stress and hypoxia in lymphatic tissue, impairing the lymphatic system. In response to damage, vascular endothelial growth factor C (VEGF-C) levels increase to induce lymphangiogenesis. Unfortunately, VEGF-C often fails to repair the lymphatic damage in lymphedema. The underlying mechanism contributing to lymphedema is not well understood. In this study, we found that surgery-induced tail lymphedema in a mouse model increased oxidative damage and cell death over 16 days. This corresponded with increased VEGF-C levels in mouse tail lymphedema tissue associated with macrophage infiltration. Similarly, in the plasma of patients with secondary lymphedema, we found a positive correlation between VEGF-C levels and redox imbalance. To determine the effect of oxidative stress in the presence or absence of VEGF-C, we found that hydrogen peroxide (H2O2) induced cell death in human dermal lymphatic endothelial cells (HDLECs), which was potentiated by VEGF-C. The cell death induced by VEGF-C and H2O2 in HDLECs was accompanied by increased reactive oxygen species (ROS) levels and a loss of mitochondrial membrane potential. Antioxidant pre-treatment rescued HDLECs from VEGF-C-induced cell death and decreased ROS under oxidative stress. As expected, VEGF-C increased the number of viable and proliferating HDLECs. However, upon H2O2 treatment, VEGF-C failed to increase either viable or proliferating cells. Since oxidative stress leads to DNA damage, we also determined whether VEGF-C treatment induces DNA damage in HDLECs undergoing oxidative stress. Indeed, DNA damage, detected in the form of gamma H2AX (γH2AX), was increased by VEGF-C under oxidative stress. The potentiation of oxidative stress damage induced by VEFG-C in HDLECs was associated with p53 activation. Finally, the inhibition of vascular endothelial growth factor receptor-3 (VEGFR-3) activation blocked VEGF-C-induced cell death following H2O2 treatment. These results indicate that VEGF-C further sensitizes lymphatic endothelial cells to oxidative stress by increasing ROS and DNA damage, potentially compromising lymphangiogenesis.
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Apoptosis , Daño del ADN , Células Endoteliales , Peróxido de Hidrógeno , Linfedema , Mitocondrias , Estrés Oxidativo , Factor C de Crecimiento Endotelial Vascular , Factor C de Crecimiento Endotelial Vascular/metabolismo , Estrés Oxidativo/efectos de los fármacos , Animales , Humanos , Células Endoteliales/metabolismo , Células Endoteliales/efectos de los fármacos , Linfedema/metabolismo , Linfedema/patología , Linfedema/etiología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Ratones , Apoptosis/efectos de los fármacos , Peróxido de Hidrógeno/farmacología , Especies Reactivas de Oxígeno/metabolismo , Linfangiogénesis/efectos de los fármacos , FemeninoRESUMEN
The invasion of toxic weeds was detrimental to the growth of original vegetation and speed up the degraded grasslands. The purpose of this study was to explore the difference in microbial community, soil physicochemical properties, and enzyme activity in the rhizosphere of Stellera chamaejasme and its associated forages (Stipa purpurea and Polygonum viviparum). The rhizosphere soil microbial communities of S. chamaejasme and its associated forages were determined by high-throughput sequencing technology, the physicochemical properties, and enzyme activities were also measured using soil chemical methods. We performed biological statistical analyses to explore the correlation of rhizosphere micro-ecological environment between the invading poisonous herb S. chamaejasme and its associated forages. The Ascomycota community in the rhizosphere soil of S. chamaejasme was significantly decreased when compared with its associated forages. S. chamaejasme and S. purpurea had a similar bacterial composition, while the rhizosphere of P. viviparum was associated with more Acidobacteria and Bacteroidetes. The RDA analysis showed S. chamaejasme had highly correlated with acid proteinase, invertase, polyphenol oxidase, cellulose, and neutral protease and S. purpurea had highly associated with N-acetyl-beta-D-glucosaminidase, ß-D-Glucosidase, and the P. viviparum had highly associated with total phosphorus, total nitrogen, ammonium nitrogen, soil organic matter, pH, acid phosphatase, and catalase. Along with the invasion of S. chamaejasme, the microbial composition, soil physicochemical properties, and enzyme activity of the growing area changed considerably compared with the associated forages. Taken together, our results suggested that the composition and diversity of microbial communities associated with S. chamaejasme and its associated forages exhibited different patterns, and the rhizosphere soil microbial communities in different plants were regulated by different environmental factors in this alpine grassland ecosystem.
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Microbiota , Thymelaeaceae , Pradera , Suelo/química , Rizosfera , Microbiología del Suelo , China , NitrógenoRESUMEN
Axon regeneration requires the mobilization of intracellular resources, including proteins, lipids, and nucleotides. After injury, neurons need to adapt their metabolism to meet the biosynthetic demands needed to achieve axonal regeneration. However, the exact contribution of cellular metabolism to this process remains elusive. Insights into the metabolic characteristics of proliferative cells may illuminate similar mechanisms operating in axon regeneration; therefore, unraveling previously unappreciated roles of metabolic adaptation is critical to achieving neuron regrowth, which is connected to the therapeutic strategies for neurological conditions necessitating nerve repairs, such as spinal cord injury and stroke. Here, we outline the metabolic role in axon regeneration and discuss factors enhancing nerve regrowth, highlighting potential novel metabolic treatments for restoring nerve function.
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Despite advanced clinical treatment, the mortality rate of cancer patients is high. Recent studies have linked the development of cancer to inflammation. Many cancers are exacerbated by the emergence of inflammatory responses, and non-coding RNAs play an important role in inflammation. Non-coding RNAs include microRNAs, circular RNAs, long-chain noncoding RNAs, etc. The non-coding RNA regulatory network composed of microRNAs, circular RNAs and long-chain non-coding RNAs is involved in the regulatory process of multiple gene expression. They can act on various signaling pathways, such as wnt/ß-catenin, nuclear factorkappa B, phosphatidylinositol 3 kinase/ AKT, mitogen-activated protein kinase, and so on. These signaling pathways can control the occurrence of inflammatory response to some extent, such as regulating the expression of inflammatory cytokines (such as interleukin-6, interferongamma, tumor necrosis factor-α, and so on), making them upregulated or down-regulated. Therefore, it is important to study the role of non-coding RNAs in inflammation to contribute to the future of cancer.
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In the process of chemotherapy, drug resistance of cancer cells is a common and difficult problem of chemotherapy failure, and it is also the main cause of cancer recurrence and metastasis. Non-coding RNAs (ncRNAs) refer to the RNA that does not encode proteins, including microRNA (miRNA), long non-coding RNA (lncRNA) and circularRNA (circRNA), etc. NcRNAs are involved in a series of important life processes and further regulate the expression of ABCC1 by directly or indirectly up-regulating or down-regulating the expression of targeted mRNAs, making cancer cells more susceptible to drug resistance. A growing number of studies have shown that ncRNAs have effects on cancer cell proliferation, invasion, metastasis, and drug sensitivity, by regulating the expression of ABCC1. In this review, we will discuss the emerging roles of ncRNAs regulating ABCC1 in chemotherapy resistance and mechanisms to reverse drug resistance as well as provide potential targets for future cancer treatment.
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MicroARNs , Neoplasias , ARN Largo no Codificante , Humanos , Proliferación Celular , ARN MensajeroRESUMEN
As an important enterprises' practice in implementing the UN 2030 sustainable development, environmental, social, and governance (ESG) performance has drawn escalating attention from government, business and academia. This focus substantially impacts internationalization of enterprises. This paper tries to provide quantitative evidence of the impact of ESG performance of Chinese A-share listed companies on their international operation from 2009 to 2021. The results show that: (i) the ESG performance of listed enterprises exercise a significant positive impact on the internationalization operation. (ii) The effect of ESG performance on enterprises internationality is driven by increasing total factor productivity, enterprise reputation, and green innovation, as well as by mitigating financing constraint. (iii) Good ESG performance significantly boosts enterprise internationalization for non-heavy polluting, large-scale enterprises. This effect is also pronounced for enterprises with local government reports featuring a high frequency of environmental terms or those in high-tech industries.
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CircRNA is stable due to its ring structure and is abundant in humans, which not only exists in various tissues and biofluids steadily but also plays a significant role in the physiology and pathology of human beings. CircPVT1, an endogenous circRNA, has recently been identified from the PVT1 gene located in the cancer risk region 8q24. CircPVT1 is reported to be highly expressed in many different tumors, where it affects tumor cell proliferation, apoptosis, invasion, and migration. We summarize the biosynthesis and biological functions of circPVT1 and analyze the relationship between circPVT1 and tumors as well as its significance to tumors. Further, it's noteworthy for the diagnosis, treatment, and prognosis of cancer patients. Therefore, circPVT1 is likely to become an innovative tumor marker.